Neurology Flashcards

Question

central fever (how common, 2 reasons why and 3 areas damage might be, 6 features, 13 causes of extreme hyperpyrexia)

Answer 1

seen in almost 70% of neurocritically ill patients inflammatory markers causing fever may be triggered by extreme physiologic stress in acute neurologic injury; brain injury may also lead to the disruption of the mesencephalic-diencephalic mechanisms responsible for the inhibition of thermogenesis: damage may be in hypothalamus, midbrain, or pons diagnosis of exclusion. CF occurs early, typically within 72 hours of admission after acute brain injury. All the cultures are negative and the chest radiograph is normal. Fever is disproportionately high and persistent without diurnal variation; tends to be sustained and resistant to antipyretics; also tend to see relative bradycardia note that extreme hyperpyrexia, defined as fever ≥41.1℃ (106°F), is usually noninfectious. Examples include CF, drug fever, malignant hyperthermia, transfusion reactions, adrenal insufficiency, thyroid storm, neuroleptic malignant syndrome, heat stroke, acalculous cholecystitis, mesenteric ischemia, acute pancreatitis, deep vein thrombosis, and pulmonary embolism

Answer 2

within 1 hr if any of: -a GCS score of 12 or less on initial assessment in the emergency department -a GCS score of less than 15 at 2 hours after the injury on assessment in the emergency department -suspected open or depressed skull fracture -any sign of basal skull fracture (haemotympanum, 'panda' eyes, cerebrospinal fluid leakage from the ear or nose, Battle's sign) -post-traumatic seizure -focal neurological deficit -more than 1 episode of vomiting within 8 hrs if some loc or amnesia + one of: ->65yo -bleeding/clotting disorder (inc anticoag) -dangerous mechanism of injury (a pedestrian or cyclist struck by a motor vehicle, an occupant ejected from a motor vehicle or a fall from a height of more than 1 m or 5 stairs) -more than 30 minutes' retrograde amnesia of events immediately before the head injury. if <16yo then within 1hr if: -suspicion of non-accidental injury -post-traumatic seizure -on initial emergency department assessment, a GCS score of less than 14 or, for babies under 1 year, a GCS score (paediatric) of less than 15 -at 2 hours after the injury, a GCS score of less than 15 -suspected open or depressed skull fracture, or tense fontanelle -any sign of basal skull fracture (haemotympanum, 'panda' eyes, cerebrospinal fluid leakage from the ear or nose, Battle's sign) -focal neurological deficit -for babies under 1 year, a bruise, swelling or laceration of more than 5 cm on the head. or if more than 1 of: -loss of consciousness lasting more than 5 minutes (witnessed) -abnormal drowsiness -3 or more discrete episodes of vomiting -dangerous mechanism of injury (high-speed road traffic accident as a pedestrian, cyclist or vehicle occupant, fall from a height of more than 3 m, high-speed injury from a projectile or other object) -amnesia (anterograde or retrograde) lasting more than 5 minutes (it will not be possible to assess amnesia in children who are preverbal and is unlikely to be possible in children under 5) -any current bleeding or clotting disorder. if only one of above then observe for 4 hrs and do CT if GCS falls, vomits again, or has more abnormal drowsiness

Answer 3

Raised ICP: raise head, O2, hypernat, hypervent to drive down co2; inotropes/fluids, hypothermia, decompressive craniectomy base of skull fracture: ICA and CNVII at risk SAH: treat hydroceph or haematoma mass effect; coil or clip (former through vessels, latter open head), bed rest, analgesia, prophylactic nimodipine 60mg 4-hrly and keep well hydrated Around a third of patients develop symptomatic vasospasm (SAH big risk factor hence nimodipine) with feature of delayed cerebral ischaemia: – Reduction in GCS – New focal neurological deficit If BP raised use labetalol to keep sys <160mmHg, not GTN as can cause cerebral vasodilation -> worsen ICP For bleeds, inc spontaneous intracerebral bleeds, need to reverse anticoag: vit K for warfrain (but as acts via synthesis takes up to 24hrs to work so also give beriplex, give antidotes to DOAC if available and 1 dose of desmopressin for antiplatelets (may need to fluid restrict afterwards for 24hrs)); IPC for VTE prophy, aim for D5 LMWH switch

Answer 4

triad of retinal haemorrhages, subdural haematoma, and encephalopathy. This is caused by the intentional shaking of a child (0-5 years old). The diagnosis of shaken baby syndrome has often made the headlines due to the controversy amongst physicians as to whether the mechanism of injury is definitely an intentional shaking of a child. This has often resulted in difficulty for the courts to convict suspects

Answer 5

A cephalhaematoma can often be confused with a caput succedaneum. Distinguishing features of a cephalhaematoma are that they usually develop after birth and do not cross the suture lines of the skull as the blood is confined between the skull and periosteum. It resolves within a few months of birth. Caput succedaneum is an extraperiosteal collection of blood therefore can cross over the suture lines and can be present at birth. It resolves within a few days of birth. Subaponeurotic haemorrhages are a serious condition caused by bleeding in the potential space between the periosteum and subgaleal aponeurosis. Typically there is a boggy swelling that grows insidiously and is not confined to the skull sutures. The neonate may present with haemorrhagic shock. Chignon's are birth traumas that occur after use of a ventouse device during delivery

Answer 6

As adults + Loss of consciousness lasting more than 5 minutes (witnessed) Amnesia (antegrade or retrograde) lasting more than 5 minutes Clinical suspicion of non-accidental injury If under 1 year, presence of bruise, swelling or laceration of more than 5 cm on the head Dangerous mechanism of injury (high-speed road traffic accident either as pedestrian, cyclist or vehicle occupant, fall from a height of greater than 3 m, high-speed injury from a projectile or an object)

Answer 7

open/penetrating or closed/concussional causes of coma: head injury, CVA, SAH, epilepsy, cerebral tumour/abscess or meningitis; alcohol, CO, barbiturates/aspirin/opiates; hyper/hypoglyc; uraemia; encephalopathy (hepatic, hypertensive, metabolic disease); toxaemia signs of skull fractures: nasal bleeding, orbital haematoma, CSF rhinorrhoea, CN injuries, if mid fossa then maybe bleeding from ear or csf otorrhoea; bruising behind ear/suboccipital region (Battle's sign) suggests post fossa; open fractures inc basal skull fractures have risk of meningitis brain injury may be traumatic or secondary (from hypoxia, hypercapnia, hypotension, intracranial bleeding, or infection); coup and contre-coup injuries w/ coup often front or temp lobes and contre-coup occipital, be aware of both cerebral perfusion pressure = MAP - ICP so raised ICP will dec perfusion and this leads to the Cushing reflex: irreg breathing, bradycardia and (sys) hypertension in head trauma cases (unless trauma elsewhere causing an overriding hypotension); note this reflex may progress to death within minutes, so brady + hyper = manage quickly persistent headaches, dizziness, concentration problems may be problem for months after even a minor head injury, will go with time amnesia even of a few hours can carry good prognosis, if days/weeks then full recovery less likely

Answer 8

history: mechanism of injury, condition of pt immediately afterwards (GCS, limb movements, pupils and vitals if poss); any change in condition since; how pt was before the injury inc were they drunk? diabetic? do they have false eye or chronic glaucoma (explaining abnormal pupil responses) always assume cervical spine injury and immobilise until CT or good x-ray proves otherwise, and do ABCDE and a full secondary survey; note GCS raising pressure from haematoma or oedema on one side will pressure CNIII on that side causing ipsi pupil to dilate and lose light reactivity but consensual constriction intact until compression of the other CNIII by continuing inc in pressure; bilat fixed dilated pupils is thus a poor sign; local trauma from skull base fractures might sometimes produce the same thing; pupil dilation can thus be false localising sign injury to brainstem can cause pyrexia >40deg as temp reg centre damaged

Answer 9

inflamed meninges secondary to infection, autoimmune antibodies or paraneoplastic processes Infections may be secondary to: Bacteria e.g. Neisseria meningitides (‘meningococcal’ = most common), Streptococcus pneumoniae (‘pneumococcal’ = 2nd), Haemophilus influenza b, Listeria monocytogenes, Group B streptococcus (high risk in newborns) Viruses e.g. Enteroviruses (Echo/Coxsackie), Herpes Simplex Virus (2>1), VZV, HIV; Fungal causes e.g. Cryptococcus; Parasites e.g. Amoeba Typically patients present with a headache ◦ Fever is usually present ◦ +/- Photophobia ◦ +/- Confusion/altered mental state ◦ +/- Vomiting ◦ +/- Neck pain or stiffness ◦ Altered neurology may have led to their presentation e.g. altered speech/weakness on one side/reduced hearing ◦ If a non-blanching rash is present this is severe – it indicates septicaemia; seizures also late feature In children they may not be able to describe the above, but parents may describe them as being ‘’irritable’’ or ‘’drowsy’’. On examination, if <6 months, they may have a bulging fontanelle on examination: ◦ AMTS + GCS ◦ Neurological examination – any focal neurological changes (loss of power/coordination/speech/sensation/hyperreflexia)? ◦ Check fundi for any signs of increased intracranial pressure (papilloedema) ◦ Other systems – look for possible causes of the meningitis and look for any signs of bacteraemia/sepsis e.g. non-blanching (petechial) rash – can be elicited by pressing on the rash and seeing if it blanches or not (parents may have done the ’tumbler test’) ◦ Key signs of meningism are: ◦ Brudzinski’s sign = forced flexion of the neck causes reflex flexion of the hips, if meningism is present ◦ Kernig’s sign = with the knees and hips flexed at 90 degrees, subsequent extension of the knees causes resistance, due to pain in the back/neck bloods (4 bottles: FBC, culture, lab glucose for comparison to csf, baseline biochem), pcr/viral cultures, CT head bacterial: turbid/cloudy csf with high opening pressure, wcc, neutrophils esp, protein, and low glucose (<0.4 ratio csf:blood) viral: clear csf with normal opening pressure, wcc <1000 with more lymphocytes, normal/high protein, normal glucose TB: very thick/turbid with normal/high opening pressure, more lymphocytes than neuts, high protein, low/very low glucose

Answer 10

urgent transfer to hospital, in community give benzylpenicillin IM: ◦ <1 year of age — 300 mg ◦ Children 1–9 years of age — 600 mg ◦ Adults and children 10 years of age or older — 1200 mg in hospital: Ceftriaxone IV + Dexamethasone (to reduce inflammation), then guided by cultures ◦ If Penicillin allergic – check the severity of the reaction – if severe (e.g. anaphylaxis) = Chloramphenicol (N.B. supply issues) ◦ If <3 month or ≥60 years old or immunocompromised/pregnant or Listeria suspected = add in Amoxicillin cover too ◦ If possibly viral in nature/signs of encephalitis = Aciclovir is added in ◦ Close contacts may need prophylactic antibiotic treatment cover – typically this is with either: rifampicin or ciproflox If a more unusual cause: ◦ TB = needs TB meds = ‘RIPE’ quadruple therapy for 2 months (Rifampicin, Isoniazid, Pyrazinamide and Ethambutol) followed by Rifampicin and Isoniazid for a further 10 months (12 months total treatment) ◦ Cryptococcus = Amphotericin B and Flucytosine (IV) and then oral Fluconazole also: If you're treating empirically for suspected bacterial meningitis (either contracted abroad or from a patient who has spent extended duration abroad in recent history or have had prolonged or multiple exposure to antibiotics (within the past 3 months)) and you haven't yet identified the causative organism, you need to take into account the possibility of penicillin-resistant Streptococcus pneumonia and add vancomycin. this is because because in the UK Pneumococcal penicillin resistant is exceedingly rare, whereas around many other parts of the world it is common enough that you can't afford to not cover for it in the case of meningitis. This is largely driven by the over-use of penicillin-based antibiotics (both by prescribers and over-the-counter). once cultures and sensitivities are back you can stop the vanc

Answer 11

dissemination of malignant cells from the primary tumor sites to leptomeningeal (ie arachnoid/pia) layers of the CNS. Can occur in the advanced stage of any cancer, solid as well as hematological malignancies (5-8% solid, 5-15% haem, and B-cell lymphoma commonest source). It is a rare complication with a dismal prognosis may present with raised ICP sec to obstructing or non-obstructive hydrocephalus (depending on where block is), meningeal irritation causing a meningitis, metabolic depression of cortex due to glucose/O2 being used by cancer cells giving encephalopathy, seizures depending on site involved, often temporal lobe seizures giving deja vu, stereotypical movements, euphoria, hallucinations, and amnesia posterior fossa involvement can give cerebellar signs and CN involvement if spinal cord involved can give segmental numbness, dysesthesia, pain, and lower motor neuron pattern limb weakness, or even cauda equina CSF: pleocytosis (esp lymphocytes), high protein, low glucose, positive cytology (differential may be eg chronic fungal infection) MRI: findings may include hydrocephalus and leptomeningeal enhancement of the brain in the T1 weighted image with contrast. T2/FLAIR hyperintensities may be seen in the subarachnoid space. The cerebral convexities, cerebellar folia, basal cisterns, and ventricular ependymal regions are the common areas that display enhancement or nodular deposits in CM. linear and nodular leptomeningeal enhancements may occur along the nerve roots in cord involvement Appearance similar to infectious or inflam meningitis, hence need for cytology depending on performance status, palliative care may be recommended; however, if for active rx then intrathecal chemo (+/- radio and systemic chemo); note intrathecal chemo cannot be done if VP shunt in situ as toxic drugs then straight into other part of body

Answer 12

The patient may either have self-presented or may have been brought in by a concerned relative, partner or friend ◦ May have had an onset over a few days – weeks, can be faster ◦ Try to exclude drug use in history key poss features: ◦ Headache/prodromal symptoms (e.g. GI upset) ◦ Fever ◦ Confusion ◦ Drowsiness ◦ Altered behaviour ◦ Psychosis/hearing voices ◦ +/- Vomiting ◦ +/- Photophobia ◦ Stiffness in the neck/meningism indicates that this may be a meningoencephalitis ◦ Autonomic dysfunction may be present (more commonly in autoimmune cases) ◦ Seizures may occur on examination: ◦ They may have an altered mental state (labile emotions/psychosis may be present) ◦ GCS ◦ Full neurological examination ◦ Any meningeal irritation present (Brudzinski’s and Kernig’s tests)? ◦ Check for any signs of a seizure/head injury that may otherwise explain their behaviour ◦ Full examination to exclude other infections as a possible cause for fevers/confusion etc. bloods and cultures (consider toxicology screen of blood and urine to rule out drugs causing altered mental state) CT head; LP (if no virus can check for anti-NMDAr antibodies); EEG; MRI key causes: ◦ Viral = most commonly HSV ◦ Bacterial = may a complication of meningitis causes, Lyme disease, Syphilis etc ◦ Parasitic/protozoal = Toxoplasmosis, malaria etc ◦ Autoimmune = NMDA-receptor Abs, ADEM treatments: ◦ Aciclovir if viral (cover with this until proven not viral) ◦ If autoimmune = may need steroids/IVIg/plasmapheresis ◦ If driven by a malignancy (e.g. ovarian teratoma (NMDAR), small cell lung cancer (Hu)) = remove the tumour

Answer 13

Meningitis triad Reduced GCS + focal neurological deficits (ophthalmoplegia, dysphasia, hemiparesis) Fever, vomiting, seizures Diffuse oedema, esp in temporal lobes on CT/MRI CSF microscopy, culture & biochem PCR, Acute & convalescent serology Slow-wave changes on EEG

Answer 14

encephalitis caused by various different autoantibodies; classically presents with the subacute onset (<3mo -> if longer then this consider neurodegen disease, although some antibodies can give a longer course - ask careful history to family for subtle changes) of short-term memory deficits, seizures or psychiatric symptoms, these may be fluctuating ie sometimes normal and then odd behaviour various types of autoimmune encephalitis antibodies can be categorized into three groups: intracellular paraneoplastic Ab, cell-surface or synaptic Ab, and with Ab of unclear significance. Intracellular paraneoplastic antibody is frequently associated with systemic tumors (in more than 90% of cases). These patients are less responsive to immunotherapy because the antibody causes neuronal damage. Cell-surface or synaptic Ab is variably associated with systemic tumors, and patients with these Ab are more responsive to immunotherapy. For the diagnosis of definite autoimmune limbic encephalitis, all four of the following criteria have to be met: subacute onset, bilateral brain abnormalities on T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI highly restricted to the medial temporal lobes (may see unilateral high signal in some cases but consider stroke and tumour), cerebrospinal fluid (CSF) pleocytosis or EEG with epileptic or slow-wave activity on the temporal lobe, and reasonable exclusion of alternative causes. Although detection of auto-Abs is the best diagnostic method for autoimmune encephalitis, there are many Ab-negative probable autoimmune encephalitis cases. Then depending on type consider workup for systemic tumours -> SCLC, ovary, breast are commonest (CT CAP +/- pelvis MRI and USS breast/testes + relevant bloods should pick up most, consider CT PET if >65yo) Although about half of all autoimmune encephalitis series are Ab-negative cases, the detection of auto-Abs is a confirmatory diagnostic test, panel includes anti-NMDAR, AMPA1, AMPA2, LGI1, CASPR2, DPPX, GABAR B1; send blood and CSF as some will show up better/only in one or the other; also send the intracellular Abs Hu, Ma2 and GAD

Answer 15

amoeba found in freshwater that is usually contaminated with soil infection with N. fowleri leads to amebic meningoencephalitis. Infection occurs when warm freshwater enters nasal passages and makes its way through the cribriform plate into the central nervous system. The incubation period can last anywhere from 1-14 days N. fowleri elicits a significant innate immune response; combination of the intense immune response and virulence of this organism lead to the significant destruction of brain parenchymal tissue should be suspected in patients with meningoencephalitis or meningitis when a recent history of freshwater exposure is present. Cerebrospinal fluid (CSF) analysis can be similar to that in bacterial meningitis with glucose being low to normal, elevated proteins, and polymorphonuclear cells. CSF pressures are elevated Identification of N. fowleri can be missed on gram stains and cultures as the fixation procedure destroys them. Visualization can be achieved on wet mounts and stains like H&E; Antigen detection by immunohistochemical staining techniques can be performed on CSF or tissue sample, along with PCR and cultures v high doses of amphotericin B is main mx; therapeutic cooling has been used to buy time for mx to work

Answer 16

very rare, chronic inflammatory neurological disease that usually affects only one hemisphere. It most often occurs in children under the age of 10 but can also affect adolescents and adults chronic inflammation of the brain, with infiltration of T lymphocytes Frequent and severe seizures (often focal but may be mixed or generalised) Encephalitis Progressive loss of neurological functions including motor skills, speech, and eventual hemiparesis +/- hemianopia Children with RE frequently enter a second phase of permanent, but stable, neurological deficits after eight to 12 months dx can be made clinically, EEG will usually show the electrical features of epilepsy and slowing of brain activity in the affected hemisphere, and MRI brain scans will show gradual shrinkage of the affected hemisphere with signs of inflammation; brain biopsy definitive but not always needed steroids, IVIg, plasmapharesis, tacrolimus; in chronic phase try to control remaining sx; standard AEDS often not effective, so surgery to disconnect affected half which can give further weakness and hemianopsia (but in v young children plastic brain can take over many or all lost features); may avoid if left side affacted as would lose speech centre

Answer 17

non-blanching rash indicates the infection has caused disseminated intravascular coagulopathy (DIC) NICE recommend lumbar puncture as part of the investigations for all children: Under 1 months presenting with fever 1 – 3 months with fever and are unwell Under 1 years with unexplained fever Steroids are also used in bacterial meningitis to reduce the frequency and severity of hearing loss and neurological damage. Dexamethasone is given 4 times daily for 4 days to children over 3 months if the lumbar puncture is suggestive of bacterial meningitis - not if signs of men septicaemia

Answer 18

pitu apoplexy: usually into pitu adenoma which usually hasnt been diagnosed sudden headache +/- worsening visual field defect or double vision, then acute panhypopitu, notably adrenal crisis; oft nausea and vomiting, sometimes meningism, may have dilated pupils due to CNIII compression adrenal crisis: hypotens, hypogly, abdo pain generally idiopathic, though low incidence CTH, MRI, LP (rule out SAH/mening), basic bloods inc pitu tests, visual field testing treat adrenal crisis with hydrocortisone, refer to neurosurg (+ urgent ophtho review to assess visual fields) *if seeing a sag MRI in exam quite likely due to pitu adenoma

Answer 19

fever, n&V, lethargy, irritability, toxic appearance, anorexia, myalgia, arthralgia, headache, difficulty breathing; sometimes chills, sore throat, abdo pain, diarrhoea specifics: non blanching rash, stiff neck, crt up, cold extremities, shock, leg pain, bulging fontanelle, photophobia, kernigs sign pos (cant extend knee when hip flexed), seizures, focal neuro deficit children oft present with the non specific signs eg look like urti, fever, vomiting, irritability; may have seizures; so take into account speed of progression, parental concern, overall severity, and transfer to sec care if any doubt rash may be petechial or purpural: examine whole body, inc palms/soles/conjunctiva/palate (esp if darker skin); disease can be advanced before rash appears; rapidly evolving rash risk factor for fatal outcome; risk of meningococcal disease high is rash spreading, evolves to purpura, signs of meningitis or shock consider other causes of petechiae, purpura; sah; aseptc, viral, fungal, drug induced meningitis; encephalitis; sepsis if septic or rash present: emergency admission, single iv/im benzypenicillin 300mg if <1yo, 600 if 1-9, 1200 if >9yo, withhold this if history of penicillin allergy non nonblanching rash: admit but no antibiotic unless hospital admission going to be delayed; if cant exclude them having this but no spec signs, still admit to sec care for full investigation bact men is notifiable disease, hpu will give advice what to do with contacts: proph if living together for 7days+, or exposed to large dose of resp droplets around time of admission 4-6wk review after hospital discharge with paediatrician

Answer 20

Antibiotics < 3 months: IV amoxicillin (or ampicillin) + IV cefotaxime - note no ceftriaxone if <3mo as it displaces bilirubin from albumin binding sites, resulting in higher levels of bilirubin that accumulate in the tissues > 3 months: IV cefotaxime (or ceftriaxone) 2. Steroids NICE advise against giving corticosteroids in children younger than 3 months dexamethsone should be considered if the lumbar puncture reveals any of the following: frankly purulent CSF CSF white blood cell count greater than 1000/microlitre raised CSF white blood cell count with protein concentration greater than 1 g/litre bacteria on Gram stain 3. Fluids treat any shock, e.g. with colloid 4. Cerebral monitoring mechanical ventilation if respiratory impairment 5. Public health notification and antibiotic prophylaxis of contacts ciprofloxacin is now preferred over rifampicin

Answer 21

Meningism (inflammation or irritation of the meninges) can lead to increased resistance to passive flexion of the neck (neck stiffness) or the extended leg (Kernig’s sign). Patients may lie with flexed hips to ease their symptoms. Meningism suggests infection (meningitis) or blood within the subarachnoid space (subarachnoid haemorrhage absence of all three signs of fever, neck stiffness and altered mental state virtually eliminates the diagnosis of meningitis in immunocompetent individuals put patient supine: Neck stiffness * Place your hands on either side of the patient’s head, supporting the occiput. * Flex the patient’s head gently until their chin touches their chest. * Ask the patient to hold that position for 10 seconds. If neck stiffness is present, the neck cannot be passively flexed and you may feel spasm in the neck muscles. * Flexion of the hips and knees in response to neck flexion is Brudzinski’s sign. Kernig’s sign * Flex one of the patient’s legs to 90 degrees at both the hip and the knee, with your left hand placed over the medial hamstrings Extend the knee while the hip is maintained in flexion. Look at the other leg for any reflex flexion. Kernig’s sign is positive when extension is resisted by spasm in the hamstrings. Kernig’s sign is absent with local causes of neck stiffness, such as cervical spine disease or raised intracranial pressure.

Answer 22

rbcs and wbcs can be due to bloody tap/ivh, or inflam; in blood white:red is 1:500/600, if white cells inc'd then suggests some inflam component csf should always be clear; white cells 0-100 in premie, 0-15 in neonate, 0-10 in infant and 0-5 in child; low or no polymorphs (so wcc all lymphocytes); red cells 0-1000 in premie, 0-500 in neonate, absent in infant or older; protein 1-4 in premie, 0,3-2 in neonate, 0,2-1 in infant, 0.2-0.4 in child; glucose always 2/3 of blood polymorphs up to 50,000 in bacti, 1000 if partially treated or TB, few in viral; lymphocytes few in bacti, up to 1000 in partially treated, viral, TB; protein raised in bacti and TB most, a little in others; TB glucose v low, bacti low, partially treated or viral normally normal cerebral abscess can be sterile but may see protein and lymphocytes; this and TB both have long history of several weeks fever, headache, non-specific symptoms and both give sterile culture with raised protein, but TB will have low glucose leukaemia can cause csf lymphocytosis (check blood film!) herpes encephalitis oft haemorrhagic so bloodstained csf, glucose low in 20% of cases mumps meningitis has low glucose

Answer 23

protein: GBS, spinal block, meningitis, cerebral abscess, neurosyphilis, SDH, cerebral malignancy oligoclonal bands: MS, sarcoidosis, SLE, SSPE, SAH, neurosyphillis

Answer 24

in neonates: GBS, e coli, listeria after neonatal: neisseria, strep pneum, staph aureus, epidermidis (esp if indwelling prosthesis like a shunt), HiB, pseudomonas, klebsiella, TB, salmonella pneumococcalis most likely to cause neuro sequelae (but all can), HiB meningitis sequelae most reduced by dexamethasone

Answer 25

look for fracture, intracranial calcification, enlarged/destroyed sella turcica (raised icp or tumour), craniosynostosis, punched out lesions (due to histiocytosis, leukaemia, neuroblastoma), wormian bones (clediocranial dysostosis, hypothyroidism, down syndrome), increased density (oestopetrosis, hair on end appearance of beta thal)

Answer 26

choroid plexus calcification intracranial bleed infection (toxoplasmosis causes diffuse [triad of hydroceph, bilat chorioretinitis, intracran calcification], CMV causes perivent, also TB menin, cerebral abscess, cysticercosis) TS (perivent and subependymral esp around foramen of munro, may look like candle dripping into ventricles) sturge-webe syndrome (tram line on plain x ray with linear parallel calcification commonest in parieto-occipital, usually not if <2yo) hypo/hyperparathyroid tumours (craniopharyngioma, astrocytoma + others) SDH and EDH

Answer 27

copper beating of skull, widening of sutures, thinning of the vault, and erosion of clinoid processes/sella turcica

Answer 28

1. red flags? 2. probably migraine, maybe tension, maybe cervicogenic, are you unable to convince yourself it's these? 3. if yes to above -> neuro r/v may be helpful, not necessarily same day red flags: thunderclap (SAH, apoplexy), recurrent or progressive severe (CVST -> remember sertraline incs risk, HTN -> PRES type picture), altered mental status or fever (encephalitis, start aciclovir asap), visual changes or 6th nerve palsy (CVST, IIH, raised ICP), positional (CSF leak, consider SDH so scan), new neuro signs, pregnant (CVST) also don't forget to consider acute glaucoma ask about FH, ask if catamenial, ask about opioid/triptan/analgesia use, ask about sleep hydration and caffeine + elicit drugs; ask about factors influencing migraine prophylaxis choice eg plans for pregnancy, ideas re: weight gain, do they have vasovagals, on other meds examination: minimum limbs, eye movements, acuity + fundoscopy ix: CT if red flag, CTV if think CVST mx (assuming red flags ruled out ie treating as possible migraine) -> hydrate them well, couple of bags would be okay; triptan +/- NSAIDs (naproxen a good option or high dose aspirin 900mg if old enough) acutely, if nausea present or quite bad give metoclopramide too (helps as migraines reduce gastric motility, thus you need a prokinetic to improve gastric emptying and so absorption of your oral meds - it also has a role in reducing pain independent of this too; prochlorperazine is an alternative that may be more effective); then home with NSAIDs over next few days, tell them to rest and the lingering headache should resolve, and safety net; if can't control in ED using above get neuro input; also d/c with plan for next one (eg NSAIDs, triptans, maybe antiemetic) and advise them to speak to GP re: prophylaxis re: CTH, if within 6 hours of onset for SAH and read by neuroradiologist then >99% sensitivity, if negative then no need for LP; if either of above not true and neg then need delayed LP to rule out; alternative if can't get LP is MRI (picks up haemosiderin from chronic or previous bleeds

Answer 29

be alert to meningism (stiff neck, pos kernig + brudzinski) -> (meningitis, SAH, pitu apoplexy), tonsillitis (or other jaw or salivary gland infection), otitis media, upper lobe pneumonia, torticollis, JCA, dermatomyositis, neck lump, presentation of a neuromuscular disease

Answer 30

most likely partially treated meningitis but don't forget viral meningitis or brain abscess; latex agglut studies can identify cell walls of killed bacti

Answer 31

may be benign intracranial hypertension, which presents with headache, vomiting, and poss diplopia (6th nerve palsy) csf pressure distributed evenly meaning normal appearing ventricles and sulci (or often slit like but pressure still evenly distributed) due to impaired absorption at the arachnoid villi; LP has low risk of coning as no pressure gradient 90% of time is idiopathic but also tetracyclnes, steroids, obesity, cushings, addisons, following acute OM main danger is visual loss as blind spot enlarges treat causes (eg weight loss), acetazolamide or csf drainage (though therapeutic tap not advised anymore as just accumulates again), shunt may be required

Answer 32

first: Blood pressure must be measured to exclude malignant hypertension, as defined as a diastolic blood pressure greater than or equal to 120 mm Hg or systolic blood pressure greater than or equal to 180 mm Hg patients should have papilloedema confirmed and an assessment made of the imminent risk to their visual function. The following should be recorded in the presence of papilloedema: visual acuity pupil examination intraocular pressure (to exclude hypotony, a rare cause for disc swelling) formal visual field test (perimetry) dilated fundal examination to grade the severity of the papilloedema and exclude ocular causes for disc swelling. Where possible, document the fundus picture with drawings and document key findings on the optic nerve head (hyperaemia, haemorrhages, cotton wool spots, obscuration of the vessels and so on). Photographs and/or optical coherence tomography (OCT) imaging are useful then within 24 hours should have MRI head and venography (CT or MR) then do LP and record opening pressure (>25) need to also exclude other secondary causes of raised intracranial prssure: FBC (polycthemia or anaemia), CKD (U&Es), OSA (history/sats monitoring), sle (inflam markers), TFTs (high or low function), hypopara (vit D levels, bone profile, PTH, Mg), cushings addisons and adrenal insuff (U&Es and BM as first clue + history) mx: if BMI >30 weight management advice should def be given if vision threatened then lumbar drain and refer to surgery (CSF diversion) if vision not threatened consider acetazolamide - LP relief temporary as fluid replaced so serial LP not recommended can manage headache short term with paracetamol/NSAIDs but medication overuse is a big problem topiramate may have a role, and sometimes triptans and migraine prophylaxis - assessment by neurologist is helpful long term weight loss >15% may cause remission acute headache if have shunt: meningitis? LP and treat; no meningitis but vision worsening: shunt reviison; no vision threatened either, may be eg medication overuse, evaluate and treat but exclude genera ddx for acute headache

Answer 33

metabolic acidosis; nephrolithiasis; paraesthesia increased urine output leucopenia, thrombocytopenia, anaemia, tinnitus or reduced hearing, skin blistering, electrolyte abnorms giving cramps or dizziness it is a sulfonamide and so can inhibit CYP enzymes

Answer 34

periodic, usually unilat, usually pulsatile headaches; may be migraine with or without aura former is disturbance of neurological function then after a few minutes or hours hemicranial (bilat in 1/3 cases) headache, nausea, vomiting lasting for hours to day or more; latter is unheralded onset over minutes of hemicranial headache, sometimes generalised but rarer, with or without nausea and vomiting, and following same temporal pattern as with aura; photophobia, sonophobia, and often osmophobia attend both types; movement of head intensifies; pt often likes to sleep in darkened quiet room; hemicranial and pulsatile characteristics are most defining of migraine more common in women, sometimes in children but usually adolescents through to middle age; less common as get older; be cautious saying it's migraine if first time having it pt is >30yo (although it still can be) may sometimes or exclusively occur in premenstrual period; sometimes migraines occur for first time in first trimester, but usually pregnancy reduces migraine frequency tyramine, alcohol, jarring of head, strong sensory stimuli, excess or withdrawal from caffeine have been implicated as triggers visual aura may be flashes of light, scintillating scotoma,and zigzag fortification spectra; sometimes vision may blur or shimmer, these hallucinations moving across visual field and leaving homonymous scotoma in wake sometimes other aura less common but may be numbness/tingling of lips, face, hand on one or both sides, confusion, weakness in one arm or leg, aphasia or dysarthria, dizziness, unstable gait, drowsiness; if one symptom follows another or eg tingling spreads this is over minutes rather than instant as in tia or over seconds as in seizure; aura usually lasts for 30mins

Answer 35

may be bilat or not that pulsatile; sometimes crash migraines occur with abrupt and severe pain resembling a thunderclap headache but usually will find the peak of pain took minutes to evolve rather than being very rapid but CSF and imaging needed to truly distinguish this migraine from SAH any 2 out of the 3 main things of aura, headache (yes really), GI upset may be absent; eg oft in advancing age only the aura occurs, and that with dec freq; migraine w/o headache is fully possible; sometimes sudden transient blindness or hemianopia with only mild headache can occur migraine with brainstem aura: often kids with FH of migraine, visual aura over most of visual fields, some of vertigo, incoordination, tingling in hands and feet, dysarthria lasting 10 to 30 mins then headache, usually occipital; may faint or become v confused when headache about to begin; imaging to exclude disease of basilar a and brainstem; rec attacks makes diagnosis clearer and imaging w/ associated stroke risk less neccessary familial hemiplegic migraine: episode of unilat paralysis in children, sometimes massive unilat brain swelling cranial trauma may precipitate migraines in ppl prone to getting them; some children and teens may, after mild head injury, lose vision, have severe headache, or be plunged into state of confusion lasting hours or days; another version has abrupt onset unilat paralysis or aphasia after virtually every minor head injury, may see in eg athletes or sporty ppl, with no headache or visual disturbances; subdural haematoma and carotid a dissection should also be considered; will often see FH of migraine but not always migraine and aura seems to double risk of stroke esp if also eg smoke or on ocp

Answer 36

treatment of acute attack should begin during prodrome for mild headaches, paracetamol, NSAIDs may control pain; worth trying a few diff combos to see what works best and using high-ish doses if needed for severe attacks can use sumatriptan (naratriptan or others) or dihydroergotamine; if given subcut then ineffective if given during the aura, give at onset of headache instead; oral and nasal sprays on other hand should be given during aura if poss these drugs cause cerebral hypertension so dont use if poorly controlled hypertension or cerebral/coronary/peripheal artery disease or if on other sympatheticomimetic drugs due to risk of vasospasm or haemorrhage in refractory cases corticosteroid may be used iv or po, and failing that narcotics to provide restful sleep until it passes propranolol can be used as prophylaxis, 10-20mg po tds titrating dose up; atenolol may also be tried from 40-160mg/d; side effects inc fatigue etc so not first choice topiramate or amitriptyline 10, 20mg nightly may be tried; verapamil, nifedipine, indomethacin worth trying too if those fail; botox injection into sensitive muscles like temporalis can also help avoiding triggers and limiting caffeine may be helpful acupuncture worth trying too Acute treatment first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide (caution in young ppl due to acute dystonia risk) or prochlorperazine and consider adding a non-oral NSAID or triptan Prophylaxis prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. NICE advise either topiramate or propranolol 'according to the person's preference, comorbidities and risk of adverse events'. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives if these measures fail NICE recommend 'a course of up to 10 sessions of acupuncture over 5-8 weeks' NICE recommend: 'Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people' for women with predictable menstrual migraine treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of 'mini-prophylaxis' Mg supplements also help to reduce migraine intensity Pizotifen can also be used as a prophylactic agent

Answer 37

prescribe ibuprofen oral solution (OS) (10 mg/kg) as an initial treatment option For adolescents with migraine, clinicians should prescribe naproxen and a nasal triptan Clinicians should offer an alternate triptan, if 1 triptan fails to provide pain relief, to find the most effective agent Consider giving ondansetron to all even in absence of nausea If oral meds not tolerated then IV metoclopramide or prochlorperazine + IVF + non-oral NSAID and triptan if not given Explain to parents that metoclop/prochlor and oral triptans not licensed in kids and explain risks, document if they consent Clinicians must not prescribe triptans to those with a history of ischemic vascular disease or accessory conduction pathway disorders Advise them to take triptan at start of headache not during aura Advise re: medication overuse headache prophylaxis: riboflavin and Mg supplements, and choose between topiramate, propranolol, and pizotifen; can r/v and adjust these also note that there is a probable relation between colic and migraine, therefore, migraine and colic as 2 pain syndromes may have a common pathophysiology; continued research is needed

Answer 38

usually adult men (5:1 m to f) age 20-50 months at a time with nothing then several a day for several days is usual pattern; occurring around night time is most common but can be at other times severe unilat pain deep in and around eye, usually nonthrobbing; often radiate to forehead, temple, cheek blocked nostril, rhinorrhoea, lacrimation, miosis, flush of cheek for 15-180 mins; sometimes ptosis which may become permanent after repeated attacks; ipsilat temp artery may become enlarged and tender during attack; most patients pace or rock on spot with hand to head linked to circadian rhythm with parts of SCN seeming to be active on pet scan before attack and stimulation of hypothalamus is experimental treatment to stop the headaches ICA wall may expand during attack, compromising the symp plexus on the ica leading to the horner syndrome symptoms; this seen in pt coincidentally having arteriogram but not yet replicated 100% O2 for 15 mins at start of attack may abort it; at start of attack give subcut or nasal sumatriptan, can give subcut injection up to 2x a day verapamil may be used to terminate a cluster of headaches and is main form of prophylaxis partial section of trigeminal nerve may be attempted if intractable or block with LA alcohol or smoking may trigger an attack! first bout needs specialist confirmation (and may neuroimage to exclude other causes)

Answer 39

bilat and may be frontal, tempotal, or occipitonuchal or diffuse across cranium; dull aching or tightness/pressure; may be interpreted as waves or throbbing, but isnt pulsatile ie related to the pulse; nausea, photo and phonophobia, unilat, pulsatile main ways to tell migraine from this, also the onset of these is more gradual and may persist for days, weeks, months, even years; one of few headache types persistent throughout the whole day (sometimes) more likely to arise in middle age and coincide with anxiety, fatigue, depression not more than 2 in 1000 pts with persistent tension headache will be found to have eg intracranial tumour; 1/3 will have symptoms of depression sometimes chronic daily headache may dev pulsatile quality, blurring distinction with migraine a little persistent muscle contraction unclear if related as some emg studies dont show this simple analgesia for brief or mild headaches; persistent, severe, or freq respond best to drugs for dep or anxiety eg amitriptyline at night; stronger analgesics not helpful; massage and meditation can help, yoga and exercise too usually lasts 30mins to several hours squinting, poor posture, skipping meals, dehydration, lack of physical activity, strong sensory experiences can act as triggers acute treatment: aspirin, paracetamol or an NSAID are first-line prophylaxis: NICE recommend 'up to 10 sessions of acupuncture over 5-8 weeks' low-dose amitriptyline is widely used in the UK for prophylaxis against tension-type headache. The 2012 NICE guidelines do not however support this approach '...there was not enough evidence to recommend pharmacological prophylactic treatment for tension type headaches. The GDG considered that pure tension type headache requiring prophylaxis is rare

Answer 40

subdural haematoma will be dull, steady, unilat, with drowsiness, confusion, hemiparesis, may get worse when lying down or on one side; headaches in this case inc in freq or sev; may have fluctuating cognition also postconcussion syndrome: dizziness, tiredness, nervousness, irritability, problems concentrating or some confusion, the headache may resemble a tension type one and needs reassurance, get pt active, maybe treatment for dep or anxiety whiplash injuries can give bilat or unilat retroauricular or occipital pain

Answer 41

headache actually infreq as sign of brain tumour, particularly as a heralding symptom usually deep, nonthrobbing (not always), aching or bursting; positional changes may worsen it; unexpected projectile vomiting may occur in late stages, or early stages if in post fossa; supratentorial tumours give pain felt anterior to interauricular circumference of skull; if pain bilat suggests rising icp due to tumour; greatly raised icp may also cause vomiting, transient blindness, leg weakness leading to collapse, and loc

Answer 42

almost always >55yo intense throbbing or non throbbing headache, sometimes with stabbing pains, may dev rapidly; usually unilat, sometimes bilat, usually localised to site of temp a's; these a's often thickened and tender; jaw claudication in extreme cases often feel unwell, may have lost weight, be running fever; esr up, crp up; aching of prox limbs in 50% cases reflecting concurrent polymyalgia rheumatica masticatory claudication is specific but not sensitive sign predisolone 40-60mg po od over several weeks down to 10-20mg po od for months or years if needed to prevent relapse; if doesnt improve within a few days of starting then question diagnosis; esr and crp should return to normal; biopsy the temporal a If there is new visual loss (transient or permanent) or double vision: Arrange an urgent (same day) assessment by an ophthalmologist. Depending on the clinical situation, the specialist may advise one-off high dose corticosteroid treatment in primary care while the person awaits transfer to ophthalmology. Acute or intermittent visual loss due to GCA is usually treated with intravenous glucocorticoid therapy; if this is not possible, 60–100 mg oral prednisolone may be given for up to 3 consecutive days. For all other people with suspected GCA: Urgently discuss with a specialist and refer using a fast track local GCA pathway. Specialist assessment (usually a rheumatologist) should be on the same working day if possible, and in all cases within 3 working days. Suspected GCA should be immediately treated with glucocorticoids. Discuss the need for initiation of glucocorticoid treatment in primary care with the specialist — the standard initial dose for active GCA without visual symptoms is 40–60 mg oral prednisolone per day. Consider arranging the following blood tests to support diagnosis unless there is evidence of critical ischaemia (such as visual loss or diplopia) or no immediate access to phlebotomy but do not delay referral while waiting for results: Full blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Diagnosis will be confirmed in secondary care with investigations such as ultrasound and biopsy.

Answer 43

when csf pressure falls, eg after 5% of lp cases; vertical traction on cerebral blood vessels ensues; pain and vomiting nearly always relieved by assuming supine position; neck pain may be prominent or only feature

Answer 44

may be tension type building up during sexual excitement, or may be explosive type at point of orgasm, almost like a ruptured aneurysm often on several consecutive sessions indomethacin may be helpful if chronic, but usual mx is reassurance ofc exertion of sex may lead to carotid dissection, MI, aneurysm rupture etc so be cautious before saying it's benign

Answer 45

sudden severe headache like being kicked in the head; often benign though and idiopathic may be crash migraine, sah, cvt, cerebral vasospasm, hypertension, pitu apoplexy, cocaine and adrenergic drugs Confirmation of SAH: Computed tomography (CT) head Acute blood (hyperdense/bright on CT) is typically distributed in the basal cisterns, sulci and in severe cases the ventricular system. CT is negative for SAH (no blood seen) in 7% of cases. Lumbar puncture (LP) Used to confirm SAH if CT is negative. LP is performed at least 12 hours following the onset of symptoms to allow the development of xanthochromia (the result of red blood cell breakdown). Xanthochromia helps to distinguish true SAH from a ‘traumatic tap’ (blood introduced by the LP procedure - another way to tell is to see a >30% decrease in RBC count from pot 1 to pot 3 (you my need to specifically ask lab to give you these results)). As well as xanthochromia, CSF findings consistent with subarachnoid haemorrhage include a normal or raised opening pressure Referral to neurosurgery to be made as soon as SAH is confirmed

Answer 46

Indication for lumbar puncture procedure:  Suspected meningitis/encephalitis- for diagnosis  As part of neuro-metabolic investigations  For diagnosis of Benign (Idiopathic) Intracranial Hypertension (BIH)  Intrathecal chemotherapy Contraindication for lumbar puncture procedure: Signs suggesting raised intracranial pressure  reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)  relative bradycardia and hypertension  focal neurological signs  abnormal posture or posturing  unequal, dilated or poorly responsive pupils  papilloedema  abnormal ‘doll’s eye’ movements Shock Extensive or spreading purpura After convulsions until stabilised Coagulation abnormalities  coagulation results (if obtained) outside the normal range  platelet count below 100 x 109/litre  receiving anticoagulant therapy Local superficial infection at the lumbar puncture site Respiratory insufficiency (lumbar puncture is considered to have a high risk of precipitating respiratory failure in the presence of respiratory insufficiency)

Answer 47

meningitis - fever, stiff neck (get them to do chin to chest then look high up); headache can also occur in less serious infections, esp viral eg flu; neck pain and stiffness often accompanies this; sah and meningitis suspected but there wont be meningism headache can raise bp, but if bp >200/120 or so then that can cause headache; can be malignant hypertension or eg tyramine food straight after maoi; also phaeochromocytoma headaches maybe after 50% of seizures generally also fevers, hypercapnia (chronic lung disease, usually in morning), withdrawal, acute severe anaemia, hypothyrodism etc facet arthropathy, C2 dorsal root entrapment, hypertrophy of post long lig, RA of atlantoaxial region may give headaches

Answer 48

most common reason is dental problems so start by ruling that out may be non-neurological in which case you may see signs of related disease: GCA, glaucoma, chronic sinusitis, poet-herpetic neuropathy, malignancy, central pain if neurological + episodic 3 classes based on time and sx: 1-120s may be trigeminal neuralgia or SUNCT/SUNFA and need NaV block unilat +/- lacrimation, salivation, rhinorrhoea, sweating think cluster headaches or paroxysmal hemicrania (15-180 mins vs 2-30mins) if 4-72 hours with sensitivity to noise/light or nausea then can be V2 distribution migraine: try triptans, then migraine prophylaxis + regular mag and B2 supplements, if not working move to anti CGRP therapy pain for the above may be felt in the upper teeth/jaw, even bridge of nose, rarely also mandible; generally V2 migraines don't have aura and facial CH have less trigeminal autonomic sx persistent idiopathic facial pain is a bit like a chronic form of trigeminal neuralgia without the attacks of obvious cause note that V2 most commonly carries trigeminal neuralgia, but can carry primary headaches (migraines) as it innervates parts of the middle cranial fossa (as does V3 making V3 migraines also possible) everyone with these conditions should have MRI at first presentation to pick up other causes eg maligancy

Answer 49

group of primary headache disorders characterized by unilateral head pain that occurs in association with generally prominent ipsilateral cranial autonomic features include cluster headache (CH), paroxysmal hemicrania (PH), hemicrania continua, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and its close relative, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) Paroxysmal hemicrania (PH), like CH, is characterized by strictly unilateral, brief, excruciating headaches that occur in association with cranial autonomic features. PH differs from CH mainly in the higher frequency and shorter duration of individual attacks; unlike CH, PH responds in a dramatic and absolute fashion to indomethacin; Typically, patients have more than five attacks daily, although the frequency of attacks shows a considerable fluctuation, ranging between one and 40 daily. The attacks occur regularly throughout the 24-h period, without a preponderance of nocturnal attacks as in CH. for SUNCT: pain is usually maximal in the ophthalmic distribution of the trigeminal nerve; attacks are stabbing, burning, prickling, lasting for 5–240 s, and have one of three different types of attack profiles: They can occur as single short-lasting stabs; longer-lasting groups of repetitive stabs; or a serrated pattern; Symptomatic periods generally last from a few days to several months, and occur once or twice annually. Remissions typically last a few months, although they can range from 1 week to 7 years; attacks are virtually always accompanied by both ipsilateral conjunctival injection and lacrimation. Ipsilateral nasal congestion, rhinorrhoea, eyelid edema, ptosis and facial redness or sweating are less commonly reported; majority of patients can precipitate attacks by touching certain trigger zones within trigeminal innervated distribution and, occasionally, even from an extratrigeminal territory - note similarity to trigeminal neuralgia (autonomic features and V1 instead of V2/3 help to differentiate) a full diagnostic work-up for SUNCT/SUNA must include a brain MRI scan with dedicated trigeminal views and a trial of indometacin to exclude indometacin-responsive headaches Note although the 2 present similarly, the key difference is that a person with SUNCT must have both eye redness and tearing on the same side as the pain compared to SUNA which may have only one or neither symptom but will often have other cranial autonomic symptoms.

Answer 50

present with a continuous unilateral headache that is present for months. It is mild-to-moderate in severity, dull in character, and often does not affect physical activity. It is commonly located in the first division of the trigeminal nerve involving the frontal and periorbital regions, but other extra-trigeminal areas may also be involved often has superimposed fluctuating headache exacerbations, which may last for a few minutes to days with a frequency ranging from more than 20 attacks daily to one attack in 4 months; moderate-to-very severe in intensity and throbbing or stabbing in character - may become restless migrainous features of photophobia, phonophobia, nausea, and/or vomiting may occur during exacerbations; Like other TACs, HC is associated with ipsilateral cranial autonomic symptoms, especially during exacerbations. Still, these autonomic symptoms are generally less prominent than other TACs, including cluster headache (CH) and paroxysmal hemicrania (PH). The cranial autonomic features may include forehead sweating, lacrimation, conjunctival injection and swelling, ptosis, miosis, a feeling of foreign body sensation in the eye, nasal congestion, rhinorrhea, and/or aural fullness criteria: unilat, for 3mo+ w exacerbations, either or both of autonomic signs or agitation (/movement worsens), and responds to indomethacin complete response to indomethacin is one of the pathognomonic features of hemicrania continua; proposed that indomethacin is more effective than other NSAIDs, probably due to the highest central nervous system penetration, central serotonergic effects etc

Answer 51

common in middle age+; stabbing pains usually of a few seconds to a few minutes, both day and night, for several weeks or months at a time; may be triggered by shaving, brushing teeth, cold wind, yawning; no sensory or motor loss usually atypically but not infreq may get itching or sensitisation of the face usually idiopathic but can be due to 5th CN involvement in MS (bilat often), aneurysm of basilar a, tumour in cerebellopontine angle; somtimes by compression by branch of basilar a: mri angiography shows, and surgery to separate relieves; this not most cases though carbamazepine 600-1200mg od works in 70-80% of ppl, half become tolerant over years; oxcarbazepine and lamotrigine as alternatives; others inc gabapentin, pregabalin, phenytoin, valproic acid may be used; short course of steroid can be used during a flare of attacks or eg to cover while uptitrating/switching meds and a large pulse of eg dex can be used if pt presents in crisis with frequent severe attacks; baclofen PRN can be used as an adjuvant for relief during an attack rarely can get glossophayrngeal neuralgia, resembles the above but pain in throat and tonsillar fossa, often provoked by swallowing, yawning, talking etc; pain may localise to ear or radiate from throat to ear so auricular branch of vagus nerve; vagus pain afferents trigger bradycardia and even syncope; tumours may also cause by compression but this even rarer; treat as for trigeminal

Answer 52

often due to disruption of the bite and may have deviation of mandible to affected side and clicking sounds from joint when moving it; jaw may lock in open or closed position jaw opening limited, tenderness and crepitations over joint; headache in front of ear radiating over temple and face; may also be involved in joint disease like RA palpating joint from eam may reproduce pain, this gives confidence in the diagnosis; MRI to show joint effusion adjust bite by dental specialist and maybe amitriptyline at night

Answer 53

3rd most common after migraine and tension is drug misuse headache; caused by taking painkillers or triptans regularly, usually for headaches but sometimes eg back pain, this much less common and generally not seen headache will happen most days, sometimes every day; must be present at least 15 days of the month, developed while using medication; diagnosis only confirmed if headache resolves or reverts to previous pattern within 2mo of stopping the medication codeine, triptans, ergotamine (rarely used) are the most common causes, nsaids less so but can constant dull headache, spells where gets worse; usually worse in the morning or after headache stop the medicine and maybe replace with less provocative one eg replace codeine with ibuprofen once headaches back to normal can resume taking the original medicine but beware overuse; in meantime things may get worse before they get better, and giving antiemetic may help avoid taking the medicine on more than 2 days a week, maybe consider prophylaxis

Answer 54

present with symptoms of recurrent sudden-onset most intense headache peaking immediately to maximal intensity over seconds to minutes (thunderclap); generally b/l; may present with vomiting, photophobia, phonophobia, confusion, and blurred vision; may be accompanied by seizures, FNS or stroke; headaches may be trigger by valsalva manoeuvre Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use (SSRIs, sympathomimetic decongestants, adrenaline (inc phaeochromocytoma), cocaine, cannabis), pre-eclampsia subarachnoid hemorrhage, ischemic stroke, pituitary apoplexy, cerebral artery dissection, meningitis, PRES (25% of kids with RCVS have PRES too), and spontaneous cerebrospinal fluid leak CTH and LP ?SAH first ix if NAD may proceed to eg CT angio, formal angiography, or MRA; string-of-beads sign supports RCVS diagnosis but note imaging can be normal in first week of sx If the clinical and radiological findings are inconclusive or the underlying cause is still missing, routine blood tests, urinalysis, urine vanillylmandelic acid and 5-hydroxyindoleacetic acid levels, serum and urine toxicology screens, ESR, CRP, infectious and rheumatological panel tests, and CSF examination are indicated mx inc trigger avoidance, calcium channel blockers such as nimodipine and verapamil are used to relieve the headache acutely and can work as prophylaxis

Answer 55

concerning headache features: Constant Nocturnal Worse on waking Worse on coughing, straining or bending forward Vomiting Gliomas are tumours of the glial cells in the brain or spinal cord. There are three types to remember (listed from most to least malignant): Astrocytoma (glioblastoma multiforme is the most common) Oligodendroglioma Ependymoma

Answer 56

Common following any form of acute brain injury * Important to control early before they become more frequent or evolve into status epilepticus – Levetiracetam is now the favoured anti-convulsant in most circumstances (in adults can load on valproate if keppra not working) – Tend to avoid benzodiazepines hydrocephalus may be part of trauma: In the acute setting this is usually managed with an external ventricular drain hyponat (SIADH, fluid restriction maybe contra so eg hypertonic saline); maybe hypernat if diabetes insipidus cerebral contusions: Often multiple and bilateral – Contre-coup (opposite site of impact) – Predominantly frontal and temporal lobes * Higher velocity injuries associated with deeper contusions (including brainstem)

Answer 57

raised ICP: dull headache, worse when lying down/on waking; maybe pulsatile tinnitus; maybe diplopia (CNVI), valsalva things might bring on; papilloedema, scotoma/enlarged blind spot, UMN signs; coning (CNIII, coma, resp arrest); need imaging, LP if safe tumour or sol*, but also CVST: progressive headache etc, seizures; risk factors smoking, COCP, cancer, pregnancy, dehydration, hyperviscous give anticoag, manage sequelae; if cavernous then CNIII-VI, proptosis maybe, in transverse sinus maybe tinnitus; straight sinus may give motor deficits or mental status changes; do CT, MR venogram; low index of sus if progressive/seizures, headache fits abscess may be from neurosurg, parameningeal infection, cranial trauma, haemat spread (maybe multi abscesses - consider echo) T1 with contrast enhances tumour, on T2 can see oedema around the tumour which will be dark like brain (not as dark as abscess); biopsy and histo of the mass

Answer 58

CH picture but w/o red eye - maybe carotid artery dissection? MRI can help; CAD can give horners, signs eg CNXII palsy GCA: artery wall thickened due to lymphocyte/histiocyte infiltration, narrowing lumen so distal ischaemia; maybe multinuc giant cells too GCA may see dipolopia, jaw claudication, tender temples, beading/enlarged artery; systemically unwell; high dose steroids, biopsy asap also in CH picture consider trigem neuralgia and the autonomic cephalgias, sinusitis

Answer 59

most common solid tumours in children; 70-80% infratentorial (glial tumours, medullablastoma) or midline (germinoma (pineal), craniopharyngioma); 43% of childhood brain tumours are astrocytomas headache, n&v, abnormal gait; worsening, headache oft worse on waking; seizures at any age poss <4yo oft macrocephaly, n&v, irritability, lethargy <2yo non specific vomiting, irritability, failure to thrive, maybe hyperreflex, CN palsies, macroceph post fossa tumours gives hydrocephalus (morning headache, vomiting, ataxic unsteady gait, double vision, papil); squint, CN palsies, pyramidal signs from brainstem or central brain tumours (and involvement from post fossa) occipital lobe maybe visual deficits, frontal maybe behavioural changes if suspect, esp if new CNS changes in child, very urgent MRI; then biopsy surgical resection, chemo (usually inc vincristine), radiotherapy can be used but try to wait until 5yo or so; 6mo'ly MRI for 2 yrs after then annualy long term intellectual decline (esp if irradiated), esp attention span and reaction times, so monitor for this; GH def common, intellectual disability, risk of second tumour 10-20 yrs down line esp if radiotherapy used

Answer 60

progressive subacuteCNS sx (seizures, headache (oft worse in morning), nausea, drowsiness, visual change, personality change, dysarthria, upper/lower limb defects) - 2ww MRI of brain new abnormal cerebellar or other central neuro function in kids - 48hr appt referral benign often not as SOL, so think of high grade (aggressive) and low grade adults: mets from elsewhere 10x more common than prim tumours; high grade prim inc gliomas, glioblastoma multiforme, medulloblastomas, prim cerebral lymphomas; low grade meningiomas, acoustic neuromas, neurofibromas, pitu/pineal tumours, craniopharyngiomas; resection if poss; if not external beam therapy can be curative, is preferred option for mets; whole brain irradiation for PCL, medulloblastomas; CNS lymphoma has intrathecal and iv chemo, other types chemo less important; platinum types for medulloblasts analgesics, steroids, anticonvulsants; bleeding into tumour, hydrocephalus can occur raising icp to life threatening levels w brain herniation; subacute encephalopathy (somnolence, headaches) 1-16 wks after radiotherapy

Answer 61

60% of paeds brain tumours are in post fossa Posterior fossa tumors (PFTs) include medulloblastomas, atypical teratoid/rhabdoid tumors, pilocytic astrocytomas, ependymomas, and brainstem gliomas Paediatric low-grade gliomas (LGGs) are the most frequent brain tumours diagnosed in children and young adults, accounting for approximately 40% of all reported cases; NF1 and TSC are linked to these accounting for around 20% between them astrocytomas and other gliomas make these up; pilocytic astrocytoma is the most common type of astrocytoma diagnosed in children and these are seen in cerebellum 60% of time with next commonest area the optic pathway; slow growing with gradual symptom onset usually 1. Features of raised intracranial pressure – headaches, vomiting, cranial nerve palsies, papilloedema, macrocephaly, ataxia, reduced consciousness. 2. Tumours of the floor of the 3rd ventricle / hypothalamus – diencephalic syndrome 3. Tumour of the cerebral hemispheres – seizure activity 4. Tumours of the cerebellum – ataxia, incoordination 5. Tumours of the brainstem – long tract motor / sensory signs, cranial nerve palsies including hearing loss. 6. Tumours of the suprasellar area – visual and endocrine anomalies (delayed/ precocious puberty, diabetes insipidus, anomalous weight gain / loss, short stature) assess visual acuity and fields as appropriate (modified techniques for young kids) MRI Excluding a secreting germ cell tumour (serum AFP and b-HCG) is an important consideration in suprasellar lesions detected on imaging. Likewise, for suprasellar lesions involving the hypothalamic-pituitary axis, baseline pituitary function tests including the assessment of salt/water balance are advised before any surgical intervention is undertaken. surgery for 80% and sent for histopath, biopsy if can't resect chemo if not managed surgically - usually vincristine and carboplatin +/- radiotherapy (generally avoid giving radiotherapy treatment to children under the age of 10 or with NF1) proton beam therapy occasionally performed - manchester and UCLH only have these then follow up scans for recurrence Medulloblastomas are the most common malignant brain tumours of childhood, most often presenting as midline masses in the roof of the 4th ventricle with vast majority arising from cerebellum and most of these from the vermis; they are a small round blue cell tumour; Treatment typically consists of surgical resection, radiation therapy, and chemotherapy; growth of these very cellular tumours is often rapid and accounts for their relatively rapid clinical onset. Typically, presentation occurs over a few weeks with features that are dominated by symptoms of raised intracranial pressure as a result of obstructive hydrocephalus; they are all considered at least grade 4; As CSF seeding is common at presentation, imaging with contrast of the whole neuraxis is recommended to identify drop metastases and leptomeningeal spread ependymoma usually arises from the floor of the 4th ventricle and typically squeezes out the foramen of Luschka; Although medulloblastomas project into the fourth ventricle, unlike ependymomas they do not usually extend into the basal cisterns; Enhancement is significantly greater in medulloblastomas compared with ependymomas, and greater still in astrocytomas

Answer 62

pitu - symptoms from hormones eg acromegaly, gigantism (kids), cushings, high prolactin; if nonfunctioning, visual field loss may be first symptom; headaches worse in morning, maybe sudden severe pitu apoplexy, hydroceph, squint; hypopitu also poss eg low libido, ed, oliomenorrhoea or in kids delayed puberty, diabetes insipidus rarely (note: these may follow pitu removal surgery too); pitu function tests, visual field mapping, MRI; transsphen surg, radiotherapy if incompletely resected; bromocriptine in prolactin secreting tumours; radiotherapy if rec pineal - germinomas, teratomas, pineocytomas, pineoblastomas; morning headache, n&v, hydrocephalus -> death; vertical gaze palsy ie cant move eyes up and down +/- CNIII paralysis; mydriasis, convergence, unequal pupils; maybe cerebellar signs; surgery, stereotactic radiotherapy meningiomas - grades I, II, III (inc aggresiveness), arise from dura mater and slow growing; present as other tumours but if in spine then brown sequard syndrome, panhypopitu if in sella turcica; MRI; conservative management if small and in elderly pt; surgical excision, radiotherapy as for pitu or if high grade/anaplastic acoustic neuroma - from CNVIII schwann cells; low grade slow growing, life threatening eventually through mass effect; neurofibro is risk factor, radiation as kid for adenoids/tonsils also; consider if unilat hearing loss/tinnitus (progressive or acute), impaired facial sensation (affect trigem, may also give facial pain), unexplained balance issues; earache, ataxia; audiology for hearing loss, MRI; small + good hearing then watch and wait, active treatment if growth detected; surgery, maybe stereotactic radiotherapy glioblastoma multiforme - most common and aggressive primary brain tumour, has ring enhancement, surgery, radiotherapy, and chemo (temozolomide)

Answer 63

following features may be observed during fundoscopy: venous engorgement: usually the first sign loss of venous pulsation: although many normal patients do not have normal pulsation blurring of the optic disc margin elevation of optic disc loss of the optic cup Causes of papilloedema space-occupying lesion: neoplastic, vascular malignant hypertension (will see other hypertensive retina signs, note raised ICP can also cause hypertension as part of Cushing triad in which case you wouldn’t see hypertensive retina changes) idiopathic intracranial hypertension hydrocephalus hypercapnia Rare causes include hypoparathyroidism/hypocalcaemia vitamin A toxicity

Answer 64

provide a stable environment for the neurons, which they outnumber (2-10x as many) oligodendrocytes myelinate neurons (1-30 internode regions) astrocytes maintain homeostasis as part of BBB and regulate CSF composition by taking up K (high K permeability from high conc of K channels) from repetitive AP firing (most numerous, have end feet that interact with capillary endothelial cells), separate cells to insulate neuronal groups from each other, high affinity uptake of glutamate, converting it to glutamine then transferring back to neurons (also other NTs) microglia phagocytose debris and play a role in inflammation and ependymal cells form a columnar epithelium lining the ventricles and forming CSF, with cilia to help circulate the CSF 80% of all cells in brain are macroglia, 1/2 astro and 1/2 oligo

Answer 65

increased amount of csf, normally under inc'd pressure and so dilates ventricles can be obstructive (non-communicating), dec'd csf absorption (communicating), inc'd csf production obstructions can result from tumours, and congen abnorms eg dandy walker cyst (deficiency of cerebellar vermis and 4th ventricl foramina + cystic dilatation of 4th ventricle), arnold-chiari malform (small post fossa, downward displacement of cerebellar tonsils and medulla into foramen magnum, oft associated with spina bifida), aqueduct stenosis (x linked or sporadic -> x linked form oft has overlapping fingers and/or adducted thumbs so if this plus large head consider hydroceph, tho sporadic majority of cases), aneurysm of vein of galen (obstruction at level of aqueduct), achondroplasia dec'd absorption due to meningitis/encephalitis (inc intrauterine toxoplasmosis/CMV), intravent/intracranial bleeds, sagittal sinus thrombosis, arachnoid villi hypoplasia inc'd production rare, usually choroid plexus papilloma

Answer 66

congenital condition usually diagnosed at birth but sometimes not until adolescence will have 2 or 3 out of: optic nerve hypoplasia (causing serious visual impairment) absent or small septum pellucidum or corpus callosum giving dev delay and some movement or coordination problems hypopituitarism commonest pattern is GH deficiency and visual impairment; often will have sleep disturbances, ASD behaviour, and tendency to weight gain; may also present with seizures or cerebral palsy MRI will show, need bloods for pitu function and an ophthalmological assessment

Answer 67

Cavum septum pellucidum (CSP) is a common incidental finding, defined as a midline cerebrospinal fluid (CSF) space delimited superiorly by the crus of the fornices and inferiorly by the tela choroidea of the third ventricle. It is anatomically distinct from cavum vergae (CV) which is a CSF space extending posteriorly to the columns of the fornix. However, CSP and CV cysts are used interchangeably in the literature and may co-exist in many cases CSP normally exists in the fetal period but begins to close from the posterior part starting the 6th month of gestation). It remains as a small slit but usually becomes to close completely around the 2nd month of birth as brain develops They are usually asymptomatic but may present with symptoms related to obstructive hydrocephalus where symptomatic/causing hydrocephalus, neurosurgeons can remove the cyst Septum pellucidum itself cannot cause epilepsy because it does not consist of pyramidal cells, and is in the wrong place, however it is observed more frequently in people who have epilepsy - it is thought that the same dev problems leading to the epilepsy might also lead to the leaflets not fusing properly

Answer 68

through ant fontanelle IVH grade 1 confined to germinal matrix, 2 extension with blood in LV, grade 3 similar but ventricles now dilated, grade 4 has parenchymal involvement the bleed is in subependymal matrix antlat to lat ventricles, 90% in first 4 days of life; posthaemorrhagic hydroceph in up to 40% perivent leucomalacia where isodense lesions become echolucent cysts, usually after 2nd week of life, associated with cerebral palsy also may see hydranencephaly where brain above thalamus replaced with csf, dies soon after birth (may also see transilluminated skull to demonstrate this) porencephaly is cystic cavities in one cerebral hemisphere which may be continous with lat ventricle, commonly after intraparenchymal h+ lenticulostriate vasculopathy: hyperechogenic linear or branching tubular streaks in the thalami or basal ganglia; association with TORCH infections, esp CMV, perinatal hypoxia-ischaemia IEM, FAS, and cr abnorms; higher risk of IVH

Answer 69

T1 more for anatomy, T2 more for pathology and CSF is white in T2 may see lissencephaly (smooth brain, due to problem with neuronal migration, get microceph, microphthalmia, seizures, severe dev delay) macrogyria or microgyria schizencephaly (symmetrical clefts in hemisphere from cortex to ventricle) EDH (look for bubbles in this as evidence of skull fracture sol inc any midline shift? raised icp (loss of differentiation between grey and white matter due to oedema, loss of gyri, reduced space between skull and brain, poss compression of ventricles, flattening of sella turcica, and distension of optic nerve sheath) cerebral atrophy (with compensatory ventricular enlargement, may look like hydroceph)

Answer 70

ventriculo-atrial or ventriculo-peritoneal shunt in situ for hydrocephalus - there are also other types like ventriculo-pleural, lumboperitoneal but these less common child may be generally unwell or have fever, headache, vomiting, papilloedema often due to infection (staph epidermidis, corynebacterium); neurosurgeons to manage if also hypertension, haematuria, splenomegaly may be shunt nephritis (due to staph epidermidis), C3/4 will be low

Answer 71

Symptoms that are typical of shunt dysfunction include * Drowsiness * Headache * Vomiting * Irritability child may complain of headache or nausea and may vomit, often in the morning. Babies may have symptoms such as increasing head size, tense bulging fontanelle, a high pitched cry, irritability, sun-setting eyes or distended scalp veins. Other symptoms that may be particular to the child could include seizures and cranial nerve palsies, such as a squint Often children only have a drop in their level of consciousness in the latter stages and so any patient with a shunt who has a reduced level of consciousness should be treated as a medical emergency CT brain scan and shunt series X-rays should be obtained in a timely manner. A shunt series for a VP shunt comprises of an AP and lateral skull and neck X-ray, AP chest X-ray and AP abdominal X-ray so the whole shunt tubing can be followed throughout its course. If the child has a VA or VPleural shunt then abdominal x-ray is not required. It should be remembered that 15% of shunt blockages do not produce a change in the scan appearance Make these images available to neurosurgery team and discuss with them Minimum of hourly observations: pulse rate, respiratory rate, blood pressure, neurological observations and continuous oxygen saturation monitoring Where there is a clinical deterioration or reduced conscious level then the child may require urgent intubation and ventilation for transfer directly to neurosurgical theatres or to Paediatric Intensive Care - will need to liaise with neurosurgery and transport teams; if stable can still transfer to neurosurgery urgently but not emergently; If the CT scan is not diagnostic of shunt dysfunction but the child remains clinically unwell then transfer may still be appropriate after discussion with on-call neurosurgery team If Shunt is blocked or disconnected then child to go to theatres for revision of VP shunt as soon as possible If the child is pyrexial, WCC is raised and remains symptomatic of shunt dysfunction then CSF tap from shunt reservoir - done by neurosurgeons or under their direction. If CSF has a raised WCC then for removal of VP shunt, insertion of EVD and commencement of antibiotics. If no change on scan and the child remains symptomatic then ICP monitoring to be considered. If ICP raised then VP shunt may need to be revised If investigations are all within normal limits, the child may need Neurology review

Answer 72

set of fluid filled cavities with lateral ventricles in the cerebral hemispheres the largest and communicating with 3rd ventricle in the midline around the hypothalamus which connects to the 4th ventricle via the cerebral aqueduct in the midbrain; the 4th lies deep to the cerebellum and communicates with the subarachnoid spaces around the brain; floor of 3rd ventricle has infundibular recess into the pituitary stalk with supraoptic (above chiasm), suprapineal and pineal (into pineal stalk) recesses; lat divided into ant horn (frontal lobe) post horn (occipital lobe) inf horn (temporal lobe) and body

Answer 73

continuously produced by choroid plexus (capillary beds embedded in ependymal cells, largest and most obvious in lateral ventricles), with transport through cells required as ependymal cells connected by tight junctions also continually resorbed into the venous system from the subarachnoid space via the arachnoid granulations, primarily into the sagittal sinus the brain floats in CSF and this cushions it against mechanical stress from impacts and prevents it collapsing under its own weight; CSF also provides metabolites to the brain and removes waste to the venous system normally under pressure of 7-18mmHg (measured via lumbar puncture, >25 often considered raised) pressure gradient filters plasma from caps to choroid interstitium; basolateral exchange of Na for H+ and Cl for HCO3 (CA in interstitium) with apical Na/K/Cl cotransport (both directions) and HCO3/Na cotransport establishing osmotic pressure, water drawn into ventricle lumen through aquaporins; similar comp to plasma but lower protein, glucose and higher Cl (and ofc no cells!), same comp as brain ECF

Answer 74

two large lateral ventricles develop from the cavity within the cerebral vesicles and connect via the inter-ventricular foramen of Munro with the 3rd ventricle on the midline in the diencephalon (thalamus etc); cavity of the midbrain narrows during development to form the cerebral aqueduct which connects the 3rd and 4th ventricles in the hindbrain with its roof formed by the cerebellum; the 4th ventricle is continuous with the central canal of the spinal cord and the subarachnoid space via the foramina of Magendie (median) and Luschka (lateral, paired); plexi of capillaries wrapped in choroid epithelium (ependymal cells and pia mater) form CSF from blood in the ventricles which then escapes via the foramina of Magendie/Luschka into the subarachnoid space around the brain/spinal cord

Answer 75

hydrocephalus - inc in csf volume occupying ventricles; maternal hypertension, preeclamp, alcohol use are risk factors cogen eg agenesis or atresia of foramen of munro, or lusckha/magendie foramina, congen toxoplasmosis, other malforms; acquired from infection (eg exudate block foramina of l/m), h+ after eg injury, tentorial herniation, intravent haematoma, ventricular pineral and post fossa tumours communicating if thickening of leptomeninges or involvement of arachnoid granulations eg meningitis, sah, choroid plexus papilloma; inc'd csf visc from high protein count; venous sinus thrombosis infants present with inc'g head circ (or is in 98tj percentile), tense fontanelle, dilated scalp veins, setting sun sign, inc limb tone; older children/adults may have headache, papill, 6th nerve palsy, unsteady gait from leg spasticity, blurred vision, cognitive decline, n&v, neck pain epilepsy, learning/dev disorders may come from it microcephaly - smaller than normal head, oft have intellectual disability, poor motor/speech function, seizures; genetic, fas, stroke, congen CMV rubella varicella zika toxoplasmosis; maternal radiation, phenylketonuria, malnutrition, hypothyroid, placental insuff, gest diabetes poorly controlled

Answer 76

33 vertebrae formed from intersegmental somite fusion; 7c,12t,5l,5s,3-4c; bodies are weight bearing parts linked by discs and ligaments with an arch forming foramina which unite to form vertebral canal, continuous with cranial cavity through foramen magnum; pedicles are pillar like extensions with 2 laminae meeting in midline; spinous process projects posteriorly, transverse laterally from each side, sup/inf articular processes from where pedicles join laminae (also where tps come off) atlas/axis special with atlas no body as it becomes dens of axis, no IV disc between them; sacrum is fused vertebrae with 4 pairs of anterior/posterior sacral foramina for ant/post sacral rami; in spine movement between individual vertebrae is small but can add up coccyx has no canal or arches; cervical has large triangular foramen, small body with uncovertebral processes, bifid spinous processes, transverse foramina in transverse processes and tubercles for scalene muscles; facets in oblique plane and can do flexion, extension, lateral flexion and rotation; thoracic have circular foramen, demifacets in body for ribs, long spinous processes which point down, articular facets for ribs in tps, facets in arc of a circle, rotation limited by thoracic cage; lumbar have small triangular foramen, large and thick body, thick and oblong sp, large lateral tps, interlocking vertical and sagittal facets, does flexion, extension and lateral flexion; space between adjacent laminae in lumbar region allowing for lumbar puncture; lumbar vertebra may fuse with sacrum and cervical may fuse in klippel-feil syndrome

Answer 77

typical vertebra has 6: 4 synovial and 2 symphyses: IV disk is secondary cartilaginous (each body has layer of hyaline cartilage) with anulus fibrosus (collagen and fibrocartilage lamellae arranged concentrically to limit vertebral rotation) and nucleus pulposus at centre, gelatinous to absorb compressive force, 23 in total; zygapophyseal joints synovial between articular processes

Answer 78

ant/post longitudinal from skull to sacrum either side of bodies ligamentum flava between laminae of adjacent vertebrae to resist separation in flexion supraspinous ligament along tips of sp from C7 to sacrum; before this ligamentum nuchae sheet like structure in midsagittal plane from external occipital protuberance to foramen magnum with apex at C7 continuous with suprapinous ligament interspinous ligament between adjacent sp blending with ligamentum flava and supraspinous capsular ligaments for joints intertransverse ligaments thin and membranous in l region, irregular and often replaced by muscle in c region, cordlike and connected with deep muscles of back in t region

Answer 79

from foramen magnum to lower border of L1 where it tapers to cone shaped ending, conus medullaris which is attached to end of dural sac at S2 by stalk of pia mater and nerves from L2 down passing as cauda equina; diameter not uniform with enlargements at C5-T1 and L1-S3 corresponding with limbs, small central canal in cord with longitudinal vessels descending on its surface and segmental spinal arteries from vertebral, deep cervical, posterior intercostal and lumbar arteries; spinal nerve roots from ventral and dorsal horns, make mixed spinal nerve in intervertebral foramen with covering of all 3 meningeal layers that fuse with epineurium as nerves emerge; 8 C roots and 7 verterbra, after this root emerges below corresponding vertebra; dura mater, arachnoid mata, subarachnoid space then pia mater; epidural space between dura mater and vertebral periosteum contains loose connective tissue, venous plexuses, lymphatics; subarachnoid contains CSF and extends to terminate at lumbar cistern at S2, facilitating lumbar puncture

Answer 80

load to spine stresses stiff vertebral body and relatively elastic disc so strain more easily produced in disc; even at rest pressure within nucleus pulposus >0 to provide preload mechanism for resistance to applied forces, when hydrostatic pressure rises exerts pressure on anulus fibrosus whose concentric fibres bulge and experience tensile forces, transferring the force to slow application of force and thus act as shock absorber; annular fibres thinner posteriorly with less strictly arranged collagen hence herniation backwards; zygapophyseal joints help resist shear forces

Answer 81

one pathway for tactile sensation/proprioception, one for nociception and thermal sensation; the latter carried by afferents through dorsal roots, terminating in dorsal horn close to entry; after at least one relay, projection cells send axons across ventral commisure to contralateral anterolateral white matter where they ascend, fibres terminating in medulla, pons, midbrain and several parts of thalamus; this anterolateral ascending system also called spinothalamic tract axons of tactile system (propioception and touch) enter spinal cord and ascend in ipsilateral dorsal columns without synaptic relay (though do give branches to spinal cord); terminate at rostral end of spinal cord in gracile and cuneate (dorsal column) nuclei; axons from these cross midline and ascend in large tract of fast conducting fibres (medial leminiscus, found in medial brainstem); hence this system is is dorsal column medial meniscus system; fibres project to thalamus from where 3rd order neurons project to somatosensory cortex in postcentral gyrus of parietal lobe

Answer 82

white matter: 3 basic columns/bundles/fasciculi: dorsal, ventral and lateral; anterolateral system runs ventrally in lateral column; dorsal column can be subdivided at high thoracic/cervical levels into lat cuneate and medial gracile divisions (fibres from upper/lower limbs respectively); dorsolateral column has many descending motor fibres, as does the ventral column; in ventral horn, motor neurons for axial muscles are more medial grey matter can be divided into layers: Rexed's laminae; these represent functional specialisations; most important is layer 2, substantia gelatinosa which is critical for processing noxious information and thus a therapeutic target; overlying this is Lissauer's tract which contains afferent axons carrying pain/temp that travel up or down the cord to an adjacent segment before entering the dorsal horn; deeper layers of dorsal horn (IV/V) have relay neurons with axons crossing midline in ventral commisure for anterolateral system; largest cells in spinal cord are motorneurons projecting to muscles, found in groups in ventral horn; major region in centre of cord (lamina VII) has interneurons for local processing ie reflexes

Answer 83

medulla, pons and midbrain; from dorsal surface can see thalamus on top at either side with sup/inf colliculi inferior to it; inf to these are sup/mid/inf cerebellar peduncles; inf to this are cuneate swelling/tubercle and gracile swelling/tubercle (former lat, latter med) section through caudal medulla can see dorsal columns, anterolateral tract and between them the prominent spinal nucleus of the trigeminal nerve; this and the tract of CNV are continuous with and homologous to substantia gelatinosa and Lissauer's tract; section more rostrally in medulla (at level of sensory decussation) can see gracile and cuneate nuclei, medial leminiscus arching from them to midline where sensory decussation is; lateral to ML is prominent spinal trigeminal nucleus with overlying fibre tract; section through upper/rostral medulla, all ascending sensory fibres have terminated so tactile pathway represented by ML in midline; still large trigeminal sensory nucleus though not as clear as at lower levels section through upper pons reveals ML dorsally and more lateral; along ventral midline is groove for basilar artery; section through midbrain has prominent tectum (roof) formed by colliculi, which is dorsal to narrow aqueduct running through midbrain to link 3rd/4th ventricles; in lower midbrain, IC is visible either side, with ML more lateral and joined by fibres of anterolateral tract (so sometimes called spinal leminiscus); section through upper midbrain is similar but with sup colliculi visible instead

Answer 84

major route to cerebral cortex, relaying info from medulla, cerebellum and brainstem and other areas of hemisphere; has many component nuclei, some that project specifically to defined areas and others with more extensive/diffuse projections; ventral nuclei concerned specifically with sensory relay/motor coordination; internal capsule is massive white matter tract linking cortex to thalamus that also contains descending fibres and fibres running between nuclei of thalamus and different cortical regions

Answer 85

fine touch/prop: primary sensory axons enter dorsal root and ascend in dorsal columns, no synapse and so very long; above mid thoracic level each dorsal column has medial gracile fasciculus for lower body fibres and lat cuneate fasciculus for upper body fibres; in dorsal column nuclei second order neurons arise, sending axons in ribbon like ML that decussates across midline, reaching thalamus to synapse onto third order neurons that project to primary SSC by internal capsule thermal/pain: primary afferent bifurcating into short ascending/descending branches running in Lissauer's tract for about a spinal segment and giving branches that enter/synapse in dorsal horn, principally in substantia gelatinosa (pale, jelly like appearance and containing unmeyelinated fibres, small cell bodies and processes); this first synapse allows modulation/gating of pain by eg endogenous opioid peptides; second order axons arise on same side of body as stimulus; diversity of second order neurons: some in lamina V also have input from tactile system and called wide dynamic range neurons; another group in lamina I are nociceptor specific; axons from both groups cross midline in ventral commisure below central canal and ascend contralaterally in anterolateral white matter (not a distinct tract though major component with fibres terminating in thalamus called spinothalamic tract); from thalamus, 3rd order neurons ascend via internal capsule to processing areas; many fibres of anterolateral system also terminate in brainstem, esp in reticular formation, where they influence level of arousal through actions on symp system (medulla) and other ascending systems; considerable modulation of this system by descending pathways from higher centres like raphe nuclei in reticular formation of medulla and periaqueductal grey of midbrain lesions of primary SCC don't lead to pain loss; lesions in other areas did; some project to primary SCC helping with localisation of pain; others to insula (seems to be major relay station for pain processing); also anterior part of cingulate gyrus (medial part of frontal lobe, esp important for affective part of pain perception

Answer 86

motor areas of cerebral cortex: PMC (executing movements once planned and prepared in other areas), premotor cortex (externally guided movements eg response to visual stimulus, postural adjustments to prep for movements) and supplementary motor area (internally triggered movements eg remembered sequences + coordinating hemispheres) main route from brain to spinal cord is corticospinal tract with axons from motor cortex running in internal capsule, cerebral peduncles, pons, emerge as medullary pyramids and continue as crossed lateral and uncrossed ventral corticospinal tracts in spinal cord; damage can give paresis/paralysis; motor structures prominent on ventral surface of brainstem and in cross section cerebellum involved in motor co-ordination and learning and humans is esp large, reflecting use of tools, dexterity and speech; cerebellum connects with other structures via cerebellar peduncles; cerebellar cortex one of best understood parts of brain in terms of connectivity; damage to cerebellum can result in ataxia; brains originally evolved to control movement; cerebellar disease often worsens on movement and extra pyramidal often improves

Answer 87

collectively the two pyramidal tracts corticobulbar tract is equiv of corticospinal tract for nerves innervating musculature of head and neck motor areas of cortex in frontal lobe, anterior to central sulcus; axons of pyramidal neurons in layer V of motor cortex form corticospinal tract and run in internal capsule which forms cerebral peduncles; after emerging as medullary pyramids, corticobulbar fibres leave to innervate motoneurons of CNS (but not the ones controlling eye movements); 90% of corticospinal fibres cross midline at base of pyramids and continue as lateral corticospinal tract, with uncrossed ventral corticospinal tract also continuing into spinal cord; descending corticospinal tract massive in humans: over 1mil axons enter spinal cord either side corticobulbar fibers exit at the appropriate level of the brainstem to synapse on the lower motor neurons of the cranial nerves. In addition to endings in these motor neurons, fibers of the corticobulbar tract also end in the sensory nuclei of the brainstem including gracile nucleus, cuneate nucleus, solitary nucleus, and all trigeminal nuclei

Answer 88

in midbrain, fibres from internal capsule form cerebral peduncles; cortical fibres hard to spot in pons, some pass through as corticospinal/bulbar tracts and corticopontine fibres terminate; in medulla, medullary pyramids are emerging corticospinal fibres which decussate with motor decussation marking boundary between medulla and spinal cord; corticobulbar fibres leave tract at various points to synapse with motor nuclei in medulla and pons, many distribute bilaterally (trigeminal motor nucleus in pons, facial motor nucleus, nucleus ambiguus); eyes not as need to move consensually so controlled directly by brainstem; inferior olives either side of pyramids, associated with climbing fibre input to cerebellum CPs are massive bundles of white matter on ventral midbrain; just deep to this are dopaminergic neurons of substantia nigra and deep to this are red nuclei; most fibres in CPs terminate in pons onto neurons that project as mossy fibres into cerebellum, thus peduncles larger than pyramids upper medulla ventrally has medullary pyramids and deep/lateral to them inf olivary nuclei; in lower medulla is motor decussation (85% cross and continue contralaterally, almost all other descending ipsilaterally, mainly in medial part of ventral funiculus and most of these will cross midline before terminating); in spinal cord can see dorsolateral area containing lateral corticospinal tract containing crossed fibres from contralateral cortex, and ventral area containing ventral corticospinal tract containing uncrossed fibres from ipsilateral cortex most terminate on spinal interneurons to influence both motor and sensory processing and in most mammals this is main route for movement control; primates also have direct cortico-motoneuronal connections, esp the large corticospinal fibres; this latter connection especially common for distal muscle control (ie intrinsic foot/hand muscles); this connection esp developed in great apes and esp humans, underlying our dexterity

Answer 89

gives rise to other descending pathways which are smaller and less obvious as their fibres mingle with ascending/descending ones vestibulospinal tracts descend in ventral columns of spinal cord, arising in vestibular nuclei of dorsal medulla and acting mainly on extensor/antigrav limb muscles and proximal neck/trunk muscles to maintain posture/equilibrium; reticulospinal originate from cells of reticular formation of pons/medulla and send fast conducting axons through length of spinal cord, involved in posture too; rubrospinal tract fibres from red nuclei of midbrain are numerous in mammals, nuclei large in humans but sends few fibres to spinal cord, mainly involved in big upper limb movements (flexion); receiving input from cerebellar nuclei and areas of cortex; besides rubrospinal, red nucleus majority output mainly to inf olivary nucleus; thought to be involved in motor skills learning ventral system involved in posture and contains ventral corticospinal (some decussate, meaning both sides innervated by neurons from both sides so lesions often masked) as well as med/lat reticulospinal and lat vestibulospinal tracts; meanwhile dorsolat system is for appendicular muscles and contains lateral corticospinal and rubrospinal tracts also cranial nerve motor nuclei: trigeminal, facial, nucleus ambiguus Two major descending systems carrying signals from the brainstem and cerebellum to the spinal cord can trigger automatic postural response for balance and orientation: vestibulospinal tracts from the vestibular nuclei and reticulospinal tracts from the pons and medulla. Lesions of these tracts result in profound ataxia and postural instability. Physical or vascular damage to the brainstem disconnecting the red nucleus (midbrain) and the vestibular nuclei (pons) may cause decerebrate rigidity, which has the neurological sign of increased muscle tone and hyperactive stretch reflexes. Responding to a startling or painful stimulus, both arms and legs extend and turn internally. The cause is the tonic activity of lateral vestibulospinal and reticulospinal tracts stimulating extensor motoneurons without the flexion input from rubrospinal and corticospinal tracts. Damage above the red nucleus level may cause decorticate rigidity (so eg cerebrum, internal capsule, thalamus). Responding to a startling or painful stimulus, the arms flex and the legs extend. The cause is disinhibition of the red nucleus, via the rubrospinal tract, counteracting the extensor motorneuron's excitation from the lateral vestibulospinal and reticulospinal tracts. Because the rubrospinal tract only extends to the cervical spinal cord, it mostly acts on the arms by exciting the flexor muscles and inhibiting the extensors, rather than the legs -> which extend due to loss of corticospinal flexor input

Answer 90

mechanical back pain most common but diagnosis of exclusion vertebral fracture if onset coincides with injury or if bony tenderness, LXR -> CT prolapsed disc, straight leg test renal colic from loin to groin, micro haematuria in 95% cases; pyelonephritis; renal cancer; symptomatic aortic aneurusm: shock and sudden pain if noncontained bleed, pain if contained bleed, rapidly growing w/o rupture hurt due to stretching of the a wall; beware esp in those >55, and often they present with what seems to be left sided renal colic due to bleed contained in left retroperitoneal space, but may have abdo tenderness; abdo uss to rule out as exam alone often doesnt pick up bony mets - constant, chronic, unremitting, worse at night - needs myeloma screen and MRI, may present with fracture pancreatitis relatively common but usually abdo pain radiating to back, check serum amylase discitis, osteomyelitis, epidural abscess prostatitis often has severe pain in lower back and perineum, prostate exam v tender, sometimes fevers and rigors, often associated uti many of above can cause cauda equina or spinal cord compression red flags for cauda equina: saddle area paraesthesia, urinary retention or incontinence, faecal incontinence red flags malignancy - constant pain inc at rest and night red flags infection - fever, constant pain inc at rest aaa red flags - abdo pain, sudden onset or cv collapse, >55yo fracture red flags - history of trauma w/ pain starting soon after; fractures unlikely if pain free after accident then pain devs, or if no bony tenderness mechanical cause unlikely if pain not made worse by movement

Answer 91

anterior horn cell damage (ie LMN) werdnig-hoffman disease, poliomyelitis, syringomyelia, cervical spondylosis, denervation of a nerve root, hyponat, hypomag/calc

Answer 92

SACD (pyramidal tracts and dorsal column), periph neuropathy, optic neuritis, dementia/personality changes

Answer 93

required for DNA synthesis and myelin sheath formation; deficiency usually results in megaloblastic anemia (due to impaired hematopoiesis) and/or neurologic manifestations (due to myelin damage). A minority of patients have neurologic findings alone; therefore, the lack of hematologic abnormalities (eg, macrocytosis) does not exclude the diagnosis. Neurologic abnormalities generally arise because of damage to the following: Dorsal columns, leading to impaired vibratory sensation/proprioception and sensory ataxia (gait impairment that worsens when the eyes are closed [positive Romberg sign]) Lateral corticospinal tracts, leading to positive Babinski sign Myelinated peripheral nerves, leading to lower extremity paresthesias Myelinated fibers in the brain, leading to neuropsychiatric manifestations (eg, irritation, mood changes) Workup begins with a serum vitamin B12 level, but methylmalonic acid and homocysteine levels may be required if results are inconclusive -> raised MMA can indicate deficiency if borderline, or as some ppl show signs with normal levels, or can have functional/uptake related deficiency without true deficiency, so MMA and HC raised if deficient at tissue level even if not in serum it’s more common to have a folate deficiency than B12 but a folate deficiency can give a functional B12 deficiency due to the two being co-factors in the methylation cycle. The same is true vice versa, and B12 should always be checked as well before supplementing folate if folate found to be low Homocysteine is consumed in folate aspect & MMA in B12 aspect of methylation cycle. Raised levels = not enough of B12/folate in respective arm of the cycle. However, since they are co-factors, it’s possible to have a true deficiency in one (measurably low serum) and a functional deficiency in the other (normal serum but high levels of the substrate (MMA/homo)) as the process of both is impaired by the absence of one; hence raised levels of MMA is very sensitive for B12 deficiency it’s a false reassurance if a patient tells you they use NO2 but supplement B12, as the nitrous doesn’t interfere with absorption of B12 but impairs one of the enzymes involved in the methylation cycle which utilises that B12. So clinically the symptoms are of B12 deficiency and often serum B12 is adequate, it’s just that it can’t be used also note 30% of patients on metformin develop clinically significant vitamin B12 deficiency after ≥5 years of treatment. The mechanism is not entirely elucidated but may be in part due to metformin altering calcium homeostasis in the gastrointestinal tract, thereby impairing calcium-dependent vitamin B12 absorption

Answer 94

a mixture of umn and lmn signs seen in B12 def, werdnig-hoffman disease, friedreich ataxia, conus medullaris lesion, taboparesis

Answer 95

foot tapping (hold foot slightly off floor, rapidly tap toes up and down) as much higher sensitivity for UML than babinski - babinski maybe 37% where this is >90%, and will look abnormal due to spasticity however, babinski still has a place as it is more specific, with abnormal foot tapping also a type of dysdiadochokinesia

Answer 96

aka SMA type 1, is an AR disease with prog destruction of ant horn cells variable presentation may start in intrauterine life (reduced fetal movements, polyhydramnios) or after (breathing difficulties inc cyanosis, poor feeding); earlier onset, quicker decline in function; see prox muscle weakness, hypotonia, muscle wasting, facial diplegia, flaccid quadriplegia, loss of reflexes (unlike myotonic dystrophy), bulbar palsy, abdominal see-saw breathing, and bell shaped chest; fasciculations and resp failure, up to death milder form starts in late childhood, prox leg weakness progressing over years with normal mental function; emg may show spont fasciculations and biopsy may show atrophy; treatment supportive

Answer 97

remember that trauma to spinal cord will first show spinal shock with predominantly LMN signs slowly replaced by UMN (which will include loss of sphincter tone and urinary retention or incontinence if at high enough level) cord compression caused by tumour, abscess, bone (trauma) also consider transverse myelitis (oft after viral illness like chickenpox and treated with steroids), discitis, GBS, hysterical paraplegia, MS, SACD, sagittal sinus thrombosis, anterior spinal art thrombosis, friedreich ataxia

Answer 98

Clinical Indications Suspicious of an Infectious Myelopathy: Fever Confusion Meningism Rash (lyme, zoster) Lymphadenopathy Causes: HSV, VZV, CMV, EBV, HHV 6/7 Flaviviruses Influenza A Measles, mumps Enteroviruses including polio Mycoplasma Borellia Treponema TB Rarely fungi and parasites Blood culture and serology, CSF culture, microscopy, viral PCR and serology Poliomyelitis, or gray matter myelitis, is usually caused by infection of anterior horn of the spinal cord by the enteroviruses (polioviruses, enteroviruses (EV) 70 and 71, echoviruses, coxsackieviruses A and B) and the flaviviruses (West Nile, Japanese encephalitis, tick-borne encephalitis). On the other hand, transverse myelitis or leukomyelitis, or white matter myelitis, are often caused by the herpesviruses and influenza virus. VZV, HSV, and lyme among others can also cause an infectious radiculopathy/radiculitis

Answer 99

degen of dorsal tracts, lat corticospinal tracts and spinocerebellar tracts AR inheritance 1-15yo cerebellar ataxia first of lower then upper limbs; broad-based gair, spasticity of legs with upgoing plantars; dorsal column changes inc absent ankle jerks scoliosis and pes cavus common; cardiomyopathy giving arrhythmias and heart failure; optic atrophy; dementia and death in middle age

Answer 100

idiopathic friedreich ataxia duchenne spina bifida CMT tethered spinal cord syndrome

Answer 101

at 3mo in utereo conus medullaris at end of spinal cord, but descends to L3 due to differential growth, then L1/2 after a few months interference in growth may tether the spinal cord, eg myelomeningocele, tight filum terminale syndrome, diastematomyelia, intradural lipoma etc occult spina dysraphism in 15-30% of pop, with spinous process absent in a vertebra sx usually after period of growth and exacerbated by exercise hypertrichosis may overly the dysraphism; weakness of legs or sensory problems may occur as well as eg club foot or pes cavus, incontinence; uss or ideally MRI to diagose; urodynamics to assess urinary dyfunction untethering to treat, more succesful the earlier it's done

Answer 102

reflex sympathetic dystrophy, may also have autonomic features eg sweating, erythema; long term get skin atropy and disuse atrophy initial injury provokes hyperactive autonomics physiotherapy, sympathetic blockade, may improve w time

Answer 103

pain is heavily modulated, allowing it to be integrated with other systems like skin reflexes, attention, emotion and autonomics descending systems located in periaqueductal grey (PAG) matter of mid brain, the raphe nuclei and other nuclei of the rostral medulla; electrical stim of PAG can produce sufficient analgesia for abdo surgery though other, non-painful sensations left intact; PAG thought to control nociceptive gate in dorsal horn by integrating inputs from cortex, thalamus and hypothalamus; morphine induced analgesia blocked using naloxone (opiate antagonist) introduced into PAG, can also block electrical analgesia; bilateral transection of dorsolateral funinculus blocks both this and morphine induced analgesia; many PAG neurons excite serotonin neurons in rostroventral medulla which inhib neurons in laminae 1/2/5 placebo analgesia (non-analgesic gives analgesia) when subject told it's a painkiller; placebo effect also works for diabetes, cough, asthma, MS, ulcers and parkinsonism; pain modulation thought to be targeted to whole body, recently suggested opioid modulation can be targeted (volunteers have capsaicin applied to distal limbs, asked to report pain intensity, placebo cream applied with placebo analgesia only on treated part; naloxone intravenous infusion abolished placebo response suggesting it is mediated by one of endogenous opioid systems; attentional mechanisms can be directed to specific parts of body, with argument that spatial specific organisation retained by endogenous opioid systems and indeed rats found to have somatotropic PAG, stimulating different areas producing analgesia in different cutaneous regions

Answer 104

SNRIs like duloxetine and TCAs like amitryptiline provide pain relief in neuropathic pain, presumably by descending inhib modulation from locus coeruleus via NA; gabapentin (GABA analogue developed as epilespy drug) has no activity at GABAr, but can block neuropathic pain in some patients (not acute pain), appears to decrease PM CaV a2d1 subunit localisation (upregulated in some neuropathic pain to inc Ca current) thus gabapentin decreases CaV current density and decreases spinal NT release with pregabalin a successor with better pharmacokinetics; lidocaine acts by blocking NaVs, providing anaesthesia via local application by preventing spontaneous peripheal neuron discharge associated with neuropathic pain, carbamazepine and lamotrigine also NaV blockers used as anti-epileptics and neuropathic pain relief

Answer 105

usually from violent impact eg fall or jump from height or vehicle accident; osteoporosis often the cause, esp in older ppl, or bone weakness due to hyperparathroidism, prolonged corticosteroid use, osetomalacia, myeloma, carcinoma met to the bone pain usually immediate but may be delayed up to days after; all lumbar movements limited, spasm of lower lumbar muscles, radiographic appearance high impact rotary injury can break transverse process and tear paravert muscle giving limited movements, deep tenderness, local haematoma, and poss bleeding into retroperitoneal space giving groin pain, prox leg weakness and loss of patellar reflex, and grey turner sign body fractures usually need bed rest and analgesia

Answer 106

usually in 3rd/4th decade where nuc pulp still gelatinous L5-S1 most common, then L4-5, L3-4, L2-3, and finally L1-2 quite rarely flexion injury likely cause of herniation but pt often wont recall a particular trauma; sneeze, lurch, or trivial movement may be enough if sufficient degen of post long ligs and ann fib; nuc impinges on root or roots giving radicular pain typical picture: sacroiliac pain radiating into buttock, post thigh and calf (sciatica), maybe feet, stiff spinal posture, some of paraesthesia, weakness, reflexes may be lessened in affected root straight leg raise should provoke pain, as often will dorsiflexion of foot or even great toe; if other leg straight raise provokes pain then specific but not sensitive for herniated disc flexion of head and neck can exacerbate as should coughing if inconsistencies in these tests suspect psych component or muscle injury antalgic posture (sciatic scoliosis) is maintained; limp with knee slightly flexed and brief cautious weight bearing, going up/downstairs esp hard foot inversion will be weak, unlike foot drop due to peroneal nerve damage which spares inversion as this controlled by tibial nerve; S1 achilles reflex lost, whereas not in L5 L3 and 4 give diminished knee jerk clinical pic should be enough, MRI to confirm esp if persistent symptoms some bed rest although sciatica tends to resolve within 3-6 months NSAIDs, if not add codeine, if together dont work can try amitryp; still no luck can consider referral for surgery

Answer 107

besides disc herniation may get entrapment due to spondylotic spurs, cysts of synovium due to facet joint degen; this is not uncommon and cyst can be removed if pain intractable; may also get cyst like dilatation of perieural sheath compressing sacral roots where they penetrate the dura endometriosis of the nerve at the sciatic notch may give premenstrual sciatica; uterine traction on nerve can give sciatica during each pregnancy nerve damage from DM, herpes zoster, infarction, retroperitoneal mass; sometimes lumbosacral plexus neuritis; also tumours affecting sciatic nerve also oa or other degen cause narrowing of canal compressing lumbar or sacral roots - flucutating ache often precipitated by prolonged sitting, standing, walking, rest relieves pain

Answer 108

BBKPT commonest mets to spine (breast, bronchus, kidney, prostate, thyroid) also pancreas; constant dull pain unrelieved by rest and worse at night, often interrupting sleep; may become radicular if met extends lat; may cause fracture of vert body, esp suspicious if in young or middle aged person; tuberculous infection giving kyphotic deformity common in developing countries spinal epidural abscess needs surgical drainage, otherwise paraplegia and poss sepsis; often from blood, osetomyelitis, ivdu, sometimes lp or epidural; low grade fever, leucocytosis, persistent severe localised pain intensified by percussion; may become radicular discitis

Answer 109

Reflex Root Triceps C7*/8 Supinator C5/6* Biceps C5*/6 Knee L3/4* Ankle S1/2 Dermatome Root Angle of the Jaw C2 Middle Finger C7 Nipples T4 Umbilicus T10 Middle of foot L5 Lateral border of foot S1

Answer 110

Typically presents with – Neck pain – Sensory symptoms in both hands – Unsteadiness and falls – Upper limb weakness, eg. difficulty opening bottles or using a mobile phone – Can get bladder involvement – Gradual progression * Abnormalities on examination can be mild and presentation can be asymmetrical MRI to ix * Treatment is surgical when indicated, and avoiding falls

Answer 111

(ant horn syndrome): Not common; about 1% of all strokes * Pain is often a prominent feature, presumably because of involvement of the spinothalamic tracts * Dorsal columns are typically spared * Initial imaging may be normal, as in stroke * Radiologically it can be difficult to differentiate from inflammatory lesions * Classic presentation is of weak floppy legs with a sensory level to pinprick but preserved JPS and VS, with bladder and bowel involvement * Spinal shock (floppy legs with absent reflexes) can last several days * Further investigations may include a thrombophilia screen, vascular imaging from aorta to carotids as well as echo, rheumatological and vasculitic (including syphilis) investigations. CSF is often examined. Often no cause found. * Can occur after aortic aneurysm repair (artery of Adamkiewicz) * Treatment is with aspirin; rehabilitation via spinal injuries unit

Answer 112

Syringomyelia: Prevalence 8-10 per 100,000 - Typically presents in 20s and 30s - Congenital, usually associated with Arnold Chiari malformation - More usually presents with suspended sensory loss (arms > legs); cape distribution and typically spares dorsal columns - As the syrinx expands, it can affect motor function (hands first, spreading proximally) - Can extend into the brainstem - Treatment is surgical decompression - Need to make sure there is no associated lesion eg. tumour neuromyelitis optica: Aquaporin IV antibodies; targets astrocytes (foot processes so often see along BBB), not oligodendrocytes - Longitudinally extensive transverse myelitis - Also affects the optic nerves and area postrema (loss of vision with colours appearing faded and nausea/vomiting respectively) - Treat with steroids and consider plasma exchange - In longer term, immunosuppression with azathioprine, mycophenolate or rituximab thoracic meningioma: Tend to be slow growing, hence fairly significant radiological cord compression with often mild clinical findings - Like cerebral meningiomas, typically enhance uniformly - Can be removed surgically

Answer 113

cauda equina: back pain with lower motor neurone syndrome (with loss of reflexes) * Multiple roots compressed, with variable weakness * Red flags include saddle anaesthesia, bilateral radicular pain, impaired bladder/bowel/sexual function * Requires urgent MRI and neurosurgical intervention * Don’t forget other causes, such as prostate mets (bones) and epidural abscesses + back pain with urinary retention due to pain and opiates (which can also cause constipation, another cause of urinary retention) spinal AV fistula: >80% between T6 and L2 - Typical combination of slowly progressive walking problems, sensory symptoms and sphincter involvement - Often get combo of upper and lower motor neurone involvement - Treatment is to identify the site of the fistula and attempt to embolise it. Surgery may also be considered

Answer 114

Congenital: syringomyelia (suspended sensory loss, dorsal columns oft spared,motor involvement later) – Degenerative: cervical myelopathy, lumbar canal stenosis – Functional: important differential, especially in context of pain – Infective: eg. varicella zoster, syphilis – Inflammatory: MS, Neuromyelitis optica – Metabolic: vitamin B12 deficiency and subacute combined degeneration of the cord (posterior and posterolateral columns) – Traumatic: cauda equina – Tumour: spinal meningioma (slow growing), lymphoma (quick growing) – Vascular: spinal cord infarct (dorsal columns usually spared), dural AV fistula

Answer 115

clinical syndrome occurs in patients who have had a spinal cord injury at, or above T6 spinal level. Briefly, afferent signals, most commonly triggered by faecal impaction or urinary retention (but many other triggers have been reported) cause a sympathetic spinal reflex via thoracolumbar outflow. The usual, centrally mediated, parasympathetic response however is prevented by the cord lesion. The result is an unbalanced physiological response, characterised by extreme hypertension, flushing and sweating above the level of the cord lesion, agitation, and in untreated cases severe consequences of extreme hypertension have been reported, e.g. haemorrhagic stroke. Management of autonomic dysreflexia involves removal/control of the stimulus and treatment of any life-threatening hypertension and/or bradycardia.

Answer 116

Brown-Sequard syndrome (spinal cord hemisection) 1. Lateral corticospinal tract 2. Dorsal columns 3. Lateral spinothalamic tract 1. Ipsilateral spastic paresis below lesion 2. Ipsilateral loss of proprioception and vibration sensation 3. Contralateral loss of pain and temperature sensation Subacute combined degeneration of the spinal cord (vitamin B12 & more rarely vit E, cu, folate deficiency) 1. Lateral corticospinal tracts 2. Dorsal columns 3. Spinocerebellar tracts 1. Bilateral spastic paresis 2. Bilateral loss of proprioception and vibration sensation 3. Bilateral limb ataxia Friedrich's ataxia Same as subacute combined degeneration of the spinal cord (see above) In addition cerebellar ataxia → other features e.g. intention tremor Anterior spinal artery occlusion 1. Lateral corticospinal tracts 2. Lateral spinothalamic tracts 1. Bilateral spastic paresis 2. Bilateral loss of pain and temperature sensation Syringomyelia 1. Ventral horns 2. Lateral spinothalamic tract 1. Flacid paresis (typically affecting the intrinsic hand muscles) 2. Loss of pain and temperature sensation Neurosyphilis (tabes dorsalis) 1. Dorsal columns 2. Loss of proprioception and vibration sensation

Answer 117

former projects from laminae VII/VIII and terminating in reticular formation and thalamus to promote arousal and automatic responses to pain; some of these axons don't cross midline; latter projects from laminae I and V via anterolateral quadrant of spinal cord to mesencephalic reticular formation and periaqueductal grey

Answer 118

4 principle mechanoreceptive systems innervating glabrous skin of hand: slowly adapting type 1 (end in merkel cells), rapidly adapting type 1 afferents that end in Meissner's corpuscles, rapidly adapting type 2 pacinian corpuscles and slowly adapting type 2 afferents (end in Ruffini endings); all respond to mechanical stim by producing depol receptor pot, and type of stim they respond best to determined by accessory structures (like lamellae in pacinian corpuscles) RA2; pacinian corpuscle is concentric layers of cellular membranes alternating with fluid filled spaces, and distributed widely (inc periosteum of bones, connective tissue in muscles, and mesentery) and extremely sensitive, responding to 10nm of skin motion at 200Hz; sense pressure and higher freq vibration; play role in perceiving edges of objects held in hand etc RA1; receptive fields averaging 3-5mm in diameter and respond best to low freq (10-40hz) vibration; perceive slip between skin and object eg in feedback signals for grip control; rapid adapting hence eg stop feeling your clothes rapidly adapting receptors respond only to onset of stimulus whereas slowly adapting receptors give tonic response to constant stimulus; rapid adaptors respond to low freq sinusoidal mechanical stim with single AP for each phase of stim, treating each period as new stimulus; this is phase-locking and intensity of sinusoidal stim must thus be encoded by number of active sensory fibres rather than freq of firing; number of active fibres is linearly related to amplitude of vibration SA1; small, highly localised receptive fields that innervate skin densely and give linear response to indentation up to 1500 microns; can resolve points, edges, curvature and spatial detail of 0.5mm; firing rate can encode perceived stimulus magnitude SA2 detect skin stretch

Answer 119

property of nociceptors: if stimulus great enough to cause tissue damage, response to subsequent stim increases thus hyperalgesia to previous painful stim and allodynia to previously innocuous stim; allodynia example is taking shower when sun-burned, hot water suddenly painful when normally not; excitatory agents such as ATP (from damaged cells) bradykinin and acid released by anaerobic metabolism during anoxia or metabolic overload) second class of sensitising agents don't directly excite nerve terminals, instead enhance responsiveness to excitatory stimuli eg prostaglandins, NGF; the previous 3 examples excite and sensitise stimulated nociceptor terminals release factors such as calcitonin gene related peptide CGRP and subtance P, vasodilatory peptides both directly and indirectly (mast cell degranulation via SP), inducing neurogenic inflam

Answer 120

Spinal muscular atrophy (SMA) is a rare autosomal recessive condition that causes a progressive loss of motor neurones, leading to progressive muscular weakness. Spinal muscular atrophy affects the lower motor neurones in the spinal cord SMA type 1 has an onset in the first few months of life, usually progressing to death within 2 years. SMA type 2 has an onset within the first 18 months. Most never walk, but survive into adulthood. SMA type 3 has an onset after the first year of life. Most walk without support, but subsequently lose that ability. Respiratory muscles are less affected and life expectancy is close to normal. SMA type 4 has an onset in the 20s. no cure, generally supportive

Answer 121

spinal cord compression - spinal mets, esp breast, kidney, thyroid, lung, prostate; dexameth as soon as suspect, get total length MRI imaging, urgent surgical or radiotherapy treatment SIADH - consider when pt with cancer presents with hyponat; ADH from tumous, esp small cell LC leukostasis - in pt with AML/ALL 5-30% of time, infants esp affected; very high wcc, fever, papilloedema, focal neuro deficits(inc headache, dizziness, confusion, lethargy), retinal H+, RVT, MI, limb ischaemia, DIC, resp failure - dyspnoea, hypoxia; cytoreduction w chemo or leukophoresis; high risk of tumour lysis syndrome raised ICP - cranial mets affect 1/4 of pts who die of cancer; lung, breast, melanoma most common to met here; headache, n&v, behaviour changes, seizures, other signs of raised icp; urgent MRI, dexameth, mannitol, irradiation or surgery

Answer 122

high dose steroids: dex 16mg/d PO stat Urgent MRI + consult neurosurgeons. Analgesia, catheter, laxatives, bed rest Definitive management Surgical decompression appropriate if one site, limited disease, histology needed, skeletal instability. Most pt: urgent radiotherapy - initially induces oedema so things worsen before get better.

Answer 123

compression of single nerve root - pain - Straight leg raise replicates pain - Pain radiates neck/back in dermatomal distribution - weakness/reflexes limited to specific myotome / Absent - numbness ditto - bladder normal - imaging not required Compression of cauda equina (bundle of nerve roots below spinal card termination at L2) - Severe lower back pain - Bilateral radicular pain - weakness/reflexes Severe, bilateral, multiple nerve roots - numbness ditto - Incontinence/ dysfunction - Lax anal tone on PR - Perianal anaesthesia - Urgent MRI

Answer 124

hydroceph, incontinence, paralysis of legs, lumbar kyphosis

Answer 125

friedreich ataxia, duchenne, spina bifida, tethered cord syndrome, CMT, idiopathic, and familial

Answer 126

notochord is dense cell rod that forms along midline axis from mesoderm, its remnant in adults the nucleus pulposus; produces proteins like SHH to induce specialisation of ectoderm to form midline floorplate of neural tube ectoderm thickens into neural plate which folds inwards to become a groove, then a tube in neurolation; neural groove cells express N-cadherin (lateral ectoderm E-cadherin) which helps keep two populations separate; 2 lips of groove come together and fuse in midline to give neural tube with overlying ectoderm to internalise the neural tube; cells at leading edge of lip break away and migrate into surrounding tissues as neural crest cells, cranial ones give rise to face bones/teeth/thymus/parathyroid/thyroid/sensory cranial neurons/PS ganglia/heart valves and trunk crest cells give rise to melanocytes, sensory neurons, symp ganglia/nerves, chromaffin cells of adrenal medulla; cranial neuropore closes in 4th week and caudal 2 days later closure of tube spreads cranially/caudally from thoracic region with defects affecting 1:300 to 1:5000 live births depending on geographical region; anencephaly (head defect) fatal, failures in spinal cord closure vary in severity eg spina bifida; ~50% defects may be prevented with folic acid supplements, cholesterol also important as involved in processing hedgehog proteins

Answer 127

neural tube is midline ectoderm dorsal to notochord, specified to form neural tissue, neural plate folds to complete the tube; defects give neural tube defects (1 in 500 births) eg spina bifida; ant/post (rost/caud) patterning of tube to regionalise (forebrain, midbrain, hindbrain, spinal cord) with regions subdivided as complexity increases; HOX genes control this by encoding tfs; signalling centres arise that secrete factors that influence fate of nearby tissue: eg mid/hindbrain boundary (isthmus) devs at caudal expression boundary of a tf and secretes FGF8 to induce special fates in dorsal neural tissue, leading to dev of tectum rostrally and cerebellum caudally; neural tissue ventral to isthmus generates substantia nigra and motot CN III/IV notochord acts as signalling centre in ventral midline, inducing neural floorplate via Shh; floorplate then acquires signalling properties, inc Shh expression, and patterns D-V axis via Shh conc (highest conc floorplate, lower induces motor neurons and suppresses dorsal spinal cord phenotypes; other genes subdivide lat/dorsal regions; for radial axis, neural tube initially organised as neuroepithelium with multipotent stem cells dividing ventricular zone, these generating neurons and radial glia which provide scaffold for neuroblast migration (for inside out dev of cerebral cortex); in mammals, neuronal stem cells disappear (prob differentiate into astrocytes) except in specialised locations (hippocampus, olfactory bulb); productions of neurons ceases in infancy in most regions of mammalian brain and neurons are post-mitotic

Answer 128

cranial: anencephaly, encephalocele (meningocele), spinal: spina bifida (occulta, meningocele, myelomeningocele) inadequate folate, sod val, carbamazepine, FH are risk factors anencephaly - cranial vault absent, prenatal diagnosis, termination; otherwise 75% stillborn, rest die shortly after cephalocele - brain matter deviates through defect in skull eg meninges in meningocele, brain matter too in encephalocele; seizures. intellectual impairment, or other disturbance spinal meningocele: meninges outside spinal canal, normal exam, 5% cases spina bifida cystica myelomeningocele: 80-90% spina bifida cystica cases, disturbed bladder/bowel control inc obstruction + chronic pyeloneph, sensory loss to level of lesion, motor weakness below lesion, hydrocephalus, associated with chiaria II malformation spina bifida occulta -often incidental finding but if naevus, hairy patch, sinus then MRI spine indicated; may give asym lower motor neuron weakness, diminished reflexes and tone; can get spasticity and impaired bladder control keep newborn warm, defect covered with sterile saline dressing in prone position, close defect promptly; shunt for hydroceph if myelomeningocele; post fossa decompression for CM if sympt; physio, occupational therapy, wheelchairs or walking aids etc usually picked up on anomaly scan (18-21 weeks)

Answer 129

distributes almost all upper limb nerves except accesory nerve formed by union and division of roots of C5-T1 roots between scalenus ant/med, trunks cross post triangle of neck, divisions at apex of axilla deep to clavicle, cords deep to pec minor and named according to relation with 2nd part of axillary artery, terminal branches relate to 3rd part of artery; roots, trunks (up,mid,low) divisions, cords branches; up/mid trunk ant divs to lat cord, low trunk ant div to med cord, all post divs to post cord; imaged with MRI due to multiplanar arrangement and tissue contrast difference

Answer 130

before divisions: dorsal scapular from C5 to levator scapulae and rhomboids giving elevation/retraction of shoulders; nerve to subclavius C5/6 to subclavius, marks Erb's point where C5/6 unite; long thoracic nerve C5/6/7 passes through cervicoaxillary canal and along serratus anterior innervating each of its digitations to help control scapula protraction and rotation; suprascapular nerve C5/6 from upper trunk along post triangle, deep to trap, through suprascapular notch to supra.infraspinatus and acromioclavicular joint branches from lat cord: lateral pec nerve C5,6,7 pierces clavipectoral fascia to reach clavicular pec major, forming ansa pectoralis loop around axillary artery with med pec nerve, block during orthopaedic shoulder procedures (like dislocation) can reduce spasm from pec major so reduce pain; musculocutaneous; lat cord median nerve branches from med cord: med pec nerve C8/T1 between axillary artery/vein to pec minor, through to pec major sternocostal head; medial cutaneous nerve of arm T1 sensory supply to skin of lower arm to medial epicondyle; medial cutaneous nerve of forearm C8/T1 sensory supply to skin of lower arm, medial forearm, branches into volar/anterior and ulnar/posterior; medial head of median nerve, ulnar nerve branches from post cord: upper subscapular nerve C6 to upper part of subscapularis, thoracodorsal nerve C6,7,8 to lat dorsi, lower subscapular nerve C6,7 lower part of subscapularis and teres major; axillary nerve C5/6 ant branch closely related to surgical neck, main deltoid innervator and some cutaneous innervation; radial nerve; axillary nerve may be damaged in dislocation, crutch compression, fracture of cervical neck giving square shoulder deformity, loss of abduction from 15 to 90 degrees and loss of sensation

Answer 131

runs on medial aspect of arm close to coracobrachialis and pierces medial intermuscular septum to lie posteriorly in groove between olecranon and medial epicondyle; enters ant forearm comp by passing between heads of FCU midforearm gives palmar cutaneous branch to supply skin on medial palm, dorsal cutaneous branch winds around ulna deep to FCU to supply dorsal aspect of ulnar one and a half fingers main nerve continues with ulnar artery to wrist, dividing into deep/superficial branches: sup to PB, palmar skin of ulnar 1.5 digits via digital branches deep trhough palm to terminate in adductor pollicis C8/T1, distal injury gives claw hand (MCP extended, IP flexed in ulnar two fingers) as interossei and lumbricals paralysed (except what median nerve does); ulnar paradox as lesion at or above elbow also paralyses ulnar FDP so less deformity but greater functional loss; guyon's canal between pisiform and hook of hamate, fibrooesseous tunnel in which nerve may be compressed although rarer than carpal tunnel; autonomous sensory area is palmar tip of little finger can suspect clinically, otherwise nerve conduction studies and electromyography can prove problem

Answer 132

C5,6,7, pierces and supplies coracobrachialis then into arm between biceps and brachialis, supplying both; just proximal to elbow becomes lateral cutaneous nerve of forearm which gives ant/post branches and innervates lateral forearm to wrist; frequent variations including interconnecting with median nerve

Answer 133

C5-T1, runs anteromedially with brachial artery then crosses anterior to artery to lie medial to it at the cubital fossa; passes between heads of PT gives ant int branch after PT which passes along IM and innervates forearm flexors palmar cutaneous branch to skin over thenar eminence superficial to FR so spared in carpal tunnel recurrent branch to thenar muscles affected in carpal tunnel gives digital branches to thumb, index, middle and radial half of ring fingers (palmar plus nailbeds) with tip of index finger for autonomous testing proximal lesions manifest like carpal tunnel but inability to flex index/middle fingers, distal phalanx of thumb (both due to losee of forearm flexors), weakness and wasting in thenar eminence, ulnar deviation distal lesion from carpal tunnel syndrome giving pain and paraesthesia, thenar wasting, skin over thenar spared; managed by night splints to prevent wrist flexion, steroid injections, surgery to divide FR, pregnant women at risk due to fluid retention martin-gruber anastomosis is communicating nerve branch between ulnar/median nerves in forearm which can serve as conduit for alternative innervation, exacerbating or attenuating problems and leading to false conclusions about injury to nerve, study found it in 27% of 50 cadavers, matching another study (found it in 23%) evaluate lesions with nerve conduction studies and electromyography

Answer 134

C5-T1, supplies triceps and runs with profunda brachii in spiral groove, perforates lateral intermuscular septum and passes anteriorly to divide into superficial and deep branches in lateral vicinity of cubital fossa deep passes between heads of supinator to emerge as post int and innervates the forearm extensors in posterior compartment superficial deep to brachioradialis and lateral to radial artery, curves around radius and pierces deep fascia to give sensory branches to dorsum of hand: thumb/index/middle/radial half of ring up to DIP joint; autonomous testing zone is dorsal aspect of first web space posterior cutaneous nerve of arm branch supplies lateral arm proximal to elbow and much of the back of the arm and forearm lesion gives wrist drop (inability to extend wrist, fingers, thumb); power grip weakness as synergism between flexors/extensors needed; dorsum of hand sensation loss proximal injury in eg axilla suggested by wrist drop and loss of active elbow extension + greater sensory loss; saturday night palsy when person falls asleep with arm across back of chair giving wrist drop

Answer 135

Erb's palsy, upper trunk C5,6, excessive downwards traction on limb in eg difficult delivery; shoulder abduction, elbow flexion, supination lost so arm hangs by side with forearm pronated and elbow extended Klumpke's palsy C8/T1 from hyperabduction of shoulder in eg breech delivery, catching yourself if you fall, gives wasting/paralysis of intrinsic muscles of hand, possible claw hand, numbness in C8/T1, may be crying/painful in babies as always NCS/EMG can help, otherwise clinical diagnosis

Answer 136

over time, usually before end of 1st year; physio to prevent contractures developing - they will do specific movements and also assess using toronto score, if scores low (poor mobility) or only marginal improvement will refer for surgery, often if little improvement by 3-4mo or adequate function not back by 9mo - surgery will include removal of scar tissue/neuroma and nerve grafting (often using small sensory nerves from legs)

Answer 137

within or posterior to psoas major, by anterior rami of L1-4, some of L4 joins L5 to form lumbosacral trunk iliohypogastric L1 to innervate genital and hypogastric regions ilioinguinal L1 to conjoint tendon, skin at root of penis/clitoris, anterior scrotum, mons pubis, labia majora genitofemoral L1,2 pierces psoas, lies on it, with femoral branch L1 to upper anterior thigh and genital branch L2 to cremasteric muscle and areas supplied by ilioinguinal lateral femoral cutaneous L2,3 across iliacus and enters thigh medial to ASIS beneath IL open repair of inguinal hernia may damage and laparoscopic repair entrap the ilioinguinal nerve, some surgeons say gives less pain but conjoint tendon denervated; meralgia paraesthetica entrapment of lat fem cut nerve as it passes beneath IL giving numbness/pain in outer aspect of thigh with restrictive clothing and weight gain common causes L2-4 give femoral nerve and obturator nerve, femoral lateral to psoas and obturator medial to it L4/L5 form lumbosacral trunk to connect to sacral plexus

Answer 138

from posterior divisions,L2-4, gives small branch to iliacus (hip flexor), ant division gives anterior, intermediate, medial femoral cutaneous nerves to medial thigh and around knee and branches to pectineus/sartorius (hip flexors); posterior division branches to quads/joints with hip joint from branch to rectus femoris and knee joint vastus intermedius gives saphenous nerve that innervates anteromedial leg/ankle penetrating trauma like knife, surgery on groin or hip, can paralyse knee extensors and give difficulty walking/standing due to injury to femoral nerve; anaesthestised in FIB, saphenous vein harvest may damage saphenous nerve giving pain or numbness in that distribution

Answer 139

from ant divisions, L2-4; gives a/p divisions after passing through obturator canal; skin of medial aspect of thigh, adductor longus/brevis/magnus, gracilis, obturator externus in general can say it innervates medial compartment of thigh with role being hip adduction

Answer 140

lumbar plexus insufficient to innervate entire lower limb, lumbosacral trunk and ant rami S1-4 form sacral plexus: trunk joins S1 which joins S2-4 on piriformis sup glut L4-S1 to med/min glut and tensor fascia latae above piriformis inf glut below, L5-S2 to glut max, if injured in post hip replacement gives glut max lurch when trunk extends on heel strike to compensate for weak hip extension direct L5-S2 branches to piriformis nerve to obturator internus L5-S2 and quadratus femoris L4-5,S1 post femoral cutaneous nerve to skin of post thigh/perineum, medial to sciatic and may be damaged in post approach to hip, S2,3 pudendal, coccygeal and sciatic (from origin onwards can be thought of bundle of tibial and peroneal nerves)

Answer 141

L4 to S3, through greater sciatic foramen, enters thigh deep to hamstrings, divides at variable distance, usually mid-thigh into tibial/common fibular (peroneal) nerves but you can think of it as being these two nerves bundled throughout tibial nerve innervates post comp leg (toe flexion, inversion, plantarflexion), gives med/lat plantar nerves to intrinsic foot muscles, sole and toes; common fibular is smaller, winds laterally round head of fibula gives sup branch to lateral leg comp (foot eversion), deep branch to ant comp (dorsiflexion and inversion), dorsal intrinsic foot muscles sural made of branches from tibial and fibular, innervates skin of posterolateral leg, foot and ankle, often used for biopsy if nerve biopsy indicated (will lose distal sensation), spared in GBS and some other autoimmune diseases, helping to differentiate from a length dependent process which won't spare; common fibular innervates some anterolateral leg, superficial fibular does much of dorsum of foot injured in intramuscular buttock injection, top right quadrant to avoid this; post hip dislocation/surgery may injure, penetrating trauma esp when emerges from buttock before passing deep to hamstrings; tarsal tunnel syndrome affects tibial nerve post to medial malleolus, more common in athletes due to chronic sustained overuse, much rarer than carpal tunnel syndrome

Answer 142

Hip L2/3 flex/adduct/med rot, L4/5 extend,abduct, lat rot; Knee L3/4 extend, L5/S1 flex; ankle L4/5 dorsiflex, S1/2 plantarflex; foot L4 invert, L5/S1 evert

Answer 143

motor axons emerge from bundle in nerve and split into branches, each forms a motor endplate with a single muscle fibre, usually near the middle; normally one axon to one fibre; motor unit is group of muscle fibres innervated by one motor neuron; fibre (1-2micron diameter) separated by synaptic cleft (50-70nm); every 1-2 microns, transverse invagination of synaptic membrane called junctional fold with thickenings above in presynaptic membrane called active zones where thousands of NT vesicles cluster, each about 50nm in diameter; cleft filled with mucopolysaccharide gel and layer of extracellular material called basal lamina AP opens VG Ca channels, causes vesicles to fuse; visualised in freeze-fracture EM; vesicle [NT] 100-200mM, ~10^4 per vesicle; release prop to [Ca]ext^4, suggesting cooperative mechanism; synaptic delay between AP arrival and start of postsynaptic response: in frogs shown to be ~1ms, maybe ~-0.75 in ppl, most in presynaptic terminal before release with ACh diffusing across cleft in ~10microsecs and postsynaptic response taking <100microsecs to begin

Answer 144

curare used to block AP to observe EPP, with time constant of 10s of ms, and faster decay with larger fibre diameter; voltage clamp at negative potential and then presynaptic nerve stimulated shows at muscle an endplate current which rises to a peak in <1ms and has TC of ~1ms, representing sum of currents through thousands of nAChRs; EPSP much slower as time needed to charge/discharge muscle membrane capacitance spontaneous MEPPs (<1mV), shown by measuring response to artificially applied ACh that one MEPP corresponds to a quantum of ~10,000 ACh molecules; occurred even when TTX blocked presynaptic APs; MEPP frequency changed decreased with decreased [Ca]ext and other factors affecting vesicle release; proposed that quantum = one vesicle and probabilistic chance of release; quantal content is mean number of quanta released during an AP recording near endplate shows upstroke of EPP in AP, moving recording electrode 5mm away and EPP not observed; curare treated muscle to make EPP subthreshold shows it decays exponentially with distance due to cable properties of muscle, no regenrative inwards current so EPP fades as endplate current leaks across PM; restricts region over which EPP can initiate an AP to that area immediately around the endplate

Answer 145

synaptobrevin, syntaxin and SNAP-25 form four-helix bundle (trans-SNARE complex) that holds vesicle close to PM; complexin inserts into complex to prevent spontaneous fusion (note, synaptobrevin may be cleaved by tetanus toxin in inhib spinal interneurons and some botulinum toxins target all 3 in motor neurons to block vesicle fusion); Ca binds to synaptotagmin which displaces complexin resulting in fusion

Answer 146

dielectric separating charge hence capacitor, shown experimentally with time taken to charge/discharge capacitance as changing Em if current applied; R is about 1 megaohm, capacitance about 2000 picofarads for mammalian motorneuron, so time constant (time to change Em by ~63%) is ~2ms; capacitance limits speed of response to stimuli that change Em by delaying depolarisation eqpot: driving force for passive, uncoupled movement of solute is electrochemical energy difference for that solute either side of PM, with chemical force based on diffusion and electrical force based on developing Em; when the forces balance such that there is no net flux, Eqpot is reached; larger conc diff needs larger balancing Em, raising temp gives greater energy to ions so greater balancing Em; higher charge for ion means more strongly affected by voltage diff so less Em needed; theoretical usually not achieved as perm to more than 1 ion, GHK combines Em factoring in perms

Answer 147

AP triggered at axon hillock by synaptic inputs, with change from analogue (continually variable) input at hillock to digital AP pulse blocking VG channels in axon and depolarising it allows observation of spatial decay of current due to electrotonic spread along path of least R, determined by transmembrane and longitudinal resistance; axoplasm has high R and PM low, causing current to leak out of cell, APs exist as passive flow is unable to carry information far Ions don't carry this current, rather entry of ions causes chain of ionic rearrangement driven by electrostatic forces which gives an impression of flow; large I with small PM C gives fast initial depolarisation, simply increasing Na current metabolically expensive as Na has to be pumped out; larger diameter neurons have lower longitudinal R, eg giant squid axons myelination increases PM R 300x to reduce current leakage so length constant increases (sheath can be 1/4 of axon diameter), saltatory conduction between nodes every 0.1-2mm; myelination reduces PM C 300x too so Em can change more rapidly (these numbers based on number of layers and R in series add directly and C in series as sum of reciprocal), though may be offset by smaller nodal currents; velocity prop to diameter for myelinated, sqrt of diameter for unmyelinated; APs less metabolically expensive too as less ions move so less pumping needed; small diameter myelinated nerves conduct slows than unmyelinated as axon very narrow, giving high R

Answer 148

Aalpha (motor) 80-120m per s; Abeta (sensory mechanoreceptors) 35-75 m per s; Agamma (motor fibres to intrafusal muscle spindles) 12-30 m per s; Adelta (nociceptive/cold receptors) 5-30 m per s; B (pregang autonomic) 3-15 m per s; unmyelinated type C (nociceptive/warm) <2m per s

Answer 149

V decays exponentially V=Voe^(-x/lambda) with lambda the length constant, due to electrotonic currents; lambda = sqrt(membrane R/ longitudinal R); multiple sclerosis with loss of myelin giving paralysis/altered sensation as PM R falls and PM C rises until cannot propagate far enough to reach next node of ranvier and nerve doesn't conduct

Answer 150

Na: open at a threshold voltage; time dependent closure after ~1ms with a period of inactivation lasting ~1ms giving absolute refractory period; gradual deinactivation when threshold raised as less Na channels available is relative refractory period; these periods ensure APs conduct in one way; stretch of aa at N terminus of Na channel can block the pore giving inactivation K channels: purely VG, open on depolarisation and close on hyperpolarisation; no obvious threshold and very slow to respond due to the kinetics of their pore opening/closing (4 separate events: colder temps, much slower than Na) probability that a channel is open varies with Em according to a Boltzmann distribution, if voltage sensing part of channel is +ve then probability of channel opening increases from 0 to 1 in a sigmoid fashion as Em becomes more positive (Em on x axis, prob on y); total current carried by an ion is equal to total number of channels, current through individual channel (conductance x difference between Em and Eeqpot) and probability that the channel is open at that Em; S4 segment in Na, Ca and K channels has Arg/Lys residues every third residue which acts as a voltage sensor depolarisation to threshold has enough Na channels open to cause +ve feedback cycle of Na channel openings until ~1ms when they close; slower K channels start to open allowing repolarisation, which overshoots (hyperpolarises) as the channels are slow to close many neurons show reduction in firing freq over time; firstly due to Na channel inactivation, and secondly the open K channels clamp the Em towards Keq (-105mV) which takes it further from threshold

Answer 151

GABA and glycine bind to gated Cl channels, increased Cl conductance opposing EPSPs as Ecl in neurons is near resting potential glutamate binds to AMPA receptors permeable to Na and K which mediate fast part of EPSC; and to NMDA receptors which allows Na/Ca through, glycine required to co-activate this and does the slow part of EPSC; inhibition by ionotropic GABAa and metabotropic GABAb, GABAa shunt and hyperpolarise, GABAb inhibits both pre and post synaptically some inhibitory synapses are closer to AP trigger zone and so may shunt excitatory current to prevent AP generation

Answer 152

[Cl]i is low giving a negative Eqpot; Cl- is primarily distributed passively such that the nernst potential is approximately equal to Em, leading to the donnan product rule where Ek=Ecl and thus (by cancelling, taking antilogs and cross multiplying) [K]o . [Cl]o = [K]i . [Cl]i; there is also secondary active transport with Cl extrusion coupled to K efflux via KCC2 and Na dependent influx of bicarbonate via NDCBE. both these processes lower the [Cl]i such that Ecl is more negative than the resting potential. in developing neurons and adult olfactory receptor neurons, inwards Na/K coupled Cl transport via NKCC1 raises [Cl]i such that opening Cl channels at the Em allows an excitatory outwards flow of Cl ions; in certain types of epilepsy/chronic pain syndrome, expression pattern of Cl cotransporters reverts to the immature state so GABA has a depolarising effect leading to abnormally high levels of excitation [Ca]i is very low and has a positive Eqpot; it is powerfully extruded via ATP driven Ca pump and secondary Na/Ca exchange via NCX, sometimes also utilising the outwards K gradient NCKX to give more powerful extrusion; thus in most cells [Ca]i is <100nM which allows use of Ca as an intracellular messenger as small fluxes cause large concentration changes, often Ca stores are released from ER after stimulation and taken back up by pumps; most neurons have relatively few ca pumps and are more reliant on Na/Ca exchange equivalent circuit for PM: 4 parallel circuits for each ion containing battery of Eion, resistor representing conductance of that ion and carrying a current for the ion with total current the sum of each individual with Iion = gion (E - Eion)

Answer 153

Ca entry through VG Ca channels serves to transduce electrical activity into chemical response at the synapse, and Ca is used due to its low [Ca]i at the Em; within immediate vicinity of Ca channel, ten or hundreds of micromolar [Ca] can be attained; quantal release of NT via vesicles occurs with synaptotagmin serving as a Ca sensor and snare proteins fusing the vesicles: vesicle docks, is primed by association between v-SNARE and t-SNARE and then Ca dependent fusion occurs, releasing contents into synaptic cleft

Answer 154

amino acids like glutamate, main CNS excitatory and acting via ionotropic like AMPA/NMDA and metabotropic like mGluR1 to mGluR5; GABA (main brain inhibitory) acting via iono GABA-A and metabo GABA-B; glycine (spinal cord inhibitory) acting only via iono glycine receptor bioactive amines such as Ach acting via nictotinic (iono) and muscarinic (metabo), catcholamines like NA acting via metabo alpha/beta receptors and associated with locus coeruleus; dopamine (DA) acting via metabo D1-like and D2-like, via cAMP cascades in substantia nigra; serotonin (5-HT) acting via iono 5-HT3 and metabo 5-HT1/2/4 and associated with raphe nucleus; histamine (H) acting via metabo H1/2/3/4 ATP and adenosine act at non-cholinergic non-adrenergic autonomic synapses via purinergic receptors such as P1/P2Y metabo and P2X iono for ATP with roles in vascular, apoptosis, cytokines etc and A1/2/3 metabo with cardiovascular roles for adenosine extremely diverse range of neuropeptides which have NT, modulatory and hormonal roles and are often co-released with more traditional NTs eg VIP with Ach; they act via diverse set of metabotropic receptors and include eg opioids, pituitary, secretins, insulins, tachykinins, somatostatins, gastrins etc gaseous transmitters such as NO acting metabotropically via guanylyl cyclase as endothelium derived relaxing factor, and possible roles also for CO and H2S

Answer 155

a stimulus results in a graded receptor current dependent on stimulus strength, which subsequently generates a graded receptor potential and depolarises the site of impulse initiation, which varies its rate of AP generation in response to magnitude of depolarisation, an exception is the retinal photoreceptors which hyperpolarise in light; long receptors send afferent axons to CNS and fire APs and short receptors without an axon synapse with a second order neuron for conduction to the CNS, these often generate a graded potential instead of spikes giving a graded change in NT release and graded generator potential in the second order cell modulating rate of spike firing; cutaneous, cranial and olfactory receptors are long, taste, hearing and vision are short transduction mechanisms: direct in mechanoreceptors with opening of stretch-sensitive channels coupled to cytoskeleton or more complex structures in the case of hearing; cations then enter and depolarise the receptor; other receptors that use a direct mechanism include salt receptors in the tongue; most others use indirect second messenger cascade (taste, smell, sight etc), similar to metabotropic synapse transmission; long receptors must have AP, short don't

Answer 156

axosomatic (input to soma), axodendritic (axon to dendrites), axo-axonic (axon to axon) cortical pyramidal cells receive type 1 (excitatory input) to dendritic shaft (mostly) and spines, and type 2 (inhibitory) to the soma AP propagates via local circuit currents, the potential of which undergoes exponential decay with a length/space constant; dendritic tree can be imagined as split into passive cable segments into which current is injected by synaptic receptors when activated, and VG Na/Ca conductances in many neurons can boost the decaying passive dendritic current

Answer 157

specialised region called axon hillock, which has the lowest threshold; shown by cortical slice of pyramidal cell with current clamp (so voltage varies freely), AP always recorded first at soma regardless of whether you stimulate dendrites or soma, in many neurons the AP then propagates actively back into the dendritic tree axon hillock has lowest threshold due to exceptionally high conc of VG Na channels as well as sensitive channels and turns graded receptor potentials into train of all-or-none APs; hillock Em must change by 10mV vs 30mV for cell body an individual synapse will influence the soma based on how far it is away on dendritic tree (due to space constant) and are also more strongly attenuated along small dendrites as space constant varies with square root of neuron diameter

Answer 158

depolarising an axon by injecting current gives a rate of firing related extremely steeply to the magnitude of injected current (ie does not fire or fires very rapidly), whereas depolarising the soma gives a rate of firing that is a graded function of the current such that magnitude of stimulus is encoded in the frequency of the spike train; a requirement for this is an additional K conductance which inactivates on maintained depolarisation, and voltage clamp experiments using a Na channel blocker (TTX) show a component of K current that inactivates and can be inactivated if the cell is held at a depolarised potential before the strongly depolarising clamp step, inactivating current is known as the A current; after each AP Ia remains inactivated and Ik remains high which holds the membrane at a negative potential, Ia then activates which prevents Em being raised to threshold before inactivating again, allowing threshold to be approached and another AP to fire, thus Ia serves to space out APs in the spike train many CNS neurons fire in bursts, and some cortical pyramidal cells show intrinsic bursting even when stimulated continuously; bursting occurs when low threshold VG Ca channels are activated: T (transient) channels have a threshold of -65mV and inactivate moderately slowly (20-50ms) to terminate the burst; thalamic relay neurons exhibit bursting when relatively hyperpolarised as in sleep as T channels can recover form inactivation and fire another bust of 2-5 APs, threshold for the T channels is reached by a hyperpolarisation activated inwards current Ih comprising Na and K; at more depolarised potentials the T channels are permanently inactivated and the relay neuron repeatedly fires single spikes in tonic mode

Answer 159

feedforward inhibition the pathway to the antagonist is inhibited when the agonist is stimulated; in feedback inhibition the excited neuron contacts an inhibitory interneuron via recurrent axon collaterals to inhibit its own firing and that of its synergists: an example is the Renshaw cell which stabilises motor neurons in the spinal cord in flexor withdrawal reflex, stimulating cutaneous nociceptors gives reflex extensor inhibition and flexor stimulation to move the limb from harm in the simultaneous crossed extensor reflex, stimulation of the contralateral extensor and inhibition of the contralateral flexor muscles provide support (eg step on nail, lift foot off and other takes full body weight); feedforward prevents agonist and antagonist contracting at same time to coordinate action about the joint, and feedback stabilises motor neuron firing rate

Answer 160

some local trigger zones in some neurons with sufficient Na channel density to fire an AP, although not regeneratively propogate it: forward propogate to hillock and are integrated with other inputs mainly however dendritic ion channels serve to amplify the EPSP and allow propagation back into dendrite; possible role for this is to provide precise temporal control over NMDA current by providing necessary depolarisation to relieve Mg block, and back propagating APs combined with presynaptic stimulation causes supralinear Ca signal in the dendritic spine head specific to the activated head which may be important in memory, aided by the thin spine neck serving as a barrier to diffusion into dendritic shaft

Answer 161

VG Ca channels clustered near the active zones as free Ca doesnt travel far, as rapidly buffered by Ca binding proteins during high frequency firing so much Ca floods into neuron that Ca binding proteins are saturated leaving residual Ca which can activate enzymes to enhance synaptic transmission, thus post-tetanic potentiation where EPSPs are larger, they increase during the stimulation (potentiation)

Answer 162

musk (muscle specific kinase) sits in muscle PM and once activated promotes clustering of nAChR at the NMJ via activating rapsyn protein as well as retrograde release of signals to stimulate presynaptic differentiation; agrin released by motorneuron binds Lrp4 which binds and activates Musk, then nAChR cluster around them while also signalling the motorneuron axon to form a synapse MG diagnosis by testing directly for the antibodies (anti-nAChR, anti-musk, antir-Lrp4); CT/MRI to look for thymoma; edrophonium test if doubt; EMG or SFEMG (aka jitter test) Treatment options Reversible acetylcholinesterase inhibitors (usually pyridostigmine or neostigmine) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms Immunosuppression (e.g. prednisolone first then if can't wean switch to azathioprine (check TMPT) or mycophenolate) suppresses the production of antibodies Thymectomy can improve symptoms even in patients without a thymoma Monoclonal antibodies Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective Myasthenic crisis: acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure or bulbar symptoms Need SALT assessment and monitor vital capacity; Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation. Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IVIg and plasma exchange if giving any meds carefully check as many can precipitate crises -> some inc iodinated contrast, gentamicin, and magnesium

Answer 163

CMS is caused by group of genetic disorders interfering with NMJ and thus causing a fatiguable myasthenia presents with a history of fatigable weakness involving ocular, bulbar, and limb muscles with onset at or shortly after birth or in early childhood, usually in the first two years; motor dev may be delayed, other dev normal; neonates may show sudden, episodic apnea and cyanosis and have joint contractures often described as arthrogryposis multiplex congenita) resulting from a lack of fetal movement; antibodies are absent, unlike in actual MG, and immunosuppression won't relieve sx decremental EMG response of the compound muscle action potential (CMAP) can be evoked on low-frequency (2-3 Hz) stimulation genetic testing will be needed pyridostigmine is generally beneficial TNMG in babies of mums with MG: antibodies cross over and disease lasts for weeks-months until antibodies are replaced; note distinct from above CMS (AR diseases due to mutations in NMJ proteins) and juvenile MG (proper MG onset very early, earliest reported in infancy); only in 10-15% of MG mothers will have, but if have once risk higher in later pregnancies; if mild then small, freq feeds and watch for aspiration, if more severe pyridostigmine, if v severe then IVIg/plasmapharesis; thymectomy not needed for these kids

Answer 164

CMT usually autodom, often symptoms before age ten but sometimes not until 40yo+ High foot arches (pes cavus) Distal muscle wasting causing “inverted champagne bottle legs” Weakness in the lower legs, particularly loss of ankle dorsiflexion Weakness in the hands Reduced tendon reflexes Reduced muscle tone Peripheral sensory loss CMT is good bet for periph neuropathy in exams; other causes: A – Alcohol B – B12 deficiency C – Cancer and Chronic Kidney Disease D – Diabetes and Drugs (e.g. isoniazid, amiodarone and cisplatin) E – Every vasculitis supportive management with eg physio, OT, podiatrists, ortho surgeons CMT duration chronic, GBS subacute (within 4 weeks of infection) GBS: nerve conduction studies, protein in CSF; IVIg or plasma exchange, VTE prophylaxis (PE big cause of death); intubation and ventilation might be needed if resp failure severe - spirometry to measure vital capacity

Answer 165

both appear 7-10 days after resp or GI illness, indeed GBS is most common acquired periph neuropathy in kids; characterised by the presence of antibodies to membrane gangliosides including GM1, asialoGM1, LM1 and GD1b; can tell it isn't a length dependent process as specific sign is sural nerve sparing note GBS can take up to 4 weeks to appear, follows 3 phases of progressive (days to 4 weeks, plateau weeks to months, then recovery); if reach maximum disability within 24 h of disease onset or after 4 weeks, alternative diagnoses should be considered suspect GBS when progressive b/l limb weakness or altered sensation, hypo/areflexia, facial or bulbar palsy, opthalmoplegia; look at Brighton GBS scoring system at this point Dysautonomia is common and can include blood pressure or heart rate instability, pupillary dysfunction, and bowel or bladder dysfunction; may have muscular, neuropathic pain brain and spine MRI with contrast (note spinal cord compression as ddx), LP (CSF for Protein, MC&S, viral PCR’s, with matched plasma samples for Glucose, Oligoclonal bands, lactate), bloods (FBC, Ferritin, U&E, Bone profile, CRP, ESR, CK, LFT’s, TFT’s capillary blood gas), NCS, spirometry, Stool culture for Polio and Campylobacter jejuni, and consider swab/testing for COVID, flu, CMV, EBV, mycoplasma admit to PICU if rapidly progressing and upper limbs involved, respiratory distress (VC reduced <15-20ml/kg, can't count to 15 in single breath, breathless at rest, accessory muscle use, increased RR/HR, low sats or abnormal blood gas), or swallowing or autonomic dysfunction give IVIg 2g/kg over 3-5 days or PLEX; regularly monitor VC, swallowing (needs SALT review and consider NGT early), bladder and bowel control, obs, muscle power; will need long term rehab be vigilant for corneal ulcers if facial palsy, aspiration, mucous plugs, arrhythmia, hypo/hypertension, urinary retention, constipation, pressure ulcers, contractures, weight loss GBS vs polio: GBS may have sensory and polio not, GBS over 1-2 weeks usually and polio 1-2 days; GBS may have autonomic involvement inc urinary problems and arrhythmias; motor nerve conduction slow in GBS and normal in polio; CSF high protein minimal wcc for GBS and viral meningitis picture for polio; GBS has inflam, oedema, demyelination of spinal nerves near nerve root, polio has destruction of ant horn cells; no virus isolated in GBS, virus from stool/throat/csf for polio

Answer 166

a rare variant of GBS associated with involvement of lower cranial nerves - esp CN3/4/6 but also most others typically find GQ1b ganglioside IgM antibodies as a result you get demyelination as with other forms of GBS typical triad is opthalmoplegia, ataxia, areflexia after preceding illness and may see eg dysarthria, dizziness, bulbar sx, facial paresis ix as for GBS: raised protein in csf, nerve conduction studies, and brain/spine MRI supportive care, IVIG or plasmapheresis (not steroids unless radicular pain); DVT prophylaxis

Answer 167

gangliosides are complex glycolipids most commonly found in brain and nerves, used for cell recognition; campylobacter LPS oligosaccharide has molecular mimicry for these conditions associated with them inc GBS (anti-GM1 IgG), miller fisher syndrome (anti-GQ1b IgG), CANOMAD, multifocal motor neuropathy (anti-GM1 IgM) etc; each condition has its own specific antibodies

Answer 168

most common cause of neuromuscular weakness in the intensive care setting and a common cause of failure to wean from the ventilator Critical illness myopathy is characterized by more proximal than distal weakness, sensory preservation, and atrophy depending on the duration of illness. Critical illness polyneuropathy, on the other hand, is characterized by more distal than proximal weakness, sensory changes, and limited atrophy. Critical illness polyneuromyopathy in turn is characterized by a combination of proximal greater than distal weakness, distal sensory loss, and variable atrophy. Initial preservation of reflexes is common, but gradual loss will occur as weakness progresses in all types; bulbar musculature is rarely involved and patients may present with a profound quadriparesis with preservation of facial expression diagnosis of CIM, CIP, and CIPNM is made via electrodiagnostic studies; Nonneuromuscular cases for ventilator failure include primary pulmonary, cardiovascular, and endocrinologic disease Other neuromuscular causes within the neural axis can present similarly including Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome, botulinum toxin exposure, and ongoing neuromuscular blockade In CIM, the most common electrodiagnostic finding is reduced compound muscle action potential amplitudes; In CIP, the findings resemble a length-dependent axonal polyneuropathy with loss of amplitudes of both sensory nerve action potentials and compound muscle action potentials without significant slowing; changes by week 2 but can be within 72 hours Critical illness myopathy is a heterogenous entity with differing pathologic subtypes—traditional CIM demonstrates myosin loss, fulminant acute necrotizing myopathy, and cachectic myopathy - results from excess catabolism, mito and energy failure, ROS production, hypoxia, cytokine production, altered Na and Ca handling exact mechanism of axonal injury in CIP is unknown. One proposed mechanism of injury is microcirculatory changes associated with systemic inflammation giving distal axonal ischaemia; second proposed mechanism of neuronal dysfunction in CIP is related to increased vascular permeability with increased leukocytes within the endoneurial space and formation of edema

Answer 169

chronic inflammatory demyelinating polyneuropathy Essentially chronic GBS; typical early symptoms are "tingling" (sort of electrified vibration or paresthesia) or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations, "vibration" feelings, loss of balance, general muscle cramping and nerve pain Symptoms such as diminished or absent deep-tendon reflexes and sensory ataxia are common. Other symptoms include proximal and distal muscle weakness in the limbs; autonomic dysfunction can occur NCS and EMG: a reduction in nerve conduction velocities the presence of conduction block or abnormal temporal dispersion in at least one motor nerve; prolonged distal latencies in at least two nerves; LP csf or blood may show diverse range of autoantibodies including against gangliosides, neurofascins and more; sural biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG IVIg, steroids, plasmapharesis are cores of mx

Answer 170

Neurofascins are a group of cell adhesion molecules. NF140 and 186 isoforms are neuronal proteins at nodes of Ranvier whilst NF155 is a Schwann cell protein at the paranodal junction in a subset of patients initially classifying as GBS, IgG autoantibodies directed against adhesion molecules of the node of Ranvier can be detected, these are also present in many ppl with chronic inflammatory demyelinating neuropathy diagnosis; however due to its growing impact, distinct clinical features and distinct pathophysiology compared to GBS or CIDP, autoimmune neuropathies with nodal or paranodal antibodies were recently categorized as a distinct entity termed autoimmune nodopathy a shared epitope on different nodo-paranodal neurofascin isoforms 140/155/186 (pan-neurofascin) has been identified as a target in acute-onset immune-mediated neuropathy; present with a severe, GBS-like onset and after initial short recovery, develop a fulminant course of disease with tetraplegia, autonomic instability, cranial nerve involvement, respiratory failure with prolonged ventilation, insufficient response to standard treatment and a high mortality only small numbers respond to IVIg, consider steroids and PLEX, rituximab if refractory to steroids

Answer 171

RAPD indicates slow conduction in that CNII MS will have high signal on T2/flair, often perivent (Dawsons fingers - as spread along venuls draining from the ventricles) or blobs along spinal cord 1st presentation of CNS demyelinating disease = clinically isolated syndrome; eg optic neuritis, transverse myelitis (sensory/motor effect); brainstem syndrome (diplopia, ataxia, vertigo) lhermittes (tingling/electric shock when bending head to chest (cervical demyelinating plaque); Uhtoff (symptoms worsen/recurs in heat/shower/exercise) transverse myelitis - often dorsal columns, tingliness in feet moving up even to chest; one patch only in spine not just MS, do LP for viruses, bacti (lyme disease etc) relapse/remit as oligodend remyelinate damaged areas MS clinical diagnosis - dissemination in space and time; history: middle ear infection may have been brainstem plaque, carpal tunnel or frozen shoulder may have been episodes too MRI can diagnose after one presentation if dissemination in space/time; space if multiple places, time if gadolinium enhanced MRI (leaky BBB, last 4 weeks) and non enhancing plaques (recovered), or new lesion compared to old scan can also diagnose oligoclonal bands, often useful if only spinal cord involved (absence can be reassuring if suspect other cause of transverse myelitis) histo of active plaque: macros/lymphos/gliosis (astrocytosis); chronic are grey, irregular, sharp bordered areas in white matter, on histo gliosis, sparsely cellular

Answer 172

optic neuritis, transverse myelitis, area postrema syndrome (intractable vomiting) can be neuromyelitis optica (eosins on histo, astrocytes not oligos affected); steroids, steroid-sparing immunosup; see in optic nerve, chiasm, spinal cord - suspect ADEM - acute disseminated encephalomyelitis; disseminated rather than local to temp (as HSV), oft preceding infection (even flu can trigger), fever, headache, seizures, odd behaviour, optic neuritis, transverse myelitis; lymphocytes in csf; oedema may need craniotomy; steroids, IVIg or plasma exchange; demyelination mostly around veins central pontine myelinolysis - too rapid hyponat correction, UMN all 4 limbs, demyelination of pontine base (in middle, not scattered as in MS) so symmetrical about centre

Answer 173

High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse Interferon-beta-1-a has been shown to reduce the relapse rate by up to 30%. natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available spasticity: baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine physiotherapy is important cannabis and botox are undergoing evalulation fatigue: amantadine first line, also consider modafinil, CBT and mindfulness (before drug need to rule out anaemia etc) Bladder dysfunction may take the form of urgency, incontinence, overflow etc assess bladder emptying with pre and post void bladder scan - anticholinergics may worsen symptoms in some patients if significant residual volume → intermittent self-catheterisation if no significant residual volume → anticholinergics may improve urinary frequency

Answer 174

eye pain worse on movement, reduced vision, red desaturation, flashing lights, blurriness Multiple sclerosis is the main cause of optic neuritis, however it can also be caused by: Sarcoidosis Systemic lupus erythematosus Diabetes Syphilis Measles Mumps Lyme disease dmards for ms inc interferon beta 1 a (flu like side effects), injection site reaction; natalizumab (PML risk, fingolimod if at high risk of that)

Answer 175

multiple sclerosis: the commonest associated disease diabetes syphilis Features unilateral decrease in visual acuity over hours or days poor discrimination of colours, 'red desaturation' pain worse on eye movement relative afferent pupillary defect central scotoma Management high-dose steroids recovery usually takes 4-6 weeks MRI is investigation of choice

Answer 176

Also known as the Marcus-Gunn pupil, a relative afferent pupillary defect is found by the 'swinging light test'. It is caused by a lesion anterior to the optic chiasm i.e. optic nerve or retina Finding the affected and normal eye appear to dilate when light is swung from normal to affected causes: optic neuritis. ischemic optic disease or retinal disease. severe glaucoma causing trauma to optic nerve. direct optic nerve damage (trauma, radiation, tumor) retinal detachment. very severe macular degeneration. retinal infection (CMV, herpes)

Answer 177

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons inflammatory pathophysiology not yet clear exactly what cause is generally subacute symptoms related to multilocular brainstem including cranial nerve and cerebellar involvement, which may present in various combinations or rarely in isolation (e.g. ataxia, dysarthria, oculomotor abnormalities, tingling of the face, vertigo) +/- possible additional features such as: (i) symptoms referable to long tract affections and/or a spinal cord syndrome (e.g. pyramidal tract signs, spasticity, para-/tetraparesis, altered limb superficial and deep sensation, sphincteric dysfunction), cortical dysfunction, pseudobulbar affect, headache, fatigue Meningism, alterations of quantitative consciousness, significant systemic symptoms (such as fever, night sweating, weight loss, lymphadenopathy) and symptoms related to connective tissue diseases, rheumatic disorders or Behçet's disease are generally not a feature of CLIPPERS patients. hallmark feature on MRI is that of multiple ‘punctate’ (‘speckled’; ‘patchy spot-like’) and/or ‘curvilinear’ gadolinium enhancement ‘peppering’ the pons with or without spread into the cerebellar peduncles and the cerebellum there is prompt and significant clinical and radiological response to glucorticosteroids, long term maintenance is needed; should be steroid responsive (treat initially with eg high dose methylpred), if not reconsider; in CSF marked pleocytosis (> 100/μl) or malignant cells should prompt reevaluation of the diagnosis

Answer 178

dd neurosarcoidosis, neuro-Behçet's disease, Sjögren's syndrome, inflammatory demyelinating CNS diseases such as multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), Bickerstaff brainstem encephalitis and other autoimmune encephalitides, CNS vasculitides, CNS infections, CNS histiocytosis, lymphomatoid granulomatosis, CNS lymphoma, glioma and paraneoplastic disorders

Answer 179

autoimmune vasculitis, most commonly presenting with some combination of recurrent oral ulcers, genital ulcers, uveitis, and cutaneous lesions. Neurological symptoms are involved in less than 10% of cases, normally years after other sx start; broad range of possible symptoms, dependent on the specific location of neurological lesions caused by vasculitic thrombosis sx subacute motor dysfunction, pseudobulbar symptoms, memory impairment, and personality changes most common but can be all sorts of things; can damage spinal cord, cerebellum; may also manifest with non-parenchymal disease, including thrombotic stroke, and dural sinus thrombosis MRI used to evaluate with contrast enhancement and T2 hyperintense foci - can be large and in cerebrum, diencephalon, brainstem (other times may be small and punctate) azathioprine and other immunomodulators are mainstay of therapy (mild non-neuro behcets can have steroids or colchicine)

Answer 180

accurate movements require appropriate force generation, with several hundred motor units, each of one type: slow (small fibres, few per unit, slow axons, low tension, highly vascular), fast fatigue resistant, fast fatiguable (large fibres, many per unit, fast axons, high tension, few caps) motor units with diff properties allows both precise low force (slow) or high, strong forces (FF) force control can be varying motoneuron firing rate at low freqs (but quickly fuse into tetany) more important way to ensure smooth force is varying recruitment from lowest to highest force 'size principle': as you inc force of movement, next recruited unit is lowest force generating so force always increases by smallest increments and is smooth as possible mechanism for this is developmental plasticity: motoneurons with low firing threshold innervate few muscle fibres and induce them to become slow twitch, likewise highest thresholds induce theirs to become fast twitch; thus don't need to control motoneurons individually: random input to all for a muscle automatically recruit weakest first 3 sources drive them to fire: afferent fibres (only muscle spindles), descending fibres from brain (rare except in primates), spinal interneurons (most numerous, usually input from sensory pathways and descending pathways smaller first as smaller surface area so larger PM resistance, a given current thus giving bigger change in potential

Answer 181

mechanoreceptors from muscles/joints with spindle afferents sending length related signals, tendon organ afferents force related signals, and joint receptors position related signals; proprioceptors one part of info for balance (alongside ruffini endings, vision, inner ear) muscles typically have 20-100 spindles signalling muscle length and change in length; each spindle encapsulates bundle of intrafusal muscle fibres which are striated but small; spindles will contain several of each type of IFMF 2 types of IFMF: bag and chain and send both group 1a (Aalpha) primary afferents and group II (Abeta) secondary afferents; they increase firing rate in response to stretch with chain uniformally contractile and uniform in diameter (stretches act uniformally along fibre) giving inc firing rate throughout stretch; bag fibres have noncontractile bag centres (containing many nuclei) but contractile ends, with rapid stretch initially at centre where 1a are so very sensitive, then ends even out length change, giving more dynamic changes in AP freq than chain at start/end of stretch 1a end in anunulospiral endings which wrap around IFMF central region, II end adjacent to centre; gamma motor neurons innervate ends beta innervation refers to innervation of extrafusal muscle fibres by alpha motoneurons, some mammalian spindles (and all amphibian/reptile) may have alpha instead of gamma motoneurons for spindles but not common; afferents activated by stretch of central regions of IFMF, chain signal muscle length linearly (approx) and bag do changes in IFMF length; by shortening contractile ends, gamma motoneurons can elongate centre intrafusal fibres innervated by small calibre gamma motoneurons which adjust afferent sensitivity by adjusting length of centre of spindle where receptors are (fibres fire faster if muscle/spindle stretched, relax intrafusal fibres to restore firing rate- or vice versa when muscle/spindle shortens from rest) to allow spindles to have similar sensitivites to length changes from diff starting lengths (adaptation as also seen in eg vision); changes in spindle afferent firing could come from stretching muscle or contracting intrafusal fibres (or more liely both) so to interpret signals brain needs to know what gamma motoneuron signals were recently sent (efference copy) golgi tendon organs: found in tendon, activated by tension in tendon, another type of proprioceptor; in passive stretches of muscle, tension in tendon doesn't rise much due to elasticity of muscle fibres, but muscle contractions do, thus these organs signal active tension with signal strongly prop to load on muscle; thus spindles signal length/length change, and tendon organs tension generated by muscle contraction

Answer 182

muscle spindles underly this: muscles respond to stretch by contracting; monosynaptic connection from spindle afferents to motoneurons underly - this is only monosynaptic reflex, rest use interneurons; most muscles have stretch reflex with eye/tongue muscles notable exceptions; spindles also excite close synergists and interneurons that inhibit antagonists (reciprocal inhibi) to prevent further stretch; thus compensating for unexpected loads that stretch the muscle, keeping muscles at desired length; absence in eyes supports this idea: they don't face unexpected loads proposed the reflex could be used to drive movement by changing the set length via gamma motoneuron firing, with brain only needing to set required length and spinal cord sorting out forces, thus movement with different attached loads easier; this would require gain of 1 (precise counteracting of stretch); both gain and delays in system stop this idea working in pathology of descending systems, stretch reflex exaggerated unmasking delay with oscillation seen as myoclonus following stretch thus muscle spindles play some role in feedback but not true -ve feedback; gain/strength of reflex can be set by activity in gamma motoneurons so possibility that brain controls strength of reflex to suit conditions: high gain (high spindle sensitivity) in slow movements and where precision needed, lower gain for fast movements where high gain could cause clonus; good evidence for brain adjusting strength of stretch reflex to suit circumstances reciprocal inhibition parallels stretch reflex: spindle primary afferents excite glycinergic interneurons to inhibit anatagonists when muscle stretched with group of inhib interneurons associated with each motoneuron pool recurrent inhib by glycinergic renshaw cells: recurrent collateral axons from motoneurons innervate renshaw cells (along with from afferents and descending inputs) which regulate timing of motoneuron firing and prevent synchrony/jerkiness/tremor as well as damping noise by preventing weakly excited motorneurons from firing, synapsing back on motoneuron which synapsed on it, descending fibres stop it working during voluntary action, tetanus acts on it by cleaving syanptobrevin in the renshaw cell presynaptic terminal to prevent glycine release and strychnine is glycine r antag, both leading to excessive/tetanic firing of alpha motorneurons golgi tendon organs generate reflex using various groups of spinal interneurons with complex actions giving diff effects depending on motor state thus context dependent: in static/resting postures, activation of tendon organ inhibs parent muscle, during movement effect reversed to excitation to support contraction against a load

Answer 183

ventromedial pathways control axial and proximal limb muscles with role in posture/locomotion (whole body movement); have reticulospinal (from reticular formation), vestibulospinal (from vestibular nuclei) and tectospinal (from sup colliculus) pathways dorsolateral systems more complex: most important route for goal directed movement of limbs, esp hands/feet/face (and other prehensile structures like lips)

Answer 184

fibres (wrapped in endomysium) organised into fasicles (wrapped in perimysium) which are in teurn grouped to form a muscle (wrapped in epimysium); each fibre diameter 50-150 microns and multinucleate, continuous with tendons formed from extension of the three mysial layers and attached to bone upon which force is exerted myofibrils run along fibre, 1-2 microns in diameter; t-tubules are extension of sarcolemma with lumen continuous with interstitial fluid and conduct APs deep into fibre, placed regularly and transverse to fibre axis; SR intracellular network of tubes/sacs, stores Ca; mitochondria, glycogen granules etc; myoglobin to facilitate O2 diffusion, creatine phosphokinase, dystrophin nebulin regulates length of thin filament dystrophin connects the actin filament to the sarcolemma and forms part of a complex that ultimately links the cytoskeleton of the muscle fibre to the surrounding ECM including the endomysium, absence allows Ca in, mitochondria swell and burst with increased oxidative stress in cell leading to necrosis (duchenne muscular dystrophy)

Answer 185

polarising light/phase contrast optics show banding pattern/striations; dark/A/anisotropic bands have thick filaments (H zone is part that only has myosin), light/I/isotropic bands have thin filaments; Z line in middle of I bands and dark M line in middle of dark bands; repeating functional unit from z line to z line is sarcomere; titin is spring like protein from z to m line, contributing to passive tension/elasticity in muscle; way to remember is MHAZI (M line in H zone, which is in A zone, and Z line is in I zone); in contraction H and I bands shorten and A stays same length, bringing the Z lines closer together myosin makes thick filaments; 1.6 microns in length (amphibian) with 2 light meromyosin strands twisted together and connected to heavy, globular meromyosin head of two components: S1 fraction contains the heads, S2 fraction contains necks attaching heads to tails; head can bind to actin, causing ATPase activity in S1 thin filaments are actin/troponin/tropomyosin; 2.05 microns in length (amphibian), with actin subunits polymerised in vivo with each unit 5nm across, these filaments twist into paired chains with periodicity of 36.5 nm, and actin can bind myosin in vitro and in vivo; tropomyosin rod-like molecule ~40nm long that packs into groove between actin chains, spanning 7 units; troponin subunits TnC, TnT, TnI with TnT associated with tropomyosin at 40nm intervals and TnI binding the actin filament; Ca binds to TnC giving conform change that results in tropomyosin being pulled deeper into groove to expose binding site

Answer 186

cyclical formation/detachment of cross-bridges gives sarcomere shortening isometric tension depends on myofilament overlap: reducing overlap reduces tension, increasing overlap increases tension; below 2.2-2 microns, ismoetric tension constant as middle of thick filament lacks myosin heads, and force production diminished if thin filaments collide with each other or M/Z lines chemical energy converted to mechanical energy, with flexible link between S2/S1 allowing S1 to make contact with thin filament, cross bridge form and power stroke occurs, with subsequent ATP hydrolysis driving dissociation of myosin from actin (lack of ATP thus gives rigor mortis) crossbridge formation is asynchronous to give smooth, sustained production of force ATP binding causes head to lose affinity for actin, ATP hydrolysed which pivots head 11nm along actin to next binding site forming weak cross bridge, Pi released to increase actin affinity and form strong crossbridge; powerstroke pulle actin 11nm, ADP released and myosin remains attached until another ATP binds

Answer 187

single activation produces a twitch of <200ms; repetitive low frequency activation gives series of twitches with no increase in peak tension, higher frequencies allow summation to higher peak tension until tetanus with sustained peak tension production passive tension developed from stretch of CT/fascia, increases with small degree of stretch then rapidly increases past a certain point, so at longer initial degrees of stretch active contraction contributes less relative to passive only enough ATP in cell for ~8 twitches, ADP + phosphocreatine -> ATP + creatine keeps ATP levels constant in light exercise for ~100 twitches; ATP generation then aerobic/anaerobic metabolism based

Answer 188

propagates over muscle PM/t-tubules to trigger Ca release from SR single twitch ~50ms in fast twitch, several hundred for slow twitch with upper frequencies of 300 or 40 per sec respectively Na channels less dense in t-tubules than on surface; at least 3 types of K (one resembles nerve, one has longer time course of hundreds of ms, inward rectifier to minimise leak currents to reduce required size of inwards current for plateau in cardiac muscle); significant Cl conductance which may stabilise Em between periods of electrical activity; absence of these channels involved in myotonia congenita ions may accumulate/be depleted from t-tubule lumen and is slow to equilibrate with rest of IF Ca sequestered to allow muscles to relax; SERCA transports 2Ca for every 1ATP and is 100kDa; thousand-fold gradient builds up with Ca sequestered by molecules such as calsequestrin (1:45 binding ratio and most abundant in terminal cisterna)

Answer 189

innervation ratio is measure of number of muscle fibres per motor unit; small number for fine precise muscles such as those controlling eye, muscles with coarse but strong muscles have more eg postural soleus muscle has ~200 L-type CaV (dihydropoyridine receptors DHPRs) in sarcolema and t-tubules arranged in groups of 4 called tetrads, each opposed and mechanically coupled to a subunit of the RYR1 tetramer in SR (facilitating ca-induced ca release) higher loads has less velocity of shortening because more cross-bridges simultaneously active isometrically resisting the load, less available to shorten the sarcomere via crossbridge cycling as each additional motor neuron excited, further motor units recruited: a given excitatory stimulus will create larger EPSP in neurons with smaller cell bodies so small neurons with small motor neurons recruited first and larger recruited as stimulus builds

Answer 190

around time neural tube closes, NCCs migrate from dorsal neural tube into embryo to generate most of PNS: all autonomic and enteric ganglia, dorsal root ganglia, schwann cells, chromaffin cells; cranial neurogenic placodes give the rest of sensory PNS in head; ventral neural tube meanwhile gives rise to motor neurons that send axons out to find muscles axon growth cone navigates using diffusible/attractive factors like nerve growth factors eg netrin which can be neurotrophic (nourish axon) and neurotropic (chemoattractant for axon) with NGF the latter; diffusible repellants include semaphorins and are chemorepulsive contact/attractive are cell adhesion molecules, with growth cone CAMs possibly adhering to: matrix proteins (laminin, fibronectin), same CAM on neighbouring molecule (homophilic adhesion), another CAM on neighbouring molecule (heterophilic adhesion); CAMs connect intracellularly to both cytoskeleton and signal transducers like tyrosine kinases contact repallant are semaphorins, ephrins and some proteoglycans and ensure nerves/bones don't mix, helping eg spinal nerve segmentation dorsal interneurons produce commisural axons with growth cone moving ventrally to floorplate: guided by netrin produced by floorplate cells and netrin produced by neuroprogenitors in VZ and transported along radial processes to pial/outer surface, associating with ECM protein laminin and acting as contact cue to guide commisural axons to ventral midline; axons decussate across it (Tag-1 adheres to Nr-CAM to overcome inhibition) and turn anterior, fasciculating together to form axon bundle, the future spinothalamic tract; while crossing, floorplate molecules direct growth cones to turn rostrally, become insensitive to netrin, become more sensitive to inhib so don't turn back (ie express more receptors for a semaphorin expressed in floorplate) and change CAM expression (TAG-1 replaced by L1-CAM for fasciculation)

Answer 191

axon must synapse with correct part of correct cell; synapses form often in vitro but in vivo only stabilised if correct; axon guided to correct target and adheres to target neurons; generic synapse formed by synapse specific adhesion molecules on axons (eg neurexin)/dendrites (egneuroligin) which recruit pre/post-synp protein complexes; activity dep selection then to stabilise synapse by mechanisms like LTP

Answer 192

axon pathfinding sets up major pathways and crude maps, then activity-dep mechanisms refine them; competition for survival of synapses, axons and whole neurons and in many developing nervous systems around 50% of neurons die just after axons reach targets while connections being refined (can revive by providing extra target tissue); this process involves neural selection in amphibian/chick ganglia, final no of motor neurons increased by transplanting extra limb bud, altering availability of target derived neurotrophic support with ganglionic neuronal survival dep on NGF; loss of NGF in mice via antibodies or gene knockout cause loss of all symp and many sensory ganglion neurons; NGF binds to receptor TrkA (on axon terminal) and transported to soma by retrograde transport to prevent apoptosis; neurons compete for NGF and losers die; GDNF supports dopamine neurons involves selection of correlated input (Hebb's rule, demonstrated in hippocampus) via LTP and selection against uncorrelated input to establish maps on a regional scale

Answer 193

following crush/cut, distal axon stump in PNS degenerates (wallerian) and axon regens: nerve soma survives and expresses genes for axon growth, schwann cells adapt to promote regen; proximal axon stumps can regen but only if endoneurial tube of living schwann cells present to guide them; after complete break >1cm, axons merely sprout into local swelling (neuroma) which may produce pain; if track is present, regen can occur for many cm - albeit slowly distal stump degens as in PNS and many adult CNS neurons can extend experimantally in vitro or into peripheral nerve grafts in vivo but not in injured CNS environment ECM lacks growth promoting molecules like laminin; oligodendrocytes and CNS myelin express axon growth inhib proteins (eg nogo, neutralising antibody to this reduces inhib by oligos); astrocytes proliferate and produce growth inhib chondroitin sulphate proteoglycans in brain ECM: in culture astrocytes are permissive to growth, producing CAMs and growth factors, but in vivo form densely interwoven glial scar that causes growing axons to stop

Answer 194

Craniosynostosis occurs when the skull sutures close prematurely. This results in abnormal head shapes and restriction to the growth of the brain. If left untreated it will lead to raised intracranial pressure; consider if ant font closed before 1 yr + odd skull shape, surgery fixes Plagiocephaly and brachycephaly are very common conditions that cause abnormal head shapes in otherwise normal health babies.Plagiocephaly refers to flattening of one area of the baby’s head. Brachycephaly refers to flattening at the back of the head, resulting in a short head from back to front. These conditions occur where a baby had a tendency to rest their head on a particular point Exclude craniosynotosis with a thorough history and properly palpating the suture reassurance key

Answer 195

one form presents at birth, other in adolesence congen form has one parent, usually mother, affected (AD inheritance), history showing anticipation; reduced foetal movements (reduced swallowing -> polyhydramnios), hypotonic at birth and may need ventilator plus NG tube, impaired sucking; facial diplegia, joint contracture, talipes; reflexes present unlike in werdnig-hoffman; if suspect then examine the mother inc slow release handshake and consider EMG and muscle biopsy (diagnostic) adult form is wasting, weakness, and myotonia (delayed relaxation) worst in face/neck and worsened by cold; may have retardation, myopathic facies (hang dog), ptosis, cataracts, frontal balding, delayed grasp release, testicular atrophy, DM, cardiomyopathy (arrhythmias commonest cause of death)

Answer 196

may be normal until 2/3yo look for prox muscle weakness with sparing of face, bulbar, hand muscles; may be late to start walking or have waddling or trendelenburg gait, freq falls, Gower sign (also seen in dermatomyositis) generalised wasting but pseudohypertrophy of calves as fat replaces lost muscle kyphosis, scoliosis, lumbar lordosis + bilat pes cavus and achilles shortening leading to toe walking usually wheelchair by puberty and death from resp complications or myocardial involvement losing weight poor prognostic sign, oft followed by rapid progression of weakness IQ<75 in 1/3 cases x-linked recessive but spont mutation in 30% diagnosis through elevated CPK enzyme (highest at disease onset) + muscle biopsy; no characteristic EMG signs, molecular genetic testing is first line becker muscular dystrophy similar but milder and slower progression

Answer 197

genetic testing has replaced muscle biopsy

Answer 198

AD inheritance starts anytime from childhood to adulthood and signs inc facial weakness (esp hard to close eyes tightly, whistle, or smile) plus prox arm weakness and wasting w winging of scapula

Answer 199

cpk is another name for CK, it exists as a dimer of different subunits MM from skeletal muscle, MB from cardiac, BB from brain raised MM-CK may be rhabdomyolysis, post surgery, post trauma, post seizure, myositis, muscular dystrophies, hypothyroidism (reduces catabolism of enzyme), sometimes raised after birth for a few days

Answer 200

insidious prox muscle weakness (though can be sudden onset) gower sign may be pos, neck pain common rash early, purple heliotrope over eyelids and poss upper trunk (shawl distribution) +/- gottron patches on extensor surfaces esp fingers/hands, nail bed telaniectasia, calcinosis of skin in kids no relationship w neoplasia CPK raised, GI h+ may occur; steroids and immunosuppression

Answer 201

in all cases of muscle weakness, check full drug history, and exclude history of alcohol abuse high CK levels, hyperkalaemia, hyperphosphataemia, and release of fatty acids which may bind Ca giving hypocalcaemia severe muscle damage may cause acute renal failure by causing shock via sequestering fluid or via rhabdomyolysis urine or plasma myoglobin too sensitive, as any minor muscle damage will cause it to be detected and it also decreases fast, however can cause blood to show on urine dip - get urine microscopy to show no red cells (and might show casts if ATN) also be aware that serum Mg may be low

Answer 202

hypoglycaemia - can cause transient neurological symptoms including weakness and may manifest as a stroke tia or minor stroke - commonest cause for unilat motor or sensory deficit; most tias resolve within an hour, and symptoms may in fact be transient <24hrs but result from an infarct ie stroke; common symptoms inc hemiparesis, hemiparaesthesia, dysarthria, dysphasia, diplopia, imbalance, monocular blindness; tia has focal symptoms that came on suddenly and were maximal at onset; also usually negative symptoms ie loss of something, gains as in pins and needles or abnormal movements suggest something else sdh - head injury within past few weeks, more common in elderly, symptoms may be vague or dev gradually; consciousness levels may fluctuate but can also get focal symptoms from mass effect hemiplegic migraine - unilat sensory or motor signs as aura usually affecting hand and arm on one side; consider if past history of migraine but if symptoms >1hr consider neuroimaging; if no known history or diff from usual migraines then diagnosis of exclusion post-ictal paresis - weakness of hand, arm, leg etc after focal seizure; unilat and from seconds to >20mins; should consider if history of epilepsy or a fit witnessed; if symptoms last >1hr then neuroimaging as small number of ppl have a fit as a result of a stroke so post-ictal masks loss from the stroke brain tumour - esp mets if past history of cancer but can be primary; esp suspicious if deficit doesnt fit within singular vascular territory or if positive symptoms; ask about headache, vomiting and nausea, cognitive impairment as these may suggest raised icp; CT or MRI needed bell's palsy - hsv activation likely cause in many but not all cases; unilat facial weakness and maybe droopy eye, cant drink or speak; pt may think its a stroke; inability to wrinkle forehead and raise brow suggests this rather than stroke as stroke is umn, however incomplete lmn sparing branch to frontalis means can still wrinkle forehead; usually progressive over several weeks, resolving in 6mo; look in eam for herpetic vesicles which support diagnosis of ramsey hunt, and look for rashes or heart block pointing to possible lyme disease; no non facial symptoms; follow up for if symptoms dont resolve peripheral neuropathy - motor and/or sensory deficit confined to distribution of a single nerve; common causes inc trauma, compression, intrinsic lesion to nerve due to eg vasculitis; may be transient and resolve before even seeing pt; unlikely if in 2+ periph nerve territories metabolic disturbance - hypocalcaemia may cause transient paraesthesia, sometimes with history of hypervent, carpopedal spasm, tetany; hypo and hyperkalaemia can cause periodic paralysis and arrhythmia so ecg needed urgently; symptoms usually generalised rather than focal decompression sickness - involves spinal cord so may give transient weakness or paraesthesia, plus delirium, joint pains, rash; usually obvious from history and also consider in ppl returning from holiday as may have been diving

Answer 203

cerebellar cortex has no direct output to other brain areas, instead directed to DCN buried beneath folds and this output is inhibitory each side is dentate nucleus, nucleus interpositus (globose and emboliform) and fastigial nucleus exception: flocculus/flocculonodular lobe, send output to medulla vestibular nuclei (from which the DCN evolved); together these nuclei transmit whole output of cerebellum, projecting to descending motor pathways, mostly to motor areas of cortex via thalamus dentate is largest and most important in humans, appearing as convoluted line of grey matter within the white

Answer 204

small inf from medulla, large mid from pons and small sup receiving DCN output; middle largest, reflecting volume of traffic from cortex to cerebellum sup is major output pathway (mainly receiving from dentate) and pathway from sup decussates in low midbrain, sending fibres through (and some to) red nucleus, continuing on to ventrolat nucleus of thalamus for PMC and ventroant nucleus of thalamus to other motor cortices roof of rostral 4th ventricle formed by bridge of tissue between sup peduncles

Answer 205

cerebellum inputs via pons and inf olive: cortex, internal capsule, cerebral peduncles, terminate ipsilaterally on neurons in pons, axons as mossy fibres (main cerebellar input) through mid cerebellar ped to contralateral cerebellum also ascending spinocerebellar uncrossed mossy fibres through inf cerebellar peduncle, many carrying somatosensory info eg proprioceptors fibres from inf olive form climbing fibre input via inf cerebellar peduncle, implicated in learning (mediate plasticity in mossy fibre-granule cell- purkinje cell pathway that refines cerebellar processing to generate/coordinate movement) output from DCN leave via sup peduncle to lower midbrain, decussate, through and around RN and terminate in thalamus; cerebellum has contralateral connections with cerebral cortex as cerebellum represents ipsilateral movement/sensation

Answer 206

basal ganglia is set of nuclei deep to cerebral cortex: large nucleus called neostriatum (caudate nucleus and putamen) and globus pallidus; name for former from grey matter being striated by white matter tracts of IC passing through which join to form IC and separate caudate/putamen more posteriorly caudate follows wall of lat ventricles, so can be found in wall of ant horn, body, inf horn; putamen lat to IC, medial to insula linked to basal ganglia are nuclei of diencephalon inc thalamus and subthalamic nucleus, and a nucleus of the midbrain: the substantia nigra outputs of basal ganglia relay in thalamus; substantia nigra has 2 divisions: dopaminergic pars compacta which innervates neostriatum and non-dopaminergic pars reticulata caudate/putamen continuous in ant coronal sections, but separated by IC posteriorly; caudate has large head anteriorly, and posteriorly the globus pallidus appears, medial to putamen; thalamus also appears in more posterior sections either side of the 3rd ventricle

Answer 207

input from all areas of cerebral cortex esp prefrontal to caudate and sensorimotor to putamen; they're similar in appearance and joined antero-ventrally where ant limb of IC peters out and no longer separates them; they are in fact one structure that IC splits during dev; caudate is tadpole shaped mass of grey matter with large head in lat wall of ant horn of lat ventricle, narrow body in mid part wall and narrow flat tail curling into roof of inf horn; ventral striatum and nucleus accumbens is in the ant/vent part output from neostriatum principally directed to globus pallidus and substantia nigra; globus pallidus has external/internal segments with neostriatum terminating in both segments and internal forming main output pathway of BG to thalamus (motor nuclei VA/VL as well as medial nucleus); external segment projects to subthalamic nucleus which sends return projection to internal segment

Answer 208

both caudate and putamen project to pars compacta (dopaminergic) and pars reticulata (BG output for control of eye movements) recieve dopaminergic innervation from pars compacta; the pars compacta appears as dark pigmented area in midbrain next to cerebral peduncles, unless in the cross section myelin has been stained in which case it will appear as a lighter area striatum receive input from most cerebral cortex and from pas compacta striatum sends inhibitory connections to GPi and to GPe and GPe in turn inhibiting subthalamic nucleus, thus inhib of GPe lifts this inhib subthalamic nucleus sends excitatory input to GPi; GPi sends inhibitory input to thalamus to inhibit information flow from thalamus to cerebral cortex dopamine loss causes increased inhib of GPe and reduced inhib of GPi, both leading to excess inhib in thalamus giving reduced motor cortical activity and thus reduced movement projection from BG to medial nucleus of thalamus in turn projects to prefrontal cortex, having role in cognition

Answer 209

involved in motor function but not specifying parameters, rather action selection: selecting and triggering movements nuclei mainly interconnected by GABA inhibitory synapses and ultimate output to thalamus is inhibitory; dorsal striatum is motor function and ventral is limbic function, which motivates decisions about future movements thus disorders: excess of paucity of movement: hyperkinesia isn't twitching, but movements made at inappropriate times eg chorea (unexpected 'dancing'), athetosis (writing of hand/face), ballismus (flailing ballistic movements), dyskinesia is unpredictable movements; hypokinesia reduction in movements with bradykinesia (slow movements -parkinsonism) and rigidity basal ganglia is not alternative descending pathway though, it influences movement through motor cortex and thence pyramids

Answer 210

inhibitory basal firing so output neurons fire all the time to inhibit movement, inhibiting these output neurons disinhibits the thalamus allowing it to respond to excitatory inputs and activate approproate neurons in the motor cortex direct circuit is corticostriate fibres activating neurons in putamen/caudate nuclei which inhibit output neurons in inner globus pallidus to disinhibit thalamus and permit movement - so of competing pool of possible actions the correct one is activated when a corticostriate signal of intended movement activates the direct circuit indirect pathway with corticostriate activating different caudate/putamen neurons that inhibit neurons in external globus pallidus which inhibit neurons in subthalamic nuclei, these excite neurons in internal globus pallidus so the pathway disinhibits them and leads to excitation of the output neurons to increase inhibition in thalamus and prevent movement - so intended movement signal can inhibit competing movement plans substantia nigra inputs into both circuits at caudate/putamen level to excite direct pathway and inhibit indirect loss of dopamine causes imbalance in pathways as via D1 receptors it activates direct pathway and via D2 inhibits indirect, thus loss of dopamine tends to lead to more indirect activity and less direct, ultimately giving increased activity of the globus pallidus and inhib of the thalamus several parallel circuits in BG: motor, sensory association input output to PMC, SMA; prefrontal (inc FEF) and visual association output to sup colliculus etc for eye movements; parietal/temporal association cortices output to prefrontal cortex for association; temporal lobe output to cingulate for limbic function

Answer 211

appears to be related to decision making, the action selection problem: what to do next, with motor component being do we want to move, and if so then how and when eg in oculomotor system visual stim drives saccades via sup coll, but this would be maladaptive if they always did this so BG tonically inhibits sup coll, cerebral cortex can activate BG to disinhibit sup coll and allow sacades to occur, thus BG determines when saccades occur advantage of this is you can have movement prepared and if decision made to make that movement, trigger it instantly dopamine from SN thought to mediate plasticity in BG: if output successful, release of dopamine reinforces the active synapses so when activated again, output generated again; this may underly habit learning/stimulus-response relationships; thus dopamine supervises learning of appropriate selection of actions

Answer 212

repeated stimulation of a synapse causes NT release to vary eg at frog NMJ can observe synaptic facilitation of post-synaptic response (bigger epsp if follows close after prior one) due to progressive build up of Ca affecting NT release, then as vesicle pool is diminished, synaptic depression occurs, then once vesicle pool given time to replenish a response is transiently enhanced, representing the action of Ca on vesicle priming, and this is called post-tetanic potentiation and can persist for several minutes LTP: necessary for eg memory, in CA1 believed to be relief of Mg blocking of NMDA allowing Ca to enter and affect long term excitability by adjusting AMPA receptor density via calmodulin, and increasing NO sythase activity so both NT and depolarisation needed; retrograde messengers (NO and arichidonic acid) may also act to modulate presynaptic NT release by unmasking silent synapses or increasing NT release; maintaining LTP requires persistent increase in kinase activity through gene transcription/protein synthesis dendritic spines: excitatory input to the spines helps isolate from chemical/electrical activity elsewhere in the cell but the high resistance of many spines will attenuate the excitatory current (smaller space constant), changing in spine shape/biochemistry may thus also underlie memory etc upon stimulation, small immature spines undergo remodelling of the cytoskeleton to enlarge the spine, followed by enlarged post-synaptic density providing extra space for AMPA they diffuse into spine and are tethered to PSD-95 by Stargazin upon its phosphorylation by calmodulin dependent CamKII, with more AMPAR containing vesicles fusing to replenish the extrasynaptic supply in CA3 of the hippocampus, special NMDA receptor properties are not required for LTP, instead it is believed to take place pre-synaptically and involve adenylyl cyclase/PKA after Ca entry via R type Ca channels

Answer 213

pyramidal cells in CA1 stimulated at low freqs (1hz) which fail to make target cell fire, long term depression of synaptic strength can result antagonism of LTP by protein phosphatases after Ca enters through NMDA, but not enough for LTP, this is a widespread feature amongst cells in the neocortex additionally metabotropic glutamate receptors act via PKC which doesn;t directly reverse LTP and is poorly understood, but may be important for motor learning in the cerebellum and it also requires Ca entry

Answer 214

glycine required as cofactor to open, usually sufficient conc extracellularly; also opening depends on Em (the Mg plug) hallucinogenic drug phencylcidine (PCP - aka angel dust) is non-cmopetitive NMDAr antagonist that binds to site distinct from Mg to block NMDA and produce symptoms that mimic schizophrenic hallucinations, defect in NMDA may be involved in schizophrenia EPSC mostly generated by AMPA due to Mg gating giving current with fast rising and decay phases, NMDA acts over longer time course giving late slow phase to EPSC NMDA also conducts Ca into cell to initiate signalling cascades however excessive glutamate leads to excessive Cai causing excitotoxicity which can contribute to cell death after stroke and that seen with repeated seizures, and to Huntington and other degenrative disorders

Answer 215

series of vertical columns, 300 to 600 microns wide and spanning all 6 layers from cortical surface to white matter all neurons within column receive input from same area of skin to preserve stimulus location; all neurons in column also respond only to single modality (touch, temp etc) thus column preserves modality thalamic afferents terminate in layers IV with layer VI projecting back to thalamus, layer II and III to other cortical regions and layer V to subcortical structures columns for related areas close so eg horizontal connections between columns for adjacent fingers allowing them to perceive a continuous edge S2 receives from S1 and is essential for recognising shape, texture etc

Answer 216

typically begins with cognitive, psychiatric or mood problems. These are followed by the development of movement disorders. Chorea (involuntary, abnormal movements) Eye movement disorders Speech difficulties (dysarthria) Swallowing difficulties (dysphagia); olanzapine often used as helpful for movements and also some neuropsych effects

Answer 217

HD - autosom dom; 30-50yo motor: fidgety eg in bed cognitive eg decision making hard psych: irritability, mood swings, social cognition eg empathy affected weight loss, apathy, poor sleep; base on signs not symptoms as cognitive effects can reduce insight fidgety fingers which may flick when eg walking is early sign; may also struggle making new memories polyQ repeat disoder; more repeats, earlier onset; HD, myotonic dystrophy, frag X show anticipation; diagnose at younger ages each gen; may explain absence in the FH despite autosom dom HD is CAG for HD stroop and symbol digit tests, must look for patterns over multiple assessments over time as performance on one off subject to lots of stuff (sleep, anxiety, morning coffee etc); also verbal fluency tasks etc; mental state exam as rudimentary measure chorea treated with olanzapine; depression treat as normal, mood swings maybe lamotrigine path - BG/striatal atrophy most prominent, esp of caudate (not bulge into ventricle, so lat vents look big); but global atrophy; SN preserved histo: lossof neurons, gliosis, lymphocyte infiltration; can do antibody staining to show htt inclusions

Answer 218

initiating movement: Parkinsonism, chorea, dystonia, tics coordinating: cerebellar (Ataxia, nystagmus, tremor) cortical execution: UMN BG disorders: Hypokinetic: * Parkinson’s Disease (Dystonia) Hyperkinetic: * Huntington’s Disease (Hemiballimus) PD: most cases idiopathic, one relative okay but two+ maybe genetic component; also maybe genetic if onset <30yo Dopamine agonists * USE TO BE FIRST LINE treatment in most cases: Ropinirole- PramipexoleRotigotine patch * Does slow down development of dyskinesias (ie fewer dyskinesias than l-dopa) *BUT not as effective as L-dopa and MAJOR BEHAVIOURAL PROBLEMS CAN BE PROVOKED BY THEM (impulse control disorders, sleepiness)..so move now to use… L-dopa * INCREASINGLY FIRST LINE treatment and many different doses = L-dopa + peripheral dopamine decarboxylase inhibitor to prevent breakdown, egs are co-careldopa and co-beneldopa and you can switch between these using conversion chart * Most effective drug treatment for PD will lead to dyskinesias amantadine at a later stage, eventually antipsychotics/cholinesterase inhibitors for psychosis/dementia; DBS at advanced stage if l-dopa repsonsive but now refractory to medical therapy Levodopa should be offered to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life. A choice of dopamine agonists, levodopa or MAO-BIs should be considered for people in the early stages of Parkinson's disease whose motor symptoms do not impact on their quality of life. choice of dopamine agonists, MAO-B inhibitors or COMT inhibitors should be considered as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy may have drooling problem: Consider glycopyrronium bromide. If treatment for drooling of saliva with glycopyrronium bromide is not effective, not tolerated or contra-indicated (eg, if cognitive impairment, hallucinations or delusions, or a history of adverse effects following anti-cholinergic treatment), consider referral to a specialist service for botulinum toxin. Degenerative (mechanical) conditions are often worse on coughing eg DCM vs MS (Trans myel)

Answer 219

parkinsonism: bradykinesia, tremor, rigidity (first + at least one other); asymmetrical, sometimes entirely unilat parkinsons disease only when ruled out other causes other causes: DLB: fluctuating attention, visual hallucinations, worsening cognition; unlike parkinsons disease dementia, in DLB cogntiive sx predate or within 1st year of motor sx, if later than this is PDD MSA: parkisonism, cerebellar ataxia, autonomic dysfunction, urogenital dysfunction, cognition generally okay, may get positive babinski - note extra-striatal sx as well as parkinsonism; may initially respond to levodopa but response will be poor overall PSP: symmetrical parkinsonism not responsive to levodopa very well withdry eyes and blurred vision often, and axial rigidity so tend to be upright vs the hunch of PD pts, slowing of saccades and restricted vertical gaze, apathy, impulsivity, reduced verbal fluency; hummingbird sign due to atrophied midbrain; rapidly progress and tends to have falls earlier than PD

Answer 220

Instability and falls Executive dysfunction (Bloody-minded/Apathy/Impulsivity) Verbal fluency <7 p-words Axial rigidity Bradykinesia (without decrement) Slow saccades Swallowing problems Unresponsive to levodopa Blepharospasm may see hummingbird sign/brainstem atrophy on imaging

Answer 221

drug induced typical antipsychs like haloperidol and chlorpromazine, atypical antipsychs like risperidone and olanzapine also can metoclopramide, domperidone, sodium valproate, phenytoin, SSRIs; parkinsonism in drug induced often but not always symmetrical vascular will usually have vasc risk factors; parkinsonism tends to be symmetrical and affect lower limbs worse, so gait problems and normal posture and arm swing; often stepwise progresison, brisk reflexes and extensor plantar response normal pressure hydrocephalus gait disorder, incontinence, cognitive impairment and in 70% of cases parkinsonism wilsons disease common neuro sx inc dysarthria, tremor, dystonia, parkinsonism then later ataxia, myoclonus, opthalmoplegia etc; parkinsonim is similar to form of PD parkinsonism also reported in huntingtons disease, SCA, mitochondrial disease (POLG) also need to rule out sx caused by arthritis, depression

Answer 222

Sporadic CJD usually presents with a clearly neurological illness that is very rapidly progressive. In vCJD, the initial presentation is often with psychiatric or behavioural changes and it may not be clear that there is neurological illness until several months after the onset Neurological features include progressive ataxia, dementia and involuntary movements that may be choreiform or dystonic, often changing into myoclonus most iconic and striking cortical abnormality has been called "cortical ribboning" or "cortical ribbon sign" due to hyperintensities resembling ribbons appearing in the cortex on MRI. The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD. Varying degree of symmetric T2 hyperintense signal changes in the basal ganglia (i.e., caudate and putamen), and to a lesser extent globus pallidus and occipital cortex Cerebellar atrophy spongiform change on histo

Answer 223

unilat - UMN (+ mimics) proximal - myopathy: hereditary (mito, chanellopathy, myopathies, dystrophies), acquired (poly/dermatomyositis, statins) distal - neuropathy (eg foot drop, cant do buttons) congen: CMT, acquired DM, alcohol, GBS, vasculitis, B12 def, leprosy, renal disease. or drugs; or mononeuropathy (mononeuritis multiplex due to eg vasculitis) NMJ: prox weak, tone/reflexes normal exercise effects (dysarth, dysphagia, diplopia, maybe dyspnoeic) wasting + weakness can be LWMN or muscle, other signs might help localise 5 normal power, 4 move against grav with some resistance, 3 move against grav, 2 move with grav eliminated, 1 flicker, 0 nothing acute limb weakness - vascular, trauma, spinal compression, infectious; cord ends at T12/L1 (lower thus cauda equina) subacute inflam (viral myelitis, dermatomyositis etc, cerebral tumour, periph neurop, MG) chronic dystrophies, MND

Answer 224

if muscle disorder then order achr antibodies (+musk, Lgfr4), CK, esr; EMG, muscle biopsy; maybe nerve conduction studies neuropathic gives big spiky motor unit potentials on EMG, myopathic very small and spiky/polyphasic, lots and lots on trace with sparse trace if neuropathic dermatomyositis has high signal on T2 weighted (as oedematous) myositis causes eg sle, scleroderma, drugs (penicillamine, statins etc), malignancy treat with steroids then azathioprine/methotrexate; can look for antimyositis antibodies: ANA, anti jo; MRI can help identify muscle for biopsy if muscle weakness but painless and chronic onset (instead of painless, subacute) consider muscular dystrophies eg duchenne also chronic painless weakness consider motor neuron disease if normal nerve conduction study block may be prox to stimulating electrode, may be UMN problem, or small change not picked up; histo of MND will show pale/atrophic lat column and ventral columun; MND associated with dementia, often FTD; high signal on T2 along corticospinal tract, with dark hypointense band in the primary motor cortex with MND also do MRI to rule out cervical myelopathy; MDT with peg, vent, OT/PT, riluzole

Answer 225

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements Cerebellar: characteristic type of irregular, uncoordinated movement that can manifest itself in many possible ways, such as overshooting (dysmetria) Individuals with cerebellar ataxia could also display instability of gait, difficulty with eye movements, dysarthria, dysphagia, hypotonia, dysmetria, and dysdiadochokinesia. These deficits can vary People with cerebellar ataxia may initially present with poor balance, which could be demonstrated as an inability to stand on one leg or perform tandem gait. As the condition progresses, walking is characterized by a widened base and high stepping, as well as staggering and lurching from side to side; vermis lesions tend to do gait more, cerebellar hemisphere affects planned periph movements eg intention tremor and past pointing sensory ataxia is used to indicate ataxia due to loss of proprioception, the loss of sensitivity to the positions of joint and body parts. This is generally caused by dysfunction of the dorsal columns of the spinal cord, because they carry proprioceptive information up to the brain. In some cases, the cause of sensory ataxia may instead be dysfunction of the various parts of the brain that receive positional information, including the cerebellum, thalamus, and parietal lobes unsteady "stomping" gait with heavy heel strikes, as well as a postural instability that is usually worsened when the lack of proprioceptive input cannot be compensated for by visual input, such as in poorly lit environments (romberg test) vestibular ataxia is used to indicate ataxia due to dysfunction of the vestibular system, which in acute and unilateral cases is associated with prominent vertigo, nausea, and vomiting Focal lesions (stroke, MS, tumour, sarcoid etc), congenital, metabolic/systemic things can all cause

Answer 226

acute: alcohol/solvents/phenytoin/pesticides, head injury, infectious (cocksackie, ECHO, influenza, varicella, starting at end or 1-2 weeks after disease, recovers after 1-2mo), cerebellar lesion (infarct, tumour, abscess, H+, hydroceph), hypoglycaemia, labyrinthitis episodic - basilar migraine (FH), seizures (post-ictal state may be seen), metabolic causes (maple syrup urine, porphyria, hartup disease, urea cycle disorders) chronic - ataxic cerebral palsy (10% of cp), degenerative (friedreich ataxia, ataxia telangiectasia, wilsons, refsum/batten disease, metachromatic leucodystrophy, spinocerebellar ataxia), neoplastic (astrocytoma, medulloblastoma, haemangioblastoma), other (hypothyroidism, MS, abetalipoproteinaemia

Answer 227

PML (JC virus - results from immunsuppression allowing JC virus activation eg HIV, leukaemia or lymphoma, post transplant, immunosuppressed for other conditions or due to congen disease etc; also seen in ppl with immune system recovering as part of immune reconstitution syndrome) subacute (weeks) cognitive decline with word finding problems, naming problems, visual neglect, maybe pyramidal weakness, ataxia, diplopia/hemianopia, and new demyelination on MRI demyelination generally b/l, asymmetric, periventricular and subcortical and doesn't usually enhance may look similar to MS early on (sharper boundaries, more specifically perivent favours MS); other ddx incs HIV encephalopathy, CNS lymphoma (enhances), ADEM (enhances, history of recent infection or vaccination, grey matter too), PRES (history of hypertension, grey matter too), toxoplasmosis (usually enhances) reactivation may also cause a granule cell neuronapthy, affecting the cerebellum, causing ataxia, dysarthria, nystagmus, gait disturbance; see loss of neurons in granule layer with sparing of intervening layers of white matter and purkinje cells, seen as hyperintensity on T2/flair MRI (often b/l) +/- cerebellar atrophy mx of JC virus is immune reconstitution: ART for HIV, withdraw immunsuppresant meds, can try IVIg note b/l small non specific T2 hyperintensities w/o clinical MS findings may be due to small vessel disease

Answer 228

influences spinal cord and descending motor pathways to exert voluntary motor control for goal-directed movements (eg reaching to grab something); these movements are feedforward and require learning; eye movement special case and controlled via brainstem; neurons respond during many movements, showing preference for one direction and gradations about that, with global population code based on vector addition motor cortex controls precise independent movement of the fingers, achieved by bypassing the spinal interneurons; evidence for all this: lesions in medulla of corticospinal tract leave permanent deficits which are worst in finger movements, projections to motorneurons arent seen in the anatomy of species which don't make independent finger movements, and evidence that in man direct connections develop postnatally, appearing ~9months which is when dexterity develops

Answer 229

penfield mapped function in awake patients having surgery for epilepsy and found different parts of cortex controlled different muscles; motor homunculus was attempt to simplify and show organisation but is misleading as suggests cortex orderly organised into individual muscles, suggesting a lesion in one part will affect one muscle, but this is not the case; individual neurons in motor cortex instead control sets of synergistic muscles which can be activated to achieve certain movements, thus different groups of neurons provide different libraries of synergies that could be used in different movements; simple synergies in spinal cord like wrist flexors/extensors for power grip/fist; cortex has more flexible synergies like hand/mouth for eating filling corticospinal tract axons with tracer shows they innervate motornuclei of several muscles association areas (direct cortico-cortical connections), cerebellum/basal ganglia via thalamus; sensory afferents via thalamus and sensory cortex proprioception/touch reach PMC quickly to allow feedback correction of ongoing movement, with these reflexes having longer delays than spinal cord but more flexible as go through cortex; eg regulating grip force when picking raspberries: estimate of appropriate force made using feedforward (inverse/forward) control, tactile afferents detect any slippage and activate PMC neurons to increase force until slippage stops; remember this feedback control not over one muscle but all involved in the grip; spindle afferents project to motor cortex as proprioception as well as to interneurons; so short and long latency reflexes, former dominate in arm and latter in hand/fingers

Answer 230

have input from higher cortical areas in parietal/prefrontal cortex, as well as from cerebellum and basal ganglia; motor association areas then input directly to PMC, and also directly to spinal cord and to cerebellum/basal ganglia (through which they influence plans for future movement) these connections suggest a role in planning; main division into lateral premotor cortex and supplementary motor area; these can be subdivided and other regions exist supplementary motor area seems most important in self paced/internally generated movement (you decide when and how to move) and controls bimanual movements as well as a role in posture and tone (seizure here can cause attacks of loss of tone); lateral premotor area seems to be more important for movements dependent on sensory trigger (ie move to catch something); cerebellum has heaviest projections to latter and basal ganglia to former (though both connect to both) frontal eye fields lie at intersection of middle frontal gyrus and precentral gyrus and guide voluntary eye movement including voluntary saccades, communicates with extra-ocular muscles via paramedian pontine reticular formation, and if damaged can get conjugate eye deviation to ipsilateral side, and if stimulated (in eg seizure) conjugate deviation to contralateral side - focal motor seizures may cause eyes then head to turn to contralateral side if spread to FEF, and this often heralds full generalisation to GTCS lateral premotor cortex lesions lead to inability to incorporate sensory info into movements like grasping; mirror neurons found here, fire to make a movement and also to seeing another person make the same movement thus suggesting circuits for imitation, and similar ones may underlie empathy PET scanning for evidence that SMA does self-paced movements: activity here suggests not just performance of movement but mental rehearsal during imagined movements, thus SMA helps predict sequence of movements required and helps understand the consequences to contribute to forward feedforward control: activity during random finger movements in PMC, in complex sequence in SMA and PMC, in imagining complex sequence only SMA

Answer 231

feeds into motor system at several levels, mostly higher, as well as oculomotor regions; cerebellum also connects to hugely expanded prefrontal cortex, underlying higher cognitive functions lesion studies of cerebellum showed its role: no sensory loss with ataxia, comprising hypotonia/weakness, dysmetria/inappropriate displacement (overreaching), dysdiadochokinesis/inability to make rapid alternating movements, decompostion of movement (inability to coordinate joint movements), summarised as it's like each movement being made for first time cerebllum involved in feedforward control of many movements, esp fast ones and thus the construction of movements (time/scale/pattern) is disordered current thinking is cerebellum accurately estimates what's happening in real world from efference copies and relatively imprecise afferent signals, then refining movements and learning; over repeated iterations, motor system learns how to interpret signals to automatically generate appropriate movements; in short, cerebellum provides model system for feedforward control

Answer 232

developmental assessment eg is brain lagging or just motor performance but not central neural indices; pregnancy problems incs central neural risk normal preg then dev after a couple of days life maybe inborn error of metabolism; fatiguable suckling may indicated NMJ problems; dysmorphic features or microcephaly points more to central cause cpk blood levels, emg, conduction studies, muscle biopsy etc may be helpful DMD - x linked recessive, but new mutations are common; proximal dystrophy with symptoms by age 3; motor milestones missed, waddling gait when try to run, toe walking, problems jumping, gower's sign; hypertrophy of calf (maybe also deltoid, quads, tongue, masseters); may have failure to thrive, speech problems, global dev delay, raised AST/ALT, fatigue, complications with anaesthetics consider in any boy not walking by 18mo or with delayed motor milestones - watch them run and rise from the floor serum CK 10-100x too high, if normal excludes (but falls later in disease so if in wheelchair nope); genetic analysis and muscle biopsy give precise diagnosis (dont need latter if former confirms) consider other musc dyst egs beckers. myopathies, polymyositis, neuro causes of weakness support under MDT, initially physio and orthotics, adequate vit d and ca intake, bisphos if fractures; consider steroids; lose walking by age 8-11, then in wheelchair, surgery for scoliosis, support with school etc resp muscle failure eventually causes death; contractures may dev; dilated cardiomyopathy also common, may get gastric dilation or pseudoobstruction, learning diffs, loss of effective cough; physio, NIV, assist coughing, treat chest infections; 6 monthly cardio reviews, maybe acei, beta blockers, diuretics; usually die in 20s/30s; female carries may have inc'd risk of DCM

Answer 233

Generally walking by 8.5-17.5 months delayed motor maturation benign, and diagnosis of exclusion but often familial; severe learning disabilities can be cause hypertonia (cere pal), hypotonia (DMD, beckers, down syndrome, prader willi, tay sachs, williams) rickets, malnutrition, head injury, cns infection, antenatal infection or toxins looking at obstetric history inc delivery, any feeding problems, prematurity, pmh (eg meningitis) FH general movement assessment, see child on floor playing with toys; muscle tone, stand child on their feet and try to encourage them to walk to mum, test plantar response if reached all other milestones can review in one month, still cant walk then refer

Answer 234

Rett syndrome - MCP2 novel mutation on X chromosome; slowing dev between 6-18mo; wringing and clapping of hands, moving hands to mouth; may have some autistic like features which may regress as a toddler, may have seizures, apraxia, motor problems; then weakness and spasticity may have breathing irregularities and microcreph (acquired); motor skill regression ~2yo sturge-weber - port wine stain in the distribution of the trigeminal nerve; MRI shows malform of blood vessels in pia mater on same side seizures on side usually opposite the birth mark, dev delay, maybe glaucoma

Answer 235

mdt follow up for first 2 years if at high risk hypotonia, spasticity, or dystonia; fidgety movements, feeding difficulties; most common delayed motor milestones are not sitting/walking by 8/18mo, hand preference before 1yo, persistent toe walking diffs: tumour (look for FNS, raised icp - headache, morning vomiting); musc dystrophies; sma; myelodysplasia, spinal stenosis if suspect, refer to paeds neuro: refer all kids with persistent toe walking, delayed motor milestones; manage any chest infection, constipation, GORD physical therapy, occupational and speech therapy; braces and assistive technology; maybe muscle relaxants with baclofen, diazepam, botulinum; risk factors inc difficult delivery, head trauma in first years of life, prematurity, toxoplasmosis/rubella in mum

Answer 236

cerebral palsy gives signs of UMNL; besides OT, PT, ortho etc also Muscle relaxants (e.g. baclofen) for muscle spasticity and contractures Anti-epileptic drugs for seizures Glycopyrronium bromide for excessive drooling

Answer 237

Cerebral palsy may be defined as a disorder of movement and posture due to a non-progressive lesion of the motor pathways in the developing brain. It affects 2 in 1,000 live births and is the most common cause of major motor impairment. Causes antenatal (80%): e.g. cerebral malformation and congenital infection (rubella, toxoplasmosis, CMV) intrapartum (10%): birth asphyxia/trauma postnatal (10%): intraventricular haemorrhage, meningitis, head-trauma Possible manifestations include: abnormal tone early infancy delayed motor milestones abnormal gait feeding difficulties. Children with cerebral palsy often have associated non-motor problems such as: learning difficulties (60%) epilepsy (30%) squints (30%) hearing impairment (20%) GORD Constipation Classification spastic (70%) subtypes include hemiplegia, diplegia or quadriplegia increased tone resulting from damage to upper motor neurons dyskinetic caused by damage to the basal ganglia and the substantia nigra athetoid movements and oro-motor problems ataxic caused by damage to the cerebellum with typical cerebellar signs mixed Management as with any child with a chronic condition a multidisciplinary approach is needed treatments for spasticity include oral diazepam, oral and intrathecal baclofen, botulinum toxin type A, orthopaedic surgery and selective dorsal rhizotomy anticonvulsants, analgesia as required

Answer 238

most commonly performed for the treatment of spastic cerebral palsy (CP) in children Gross motor function in CP is often classified using Gross Motor Function Classification System (GMFCS): Level I: walks well in all settings. Balance and speed may be limited compared with children developing normally; Level II: walks in most settings, but may have difficulty walking long distances or with balance. May utilise personal or environmental mobility aids to climb stairs; Level III: walks with the use of hand-held mobility aids such as K-walkers in most indoor settings. Uses wheeled mobility for longer distance travel; Level IV: utilises wheeled mobility aids in most settings (either attendant-propelled or powered) and requires assistance to transfer; Level V: transported in wheelchairs in all settings and has limited to no antigravity head, trunk and limb control. Therapy interventions are first line and include occupational therapy, physiotherapy and speech therapy. Their aim is often to improve functional independence and/or decrease caregiver burden. This includes the provision of orthotics and equipment to aid mobility and function; Pharmacological interventions include oral medication (such as diazepam or baclofen) intramuscular botulinum toxin A injections, and phenol nerve blocks. Pharmacological interventions target the spasticity and its complications; Surgical interventions include neurosurgical techniques that target the spasticity [intrathecal baclofen (ITB) pump or SDR] and orthopedic surgery to release contractures and manage torsional bony deformities. This stage also includes SDR SDR targets the aberrant reflex arcs in spastic CP - commonly performed as a single level procedure at the conus; rubber pad is then placed to separate the motor from the sensory nerves; each sensory nerve root is divided into 3–5 rootlets. Each rootlet is tested with electromyography, which records electrical patterns in muscles. Rootlets are ranked from 1 (mild) to 4 (severe) for spasticity. The severely abnormal rootlets are cut. it usually takes about one year from the date of surgery to achieve maximum results from SDR and intense rehab is performed criteria for NHS funding currently are: – Aged between 3 and 9 years – GMFCS II-III On a self funded basis it may be possible to perform SDR for children outside these criteria at some centres if thought they might benefit (eg symptomatic relief in GMFCS IV/V)

Answer 239

group of inherited diseases whose main features are progressive stiffness (spasticity) and contraction in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner major feature of HSP is a length-dependent axonal degeneration esp in crossed and uncrosses corticospinal tracts with mutations in mitochondrial function, endosomal trafficking, axon pathfinding, and lipid metabolism cerebral and spinal MRI note similarity to the spastic diplegia form of cerebral palsy - HSP hereditary and spastic diplegia explicitly not, and HSP does not reliably respond to dorsal rhizotomy the way cerebral palsy does - otherwise very similar baclofen, diazepam, clonazepam for spasm oxybutynin, tolterodine for bladder spasticity role for botulinum, physical therapy, orthopaedics

Answer 240

3 months Little or no head lag on being pulled to sit Lying on abdomen, good head control Held sitting, lumbar curve 6 months Lying on abdomen, arms extended Lying on back, lifts and grasps feet Pulls self to sitting Held sitting, back straight Rolls front to back 7-8 months Sits without support (Refer at 12 months) 9 months Pulls to standing Crawls 12 months Cruises Walks with one hand held 13-15 months Walks unsupported (Refer at 18 months) 18 months Squats to pick up a toy 2 years Runs Walks upstairs and downstairs holding on to rail 3 years Rides a tricycle using pedals Walks up stairs without holding on to rail 4 years Hops on one leg

Answer 241

Age Milestone 3 months Reaches for object Holds rattle briefly if given to hand Visually alert, particularly human faces Fixes and follows to 180 degrees 6 months Holds in palmar grasp Pass objects from one hand to another Visually insatiable, looking around in every direction 9 months Points with finger Early pincer 12 months Good pincer grip Bangs toys together Bricks Age Milestone 15 months Tower of 2 18 months Tower of 3 2 years Tower of 6 3 years Tower of 9 Drawing Age Milestone 18 months Circular scribble 2 years Copies vertical line 3 years Copies circle 4 years Copies cross 5 years Copies square and triangle Book Age Milestone 15 months Looks at book, pats page 18 months Turns pages, several at time 2 years Turns pages, one at time Notes hand preference before 12 months is abnormal and may indicate cerebral palsy

Answer 242

Flat feet (pes planus) All ages Absent medial arch on standing Typically resolves between the ages of 4-8 years Orthotics are not recommended Parental reassurance appropriate In toeing 1st year Possible causes: metatarsus adductus: abnormal heel bisector line. 90% of cases resolve spontaneously, severe/persistent cases may require serial casting internal tibial torsion: difference the thigh and foot ankle: resolves in the vast majority femoral anteversion: 'W' sign resolves in around 80% by adolescence, surgical intervention in the remaining not usually advised Out toeing All ages Common in early infancy and usually resolves by the age of 2 years Usually due to external tibial torsion Intervention may be appropriate if doesn't resolve as increases risk of patellofemoral pain Bow legs (genu varum) 1st-2nd year Increased intercondylar distance Typically resolves by the age of 4-5 years Knock knees (genu valgum) 3rd-4th year Increased intermalleolar distance Typically resolves spontaneously

Answer 243

oft eg worsening school performance, maybe eg rigidity or worsening motor performance SSPE, wilsons, acute psychosis, huntington chorea, leucodystrophies

Answer 244

genetic disorders affecting the white matter of the central nervous system with or without peripheral nervous system involvement there are over 30 and generally glial cells are affected patients typically present with the onset of neurologic symptoms, though some may show worsening of long-standing, and typically milder, symptoms. It should be noted that some have a slow and progressive course, and can be mistaken for static encephalopathies unless a longitudinal view of the disease is taken most present with motor symptoms. This is in contrast with primary neuronal disorders, which usually present with cognitive decline and seizures - although there is often overlap between these symptom groups may present to the clinician with concerns of delayed acquisition of motor milestones, stagnation of motor development or frank regression in motor skills. In an infant or young child, delayed motor development is more common in the hypomyelinating disorders, whilst motor regression is more common with myelin destruction. In an older child the first symptom may be frequent falls or a clumsy gait, and in an adolescent or young adult, deterioration in functional skills such as sporting activities. Occasionally there is acute deterioration in motor skills in the context of an intercurrent illness or minor head injury Patients may have early involvement of the corticospinal tracts resulting in a central pattern of weakness, upper motor neuron signs such as spastic quadraparesis or spastic paraparesis. In some cases, deep gray nuclei involvement occurs and patients may present with dystonia, chorea or a mixed movement disorder. Some lead to prominent loss of cerebellar volume and may present with slowly progressive ataxia extraneural features may be shown, such as: adrenal insufficiency (XL adrenoleukodystrophy), cataracts, retinitis pigmentosa, GI symptoms, cutaneous symptoms, dysmorphisms, organomegaly and more MRI is most important initial ix which will show suggestive white matter changes, and then proceed to genetic testing (specific if highly characteristic MRI, if less specific then panel, exome or whole genome sequencing) alexander disease - only known example of a genetic disorder affecting astrocyte cells; delayed development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia canavan disease - mutation in the ASPA gene, which results in a deficiency of the enzyme aspartoacylase. This deficiency leads to a buildup of N-acetylaspartic acid; sx typically appear in early infancy usually between the first three to six months of age.[4] Canavan disease then progresses rapidly from that stage, with typical cases involving intellectual disability, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (i.e., initial floppiness – hypotonia – that may eventually translate into spasticity), poor head control, and megalocephaly (abnormally enlarged head). Paralysis, blindness, or seizures may also occur; diagnosis of neonatal/infantile Canavan disease relies on demonstration of very high concentration of N-acetylaspartic acid (NAA) in the urine adrenoleukodystrophy - a peroxisome disorder, XLR, where VLCFAs accumulate due to ABCD1 gene mutation. Between the ages of four years and early teens, hyperactivity may develop with disruptive behaviour, and memory and learning skills may cause concern. May have adrenal crisis with minor illness. Over the course of several months or a few years will become increasingly unsteady, lose skills and, eventually, become totally dependent. Vision will deteriorate and epilepsy will develop. Bulbar palsy sets in requiring feeding tube. Eventually death due to repeated physical illnesses + mental deterioration. Experimental stem cell transplant if has disease but sx not yet appeared. Hormone replacement needed.

Answer 245

birth aspyhxia, sepsis, chromosomal abnorms (inc down syndrome and PW), congen hypothyroid, osteogenesis imperfecta, cervical cord trauma, metabolic diseases, benign hypotonia, myotonic dystrophy, myasthenia gravies, congen myopathies (inc mitochondrial)

Answer 246

causes of Neonatal Hypotonia can be subdivided into Central causes (80% of cases - brain, spinal cord, but excluding the motor neurone) and Peripheral causes (lower motor neuron including motor neurone, axon, neuromuscular junction and muscle) Hypotonia is often identified by an abnormal posture (e.g. frog-leg posture), and there can be associated weakness. Weakness: A reduction in the muscle power that can be generated (e.g. lack of muscle movement against gravity). Hypotonia (floppy) without weakness: Where there is hypotonia but strength is relatively preserved (e.g. anti-gravity limb movements are present), a CENTRAL cause of hypotonia is more likely. Reflexes normal/brisk. More likely to see seizures, dysmorphia. Hypotonia with weakness: Hypotonia accompanied by weakness is more suggestive of a PERIPHERAL, neuromuscular cause. Reflexes normal or low. May see muscle atrophy, joint contractures, tongue fasciculations. central causes: * Hypoxic-ischaemic encephalopathy * Acquired and congenital infections causing encephalopathy * Intracranial haemorrhage * Drug effects * Chromosomal abnormalities (e.g. Down syndrome and Prader-Willi syndrome) * Cerebral structural malformations * Inborn errors of metabolism (e.g. Zellweger syndrome) (may also be weak) * Birth trauma to spinal cord (may also be weak) peripheral causes: * Spinal muscular atrophy * Transient acquired myasthenia gravis * Congenital myasthenia * Infantile botulism * Congenital demyelinating neuropathy * Hypomyelinating neuropathy * Axonal neuropathy * Guillain-Barré syndrome * Muscular dystrophies * Congenital myopathies * Myotonic dystrophy and congenital myotonias * Endocrine myopathy e.g. hypothyroidism * Metabolic myopathies (e.g. Glycogen storage diseases) * Energy depletion - e.g. fatty acid oxidation and carnitine disorders, respiratory chain disorders CTDs - peripheral * Ehler Danlos syndrome * Marfan syndrome * Osteogenesis imperfecta Baseline blood tests including FBC, U&Es,CRP,LFT and bone profile (including calcium and magnesium) are important in excluding infection and electrolyte disturbances as causes for hypotonia. Thyroxine (T4) and TSH should be checked, looking for evidence of congenital hypothyroidism. Levels are therefore raised in Congenital Muscular Dystrophy (5 to 10 times normal). However, it is important to be aware that CK levels can be raised in the first hours of life and also increase with acidosis - for example following Hypoxic Ischaemic Encephalopathy (HIE). Therefore, if CK is raised in an early sample, it is worth repeating it after a few days. CK levels should also be taken prior to Electromyography (EMG) studies or muscle biopsies as these can cause raised levels. In cases of multisystemic involvement, screening for inborn errors of metabolism is recommended. Consider genetic testing if dysmorphic/clinical presentation suggests a condition. A Rapid FISH Screen can be requested for trisomies - these results are usually available within 48 hours. Microarray results take 2 weeks for a neonate (less than 28 days of age) and 4-6 weeks for a baby over 28 days old. Molecular genetics may be able to do a floppy infant screen testing for Prader Willi Syndrome, Myotonic Dystrophy and Spinal Muscular Atrophy floppy babies should undergo a cranial ultrasound scan - if abnorms found then further imaging (usually MRI head and spine) will be needed. These scans are helpful in the identification of structural malformations, neuronal migration defects, brain stem and cerebellar abnormalities, and can identify features suggestive of mitochondrial abnormalities and metabolic diseases Seizures and encephalopathy may be identified by EEG. On the neonatal unit, CFM (aEEG) can be used to classify the background cerebral activity and to detect seizures over longer periods of time. Electromyograms (EMGs) and nerve conduction studies are useful in diagnosing disorders of the lower motor neurone unit (disorders of either the muscle, neuromuscular junction or peripheral nerves.) Nerve conduction studies produce consistent and reliable results after 32 weeks of gestation Neonatal muscle biopsy results are difficult to interpret and therefore biopsies may be delayed until babies are around 6 months of age so overall route: history and exam (include examining mum for evidence of myotonia or myasthenia) and bloods as above + CRUSS and consider EEG/aEEG if central consider cr disorders and testing, MRI head for structural abnorms if peripheral NCS/EMG +/- targeted genetic testing central and peripheral features, esp if multisystem involvement, think metabolic and screen: Blood gas, lactate, serum amino acids, urine amino and organic acids, VLCFA, acylcarnitine profile If evidence of infection get an LP

Answer 247

Without therapeutic hypothermia (TH), the risk of death or severe handicap in survivors of moderate or severe HIE is approximately 25 and 75% respectively resus following NLS guidelines; cooling should only be considered once cardiorespiratory stability has been achieved including heart rate and oxygen saturation criteria for cooling: Criteria A Infants >36 completed weeks’ gestation who are less than 6 hours old with at least one of the following: ● Apgar score of <5 at 10 minutes after birth ● Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth ● Acidosis – pH <7.00 in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth ● Base Deficit > 16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birt Criteria B Moderate to severe encephalopathy, consisting of:  Consciousness: Altered state of consciousness (lethargy, stupor or coma). AND at least one of the following  Abnormal reflexes including oculomotor or pupillary abnormalities  Weak or absent suck  Hypotonia  Clinical seizures Infants who meet criteria A and B should have assessment of global electrical brain activity measured using aEEG Criteria C At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following: - Normal background with some seizure activity. - Moderately abnormal activity - Suppressed activity - Continuous seizure activit Neonatal encephalopathy evolves with time. Therefore, infants who meet at least one A criterion but on initial examination are neurologically normal should be reviewed at least twice in the first 6 hours of life failure to obtain aEEG should not prevent or delay treatment if there is evidence from A and B criteria Therapeutic hypothermia should not be started without continuous rectal temperature monitoring; max benefit if started within 6 hours of birth, but closer to birth is better Core temperature (rectal) should be monitored continuously aiming for a core temperature of 33.5oC (range 33-34oC - do not allow it to drop below this); cool for 72 hours from when temperature reaches 33.50C. Longer cooling for >72 hours has not shown to be beneficial and may infact be harmful and may increase the risk of arrhythmias, anuria and longer hospitalisations Cooling is associated with physiological changes such as fall in heart rate and prolongation of QT intervals; Immunosuppression, coagulopathy, increased insulin resistance, electrolyte alterations are more likely to occur when core temperature falls below 32°C and are unlikely to cause significant clinical abnormalities at the temperature range used for neural rescue therapy; Subcutaneous fat necrosis (SCFN) is a recognised complication of both perinatal asphyxia and total body cooling - monitor skin closely; If it develops, weekly calcium levels should be monitored until the clinical resolution of the SCFN occurs and for up to 6 months

Answer 248

clinically defined syndrome of disturbed neurological function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, sub normal level of consciousness and often seizures; therefore includes those term infants with clinical seizures that are associated with cerebral function monitoring (CFM) and/or EEG abnormalities, and those infants with CFM / EEG abnormalities that are not associated with clinical seizures. The latter is called “electro-clinical dissociation”. Some infants may also have abnormal neurological symptoms without abnormal brain electrical activity. hammersmith neuro exam good way to formally exam neuro in baby assessing posture and tone, movements, reflexes, and behaviour also look for whether: o secretions are copious o suction is needed o gag reflex present o pupils are reactive/small/large o spontaneous eye opening/movements o tongue fasciculation is present o there is excessive jitteriness or myoclonic type jerking o when sucking movements start o when feeding is established More Common: Hypoxic-ischaemic encephalopathy (HIE) (50-60%) Intracranial haemorrhage in term and preterm babies (11%) Cerebral infarction / stroke (10%) CNS structural abnormalities (6%) Intracranial infections (2%) Less Common: Inborn error of metabolism Electrolyte disturbances Drug withdrawal Trauma Pyridoxine deficiency Benign familial neonatal seizure syndromes Progressive epileptic syndromes Unknown/idiopathic Newborn babies are prone to seizures due to their immature central nervous system and the pronounced excitatory effects of GABA receptors Any baby where there are concerns about poor condition at birth, intrapartum hypoxia, abnormalities of cord blood gases should be observed closely for emerging signs of encephalopathy during the first 24 hours Clinical examination for signs of moderate to severe encephalopathy * Altered consciousness (reduced or absent response to stimulation) AND * Abnormal tone (focal or general hypotonia, flaccidity or hypertonia) AND * Abnormal reflexes (weak or absent suck or Moro or gag) OR * Seizures / Abnormal Movements Use the Grading of Neonatal Encephalopathy sheet on the Time=Brain website. If baby meets criteria and is ≥ 35 weeks gestation and within 6 hours of birth, then servo-cooling should be started Infants between 34+0 and 34+6 weighing more than 1.8kg should be considered for cooling if there are concerns about moderate or severe NE. some units will cool week 33 babies but others won't, and no evidence for younger than this likewise not if >12hours old Phenobarbitone for seizures, add second agent (Midazolam, Lidocaine, Phenytoin, Clonazepam) if needed, if not responding consider pyridoxine trial x2 (with EEG monitoring) All babies should have a septic screen and be commenced on antibiotics (Benzyl Penicillin 25 mg/kg and Gentamicin 4mg/kg) - consider aciclovir if HSV risk FBC Blood film U&E including calcium and magnesium Clotting screen including fibrinogen Cord and Blood gases including lactate and glucose Liver function including gammaGT CRP Blood culture Troponin CSF culture (consider bacterial, viral, metabolic investigations) Urine culture Congenital infection (TORCH) screen Maternal Kleihauer (if anaemia in baby or APH) Creatine kinase Metabolic screen including ammonia, amino acids, uric acid Urine for amino and organic acids, ketones, reducing substances Genetic investigations if dysmorphic features if encephalopathic from birth send placenta for histology after recording appearance, weight CrUSS should be performed on admission (<4 hrs if possible) and then daily for the first three days of life, then again at 1 and 2 weeks MRI is useful: most accurate prognostic information can be obtained at 7-10 days of age. Infants who develop signs of HIE following an acute sentinel event (e.g. placental abruption) often sustain bilateral and usually symmetrical lesions within the basal ganglia and thalami, and exhibit an abnormal appearance in the posterior limb of the internal capsule (PLIC). Abnormality seen in the PLIC is an excellent predictor of abnormal neuromotor outcome. More chronic hypoxia-ischaemia is associated with cortical and subcortical abnormalities. CFM and formal EEG are helpful

Answer 249

caused by abnormalities in the retro-geniculate system and not by pathology of the eye, however, CVI can occur together with pathology of the eye for instance in retinopathy of prematurity the most common cause of visual impairment in children in western countries. Perinatal hypoxic-ischemic damage is the most frequent cause of CVI, but the etiology is variable; congenital causes are also common risk factors: prematurity with periventricular leukomalacia; * term birth with perinatal hypoxic-ischemic encephalopathy; * hydrocephalus; * seizures (particularly those that are associated with epileptic encephalopathy, such as infantile spasms); * trauma; * infections, including meningitis and encephalitis; * structural brain abnormalities (such as schizencephaly and colpocephaly); * metabolic conditions such as hypoglycemia retro-geniculate damage results in ganglion cell layer thinning due to retrograde trans-synaptic degeneration; deficits seen may inc strabismus, nystagmus, motility disorders of the eye, delay in saccades, pallor of the optic nerve and visual field abnormalities; visual impairment in CVI can be as severe as no light perception to normal visual acuity In the past, investigators heavily relied on findings of VER and EEG for a diagnosis of cerebral visual loss. However, a normal flash VER recording can be obtained even in patients with cerebral visual loss, as results are mediated by the extra-geniculostriate visual system; due to the availability of high-resolution imaging, the role of EEG and VER in making a diagnosis of CVI has lessened in recent years; MRI done to to assess for structural abnormalities of the posterior visual pathway. However, some children with CVI (especially those with genetic disorders) have normal structural brain MRI scans; genetic testing and functional assessment also plays a role

Answer 250

usually between 12 and 18 mo bottom shuffling (may have FH) and familial delay commonest causes but consider dislocation of hip, weakness (cerebral palsy, muscular dystrophies), failure to thrive, global dev delay

Answer 251

rare neuro sequel of measles subacute sclerosing panencephalitis consider in any child/adolescent w progressive mental deterioraton + myoclonic jerks/seizures 4 stages: diminished performance at school, behavioural changes, small invol movements and falling backwards then worsens + myoclonic jerks, speech/swallowing problems, rigidity, choroidoretinitis, maybe cortical blindness then increasing rigidity and dementia then coma and death in 1-3yrs sec to bronchopneumonia onset usually 4-10 years after measles infection; clinical plus ig in serum/csf, may have eeg changes, may have cortical atrophy on CT treat symptoms

Answer 252

rapid and non-sustained, non-purposeful movements that are usually jerky and flit from one limb or part to another a child may be described as fidgety or clumsy; may find it hard to get dressed or eat think of sydenham chorea (can be 6mo after rheum fever) which resolves over weeks-months, huntington chorea (dementia, FH), benign familial chorea, kernicterus, wilsons, pregnancy or OCP related, drugs that inc or dec DA eg levodopa and metoclop, BG damage eg stroke, acanthocytosis, thyrotoxicosis, SLE athetoid movements are slow, involuntary writhing (oft of prox limbs) due to disease of BG, most commonly cerebral palsy

Answer 253

nerves arise from neurons in olfactory epithelium in roof and adjacent parts of lateral wall of nasal cavity and the septum, they are ciliated and stimulated by aerosolised odour molecules dissolved in the mucous; the fibres form fasicles which pierce the cribriform plate of the ethmoid bone via ~20 olfactory nerves to reach the olfactory bulb on the frontal lobe of the brain to synapse with cell bodies of neurons which pass posteriorly as the olfactory tract, whose fibres terminate mainly in the primary olfactory cortex of the uncus in the temporal lobe

Answer 254

fibres from ganglion cells in retina form optic nerve which passes posteriorly to the optic canal and is surrounded by the three meningeal layers; the two optic nerves partially decussate to form the optic chiasma, from which the optic tracts diverge to terminate in the lateral geniculate nucleus and the superior colliculus of the midbrain; fibres from the LGN form the optic radiation which ends in the primary visual cortex of the occipital lobe fibres from CNII also go to pretectal area and to SCN (nasal fibres are the ones which decussate)

Answer 255

nuclei found in 6 longitudinal columns in the brainstem, and in the spinal cord for V and XI; efferent divided into 3 groups based on origin and lie in discontinuous columns: somatomtor close to midline, with nuclei for III, IV lying at level of sup and inf colliculi respectively, and VI, XII found in pons and medulla, with all four having fibres that supply striated muscles; visceromotor column has pregang PS that gives fibres to III, VII, IX, X from edinger-westphal nucleus in midbrain, sup/inf salivatory nuclei in pons and dorsal nucleus of the vagus in the medulla respectively; branchiomotor column is more lateral and deep and provides nerves to innervate muscle of branchial arch origin, including V via trigeminal motor nucleus of midpons, VII via facial motor nucleus of lower pons, and IX/X/cranial part of XI via nucleus ambiguus (learn a diagram for these)

Answer 256

sensory nuclei lie laterally and can also be described in three groups; viscerosensory is received by nucleus tractus solitarius which lies most medially in medulla and receives from VII, IX, X; special somatosensory for hearing and equilibrium run in CN VIII and end in cochlear and vestibular nuclei in medulla on floor of 4th ventricle; general somatosensory enters via CN V into trigeminal sensory nucleus (largest CN nucleus) which contains mesencephalic nucleus for proprioception, pontine/chief nucleus for discriminative sensation and light tough and spinal trigeminal nucles for deep touch, pain and temperature; although all those terminate in that nucleus, somatosensory info is also carried by VII, IX and X

Answer 257

order corresponds with nuclei in rostrocaudal sequence with motor nerves lying more medially; CN IV emerges from dorsal surface of midbrain and runs to basal surface around cerebral peduncles, thus appearing to lie laterally; CN VI exits at junction of pons/medulla and passes anteriorly before entering the orbit, thus having a long intracranial course and possibly being the first to be affected by intracranial disease; spinal root of CN XI arises from motor neurons in grey matter of ventral horns at levels C1-5, axons emerging between doral/ventral roots and ascending to pass through foramen magnum to join cranial root before exiting the cranium CN exit skull through numerous foramina on its base: III, IV and Va travel through cavernous sinus, lateral to body of sphenoid to pass into orbit through superior orbital fissure; CN Vb/Vc leave via foramen rotundum and foramen ovale in the sphenoid; CN VII/VIII run together and pass into internal acoustic meatus with fibres from VIII being distributed to organs of inner ear and VII passing through middle ear to emerge via the stylomastoid foramen; IX, X and XI pass in anterior part of jugular foramen which is occupid posteriorly by the sigmoid sinus; XII exits via the hypoglossal canal in the occipital bone

Answer 258

CNVII; branchiomotor innervation to all muscles of PA2 and pregang PS to lacrimal, submandibular, sublingual and nasal mucous glands and taste from ant 2/3 of tongue via chorda tympani; also partly gives general sensation of skin lining EAM leaves brainstem as large motor root and smaller nervus intermedius (sensory and PS) with roots entering IAM alongside CNVIII then joining to form facial nerve which enters the narrow facial canal within petrous temporal bone bends posteriorly on medial wall of middle ear and ends in swelling: facial/geniculate ganglion then reaches post wall of tympanic cavity, running inferiorly to emerge from skull at stylomastoid foramen nerve enters parotid gland and divides: upper division gives temporal/zygomatic/buccal branches and lower gives mandibular and cervical branches greater petrosal nerve at geniculate ganglion, carrying PS to lacrimal gland via pterygopalatine ganglion; nerve to stapedius; chorda tympani which joins lingual nerve giving taste from ant 2/3 of tongue and PS secretomotor to submandibular/sublingual after exiting skull gives: muscular branches to post belly of digastric, occipitalis, stylohyoid before parotid

Answer 259

CNII; purely sensory with axons originating in retinal cells; partial decussation to form optic chiasma then optic tracts continue post to lat geniculate body inf to thalamus; nerve is outgrowth of brain, sheathed in meninges up to sclera with a thin but definite subarachnoid space; increased intracranial pressure thus seen as papilloedema; derived from outpuching of diencephalon (optic stalks); optic nerve damage produces irreversible blindness as central fibre tracts incapable of regen; axons terminate in LGN (vision) pretectal area (reflexes) and suprachiasmatic nucleus (sleep-wake cycle); 1mm in globe, 24mm in orbit, 9mm in optic canal and 16mm in cranial space before decussation; optic neuritis is episodic inflam often associated with MS causing vision loss and pain

Answer 260

CNIII somatic and general visceral motor (latter to sphincter pupillae and uveal tract glands);arises from ant aspect of midbrain from oculomotor nucleus (somatic) and EWN (PS), travelling below PCA and piercing dura anterolateral to post clinoid process; pierces roof of cavernous sinus and runs in its lateral wall where it receives symp from cavernous plexus; gives sup/inf divisions as it emerges from sinus, these passing into orbit through sup orbital fissure and tendinous ring; sup to levator palpebrae superioris/sup rectus and inf to inf/med rectus, inf oblique and carries PS for ciliary muscle/sphincter pupillae; pregang PS leave to enter ciliary ganglion, lying between lateral surface of optic nerve and lat rectus; postgang leave via 10-12 short ciliary nerves that run forwards in eyeball to reach PS targets eg ciliary body for sphincter pupillae in iris to constrict (so palsy give pupil dilation) CNIV somatic motor only; exits brain, enters cavernous sinus to supply sup oblique; isolated lesions uncommon but damage limited to sup ob: when eyeball maximally adducted, line of pull coincides with visual axis so in this position will depress the eye; thus to test patient looks inwards and downwards; diplopia will be experienced with activities involving looking down eg reading, going downstairs; only CN emerging from dorsal surface of midbrain, only one to fully decussate; fibres decussate within midbrain; contrecoup forces can compress nerve against rigid tentorium; lesion at nucleus causes contralateral SOF paralysis as nerve decussates within midbrain and mibrain trauma/ischaemia can give bilateral SOF paralysis; patients may tilt head away from affected side to reduce diplopia CNVI, somatic motor only; leaves pons at lower border and pierces the pontine basal cistern; then pierces dura on post aspect of clivus and arches over ridge of petrous temporal bone, travelling superolaterally to enter cavernous sinus where it lies just lateral to ICA, passes through SOF to supply lat rectus; most frequently damaged among nerves innervating 6 extraocular muscles; first nerve to be affected by raised intracranial pressure; also compressed by aneurysm of ICA within cavernous sinus or tumors at base of brain; lesion results in lateral rectus palsy with eyeball assuming an adducted position at rest due to unopposed pull of medial rectus; raised pressure stretches nerve in its intracranial course or compresses it against petrous lig/ridge of temporal bone or, since nerves passes straight forwards may be stretched by post displacement of the brainstem

Answer 261

Bell's palsy is inflam disease of unknown aetiology which affects facial nerve in facial canal just above stylomastoid foramen, with all muscles on one side paralysed; nerve at risk in parotid surgery and in ops on submandibular region as mandibular branch dips below mandible before passing up to supply muscles of lower lips; babies do not have mastoid process at birth so nerve at risk in forceps delivery complete ptosis indicates lesion of CNIII whereas partial may indicate only disruption to symp supply ie horner's syndrome; both symp supply to smooth muscle and CNIII to striated must be intact to keep eye open normally complete ptosis and paralysis of the 4 relevant eye muscles; eyeball is thus immobile with downwards and outwards gaze and diplopia due to eyes not pointing in same direction; disruption of PS to constrictor pupillae results in dilated pupil which doesn;t constrict when light shone on it or when eye focus on near object (lack of accomodation as ciliary muscle also paralysed); palsy may result from vascular disorders (eg diabetes, aneurysm (esp post comm a), tumours, MS, trauma, cavernous sinus thrombosis); medical 3rd spares pupil, surgical 3rd doesnt so dilated/fixed; complete ptosis and dilated pupil in CNIII palsy, partial ptosis and constricted pupil in Horner's syndrome as well as anhidrosis

Answer 262

First thing to do is take a proper history: was it true binoculars diplopia? (i.e. two images, which improves when one eye is closed). Is it horizontal, vertical or torsional diplopia? (Were the images side by side, one above the other, or rotated) Is there any other neurology or red flags? (Headache, other cranial nerve involvement) Are there symptoms of giant cell arteritis? (Scalp tenderness, jaw claudication, malaise, amaurosis). Are there signs or symptoms of ocular myasthenia? (Variable ptosis, worse in the evening, intermittent variable variable diplopia). Is the pupil involved? If there is an observable IIIn palsy, then they'd need urgent CTH + CTA (consider weber's syndrome stroke and pcomm aneurysm) bloods for ?GCA, otherwise may be microvascular cranial neuronopathy; consider also problems with eye alignment eg conjugate gaze problems etc, and consider MRI if needed in this case liaise with ophtho (both for advice re further ix, and also to help mx sx with eg patch if ongoing)

Answer 263

congenital ptosis associated with synkinetic movements of the upper lid on masticating movements of the jaw due to aberrant connection between motor branches of the trigeminal nerve controlling muscles of mastication and superior division of the oculomotor nerve controlling the levator palpebrae superioris. may be noticed when the child is breastfeeding may also develop after eye surgery, syphilis, trauma, pontine tumors, etc occurs at different levels: Cortical or sub cortical connections Internuclear connections or faulty distribution in the posterior longitudinal bundle Infranuclear connection exists between motor branches of the trigeminal nerve (CN V3) innervating the external pterygoid and the fibers of superior division of the oculomotor nerve (CN III) that innervates the levator muscle of the upper lid Peripherally

Answer 264

axons finer than most sensory nerves; within orbit, nerve is slightly sinuous to give play for eye movements; chiasm overlies tuberculum and diaphragma sellae to form ant part of floor of 3rd ventricle; nasal fibres take part in the decussation so eg right optic tract has nasal fibres from left eye and temporal fibres from right; pituitary tumours most common cause of lesion and gives bitemporal hemianopia; optic tract continues post, gives med/lat roots with larger lat root ending in lat geniculate body and pupillary reflex fibres travelling on to pretectal area ant to sup colliculus (suprachiasmatic nucleus part of hypothalamus and receives direct from chiasm); optic radiation sweeps from LGB to occipital cortex through post end of internal capsule with lower fibres serving superior visual field looping adjacent to temporal lobe and upper fibres serving inf visual field travelling next to parietal lobe; injury ant to chiasm gives ipsilateral total blindness; ipsilateral nasal hemianopia from after chiasm to just temporal fibres, or after chiasm to both fibres contralateral homonymous hemianopia

Answer 265

conveyed by specialised GCs travelling with optic nerve to pretectal nuclei where they synapse, then relay to the edinger-westphal nucleus via post longitudinal bundle; CNIII conveys PS fibres from here to ciliary ganglion; symp pathway from hypothalamus with first neuron passing to lateral grey column of thoracic spinal cord (ciliospinal column of Budge), second neuron from C8-T1 to sup cervical ganglion, 3rd from this along ICA to pupil/blood vessels of eye; pupillary and accommodation reflexes are bilateral tumour/H+/oedema can push uncus against brainstem which affects CNIII as medial to it, compressing it and causes a lesion (so dilation, loss of light reflex); more common + emergency is aneruysm of posterior communicating artery which also compresses 3rd; note surgical 3rd has dilation and is due to compression as PS fibres more superficial, and medical 3rd more ischaemic (diabetes linked) w/o the dilation slightly different is argyll robertson pupils are bilateral small pupils that accommodate (constrict when objects brought near) but don't constrict in response to bright light: sign of neurosyphyllis/diabetic neuropathy

Answer 266

if worse in the light than the large pupil is the abnormal one; if any ptosis or movement problem it is 3rd nerve palsy, get urgent CTH+CTA if full motility and no ptosis then apply dilute pilocarpine eye drop: if constriction it is tonic pupil, if no constriction apply higher conc pilocarpine -> if constriction reconsider 3rd nerve palsy, if no constriction consider pharmacologic mydriasis (eg ipratropium into eye from incorrect spacer use or eg atropine, MDMA); also fixed mid-dilated pupil: acute angle-closure glaucoma (will respond to pilocarpine) tonic pupil aka adie's pupil, benign condition typically affecting young women, possibly secondary to viral or bacterial infection affecting the ciliary ganglion. It is characterised by a poor or absent light reflex and an intact but slow accommodation reflex; When associated with areflexia of the knee and/or ankles, this condition is known as Holmes-Adie’s syndrome. if anisocoria is chronic, <1mm, and equal in light and dark then it is physiological - seen in up to 20% of ppl if worse in dark than light then small pupil is problem -> apply apraclonidine drops, if no dilation then it is physiological, if dilation then it is horner syndrome localise clinically and then get imaging of brain, neck, thorax (depending on level you're worried it is coming from); consider also argyll-robertson pupil, anterior uveitis, eye trauma, or pilocarpine or organophosphate poisoning

Answer 267

special sensory only, smell, and so also contributes to flavour perception; olfactory epithelium lines superior concha of ethmoid, upper medial nasal septum and inf surface of cribriform plate with fibres running in the submucosa to synapse in olfactory bulb; send fibres to prepiriform cortex (identify odour), medial amygdala (social eg mating, recognition of others from species) and entorhinal cortex (pair odour with memory) (prepiriform and entorhinal together may be considred primary olfac cortex but debates on this) though exact functions up for debate tested using characteristics smells most common cause of anosmia is upper respiratory tract infection (bilateral), and deviated nasal septum or polyps may as well; unilateral anosmia may be caused by head/midface trauma with cribriform plate fracture (associated with CSF rhinorrhoea - CSF draining into nose, giving possible risk of intracranial infection) or early meningioma of olfactory groove; 20% of cases is idiopathic; may be congenital, on its own or with eg kallman

Answer 268

tunnel vision from injury at start of nerve eg glaucoma, syphilis, papilloedema; enlarge blind spot if optic nerve head enlarged eg papilloedema; central scotomata is unilateral partial loss of vision due to injury between head of CNII and chiasm from demyelination, toxic, vascular, nutritional reasons; unilateral field loss also possible from nerve lesion like tumour, vascular; bitemporal hemianopia from chiasm lesion like pitiuitary tumour/sella meningioma; homonymous hemianopia from chiasm to occipital cortex (tumour/vascular) with incomplete lesion sparing macular vision; upper quadrant HH from temporal lobe lesion and lower quadrant HH from parietal lobe lesion; also lesion of left tract in HH affects right sided vision and vice versa

Answer 269

largest CN, with opthalmic, maxillary and mandibular divisions; Vc does muscles of mastication, tested by feeling bulk of temporalis/masseter during firm closing of mouth, or testing power of jaw opening (lat pterygoids) against resistance; damage can come from stroke or tumours in middle cranial fossa and as mouth opens, jaw deviates to weak side due to unopposed intact muscles cotton wool over forehead, medial cheek and chin to test somatosensation for Va-c with damage to trigeminal roots giving anaesthesia to corresponding area and can include cornea, conjunctiva, mucosa of nose/mouth, general sensation of ant 2/3 of tongue noxious stimuli tested: corneal reflex is rapid, involuntary blink elicited by touching cornea (with puff of air or wisp of cotton wool), however should avoid giving a looming visual stimulus as that will also generate a blink (so approach from side); this is a brainstem reflex testing Va (nasociliary) afferent and facial nerve efferent on both sides, so can be performed in unconscious patients complication in considering lesions to trigeminal nerve branches is that these are used to reach autonomic targets (PS - CN III/VII/IX/X) and symp (reaching head via blood vessels) so lesions of lingual branch of Vc may lead to loss of taste in ant 2/3 of tongue (SVA) and salivation (PS) as chorda tympani (VII) gives it those fibres

Answer 270

complex, v important damage to motor component (esp inflam at temporal bone exit in stylomastoid foramen) gives Bell's palsy: a lower motor neuron lesion with paralysis of expression muscles with loss of expression, no forehead wrinkles, widened palpebral fissure (unopposed levator palpebrae superioris), overflow of tears, food accumulating in cheek (weak buccinator), dribbling (weak lip closure) and loss of corneal reflex motor component compromised in stroke, upper motor neuron lesion where bits of brain controlling the muscles damaged; unlike in Bell's palsy, upper part of face can still be moved voluntarily as those parts of facial nucleus in brainstem are inervated bilaterally PS leave in middle ear to upper jaw structures (greater petrosal nerve) or lower jaw (chora tympani), hitch-hiking via Vb and Vc (lingual) respectively; test chorda tympani via ant 2/3 taste (liquid with glucose, saline etc) and greater petrosal via salivation note also leaving in middle ear nerve to stapedius (reduce movement of ossicles) and some somatic sensation of ear canal damaging nerve in middle ear can compromise taste, salivation by submandibular/sublingual glands and hyperacusis (compare hearing either side); more proximal damage in temporal bone (acoustic neuroma on CN VIII or Ramsay Hunt syndrome) will produce dry eyes (loss of PS to lacrimal gland via greater petrosal) as well as the symptoms described above

Answer 271

also in middle ear, so vulnerable to middle ear infection, acoustic neuroma, base of skull fracture and disease of the hair cells, effecting both hearing and vestibular function hearing tested by audiometry eg whisper in one ear while occluding the other, ask patient to repeat them aloud; damage to middle ear/tympanic membrane can compromise conduction to inner ear but bone conducted vibration can still give acoustic sensation (rinne's test: compare loudness with tuning fork outside EAM and when base pressed on mastoid process: louder by air than bone if normal or nerve damage, louder by bone if conductive hearing loss); can also record auditory evoked potentials from head vestibular systems can be powerfully activated by caloric stimulus: warm or cold water in ear canal setting up convection currents in inner ear fluid to give powerful vestibular system activation and nystagmus (continuous flicking movements of eyes)

Answer 272

best considered together as often damaged as a group; IX/X tested via gag reflex: brisk stimulation of post part of tongue/pharynx with eg wooden spatula activates afferents in CN IX provoking gag reflex efferent fibres in X, and can be tested in unconscious patient; inflam in oropharynx (tonsillitis) can produce earache through referred pain as CNIX does it and middle ear assessing X often done by observing uvula when saying 'aah', should move up and down but not deviate from midline, and damage to X will also affect speech with vocal cord adducted in partial lesions and in midposition after complete lesions; speech possible after unilateral lesion as good cord can cross midline, though voice is weak; coughing tests ability to fully close vocal cords and so recurrent laryngeal branch; PS function loss after vagus lesion only problem if damage bilateral XI (C1-5) supplies sternocleidomastoid and trapezius, so function tested by turning head against resistance or shrugging shoulders; rare to damage peripherally but neurological damage more possible; XII does motor to tongue so test by looking for wasting or involuntary fasciculation on affected side, or get patient to stick out tongue and look for deviation: lack of push after lesion leads to tongue deviating to affected side; damage most commonly neurological after a stroke (upper motorneuron lesion as with CNVII) and so function can recover over time due to bilateral central connections bulbar palsy is lower motor neuron lesion in medulla or from lesions to CN outside brainstem due to toxins like botulinum, brain stem glioma, medullary infarction, ALS etc; has dysphagia, speech slurring, atrophied/twitching tongue, dribbling saliva, absent gag reflex etc

Answer 273

leaves pons at cerebellopontine angle, runs over surface of temporal lobe, at petrous temporal bone forms trigeminal ganglion in Meckel's cave (found at posterolateral aspect of cavernous sinus, Va and Vb pass through cavernous sinus to reach SOF and foramen rotundum if feel touch but don't blink suggests CNVII damage (note aff/eff limbs often diff nerves) opthalm division: from 3 CNV nuclei, first branches tentorial nerves to dura; lacrimal to skin and picks up PS from ZT for lacrimal reflex (pregang CNVII); helps innervate sinuses and eye max division: tigeminal nuclei then first branches to meninges then through foramen rotundum; zygomatic through IOF carries lacrimal PS some way before transferring to lacrimal nerve; infraorbital gives post sup alveolar to max sinus/molars through pterygomax fissure, then main nerve through IOF giving mid/ant sup alveolar to premolars/max sinus and canines/incisors/lat nasal wall/max sinus respectively; ganglionic connections to PPG (PS back to ZT, sensory through ganglia to branches from it:) with pharyngeal nerve to nasopharynx/pharyngeal glands, lesser palatine (sense to soft palate, tonsils; PS to palatine glands, taste from soft palate), greater palatine (same but to hard palate and lat post inf nasal to nasal glands), nasopalatine (PS to nasal glands, sense to ant hard palate, taste from palate, plus post sup nasal PS to nasal glands) mandib division: branches to dura and through foramen ovale; nerve to med pterygoid (with branches to tensor tympani/palatini passing through otic ganglion) then ant division (buccal for lower cheek skin, lat gums, cheek mucosa and nerves to masseter/ 2x lat pterygoid/ 2x deep temporal); post divison gives auriculotemporal (skin round ear, picking up PS (and symp from MMA) from otic ganglion for parotid gland), inf alveolar (lower teeth then mental through mental foramen for chin/lower lip, also mylohyoid nerve through sphenomandibular lig) and lingual (through submandibular ganglion picking up taste/PS from chorda tympani and symp from facial artery (both picked up in ganglion), distributing to ant2/3 of tongue, floor of mouth and inner gums, sublingual/submandibular glands

Answer 274

neuralgia: uncertain aetiology, possibly vascular compression of trigeminal sensory ganglion by sup cerebellar a; burning pain usually affecting Vb or Vc (Va in <6% of cases); at autopsy, 50% of people with arterial compression of the nerve didn't have trigeminal neuralgia; HSV1 often spreads along mental or infraorbital nerves, so blisters found around lips

Answer 275

somatic sensory, taste, branchiomotor, GVM to PTG and submandibular; leaves pons medial to CNVIII at cerebellopontine angle as 2 roots: efferent and afferent, which both enter IAM, enter the facial canal and enlarge into geniculate ganglion, turning 90deg posteriorly (has cell bodies like DRG/trigeminal ganglion); efferent root moves deeper into brainstem from facial nucleus, loops around abducent nucleus then heads out; after ganglion has 3 major branches and small somatic sensory to EAM small branch to EAM (sensory) leaves GG; also chorda tympani through petrotympanic fissure, joins lingual to SMG (taste/PS) then continues as branches of lingual; greater petrosal through petrous, picking up deep petrosal (symp from ICA) then through pterygoid canal to PPG (picked up by Vb); and branchial branch with nerve to stapedius, through stylomastoid foramen, gives 2 motor branches (occipitofrontalis/auricularis and post belly digastric/stylohyoid), then through parotid gland giving temporal branch, 2 zygomatic branches (both to orbicularis oculi), buccal branch, mandibular branch and cervical branch (to platysma); PS comes from sup salivary nucleus, taste from nucleus solitarius, somatic sensory from sensory nucleus of V (and only going to EAM) and motor from motor nucleus of VII reflexes: efferent for corneal (orbicularis oculi), lacrimation (PS from SSN through GG, along greater petrosal to PPG, picked up by lacrimal n), aff and eff limbs of salivatory reflex in response to taste (chorda tympani to NTS, then from SSN to SMG via chorda tympani then onto glands (except parotid, CNIX involved there); raise eyebrows to test temporal branch (corrugator/occiptofrontalis), shut eyes tightly (compare how deep eyelashes buried - tests zygomatic by orbicularis oculi), puff out cheeks (test buccinator - buccal branch), grin (levator labii/levator anguli oris of buccal branch and risorius/depressor labii inferioris of mandibular branch), pout/embouchure (orbicularis oris to purse lips, buccal branch, mentalis protrudes lower lip mandibular branch), say yuck (platysma tenses neck- cervical branch); also test as efferent part of corneal blin reflex (afferent being CNV)

Answer 276

tactile and nociceptive systems separate; CNV enters brainstem in pons with primary afferents for pain/temp turning caudally and descending as spinal tract of CNV, prominent in lower medulla and extending into upper cervical spinal cord, synapsing in the adjacent spinal nucleus of CNV in caudal medulla (and continuous with substantia gelatinosa, and is pale like it); 2nd order afferents from that nucleus cross midline and ascend to thalamus as trigeminothalamic fibres with anterolateral system fibres from spinal cord; tactile fibres terminate in cheif sensory nucleus which lies in pons at level of incoming fibres (hard to find as buried among pontine fibres) with fibres crossinf from here to join ML and ascend; proprioceptive fibres ascend to small mesencephalic nucleus in midbrain

Answer 277

CNVIII fibres reach brainstem at cerebellopontine angle and bifurcate, one branch to dorsal cochlear nucleus and the other to ventral cochlear nucleus; both nuclei on dorsolateral surface of medulla, then from here to sup olivary nucleus (close to medial leminiscus of pons) and fibres come from ipsi and contra nuclei, so first site of binaural interaction; fibres from son and cochlear nuclei (bypass son) form main ascending auditory pathway (lateral leminiscus) which ascends through pons to terminate in inf colliculus, then fibres from here to MGB of thalamus, from here auditory radiation crosses IC to reach auditory cortex of temporal lobe; unilateral lesion rarely causes hearing problem as both crossed and uncrossed pathways above level of cochlear nuclei; the cochlear nuclei may be seen in cross section lateral to cerebellar peduncles vestibular nuclei: sup/inf/lat/med with lat having large neurons and giving rise to vestibulospinal tract, and sup projecting to thalamus

Answer 278

complex, projecting to cortical and subcortical structures; olfactory nerve to bulb, then mitral cell axons in tract project via olfactory stria to areas of olfactory cortex and limbic system including uncus/pyriform cortex and olfactory tubercle, which underlies anterior perforated substance (site of entry to IC for striate arteries); pyriform cortex gives inputs to amygdala and entorhinal cortex and these then project to hypothalamus and reticular formation; olfactory tubercle projects to thalamus, thence on to insula and orbitofrontal cortex; pyriform and entorhinal cortices both lie on para-hippocampal gyrus, the most medial gyrus of the inf temporal lobe; lat and deep to this si amygdala and uncus is by pyriform cortex; ant perforated substance is on brain surface above optic chiasm

Answer 279

sup coll is not involved in direct transmission of sensory info (unlike inf coll); white strip in V1 is stria of gennari and is due to dense axonal input from thalamus to layer IV of V1; oculogyric nuclei (oculomotor, trochlear, abducent nuclei) are near midbrain; several regions influence these nuclei including vestibular and sup coll; medial longitudinal fasciculus is bundle of fibres either side of midline extending through brainstem into upper cervical spinal cord, connecting vestibular nuclei to oculogyric nuclei (vestibulooptic movements) and sup coll to spinal motoneurons controlling head movements; thus MLF coordinates tracking movements of eyes/head; commonly affected in MS giving nystagmus and diplopia + defects in gaze control; eye movements inititated by eye fields in cerebral cortex (motor, visual etc), projecting to retinotopic map in sup coll, then gaze centres in reticular formation of pons translate into appropriate oculogyric motor commands carried in mlf if lesion of mlf get internuclear opthalmoplegia; if also lesion of pontine reticular formation (initiates saccades) or abducens nucleus (control of lateral rectus + sends signals to other eye by mlf) then get a conjugate gaze palsy called one and a half syndrome in which you have a conjugate horizontal gaze palsy in one direction and an internuclear ophthalmoplegia in the other

Answer 280

to convey spatial properties of stimulus eg location, dimensions, shape, posture, muscle length etc; receptive field is area of space in which a stimulus can activate a neuron; objects we see/hold larger than one receptive field so spatial distribution of active/silent receptors allows neural image of size/contours to be build up in isomorphic representation; larger receptive fields come with decreased receptor density and gives less detailed image, similarly mechanoreceptors conc in fingertips; the fragmentation of stimulus into components by receptors and reassembly in the brain within neural networks allows brain to abstract certain important features with internal representation thus exaggerating important features, our percepts being thus a creation of the mind

Answer 281

Continuous circulating dark current carried by Na/Ca flowing into outer segment and depolarising cell to -30mV, circuit completed by outward current in inner segment mostly carried by K; channels close in illumination but K continues to exit in inner segment giving hyperpolarisation; Na pump maintains ionic grads; flashes of increasing intensity close more channels giving a graded hyperpolarisation which saturates at -75mV when all cNT channels closed; using suction electrode a dark current of -50pA recorded which can be completely suppressed by bright light; in very dim lights single photon responses can be detected; some flashes result in absorption of multiple or no photons due to quantal fluctuations To avoid saturation and allow operation over wide range of bg intensities, light adapt where sensitivity reduces as steady light intensity increases; saturate at high intensities when most cGMP hydrolysed, GC must synthesise more cGMP to prevent this but is inhibited by Ca; Ca enters via channels setting up feedback loop: more Ca enters in darkness, inhibiting GC, when channels close less Ca in but extruded by Na/Ca/K exchanger relieving inhibition of GC so more cGMP made to counteract excitation; rods still saturate at relatively low intensities so under photopic conditions vision mediated entirely by cones which continue to adapt under brightest conditions cones: similar to in rods but cones 50x less sensitive and can't detect single photons however the responses are much faster

Answer 282

photoreceptors to BC to GC using glutamate as NT; GABA-ergic HC mediate lateral inhibition and AC a diverse set of interactions in inner retina using various NT; GC synapse with A and BC and photoreceptors only with BC and HC with axons of ganglion cells forming optic nerve; only ganglion cells use APs, the rest use graded potentials though AC fire spikes in response to strong stimuli, as graded potentials more efficient over short distances; retinal processing shows divergence (parallel processing) and convergence (spatial summation) with overall retina showing convergence: 6 mil cones, 120 mil rods but only 1.5 mil GC; retina doesn't sample/process info uniformly: highest resolution in fovea where 3x more GC than cones (so net divergence) but in periphery 1 GC for 16 cones so net convergence and loss of spatial info

Answer 283

potentially very complex with up to 30 discrete visual areas identified, each specialised to some extent for a certain aspect; often simplified into 2 major streams: dorsal where pathway and ventral what pathway, former dominated by M cell input and latter P cell; first visual association area, V2, directly adjoins V1 and with cytochrome oxidase staining is divided into thick and thin dark stripes and pale interstripes what: V4 receives input from thin stripes and interstripes in V2, and within this stream are 2 parallel systems: parvo-blob-thin stripe - V4 concerned with colour and parvo/magno-interblob-interstripe-V4 stream concerned with edges and analysis of fine form; lesions in V4 lead to cortical colour blindness (achromatopsia) with final destinations of these streams including inferotemporal (IT) cortex where some highly sophisticated cells, responding to eg face or hands, are found, with lesions in this area leading to inability to recognise faces (prosopagnosia) where: M input to V1 projects primarily from 4Calpha to 4B then on to thick stripes of V2, from here to V5 and V5a (aka MT and MST) then to posterior parietal cortex; all levels within pathway dominated by rapidly responding movement detecting cells with little colour preference that respond to binocular depth cues; cells in MST have sophisticated response selectivity, responding to motion illusions and flow fields (field patterns of movement normally generated by motion of eyes/head/body through space); some output destinations of MT include brainstem nuclei controlling eye movements; lesion in MT can lead to inability to see movement

Answer 284

extremely rare neuropsychological disorder, having only been documented in a handful of medical cases, in which a patient cannot perceive motion in their visual field, despite being able to see stationary objects without issue result of damage to area V5, whose cells are specialized to detect directional visual motion; found laterally and ventrally in the temporal lobe, near the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus; signals reach V5 independently of V1, so eg cortical blindness pt may still detect motion There are varying degrees of akinetopsia: from seeing motion as frames of a cinema reel to an inability to discriminate any motion

Answer 285

lowest part in pathway where neurons influenced by neurons from both ears so first place where binaural cues pertinent to sound localisation can be analysed; 2 major subdivisions: med/lat sup olive; MSO has sheet of bipolar neurons whose lateral dendrites receive input from ipsilateral ear and medial dendrites from contralateral ear; these neurons respond to small time differences between stimuli delivered to the two ears; majority of LSO neurons stimulated by ipsilateral and inhibited by contralateral stimulus and are sensitive to interaural intensity differences

Answer 286

next major nucleus in auditory pathway after SON; one major output to neurons in deep layer of sup colliculus which also respond to visual stimuli, these possibly involved in coordinating head/eye movements and moving pinnae towards sound source; other output can be crossed or uncrossed fibres travelling in brachium of inf colliculus to enter medial geniculate body of thalamus with fibres from here projecting to primary auditory cortex AI which is situated on upper bank of the superior temporal gyrus

Answer 287

primary: tonotopically organised but not essential for freq discrimination, with sound sensitivity/ability to react to changes in freq not impaired in cats after bilateral ablation of the auditory cortex; cat does require cortex to detect temporal pattern of auditory stimuli, with discriminating these temporal patterns probably important in humans for speech perception; as well as A1 also other parts of temporal cortex devoted to audition as well as at least 2 regions of association cortex where damage produces aphasias: broca's area in frontal cortex, adjacent to part of primary motor cortex that controls mouth, tongue and larynx and important for speech production including syntax; wernicke's area on post part of temporal lobe important for speech comprehension; both parts are unilaterally represented in dominant, usually left, hemisphere alone sound localisation: humans/most animals very good at localising direction of sound source, though ability to determine distance is poor except for familiar sounds like speech where experience allows memorisation of loudness at different distances; direction defined by two angles measured at mid-point between ears: angle of azimuth in horizontal plane, straight ahead as 0 degrees, to right as 90, behind as 180 and to left as 270; and angle of elevation/depression in midsagittal plane with zero ahead, 90 above, 180 behind, 270 below; at best can localise to within 1-2 degrees of azimuth and 10 degrees of elevation, though this only for source directly in front with broad spectrum of composition; can localise to some degree with just one ear, though high accuracy needs; for all directions other than 0 degrees azimuth, sound travels further to reach one ear and so arrives later with path difference and hence time differen varying with angle of azimuth; max time diff is ~660microseconds (at 90/270 degrees) and min detectable is about 10 microseconds; as well as time difference, the path difference introduces a phase diff when source is sustained and periodic eg low freq tones; phase comparisons are ambiguous above 1kHz as phase diff exceeds one cycle; due to this, and inability to encode sound's waveform in discharge > a few kHz, interaural phase diff not used to localise sounds with high freq; wavelength of sound decreases with freq so by ~2kHz is comparable to size of head; above this freq the more distant of the two ears is shadowed by the head and so intensity is reduced; the interaural intensity diff is function of azimuth and freq, insignificant <1kHz and at max of about 20 dB for sources at 90/270 azimuth for high freqs with min detectable intensity diff of about 1 dB; frequency at which shadowing begins to operate depends on size of animals heads, this physical limitation probably what provided selective pressure for small animals to hear higher freqs cones of confusion: angle of elevation/depression generates intensity/time diffs like above which implies source in many positions may possess same set of time/intensity cues: anywhere on a conical surface with apex at ear for a spherical, bodyless head with symmetrical pinnae; in practise these cones of confusion dont exist due to asymmetry of head, shadowing effect of body and complicated shape of pinnae, all of which filter sound reaching ear based on direction of source; this operates monaurally and accounts for ability to locate direction of sound with a single ear; we learn during first years to associated colourations of sound with particular directions and use this to interpret ambiguous aural cues; many animals, esp nocturnal ones, go to great lengths to make heads asymmetrical; localisation in humans majorly limited when sound in midplane: source immediately in front may also be immediately behind and vice versa as body mirror-symmetrical around midplane with only front-back asymmetry of not very asymmerical pinnae the only anatomical feature introducing colouration; barn owls grow feathers of ruff lower on one side of head than other so not symmetrical in any plane

Answer 288

airborne odourants detected by olfactory epithelium, with some species using turbinates to enlarge the olfactory epithelium and improve airflow contact; odorants dissolve in mucous film, possibly in association with odorant binding protein, and interact with receptors on olfactory cilia; basal cell division renews receptors every 60 days; transduction occurs in the cilia, odorant interacting with a receptor (1 of perhaps 1000 i the family) which couples via G protein to increase cAMP, opening cyclic NT gated cation channels in ciliary membrane, giving inwards flowing receptor current carried by Na/Ca, depolarising the cell body so it fires APs; a Ca gated Cl channel allows outwards Cl flow to augment the inwards cation current; increasing [odorant] increases receptor current to increase spike firing, and Ca acts via calmodulin to reduce sensitivity of channels to cAMP, contributing to olfactory adaptation; most the Ca that enters is extruded by a Na/Ca antiporter, with a Ca-ATPase contributing in some species; each olfactory receptor cell expresses a single receptor molecule type but responds to a range of odorants receptor axons pass through cribriform plate to reach bulb where they excite mitral cells and smaller tufted cells in the olfactory glomeruli; afferents from receptors expressing a particular receptor molecule converge on just 2 glomeruli (of 1000+) each in each bulb; periglomerular cells and granule cells make reciprocal dendro-dendritic synapses with mitral cells to mediate lateral inhib, (for latter, dendrites of afferents excite them, they inhib relay neurons which same cells connect to, dampening weak responses) which may sharpen mitral cell odour tuning; different odorants evoke different but overlapping activity patterns in the bulb; mitral cell axons leave bulb in lateral olfactory tract with anterior olfactory nucleus mediating inhib between the two bulbs via the anterior commissure; several thousand receptors converge to 40-50 relay neurons; each odorant recognsed by unique pattern of r's and onto particular combo of glomeruli with similar odorants stimulating glomeruli in same sub-region lat olfac tract synapses on neurons in 5 regions of olfactory cortex; ant olf nucleus as described above; olfactory tubercle -> medial dorsal nucleus of thalamus -> orbitofrontal cortex, for perception; pyriform cortex to other regions of olfactory cortex; amygdala and entorhinal cortex form part of limbic system and involved in affective component of odour perception, mediating emotional/autonomic responses, with entorhinal to hippocampus for motivation then hypothalamus for autonomic, amygdaloid complex to hypothelamus for autonomic and reticular formation for arousal; at higher levels of pathway, cells more odour specific with cells in bulb responding to many odours and those in orbitofrontal cortex mostly to just one or two; vomeronasal organ projects via accessory olfactory bulb to amygdala to mediate response to pheromones involved in sexual/social behaviours; MHC peptides may also function as social recognition signals; in humans, trace amine associated receptors in main olfac epith may detect volatile amines in sweat to shift mood and perhaps increase fertility

Answer 289

Involuntary eye movement; Nystagmus may be caused by congenital disorder or sleep deprivation, acquired or central nervous system disorders, toxicity (wernickes, overdose), pharmaceutical drugs, alcohol, or rotational movement; in the elderly, stroke is the most common cause; also tumour, MS, brain (cerebellar) abscess, cerebellar ataxia, vestib pathology (BPPV, labyrinthitis, menieres), chiari malform Vertical nystagmus is only seen if the cause is central. Nystagmus due to central causes may be horizontal, rotational or vertical, and does not disappear on fixing the gaze. Nystagmus in the peripheral type disappears with fixation of the gaze physiologic nystagmus is essentially conjugate. Pathologic nystagmus, on the other hand, may have different amplitudes in the two eyes (dissociated nystagmus); it may go in different directions leading to different trajectories of nystagmus in the two eyes; or may have different temporal properties red flags for urgent tertiary assessment/cons discussion include onset after 6 months along with: * Constant oscillopsia in older children. * Dysconjugate/gaze evoked/seesaw/convergence-retraction nystagmus. * Horizontal nystagmus becoming vertical in vertical gaze. * Vertical or torsional nystagmus (in the absence of retinal pathology (e.g. achromatopsia). * Any associated neurological signs and/or a systemically unwell child.

Answer 290

A bulbar palsy is a lower motor neuron lesion of cranial nerves IX, X and XII. A pseudobulbar palsy is an upper motor neuron lesion of cranial nerves IX, X and XII. Bulbar palsy Motor neurone disease Syringobulbia Guillain-Barre syndrome Poliomyelitis Subacute meningitis (carcinoma, lymphoma) Neurosyphilis Brainstem CVA Pseudobulbar palsy The commonest cause is bilateral CVAs affecting the internal capsule. Other causes include: Multiple sclerosis Motor neurone disease High brainstem tumours Head injury Bulbar palsy The clinical features include: Gag reflex – absent Tongue – wasted, fasciculations “wasted, wrinkled, thrown into folds and increasingly motionless”. Palatal movement – absent. Jaw jerk – absent or normal Speech – nasal “indistinct (flaccid dysarthria), lacks modulation and has a nasal twang” Other – signs of the underlying cause, e.g. limb fasciculations. Pseudobulbar palsy The clinical features include: Gag reflex – increased or normal Tongue – spastic “it cannot be protruded, lies on the floor of the mouth and is small and tight”. Palatal movement – absent. Jaw jerk – increased Speech – spastic: “a monotonous, slurred, high-pitched, ‘Donald Duck’ dysarthria” that “sounds as if the patient is trying to squeeze out words from tight lips”. Other – bilateral upper motor neuron (long tract) limb signs.

Answer 291

proprioceptive system in inner ear labyrinth; important to many movements, esp postural control, esp complex in man as bipedal stance inherently unstable; postural stability also contributed to by: somatosensory system (forces on each foot, intrafusal gives position of limbs etc), visual system (are we vertical wrt outside world?) and vestibular system (head position and movement) receptors are hair cells in labyrinth in semicircular canals and otolith organs (saccule and utricle); hair cells identical to those in cochlea with same transduction mechanisms, and have directional sensitivity so respond best to movement in certain direction; in utricle/saccule, hair cells project into jelly-like mass on which gravity acts, with diff hair cells arranged to have diff directional sensitivity so diff sets activated when head in diff positions, thus giving head position signal; hair cells in SCs embedded in mass that almost closes canal called cupula; cupula neutrally buoyant in endolymph in canals so when head is stationary, it is stationary; when cupula deflected, hair cells activate (usually when head moves, fluid has inertia so stays still and cupula deflectes as fixed to head); canals give dynamic signal when head moves or stops, with greater acceleration giving greater signal; primary spindle afferents similar to SCs and secondary spindle afferents similar to otolith system: both have dynamic and static systems; canals on either side act as complementary pairs (rotation causes complementary changes) and canals project to vestibular nuclei in brainstem; dynamic system more likely to provide info for predictive control

Answer 292

activation may indicate postural instability; thus vestibular signals generate rapid and powerful vestibular correcting responses through descending vestibulospinal pathways, which principally influence antigravity extensor muscles; constantly correcting posture when eg standing; though powerful, usually we're unaware of them; damage to system not uncommon: peripheral eg labyrinthitis or centraleg brainstem stroke, cerebellar damage; damage reveals potency of vestibular reflexes by producing dramatic problems; plasticity in vestibular system and cerebellum reduce pathological symptoms over time system has to differentiate between body sway with neck fixed and head movement with body stationary; cerebellum mediates this using efference copy from motor systems moving head: predict expected head movements and so expected vestibular response, and if they match then vestibular reflexes cancelled; neck reflexes can counteract vestibular reflexes if latter produced by head movement

Answer 293

highly specialised motor system of 6 muscles: eyes rotate in orbit under predictable load (no stretch reflex needed) and in binocular species eyes move consensually (together); eye movement fundamental to vision as: must know whether image moving across retina is you moving, object moving or both, visual system poor at resolving moving images so static image important for acuity, and eye movements must be consensual (hence system that coordinates 2 sides in brainstem not cortex); visual system not good at resolving moving images so gaze fixing mechanisms to stabilise, rapid gaze shifting mechanisms when eyes have to move followed by stabilising; vision suppressed during three movements gaze fixing mechanisms: to prevent vision blurring due to self movement; animals with small mobile heads have vestibulocollic movements of head to compensate movement of body - head in same place when you rotate body eg owls, chickens (also infant humans); mammals use vestibulo ocular reflex to move eyes equal and opposite to head, driven by vestibular system detecting head movement size/direction: SC afferents to vestibular nucleus then to occulomotor nuclei by way of fast conducting fibre tract in brainstem called medial longitudinal fasciculus; this is feedforward control (vestibular signals used to predict required movements to stabilise gaze) but reflex must be precisely calibrated to have gain of 1 (10 deg head move to left must do 10 deg eye move to right) and this is done by cerebellum optokinetic system: complementary system to VOR that moves eyes to follow slow movements of visual field (eg looking out of train window); optokinetic movements require detection of slow moving image so depend on visual cortex; combined the two mechanisms stabilise the image on the retina; eye movements in orbit limited and when eye deviates far from axis, saccades reset it to centre; nystagmus is characteristic saw tooth motion of drift and saccade; physiological nystagmus occurs due to optokinetic or vestibular stimuli; pathological nystagmus occurs following cerebellar/vestibular damage gaze shifting mechanisms: saccades generated by brainstem and can be very rapid responses allowing rapid shifts of gaze to potential points of interest to give detailed info about peripheral events; sup/rostral colliculus organises saccades to foveate stimuli: retina projects to SC, deep layers of SC to brainstem reticular formation, that projects to occulomotor nuclei; projection organised so stimuli in any part of visual space drive saccades to foveate stimuli; deep layers of SC also project along tectospinal tract in cervical spinal cord so neck movements can coordinate with eye movements; deep layers of SC also receive auditory input to orientate to auditory as well as visual stimuli; cerebral cortex and basal ganglia involved in permitting when SC can drive saccades; slower eye movements called smooth pursuit can be made but only to follow moving objects: these are feedforward movements involving visual and medial temporal cortices to process visual signals and regions of frontal lobe anterior to motor cortex (frontal eye fields) as well as brainstem and cerebellum

Answer 294

part of the pontine reticular formation located anterior and lateral to the medial longitudinal fasciculus (MLF). It receives input from the superior colliculus via the predorsal bundle and from the frontal eye fields via frontopontine fibers. The rostral PPRF probably coordinates vertical saccades; the caudal PPRF may be the generator of horizontal saccades In the case of horizontal saccades the "pulse" information is conveyed via axonal fibres to the abducens nucleus, initiating lateral eye movements Unilateral lesions of the PPRF produce characteristic findings: Loss of horizontal saccades directed towards the side of the lesion, no matter the current position of gaze Contralateral gaze deviation (acute lesions, such as early stroke, only) Gaze-evoked lateral nystagmus on looking away from the side of the lesion Bilateral lesions produce horizontal gaze palsy and slowing of vertical saccades note: Palsy of all types of horizontal movements implicates the abducens nucleus, whereas palsies of saccades alone are due to lesions of the parapontine reticular formation.

Answer 295

sits below/rostral to thalamus, bordered rostrally by optic chiasm and caudally by mammillary bodies; can be divided into lat/med/periventricular regions, or ant/mid/post; stimulation leads to activation of motivated behaviours and lesions to loss; contains a variety of nuclei and fibre tracts running through it; inputs are both neural and endocrine neural inputs from brainstem including somatic afferents (not somatotopic - no feature detection) used in neuroendocrine reflexes like milk ejection and in stereotypic behaviours like sex, and visceral afferents from NTS and reticular formation carrying gustatory and olfactory info; neural inputs from forebrain via amygdala/orbitofrontal cortex carrying info about motivational significance of external stimuli; many regions of hypothalamus have neurons expressing receptors for and responding to steroid hormones like oestrogen (drive sexual behaviour); other neurons in preoptic area sensitive to temp (drive thermoreg behaviour) and osmoreceptors (drive drinking) in circumventricular OVLT; hypothalamus well placed to respond to changes in blood comp as many caps fenestrated so open to entry of large molecules from blood first type via neural signal to post pitu or hormones into portal plexus (found within median eminence) draining to ant pitu; second type hypo controls simple stereotyped movements like biting, shivering, gnawing, drinking, and mounting via reflex motor circuits in brainstem; 3rd type hypo can control autonomic system, along with NTS in brainstem; more elaborate homeostatic adjustments from reciprocal connections between NTS and higher centres inc amygdala and paraventricular nucleus of hypothalamus

Answer 296

environmental cues (smells, tastes, sight and stimuli associated with food like mcdonalds logo) and physiological cues (declining blood glucose/lipids) act to initiate feeding; short and long term satiety mechanisms stop feeding; former from tasting/swallowing food and stomach distension, as well as humoral factors like CCK; long term intake affected by signals from nutrient reservoirs eg leptin secreted by well nourished adipose tissue that increases BMR, reduces food intake and increases sensitivity to CCK 2 key neuropeptides, melanin concentrating hormone hormone and orexin in LH; activated by NPY secreting neurons in arcuate nucleus, these neurons in turn containing leptin receptors that inhibit NPY release when bound so get hungry, leptin levels down, NPY deinhibited; also ghrelin from empty stomach activates NPY release directly; NPY acts on LH to cause eating and PVN to decrease metabolic rate and insulin, thus NPY acts on diff hypothalamic sites to integrate physiological mechanisms to promote feeding and preserve energy supplies; counter to this when leptin rises, and also less NPY in PVN causes ACTH release from pitu and increased tone in symp nerves, increasing metabolic activity; obesity can come from overeating or metabolic disorder with evidence for complex interaction of genes and environment, latter including modern eating habits

Answer 297

lesions of mPOA abolish copulatory behaviour in male rats, and lesions of VMH abolish female sexual behaviours (lordosis and solicitation); even intact mPOA, castration abolishes male sexual behaviour so circulating steroids are necessary; ditto for females with ovariectomy; get behaviours back by exogenous testosterone in males, oestradiol then progesterone in females; steroid dependent neurons found both in hypothalamus and brainstem with androgen r concentrated at mPOA and oestradioal/progesterone r concentrated in VMH: can restore sexual behaviour by implanting the steroid hormones right into mPOA/VMH examine motivation to press lever to obtain conditioned stimulus: a light associated with sexually active female; mPOA lesions effect copulatory behaviour but not motivation whereas castration affected both showing sex hormones are essential for motivated sexual behaviour; this is similar to temp where preoptic lesions caused loss of panting etc but still pressed lever for puff of cold air; clear that hypothalamus vital to integrate motivated behavioural responses with autonomic/endocrine responses, but motivation doesn't reside in specific group of neurons; incentive motivational responses like appetitive behaviours to obtain food/sexual partner/warmth all survive hypothalamic lesions so depend on other brain mechanisms

Answer 298

Patients use ‘dizziness’ to describe many sensations. Recurrent ‘dizzy spells’ affect approximately 30% of those over 65 years and can be due to postural hypotension, cerebrovascular disease, cardiac arrhythmia or hyperventilation induced by anxiety and panic. Vertigo (the illusion of movement) specifically indicates a problem in the vestibular apparatus (peripheral) or, much less commonly, the brain (central) TIA and stroke rarely if ever cause isolated vertigo As a guide, recurrent episodes of vertigo lasting a few seconds are most likely to be due to BPPV; vertigo lasting minutes or hours may be caused by Ménière’s disease (with associated symptoms including hearing loss, tinnitus, nausea and vomiting) or migrainous vertigo (with or without headache)

Answer 299

frontal: Disinhibition Lack of initiative Antisocial behaviour Impaired memory Incontinence Grasp reflexes Anosmia dominant parietal: Dyscalculia Dysphasia Dyslexia Apraxia Agnosia Homonymous hemianopia non dominant parietal: Neglect of non-dominant side Spatial disorientation Constructional apraxia Dressing apraxia Homonymous hemianopia occipital lobe: Homonymous hemianopia Hemianopic scotomas Visual agnosia Visual hallucinations (lights, lines and zigzags) dominant temporal: prosopagnosia, Dysphasia Dyslexia Poor memory Complex hallucinations (smell, sound, vision) Homonymous hemianopia non-dominant temporal: Poor non-verbal memory Loss of musical skills Complex hallucinations Homonymous hemianopia

Answer 300

lower: Bell’s palsy is the term used to describe an idiopathic acute lower motor neurone VII nerve paralysis, often preceded by mastoid pain. It may be associated with impairment of taste and hyperacusis (high-pitched sounds appearing unpleasantly louder than normal). Bell’s phenomenon occurs when a patient closes their eyes: as eye closure is incomplete the globe can be seen to roll upwards, to avoid corneal exposureRamsay Hunt syndrome occurs in herpes zoster infection of the geniculate (facial) ganglion. This produces a severe lower motor neurone facial palsy, ipsilateral loss of taste and buccal ulceration, and a painful vesicular eruption in the external auditory meatus. Other causes of a lower motor neurone VII lesion include cerebellopontine angle tumours (including acoustic neuroma), trauma and parotid tumours. Synkinesis (involuntary muscle contraction accompanying a voluntary movement: most commonly, twitching of the corner of the mouth with ipsilateral blinking) is a sign of aberrant reinnervation and may be seen in recovering lower motor neurone VII lesions upper: relative sparing of the upper face. This is because there is bilateral cortical innervation of the upper facial muscles. The nasolabial fold may be flattened and the corner of the mouth drooped, but eye closure is usually preserved bilat: less common, but occasionally occur, as in Guillain–Barré syndrome, sarcoidosis, or infection such as Lyme disease, HIV or leprosy. Facial weakness, especially with respect to eye closure, can also be found in some congenital myopathies (facioscapulohumeral or myotonic dystrophies). Distinct from VII nerve palsies, Parkinson’s disease can cause loss of spontaneous facial movements, including a slowed blink rate, and involuntary facial movements (levodopa-induced dyskinesias)

Answer 301

Unilateral X nerve damage leads to ipsilateral reduced elevation of the soft palate, which may cause deviation of the uvula (away from the side of the lesion) when the patient says ‘Ah’. Unilateral lesions of IX and X are most commonly caused by strokes, skull-base fractures or tumours. Damage to the recurrent laryngeal branch of the X nerve due to lung cancer, thyroid surgery, mediastinal tumours and aortic arch aneurysms causes dysphonia and a ‘bovine’ cough. Bilateral X nerve lesions cause dysphagia and dysarthria, and may be due to lesions at the upper motor neurone level (pseudobulbar palsy) or lower motor neurone level (bulbar palsy) incompetent palate closure may leed to nasal air escape when talking and liquid getting up into nose always consider MG if bulbar dysfunction Isolated XI nerve lesions are uncommon but the nerve may be damaged during surgery in the posterior triangle of the neck, penetrating injuries or tumour invasion. Wasting of the upper fibres of trapezius may be associated with displacement (‘winging’) of the upper vertebral border of the scapula away from the spine, while the lower border is displaced towards it. Wasting and weakness of the sternomastoids are characteristic of myotonic dystrophy. Weakness of neck flexion or extension, the latter causing head drop, may occur in myasthenia gravis, motor neurone disease and some myopathies Bilateral lower motor neurone damage results in global wasting, the tongue appears thin and shrunken and fasciculation may be evident bilateral lesions lead to a tongue with increased tone (spastic) and the patient has difficulty flicking the tongue from side to side

Answer 302

a. third cranial nerve palsy b. fourth cranial nerve palsy c. sixth cranial nerve palsy d. blow out fracture e. thyroid eye disease f. myasthenia gravis +hypophos and misc others

Answer 303

miosis, ptosis, anhidrosis central has anhidrosis of face/arm/trunk and inc stroke, syringomyelia, MS, tumours pregang has anhidrosis of face only and inc pancoast tumour, thyroidectomy or other trauma, cervical rib postgang has no anhidrosis and incs carotid art dissestion or aneurysm, cavernous sinus thrombosis, cluster headache

Answer 304

Causes of mydriasis (large pupil) third nerve palsy Holmes-Adie pupil traumatic iridoplegia phaeochromocytoma congenital Drug causes of mydriasis topical mydriatics: tropicamide, atropine sympathomimetic drugs: amphetamines, cocaine anticholinergic drugs: tricyclic antidepressants Holmes-Adie pupil is a benign condition most commonly seen in women. It is one of the differentials of a dilated pupil. Overview unilateral in 80% of cases dilated pupil once the pupil has constricted it remains small for an abnormally long time slowly reactive to accommodation but very poorly (if at all) to light Holmes-Adie syndrome association of Holmes-Adie pupil with reduced/absent ankle/knee reflexes

Answer 305

Once you have established that the symptom is that of true vertigo, it is imperative to ascertain the duration and frequency of attacks, as this is the key to reaching the correct diagnosis and determining if the disorder is most likely peripheral (pertaining to the ear) or central (brain). There are 3 common causes of vertigo originating from the labyrinth itself: Benign Paroxysmal Positional Vertigo (BPPV)- most common cause of true vertigo with typical age of onset 40-60 years Vestibular neuronitis Meniere’s Disease Another common condition that is seen is vestibular migraine BPPV sudden w no hearing loss, vestibular neuritis sudden or gradual with no hearing loss, menieres gradual with fluctuating hearing loss, vestibular migaine sudden or gradual and may have hearing loss so can be hard to tell from menieres BPPV- Dix-Hallpike test positive. Rotatory vertigo on moving head Meniere’s – Rotatory vertigo associated with fluctuating hearing loss often with low frequency thresholds affected. Tinnitus usually gets worse during an attack. Patients classically get an aural fullness before onset of vertigo. attacks last minutes-hours Vestibular neuritis – Rotatory vertigo that is continuous for over 24 hours often associated with nausea and vomiting. Classically they are confined to bed and it takes several days to weeks to recover. labyrinthitis is similar but also has hearing loss Vestibular migraine – Rotatory vertigo can last minutes to hours to days. Classically associated with headaches/photophobia/visual disturbance\phonophobia but these are not always present

Answer 306

Full neurological examination Pure tone audiometry Dix-Hallpike test MRI of internal auditory meatus may be appropriate with asymmetrical sensorineural loss to exclude an acoustic neuroma Video head impulse testing (vHiT) – this is performed using specialist equipment and can be used to assess the function of the semi-circular canals by measuring visual ocular reflex (VOR) function. It takes around 15minutes to perform and is a quick and sensitive measure of labrythine function Treatment BPPV - Epley’s manoeuvre can be curative in up to 90% by repositioning of the displaced otoconia crystals. In persistent cases, Brandt-Daroff exercises may be advised. Surgical management is rarely required but posterior semi-circular canal occlusion is useful in resistant cases. Vestibular neuronitis – Treatment is expectant with anti-emetics during the acute phase; chronic symptoms needs vestibular rehab exercises, short course of prochlorperazine or antihistamine can alleviate less severe cases and more severe buccal/im prochlor Meniere’s Disease – There is a hierarchy of treatments depending on the severity of the disease and response to previous treatments. The underlying pathophysiology is thought to be endolymphatic hydrops. Therefore “pressure reducing” therapies include low salt diet, medications such as betahistine and diuretics although the evidence for these treatments is weak. Intratympanic injection of steroid or gentamicin is used for those that fail conservative management. Other treatment options include saccus decompression, labyrinthectomy and vestibular nerve section. prochlor to relieve attacks; vestib rehab; dvla should be told and dont drive until symptoms controlled Vestibular migraine – Common trigger factors include dehydration, foods (classically chocolate, cheese), anxiety and a poor sleep pattern. A symptom diary can help identify these. In those that do not respond to avoidance measures, there are a variety of migraine-preventative medications

Answer 307

Early features: erythema migricans rash (80% cases), headache, lethargy, fever, arthralgia Late features: cardio (heart block, myocarditis), neurological (facial nerve palsy, meningitis) Suspect if the question mentions North America, camping, hiking Clinical diagnosis if rash present! Otherwise serology: ELISA to detect antibodies Doxycycline/amoxicillin if early Ceftriaxone if late disease

Answer 308

hyperphagia or anorexia, hyper/hypopyrexia, sleep disturbance, thirst

Answer 309

traces from odd number leads usually left of head and even numbers usually from right look at all the traces to determine if any are abnorm; then is abnorm generalised to all traces or limited to particular ones (so particular part of brain), determine whether the abnorm is spike or slow wave, and look at the amplitude for if high or low voltage petit mal - typically three spike wave complexes per second (3Hz), synchronous in all leads, may be accompanied by absence attack

Answer 310

eeg description not clinical diagnosis chaotic pattern of high voltage slow waves and multifocal spike waves, no constant pattern; 50% of time is associated with infantile spasms (the abnorms disappear when spasm begins), sleep and drowsiness enhance infantile spasms oft start between 3-12mo, strong association w mental retardation, delayed motor dev, skill regression; 30% idiopathic, prenatal causes TS and congen infection, perinatal birth asphyxia, postnatal men/enceph, head injury, severe hypo, PKU examine skin under hood's light for ash-leaf macules; skull x ray for calcification, CT; serological and metabolic screens treatment: ACTH/prednisolone/vigabatrin note may be misinterpreted as colic or constipation as bringing legs up; 50% will dev other seizures, esp grand mal type

Answer 311

subacute sclerosing panencephalitis has relatively normal eeg with regular paroxysms of high voltage slow waves (periodic complexes) synchronously in all leads, poss with myoclonic jerks; diagnosis confirmed with high anti-measles antibody titre in serum and csf herpes - periodic complexes too but only in temporal lobe leads; if suspect do lp, viral titres, restrict fluids, start iv aciclovir, consider steroids/anticonvulsants periodic complexes also seen in CJD

Answer 312

grand mal - normal interictal, during attack spike waves and polyspikes at the start of the episode, synchronous in all leads myoclonic - synchronous periodic polyspikes at 3Hz with normal interictal; attacks precipitated by sleep dep or alcohol so sleep deprived eeg may help with diagnosis high amplitude slow wave activity over space occupying lesions, substantial vascular lesions or advanced neurodegen benign rolandic epilepsy shows high amp spikes in centrotemporal region (as opposed to ant temp region for temp lobe epilepsy), usually nocturnal in onset; peaks ages 5-10 lennox-gastaut peaks between 1 and 4yo; eeg shows slow and spike waves acute encephalopathy and post-ictal eeg may have generalised irregular slow waves

Answer 313

crabbing C – Café-au-lait spots (6 or more) measuring ≥ 5mm in children or ≥ 15mm in adults R – Relative with NF1 A – Axillary or inguinal freckles BB – Bony dysplasia such as Bowing of a long bone or sphenoid wing dysplasia I – Iris hamartomas (Lisch nodules) (2 or more) are yellow brown spots on the iris N – Neurofibromas (2 or more) or 1 plexiform neurofibroma G – Glioma of the optic nerve clinical diagnosis, genetic testing if doubt; x rays for bone pain; CT/MRI for lesions in brain, spinal cord etc

Answer 314

two types (also schwannomatosis), austosomal dom for both, but 50% of cases are new mutations with no FH, type 1 much more common, type 2 has more central CNS tumours NF1 needs at least 2 out of: at least 6 cafe au lait spots or hyperpig macules, axil or inguinal freckles, two or more neurofibromas or one plexiform neurofibroma, optic nerve glioma, two or more iris hamartomas, first degree relative with NF1, sphenoid dyplasia or long bone abnorms eg tibia bowing NF2 needs at least one of: bilat 8th nerve masses on MRI, or unilat with first deg rel having NF2, or first deg rel with at least 2 of: meningioma, glioma, schwannoma, juvenile cataracts features may not dev until adolescence or later so may need to keep eye on suspicious people neurofibromas are in skin or subcut tissue, usually appearing in late teens or early 20s, may be tender, catch on clothes, or tingle in distribution of nerve optic nerve gliomas asymp but over time dec visual acuity, abnorm colour vision or visual fields (asym vis field defect most common presentation - bumping into things, failure to pick up or notice small toys etc) NF1 can also have bad scoliosis, impaired iq, high rates of ADHD, intracran lesions or spinal cord compression can give peripheral neuropathies or sphincter disturbance xrays to investigate bone lesions; MRI to investigate problems, EEG if seizures/epilepsy devs, slit lamp to find iris hamartomas NF2 usually presents in adults with deafness/tinnitus annual monitoring to inc visual acuity, skeletal involvement, head circ in first 3 yrs (tumour/hydroceph), heart for murmurs, neurodev; surgical intervention where tumours causing pressure symptoms or other problems, or in rare instances of malig change, or if on scalp, waist etc so rubbing on clothes

Answer 315

PT with NF1, rapidly enlarging painful neurofibroma may be malignant periph nerve sheath tumour pt with buzzing/hearing problems in an ear: rinne/weber, otoscopy, pure tone audiometry, tympanometry, MRI; schwanomma may be idiopathic, NF2; watch and wait, microsurgery or stereotactic radiosurgery; auditory rehab/cochlear implant may be needed; MRI syrveillance in kids of affected parents; NF2 also get many meningiomas in astrocytoma and schwannoma find biphasic architecture; menigioma has whorls, clear nuclear inclusions, pseudocyncytial cytoplasm NF1 cr 17 (nf 17 letters long) and NF2 on cr22 (nf type 2 written out is 22 letters long if spell 2 as symbol not word)

Answer 316

aka fits, aka funny turns, blackouts etc - pt may be found collapsed or may be able to recall collapses; cardiogenic syncope, seizure, psychogenic attack, hypoglycaemic; maybe migraines, TIAs but cardiac syncope or seizures are the most likely epilepsy needs 2 unprovoked seizures more than 24 hours apart; focal seizures often have a structural cause; generalised usually complex genetic cause; autonomic seizures may have hair standing on end, flushing or pallor, fluctuations in BP/heart rate, abdo discomfort/nausea EEGs can be normal, and epileptiform discharge may be seen in people w/o epilepsy; bright on DWI MRI think infarct or abscess; first seizures usually require imaging to look for cause, oft CT; unexplained (esp focal or intractable) do MRI (maybe special sequence) to look for cause eg structural abnorm, medial temp sclerois, AVM, previous brain insult, or tumours (Gliomas) infant seizures HIE, birth trauma, infection, congen malform, genetic, metabolic; 2-12yo idiopathic, febrile, trauma, infection; 12-18yo idiopathic, avm, drugs/alcohol withdrawal, trauma; 18-25 trauma, alcohol, tumour; >35 tumour, stroke, alcoholism, hypogly/hep fail uraemia, u&e disturbance also in kids consider TS: benign tumour formation in cerebral cortex; ISC1/2 genes cysticercosis is commonest cause of epilepsy worldwide sudden death in patients with epilepsy: trauma, drowning, status, arrhythmia, resp suppression surgery if eeg shows focal origin, source identified on imaging, eg medial temp lobe sclerosis; refractory to medical treatment brief convulsion w/ rapid recovery? syncope more likely (bite tongue points to seizure, twitching and loss of continence in either but more likely seizure); ECG mandatory in all cases (even over EEG) ictal bradycardia syndrome should be considered in patients with unusual or refractory episodes of syncope, or in patients with a history suggestive of both epilepsy and syncope. It suggests seizure onset in temporal lobe and is caused when epileptic discharges profoundly disrupt normal cardiac rhythm, resulting in cardiogenic syncope

Answer 317

Reflex syncope (neurally mediated) vasovagal: triggered by emotion, pain or stress. Often referred to as 'fainting' situational: cough, micturition, gastrointestinal carotid sinus syncope Orthostatic syncope primary autonomic failure: Parkinson's disease, Lewy body dementia secondary autonomic failure: e.g. Diabetic neuropathy, amyloidosis, uraemia drug-induced: diuretics, alcohol, vasodilators volume depletion: haemorrhage, diarrhoea Cardiac syncope arrhythmias: bradycardias (sinus node dysfunction, AV conduction disorders) or tachycardias (supraventricular, ventricular) structural: valvular, myocardial infarction, hypertrophic obstructive cardiomyopathy others: pulmonary embolism

Answer 318

right near start of history - sounds like it was really frightening? how are you feeling now? we're going to give this plenty of time and attention to find out exactly what's going on. then get really detailed history - include pictures (kid could draw), even layout of room, way child fell, how did they feel? which body part moved first? where were you when it started? what happened before it started? before that? video/demonstration -always remember to establish if developmental delay etc

Answer 319

Simple Complex Febrile status epilepticus < 15 minutes 15 - 30 minutes > 30 minutes Generalised seizure Focal seizure Typically no recurrence within 24 hours May have repeat seizures within 24 hours Should be complete recovery within an hour children who have had a first seizure OR any features of a complex seizure should be admitted to paediatrics overall risk of further febrile convulsion = 1 in 3. However, this varies widely depending on risk factors for further seizure. These include: age of onset < 18 months, fever < 39ºC, shorter duration of fever before seizure and a family history of febrile convulsions if recurrences, try teaching parents how to use rectal diazepam or buccal midazolam. Parents should be advised to phone for an ambulance if the seizure lasts > 5 minutes regular antipyretics have not been shown to reduce the chance of a febrile seizure occurring Link to epilepsy risk factors for developing epilepsy include a family history of epilepsy, having complex febrile seizures and a background of neurodevelopmental disorder children with no risk factors have 2.5% risk of developing epilepsy

Answer 320

Approximately 10% of the UK population will have a seizure in their lifetime. After a first unprovoked seizure 30-50% will recur, after a second 70-80% will recur all children who have an afebrile seizure should be seen in a first fit or equivalent clinic within 2 weeks by a paediatrician with training in epilepsy take a thorough history including a detailed chronological history of events before, during and after the seizure. Obtain bystander accounts if at all possible (via telephone if required) Ask questions to rule in/out potential differentials e.g. vasovagal syncope, reflex anoxic seizures, cardiac causes, psychogenic events, vertigo. Particularly was there colour change, warning – feel dizzy, muffled sounds (suggests non epileptic event). Red Flags Head injury Drug, alcohol or toxin use Prolonged seizure >10 minutes Focal seizure – consider imaging Developmental delay or regression Required >1 dose of benzodiazepines Immunosuppressed Bleeding disorders Any safeguarding concerns Conduct a thorough investigation including a full neurological examination. Determine if the child is back to their usual self, ideally from parents/primary carer. Ensure observations including BP are normal for age. Red flags Systemically unwell Reduced GCS or not fully recovered Abnormal neurological findings Signs of raised ICP Signs of meningism Abnormal cardiac examination Ix Blood sugar – should be performed as soon as possible after the event on all children. ECG – a 12 lead ECG should be performed on all children presenting with history suggestive of generalised tonic clonic seizure activity. BP – should be performed on all children as part of routine observations. Consider blood gas – to check electrolytes. Bloods – only to be considered at the discretion of the specialist to exclude other diagnoses and determine an underlying cause of the epilepsy. EEG - an EEG is not routinely indicated after a first afebrile seizure as it lacks sensitivity and specificity and can be prone to misinterpretation. NICE recommendations are to use EEG to support a diagnosis of epilepsy in children where the clinical history suggests it after a second epileptic seizure and not to be used to exclude a diagnosis of epilepsy or in isolation to diagnose epilepsy Imaging – if there are acute concerns about focal neurological signs a CT would be the investigation of choice. If this is being considered, discussion with the paediatric team on call is important. MRI is the modality of choice in patients with epilepsy particularly if they develop epilepsy before the age of 2 years or have any suggestion of a focal onset If no ‘red flag’ features identified on history, examination or investigations and the child is back to their usual self consider discharge after: Ensuring there is a responsible adult to discharge the child to All the parental/ responsible adults concerns have been addressed Discussion of first aid in event of another seizure Discussion of safety net advice post seizure Provide written information Advise parents to video future events if safe to do so Refer children with suspected or confirmed epilepsy to a tertiary paediatric epilepsy service to be seen within 2 weeks, if they: are aged under 3 years are aged under 4 years and have myoclonic seizures have a unilateral structural lesion are showing deterioration in their behaviour, speech or learning.

Answer 321

level of awareness can vary in focal seizures. The terms focal aware (previously termed 'simple partial'), focal impaired awareness (previously termed 'complex partial') and awareness unknown are used to further describe focal seizures further to this, focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura Temporal lobe (HEAD) Hallucinations (auditory/gustatory/olfactory), Epigastric rising/Emotional, Automatisms (lip smacking/grabbing/plucking), Deja vu/Dysphasia post-ictal) Frontal lobe (motor) Head/leg movements, posturing, post-ictal weakness, Jacksonian march Parietal lobe (sensory) Paraesthesia Occipital lobe (visual) Floaters/flashes these ae also the seizure type most likely to give ictal bradycardia

Answer 322

Generalised tonic-clonic seizures sodium valproate second line: lamotrigine, carbamazepine Absence seizures* (Petit mal) sodium valproate or ethosuximide sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy Myoclonic seizures** sodium valproate second line: clonazepam, lamotrigine Focal seizures carbamazepine or lamotrigine second line: levetiracetam, oxcarbazepine or sodium valproate *carbamazepine may exacerbate absence seizures **carbamazepine may exacerbate myoclonic seizures carbamazepine shows auto-induction, meaning after initial success dose may need titrating up

Answer 323

carbamazepine - drowsiness, blurred or double vision, nausea, minor rash, DRESS, SJS, blood dyscrasias ethosuximide - appetite loss, nausea, drowsiness, headachem rash, blood dyscrasias gabapentin - drowsiness, dizziness, twitching, fluid retention, weight gain lamotrigine - dizziness, headache, blurred vision, fatigue, nausea, rash inc minor to SJS levetiracetam - psych/behavioural changes, irritability, fatigue, dizziness phenytoin - poor coordination, insomnia or fatigue, nausea, rash inc minor to SJS, gum overgrowth, hairiness, coarsening of facial features topiramate - sleepiness, dizziness, slowing of thought, paraesthesia, reduced appetite, kidney stones valproic acid - liver toxicity, weight gain, tremor, hair loss, SJS, blood dyscrasias esp thrombocytopenia vigabatrin - visual loss, fatigue, weight gain

Answer 324

Loading dose: 20 mg/kg by slow IV infusion over 60 minutes. Maintenance dose: 2 - 5 mg/kg/dose twice a day by slow IV infusion, or PO. Administer at a rate not faster than 1 mg/kg/minute Start maintenance 12 hours post loading dose Contraindications Sinus rhythm bradycardia, sinoatrial or atrioventricular block If used for maintenance therapy: Monitor: Liver function and full blood count. Therapeutic Drug Monitoring (TDM): Time to steady state: 7 - 10 days (highly variable). Check trough levels at least 12 - 24 hours after IV loading dose and at regular intervals during maintenance therapy As saliva and serum levels show good concordance you can monitor using saliva sample

Answer 325

facial features seen in FVS are trigonocephaly, tall forehead with bifrontal narrowing, epicanthic folds, infraorbital groove, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, antiverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip, small downturned mouth may also see spina bifida, congenital heart defects, cleft lip and/or cleft palate, genital abnormalities, skeletal abnormalities, and developmental delay foetal phenytoin syndrome: IUGR may be seen, also minor dysmorphic craniofacial features (microcephaly, facial clefting, a broad nasal ridge, hypertelorism, epicanthal folds) and limb defects including hypoplastic nails and distal phalanges. Heart defects including ventricular septal defect, atrial septal defect, patent ductus arteriosus and coarctation of the aorta may occur in these children. A smaller population will have growth problems and developmental delay, or intellectual disability. Cleft lip and palate can be seen.

Answer 326

mechanism not fully clear but binds to SV2A, a synaptic vesicle glycoprotein, and inhibits presynaptic calcium channels, thus acting as a neuromodulator to reduce NT release common side effects of levetiracetam include sleepiness, dizziness, feeling tired, emotional lability, anxiety or depression, and aggression. Severe side effects may include psychosis, suicide, and allergic reactions such as SJS/TEN or anaphylaxis. Note due to the mental health effects might want to be cautious or try something else if significant mental health history loading dose is 40-60mg/kg max 3.5g (in kids do 40mg/kg max 3g -> note can load even if on regularly)

Answer 327

brief episode of temporary paralysis after an individual has a seizure - lasting from 30 mins to 36 hours (mean 15 hours), and partial or complete but usually unilat really broader though as the deficit follows wherever the focal seizure was - can be motor but also eg neglect, numbness, gaze palsy, psychosis, aphasia, amnesia, confusion or drowsiness; can follow focal with secondary generalisation too ct angio will be normal but ct perfusion may show hypoperfusion of the focus and T2/FLAIR may show bright area of oedema at the focus besides stroke need to consider hemiplegic migraine, stroke, hypoglycemia, hemiconvulsion, psychogenic seizure, or nonconvulsive status prognosis very good, self-resolves and just needs supportive treatment

Answer 328

6mo-6yr, seizure up to 10 mins, usually 2-3mins, of tonic-clonic type; may have foaming of mouth, pallor, cyanosis; irritability, drowsiness, confusion for up to 1 hr after; can follow vaccine inc pertussis, but unlikely another vaccine will trigger assess for fever red flags, meningitis etc; seizure can occur before or after fever, usually 24hrs before; do they attend daycare (source of infection) and have they been on antibiotics (may mask signs of infection) family history; gcs, neuro signs, temp and vitals, fluid status, signs of febrile illness cause; blood gluc if child having seizure or cant be roused; urinalysis if unclear source of fever diffs inc meningitis, delirium, rigors (no loc or involvement of facial muscles eg eyes rolling back); w/o fever may be syncope, breath holding spell, hypo, metabolic disorder, head injury, drug overdose, epilepsy, neurocutaneous syndromes monitor duration, cushion head with hands or soft material, remove harmful objects, dont restrain or put things in mouth, in recovery position once stopped; >5mins call ambulance or give benzo rescue med if rec seizures and specialist advised - call ambo if buccal midazolam or rectal diazepam hasnt helped after 10 mins, but can repeat dose immediate paeds assessment if first presentation, or subsequent w/o specialist assessment; <18mo, FND, features of complex seizure, recent abx, parental anxiety, no apparent source of infection; metabolic or neurocut disorder or dev delay; ambulance if meningitis, pneumonia, sepsis around 1 in 3 will have another seizure; no proph antipyretics, complete all immunisations

Answer 329

malforms like hamartomas, mening, encep, cysticerc, trauma, electrolyte abnorm, metabolic disorders are some causes; TV and lack of sleep two common triggers presenting with seizures needs cardio, neuro, dev, mental state assessment absence/petit mal more common in kids: up to 100 episodes a day of freezing and staring, may look pale and flutter eyelids, stops after a few seconds; may droop head and have some clonic movements of arms; 1/3 pts will have some tonic-clonic convulsions; infantile spasms - clusters of myoclonic spasms when waking up in infants ages 4-8mo dravet's syndrome - severe febrile or afebrile hemiclonic or generalised seizures w/ status epilepticus in previously healthy infant, onset by 15mo, multiple seizure types oft resistant to AEDs, also dev arrest or regression juvenile myoclonic epilepsy - early morning myoclonic jerks, later GTC, in teens, may have autosom dom inheritance; seizures worsened/more likely if sleep deprived or had alcohol; EEG in untreated individuals is typically abnormal with a specific EEG pattern, known as a 3-6 Hz generalized polyspike and wave discharge; valproate/keppra/lamotrigine; generally AEDs needed lifelong panayiotopoulos syndrome - onset around 3-6yo, prolonged seizures with autonomic features and mainly ictal vomiting; shifting or multiple foci on eeg; may be confused with occipital epilepsy or eg enceph, atypic migraine, syncope benign rolandic epilepsy - nocturnal seizures with face twitching and aphasia, children 4-10yo, may have GTC eeg after second seizure to support clinical diagnosis, not in cases of probable syncope as maybe false pos; photic stim and hypervent to try and induce; sleep eeg through melatonin or sleep dep if standard didnt help diagnosis MRI for structural causes monotherapy; if AEDs not helping can try ketogenic diet, vagus nerve stim, various surgical resections and cuts review 3-12monthly beware possibly high impact on education and support needed for this

Answer 330

SCN1A (sodium voltage-gated channel alpha subunit 1) seizure disorders encompass a spectrum that ranges from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end In most cases, including in Dravet syndrome, the variants are “loss of function,” which means that the variant leads to a non-functional sodium channel in cells called interneurons. Interneurons normally suppress brain cells from generating electrical activity, but in the presence of the SCN1A variant, they are no longer able to adequately suppress electrical activity, leading to a predisposition to seizures. Less commonly, SCN1A variants are “gain-of-function” and affect neurons directly When the following suggestive features are present, SCN1A molecular genetic testing should be considered: Precipitation of seizure with fever, warmth, or vaccination Prolonged or hemiconvulsive seizures Seizure provocation with overstimulation or flashing/patterned visual stimulus Worsening of seizures with medications that inhibit sodium channel function as the primary mechanism of action (e.g., carbamazepine, oxcarbazepine, phenytoin, lamotrigine)

Answer 331

Atonic seizures are also known as drop attacks. They are characterised by brief lapses in muscle tone. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy hyperventilation and sleepiness can bring on epilepsy both arms or eg left arm right leg are psychogenic -> how could the electrical discharge spread to only affect both arms but spare legs for eg steroids and vigabatrin -> west syndrome

Answer 332

sudden fall without loss of consciousness - so by definition exclude syncopal falls neurologic causes inc atonic seizures (lennox gastaut), falls triggered by myoclonic seizure, laugh/cough triggered epilepsy, cataplexy, breath holding spells, pure autonomic failure (including parkinsons related); periodic paralysis, startle reactions, disorders of sensation in the lower limbs or causes of weakness eg myopathies or MG vascular causes: TIA, migraine, basilar insufficiency or posterior circulation spasm/occlusion vestibular syncope, inc menieres spinal cord trauma or a brainstem mass hypoglyc/calc/mag, toxicity with a sedating drug panic attack, conversion disorder, functional, or malingering

Answer 333

Breath holding spells are also known as breath holding attacks. They are involuntary episodes during which a child holds their breath, usually triggered by something upsetting or scaring them. They typically occur between 6 and 18 months of age Cyanotic breath holding spells occur when the child is really upset, worked up and crying. After letting out a long cry they stop breathing, become cyanotic and lose consciousness. Within a minute they regain consciousness and start breathing. They can be a bit tired and lethargic after an episode breath holding attacks are associated with iron deficiency anaemia, so test and treat - some studies are showing supplementation to be beneficial even if not anaemic so could be done for everyone if more evidence found Reflex anoxic seizures occur when the child is startled. The vagus nerve sends strong signals to the heart that causes it to stop beating. The child will suddenly go pale, lose consciousness and may start to have some seizure-like muscle twitching. Within 30 seconds the heart restarts and the child becomes conscious again

Answer 334

Reflex anoxic seizure describes a syncopal episode (or presyncope) that occurs in response to pain or emotional stimuli. It is thought to be caused by neurally-mediated transient asystole in children with very sensitive vagal cardiac reflexes. It typically occurs in young children aged 6 months to 3 years Typical features child goes very pale falls to floor secondary anoxic seizures are common rapid recovery There is no specific treatment and prognosis is excellent

Answer 335

In infantile spasms the child will become distressed between spasms, whereas in colic the child will become distressed during the 'spasms' Infantile colic describes a relatively common and benign set of symptoms seen in young infants. It typically occurs in infants less than 3 months old and is characterised by bouts of excessive crying and pulling-up of the legs, often worse in the evening. Infantile colic occurs in up to 20% of infants. The cause of infantile colic is unknown. NICE Clinical Knowledge Summaries do not recommend the use of simeticone (such as Infacol®) or lactase (such as Colief®) drops.

Answer 336

lead poisoning - old house or other way for old paint flake ingestion? asian cosmetics (surma) or imported medicine? neuro features sec to cerebral oedema from inc'd cap perm and vasculitis; avoid LP, serum lead level is diagnostic lead chelation, reduce oedema, anticonvulants to prevent fitting

Answer 337

by eg anticonvulsants like phenytoin may see megaloblastic anaemia due to enhanced folate metabolism, or rickets due to vit D metabolism ofc will also see some drugs not as effective

Answer 338

Subependymal grey matter heterotopia, also known as periventricular heterotopia, is the most common form of grey matter heterotopia and is characterised by nodules of grey matter located immediately beneath the ependyma of the lateral ventricles may be: unilateral focal bilateral focal bilateral diffuse: an undulating band of grey matter surrounding the ventricles the majority of cases are sporadic, some are X-linked recessive as with other grey matter heterotopias, subependymal heterotopia is thought to result from interruption of normal neuronal migration usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability

Answer 339

beta lactam abx interact with the GABAA receptor to interfere with the inhibitory effects of GABA in a concentration-dependent manner, but CNS penetration of penicillins and cephalosporins low so normally only a problem if high doses or renal failure; carbapenems cross better so are a bit higher risk, and they can dec valproate conc; meropenem especially can provoke seizures via this route isoniazid lowers by blocking pyridoxine metabolism that leads to GABA synthesis; mefloquine and chloroquine also can macrolides and tetracyclines don't but note metabolism oft affected by AEDs via enzyme inhib/induction methylxanthines potently lower seizure threshold via adenosine receptor antag and can be hard to treat as also antag BZDs clozapine and second gen antipsychs lower threshold (may need prophylactic AEDs if known to have seizures when started on one) but aripiprazole doesnt and risperidone is also fairly safe; of first gen, haloperidol is actually pretty safe but it does technically lower the seizure threshold so be cautious, levomepromazine also lowers seizure threshold so be cautious tramadol, aspirin, diclofenac also lower threshold; all opioids can do, but especially alfentanil/fentanyl (others may be protective against seizures in low doses)

Answer 340

status epilepticus without a prominent (clinically obvious) motor component. NCSE may have zero motor components, or it may correlate with subtle movements range of causes of NCSE is broad. Overall, these resemble the range of causes of convulsive status epilepticus may manifest in a variety of ways, which will often be mistaken for other disorders, eg: Confusion, obtundation, or coma. Unexplained fluctuations in mental status. Aphasia, paraphasic errors. Mutism, reduced verbal fluency. Echolalia. Stuttering. Psychosis. Mood disturbance. Fear/agitation. Subtle rhythmic twitching (especially involving the face or eyes). Automatisms (e.g., lip smacking, chewing). Catatonia (more on this in the section below). Gaze deviation. Limb paralysis. Hallucinations (olfactory, gustatory, auditory, visual). Blindness. Sensory disturbance and pain (including headache). clues: Epilepsy or prior seizures (especially status epilepticus followed by a prolonged or unusual postictal period with lingering neurological abnormalities). Otherwise unexplained stupor/coma, especially with fluctuating mental status. Known supratentorial structural brain disorder Ocular abnormality: Subtle blinking or eyelid twitching. This may be unmasked by gentle, partial opening of the eyelids. Pupil dilation, sometimes associated with hippus (fluctuations in pupil size). Horizontal nystagmus. Gaze deviation. Subtle motor activity, often involving the face or eyelids. NCSE tends to cause facial or synchronous myoclonus with synchronized activity of multiple muscles (whereas toxic/metabolic encephalopathy tends to cause asynchronous, multifocal myoclonus). Among the various indications for EEG monitoring, facial and periorbital twitching is especially likely to correlate with an actual seizure. Automatisms (e.g., lip smacking, chewing). Autonomic disturbances (e.g., mydriasis, diaphoresis, hypertension, flushing). Inability to follow any commands. vs toxins or postictal state, EEG can differentiate: EEG findings expected in (toxic) encephalopathy include diffuse slowing or a burst-suppression pattern, in postictal states, EEG should show background slowing or suppression generally rx would be with keppra, unless continuation of active status in which case manage as per status pathway as ongoing status

Answer 341

consider focal frontal lobe seizures, temp lobe epilepsy can present like this, epilepsy-induced confusional state if first time could be acute confusional state due to drugs or anxiety; could be acute psychosis due to schizophrenia, manic depression

Answer 342

Self-limited (familial) neonatal epilepsy usually starts in babies between 2 and 7 days old, and often there will have been a history of similar seizures in one of the parents - hence it's good to ask parents to check with the grandparents if either had seizures when young In most babies or infants the seizures stop within 6 weeks, and almost always within 6 months. Up to one third of individuals have seizures in later life, which may include febrile seizure focal motor seizures usually which can alternate which side theyre on and be tonic or clonic, normally brief, and cluster over hours or days; automatisms can be seen and may generalise; autonomic features in 1/3 of cases such as apnoeas and cyanosis AD inheritance with incomplete penetrance but may be de novo; pathogenic variants in KCNQ2 commonest cause, then KCNQ3 and SCN2A SELFEs are self limited focal epilepsies of childhood 20% of epilepsies in CYP Types include focal epilepsy with centrotemporal spikes (rolandic), self limited epilepsy with autonomic features (panayiotopoulos syndrome), photosensitive occipital lobe epilepsy, and childhood visual occipital seizures (gastaut type)

Answer 343

~20% of childhood epilepsy cases between 3-13 but peak incidence 7-10 15% of time has FH aka self limited epilepsy with centrotemporal spikes aka SELECTS seizures nocturnal but may occur on waking, often start with tonic contractions of tongue/cheek/lips on one side + drooling and grunting, slurred speech if awake but grunting during sleep may alert parents or siblings that something is unusual may progress to generalised fit EEG shows high amplitude spikes in left centrotemporal region (rolandic spikes) intelligence is normal, spontaneously remits by 16yo, treated with carbamazepine

Answer 344

acute signs like seizures, poor feeding, vomiting, lethargy, irritability more chronic eg dev delay, mental retardation perhaps periodically punctuated by acute sx dont forget accidental poisoning (is kid likely to be less well supervised eg single parent, house move, new pregnancy, known to social services etc) - commonest signs inc confusion, sleepiness, lethargy, headache, vomiting, extensor plantars, FNS, seizures, coma common causes of encephalopathy in children: viral, head trauma, drug ingestion, intracranial bleed, SOL, metabolic disorders besides urine/blood drug screen do cultures, FBC, U&Es, blood ammonia, head CT, EEG treat with broad spectrum abx, aciclovir, consider dexameth, fluid restriction, anticonvulsants

Answer 345

an atypical encephalopathy seen almost exclusively in previously healthy young children or infants of East Asian descent though cases have been reported around the world While most commonly reported in young children, it can also affect adults. Although the most commonly found infectious trigger is influenza, other pathogens, including SARS-Cov-2 and human herpes viruses, have been associated with ANE key characteristic is the acute development of multifocal bilateral and symmetrical necrotic lesions, most commonly involving the deep gray matter. Seizures are commonly reported (up to 50% of cases), and intracerebral hemorrhage, cerebral edema, and coma can develop Fever is present in about 2/3 of cases, and systemic manifestations, including respiratory failure, liver dysfunction, and diarrhea can also occur. A systemic inflammatory response syndrome leading to multiple organ failure has been reported MRI reflects edema, necrosis, and in some cases, hemorrhage in the deep gray matter, and deep hypointensities on CTH (rapidly evolving so first scan may look normal) ANE must be distinguished from a number of other conditions that can result in acute neurologic manifestations and deep gray matter abnormalities on imaging. Japanese encephalitis virus and other neurotropic arboviruses can directly invade the CNS and account for a similar clinical picture, as can toxic disorders such as carbon monoxide poisoning, mitochondrial disorders such as Leigh disease, and vascular conditions such as deep venous sinus thrombosis may need AEDs, resp support, and try steroid +/- IVIg, cover with antivirals, may need medication to manage spasm and dystonia eg diazepam, and will need rehab and careful follow up

Answer 346

AD inheritance on cr9 w 70% being new mutations sclerotic tubers throughout brain tissue can cause seizures in infancy (mainly infantile spasms and later eg myoclonic); mental retardation and dev delay common tuberous obstruction may cause hydrocephalus in skin see adenoma sebaceum, ash-leaf macules, shagreen patches and ungual fibromas; sometimes cafe au lait macules, retinal phakomas kidney cysts and angiomyolipoma and in heart rhabdomyomas control the seizures

Answer 347

Identification of a pathogenic variant in TSC1 or TSC2 is sufficient for the diagnosis or prediction of TSC regardless of clinical findings; this is important because manifestations of TSC are known to arise over time at various ages a “pathogenic” variant is one that clearly prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins (e.g., nonsense or frameshift variants, large genomic deletions) or is a missense variant whose effect on protein function has been established by functional assessment. SC1 and TSC2 variants whose effect on protein synthesis or function is less certain are not definitely pathogenic and would not be considered diagnostic unless supported by additional ACMG criteria for pathogenicity Between 10% and 15% of patients with TSC meeting clinical diagnostic criteria have no mutation identified by conventional genetic testing. Therefore, failure to identify a pathogenic variant in TSC1 or TSC2 does not exclude a diagnosis of TSC. High-read-depth approaches in next-generation sequencing (NGS) demonstrate low-level mosaic pathogenic variants in some individuals with clinical signs of TSC in whom standard NGS or pre-NGS testing proved normal. Although mosaic individuals may experience fewer findings of TSC, they may develop any manifestation of TSC and are at risk to have offspring who are nonmosaic for TSC so diligent surveillance and genetic counselling still warranted Major criteria- Hypomelanotic macules (≥3; at least 5 mm diameter) Angiofibroma (≥3) or fibrous cephalic plaque Ungual fibromas (≥2) Shagreen patch Multiple retinal hamartomas Multiple cortical tubers and/or radial migration lines Subependymal giant cell astrocytoma Cardiac rhabdomyoma Lymphangioleiomyomatosis (LAM)* Angiomyolipomas (>2)* Minor criteria- Multiple renal cysts Non-renal hamartomas Sclerotic bone lesions Retinal achromatic patch >/=2 Intra-oral fibromas >3 Dental enamel pits Confetti skin lesions may see: papular salmon-coloured eruption in butterfly pattern over the cheeks/chin/forehead especially in the nasolabial folds (adenoma sebaceum: facial angiofibromas) hypertrophic gums (phenytoin/ciclosporin use) there may be signs of dialysis or renal transplant Major ddx: Neurofibromatosis type 1, von hippel landau disease, if presenting with only one sx may be ddx for that eg vitiligo for skin lesions, isolated cardiac myxoma etc inherited in an AD fashion but there are many sporadic cases (only a minority of patients have a known family history of TSC) Due to defect in chromosome 9 TSC1 gene (hamartin) and chromosome 16 TSC2 (tuberin) a phakomatosis/neurocutaneous syndrome resulting in hamartomas of the skin, brain, kidneys, retina, heart, lungs, liver and bone The TSC2:TSC1 heterodimer serves as a nexus for integrating the energy status of the cell with nutritional availability and extracellular growth factor signalling, being phosphorylated or dephosphorylated as a downstream part of many signalling pathways; for instance, Insulin or insulin-like growth factors (IGFs) inhibit the TSC2:TSC1 complex primarily through Akt-mediated phosphorylation and inactivation of TSC2; the complex is also activated by AMPK the primary function of the TSC1–TSC2 complex is as a critical negative regulator of mTOR activation, thus you get excessive signalling through this pathway when loss of function mutations in TSC1/2 occur and this leads to aberrant growth giving hamartoma formation this explains why mTOR inhibitors are used in TS, with everolimus (a rapamycin analogue) the one normally used

Answer 348

Offer genetic testing to all patients, or: * If genetic testing cannot be offered to all patients, offer it for reproductive counselling or when a TSC diagnosis is likely but cannot be clinically confirmed. Obtain a three-generation family history Perform MRI of the brain to assess for the presence of sub-ependymal giant cell astrocytoma (SEGA) or other lesions. Assess for neuropsychiatric and neurodevelopmental disorders. For people with suspected epileptic seizure activity: * Perform a standard electroencephalogram (EEG). * If a standard EEG does not explain changes in sleep, behaviour, or cognitive or neurological function, perform 24-hour video EEG. For children: * Teach parents how to recognise infantile spasms and focal seizures. * Repeat EEG urgently if there is a suspicion of seizures. Perform MRI of the abdomen to check for the presence of angiomyolipoma (AML), renal cysts or other renal lesions Combine brain and abdominal MRI scans when possible. When scanning the abdomen to assess the kidneys, also check for lesions in the liver, pancreas and other abdominal organs. Take blood pressure. Assess baseline GFR Provide advice about the risks associated with smoking. For adolescent and adult females: * Provide advice to avoid the use of oestrogen (for example, oestrogen-containing contraceptives) if possible. For females of child-bearing age: * Perform baseline high-resolution chest computed tomography (HRCT). For adult males who are symptomatic: * Perform baseline high-resolution chest computed tomography Perform a detailed clinical dermatological examination, including an investigation using Wood’s light Perform a detailed clinical dental examination, looking for abnormal tooth eruption, dental pits and oral fibromas Perform an electrocardiogram (ECG) to check for arrhythmia and conduction abnormalities. For all children: * Perform an echocardiogram to check for rhabdomyomas Perform a complete ophthalmological evaluation, including dilated fundoscopy, to assess for retinal lesions and visual field deficits

Answer 349

Offer first-degree relatives a clinical assessment and, where possible, genetic testing (unless this has already been done at diagnosis) For patients who do not have a sub-ependymal giant cell astrocytoma (SEGA) and are younger than age 25 and without symptoms that suggest raised intracranial pressure: * Perform MRI of the brain every 1–3 years For all patients who do have a SEGA and are without symptoms that suggest raised intracranial pressure: * Perform MRI of the brain every 1–3 years. Perform MRI scans more frequently for patients with a large or growing SEGA, or for patients with a SEGA causing ventricular enlargement who remain asymptomatic It is believed that the majority of SEGA lesions stop growing in the third decade of life and MRI scans will often be stopped in adulthood If enlarging or sx: raised intracranial pressure, new or progressing neurological problems, or TSC-associated neuropsychiatric disorders (TAND) and other significant deterioration in epilepsy or TAND problems. Then discuss in multidisciplinary team that includes oncologists, neurologists, neuroradiologists, neurosurgeons and TSC experts Offer surgery as first-line treatment for a growing SEGA, but in choosing surgery or an mTOR inhibitor, take into account TSC comorbidities and the wishes of the patient and (as appropriate) their family Offer everolimus to patients who have at least one SEGA lesion of baseline longest diameter 1cm as assessed by multiphase MRI that is not amenable to surgery For neurodev/psych: Use the TAND checklist at each annual review Treat anxiety, depression, ASD, learning disorders as you otherwise would if detected Need comprehensive developmental assessments at infancy, pre-school, junior school, adolescence Epilepsy Ix as in other card, then: Infantile spasms * The recommended first-line therapy is vigabatrin. If treatment with vigabatrin is unsuccessful, offer hormonal (adrenocorticotropic hormone or prednisolone) treatments Refractory focal seizures Seizures are considered to be refractory (also known as uncontrolled or intractable) when 2 different antiepileptic drugs given at therapeutic doses have failed to control a person’s seizures. * After considering epilepsy surgery or a vagal nerve stimulator, offer everolimus for refractory focal onset seizures associated with tuberous sclerosis complex in patients aged 2 years or older Ensure the risk of sudden unexpected death in epilepsy (SUDEP) is discussed with patients and families For patients who have renal lesions: * Regardless of need for a general anaesthetic, carry out annual MRI of the abdomen to assess for the progression of AML, renal cystic disease, and occurrence of renal cancer (which is rare). * If MRI scanning cannot be performed (for example, patients with a vagal nerve stimulator may not be able to have an MRI scan), use fast low-dose CT scanning. * If the MRI (or CT) scan shows anatomy and pathology that are judged to be easy to interpret by ultrasound scan, then the next 1 or 2 scans could be done by ultrasound. * Continue imaging throughout the life of the patient. For patients who do not have renal lesions: * Carry out imaging as above every 1–3 years through childhood and early adult life Annual BP and GFR check For renal angiomyolipomas (AMLs) presenting with acute haemorrhage, use embolization with a short course of corticosteroids as first-line therapy. Make every attempt to avoid nephrectomy. For asymptomatic, growing AMLs larger than 3cm in diameter, use an mTOR inhibitor as firstline therapy, selective embolisation or kidney-sparing resections are possible second-line therapies When carrying out MRI or CT scans to monitor kidneys, assess the liver, pancreas and the rest of the abdomen for lesions as well Surveillance for lymphangiomyomatosis (LAM) For asymptomatic females of childbearing age: * Carry out high-resolution chest computed tomography (HRCT) every 5–10 years if there is no evidence of lymphangioleiomyomatosis (LAM) on the baseline HRCT. * Continue this surveillance regimen until menopause. For patients with LAM detected on HRCT: * Carry out annual pulmonary function testing For patients with LAM who have evidence of progressive loss of lung function, treat with mTOR inhibitors For all adolescent and adult females: * Provide advice to avoid the use of oestrogen (for example, oestrogen-containing contraceptives) if possible Advise patients and families to use sunblock (SPF 30+) routinely Treat facial angiofibromas with topical mTOR inhibitors or laser. * Consider surgical excision for larger solitary lesions. Consider surgical excision for ungual fibromas that are causing problems Patients should have an oral evaluation every 6–12 months, in line with surveillance recommendations for the general population For asymptomatic patients with cardiac rhabdomyomas: * Take an echocardiogram once every 1–3 years until complete regression of cardiac rhabdomyomas or until the first sign of progression For all patients: * Carry out a 12-lead ECG at least every 3–5 years Patients with hemodynamic instability and/or life-threatening arrhythmia should be treated with antiarrhythmic medications, surgery or mTOR inhibitors * Carry out regular fundoscopy by direct ophthalmoscopy examination during each clinic visit.

Answer 350

sudden unexpected death in epilepsy Each year, more than 1 in 1,000 people with epilepsy die from SUDEP. This is the leading cause of death in people with uncontrolled seizures. occurs most often at night or during sleep when the death is not witnessed - there may be evidence that a person had a seizure before dying, but this isn’t always the case generally considered to result from seizure-related cardiac dysfunction, respiratory depression, autonomic nervous dysfunction, or brain dysfunction: Cardiac-related mechanisms include reduction in heart rate variability and prolongation of QT interval, which can lead to arrhythmias. Laryngospasm and amygdala activation may cause obstructive and central apnoea, respectively. Pulmonary oedema is found in some SUDEP patients (known to follow GTCS) Neural mechanisms include impairment of 5-HT and adenosine neuromodulation which further contribute to respiratory dysfunction best way to prevent SUDEP is to lower your risk by controlling seizures

Answer 351

Seizure lasting >5mins Call for senior help - priority call too High flow O2 Establish IV access Take bloods (ABG, FBC, CRP, culture, U&Es, bone profile, Mg, glucose) Rule out hypoglycaemia, hypoxia, acidosis Pre-hospital setting: Rectal diazepam OR buccal midazolam (can repeat dose after 15 mins - switch admin form) Once IV access is established : IV lorazepam 0.1mg/kg max 4mg, 15 mins later repeat dose; 10mg IM midazolam is equiv efficacious to 4mg loraz, can also look at buccal and rectal routes as above if 2 benzos of any form ineffective then IV leviteracetam 40-60mg/kg (as benzo sensitivity decreases early in status due to changes in GABA subunit expression) it's important not to underdose here even in kids give 40-60mg/kg up to max 4.5g, or can try 20mg/kg phenytoin (if works suggest seizure is NaV inhibitor responsive) then rapid sequence induction with propofol, midazolam etc So they've stopped fitting, but still drowsy? This is the expected post-ictal state. Support their airway and give oxygen if required, they should slowly start to regain consciousness and recover. Huge lactic acidosis on the blood gas and you're freaking out? Due to extensive muscle activity in tonic-clonic seizures, protracted fits often lead to significant lactic acidosis. Supportive therapy with fluids and hydration is enough and this should resolve on its own. If there's no recovery or you're concerned about non-convulsive seizures, treat as you would convulsive SE and seek senior support. note v high doses of benzos can cause somnolence, respiratory depression, and hypoxia -> if post ictal state seems prolonged; also worth checking paCO2 in case they are retaining eg seizure caused them to lose airway and still not maintaining or else some other pathology going on behind the scenes; short acting drugs and appropriate doses help avoid this, and if needed flumazenil could be given (but only in extremis as risk of going back into status is high, better to give supportive therapy inc intubation)

Answer 352

Beta-lactam antibiotics, including penicillins, cephalosporins and carbapenems, interact with the GABAa receptor to interfere with the inhibitory effects of GABA in a concentration-dependent manner; however their CNS penetration is usually low so need high does for eg CNS infection; exception is carbapenams that penetrate well; they also, esp meropenem, reduce valproate levels isoniazid inhibs enzyme that produces co-factor for GABA synthesis; seizure threshold thus lowered, treated by giving pyridoxine (the co-factor) + benzos mefloquine, chloroquine, ciproflox can trigger seizures theophylline/aminophylline can lower seizure threshold quite a bit via A1r antag clozapine and many other second gen antipsychs do, valproate as adjunct can help prevent this + is mood stabiliser low dose lidocaine raises seizure threshold and high dose lowers it; low doses of propfol/thiopentone can trigger and higher doses suppress bupropion, opioids lower seizure threshold (esp former)

Answer 353

it is important to distinguish true seizures (movements that are the result of a change in the electrical activity in the brain) from movements of differing aetiology, often physiological in many cases, and some of which may result in (rather than be caused by) changes in electrical activity ddx to consider: neonatal jitters benign neonatal sleep myoclonus - can be distinguished from epileptic myoclonus by the fact the jerks occur only during sleep, and settle on arousal, ceasing abruptly on waking; EEG is normal; tend to be b/l and repetitive but may be focal or multifocal; BNSM onset happens mostly in first 2 weeks of life, and the majority resolve by 3 months age and it is seen to occur in all stages of sleep; apnoeas syncopal attacks - breath holding spells, reflex anoxic seizures, and arrhythmias GORD - inc sandifers syndrome hyperekplexia - rare AD disorder seen in neonates characterised by generalised muscle rigidity, excessive startle, sometimes tonic spasms; it can be quite profound resulting in hypoxic seizures and may require intubation, triggers inc bathing in room temp water paroxysmal extreme pain disorder - utonomic phenomena, commonly flushing, associated with stiffening, in most resulting in tonic spasms. This is commonly associated with bradycardia or asystole leading to a syncopal episode. In the older child it becomes apparent they are characterised by attacks of deep burning pain alternating hemiplegia of childhood - presents before 18mo, repeated episodes of prolonged hemiplegia involving either side of the body or bilateral hemiplegia, as well as other paroxysmal events, especially eye movements that may accompany or be seen in isolation to the hemiplegia. The presenting clinical features are often paroxysmal eye movements noted in the first three months of life other physiological movements eg dysconjugate eye movements, or even episodes of eye rolling - EEG monitoring may be required and have low threshold for this if infant at risk

Answer 354

In term infants, the most common causes of seizures are HIE, ischaemic stroke and intracranial haemorrhage In extremely preterm infants, the most common cause is intracranial haemorrhage IEM are a rare cause of seizures but important to consider in treatment resistant seizures also consider encephalitis, meningitis,hypoglycaemia, hypocalcaemia/ hypomagnesaemia, hypernatraemia/ hyponatraemia, withdrawal from sedatives or barbiturates/opioids/alcohol, cortical dev malform, neurocut syndromes (TS, sturge weber, incontinentia pigmenti), Neonatal epileptic syndromes / Epileptic encephalopathies (Ohtahara syndrome, early myoclonic encephalopathy In the newborn, there is the unusual problem of electro-clinical dissociation. Only around one third of term infants with electrical seizures have overt clinical signs. 70% of abnormal movements have no correlating EEG seizure activity first line ix: Sodium (U&E), glucose, ionised calcium, magnesium, phosphate, LFT, blood gas (pH, bicarbonate, lactate), bilirubin FBC, coagulation screen CRP, blood culture, HSV PCR Urine culture Toxicology screen if appropriate (request maternal also) CSF: Paired (plasma and CSF) glucose Cell counts and differential Glucose and total protein HSV PCR, Enterovirus PCR Gram stain and culture aEEG (CFM, if available) EEG Cranial ultrasound Urgent CT scan if focal neurology and intracerebral bleed suspected second line: Bloods Carnitine, acylcarnitine, TFT, carbohydrate deficient transferrin, biotinidase enzyme activity, ammonia, lactate, Urate, pyruvate, amino acids, TORCH titres Urine Reducing substances, sulfites, organic and amino acids, alpha aminoadipic semialdehyde CSF Lactate, amino acids, (CSF neurotransmitter profile in consultation with paediatric neurology) MRI, MRA/MRV Due to the high frequency of EEG-only seizures, continuous aEEG or EEG monitoring should be commenced if seizures are suspected Provide ABC resus and treat cause if found Treat seizures if: * A single isolated seizure lasts ≥3 mins or ≥3 seizures per hour * Treat seizures associated with cardiorespiratory compromise Generally treat with phenobarbitone, then rpt, then phenytoin, then eg levetiracetam then midazolam + intubate if not already -> follow local guidelines Most seizures in the neonatal period are acute symptomatic and seizure burden is finite; greatest soon after injury. Hence anticonvulsant medication should be discontinued after the seizures have stopped and the neurological examination has normalised or is normalising. If the seizures are suspected to be due to a neonatal epilepsy syndrome, this should be managed in conjunction with tertiary paediatric neurologists Investigations for vitamin-responsive epilepsies and a therapeutic trial of vitamins should be given for refractory neonatal seizures where no other cause has been identified (in conjunction with tertiary paediatric neurologists). Pyridoxine may cause apnoea or cerebral depression in those with pyridoxine dependant seizures especially if they have received anticonvulsants, therefore careful observation is required Besides pyridoxine consider folinic acid, biotin, pyridoxal phosphate

Answer 355

molybdenum cofactor deficiency is disease in which the absence of molybdopterin – and consequently its molybdenum complex, commonly called molybdenum cofactor – leads to accumulation of toxic levels of sulphite and neurological damage sx include early seizures, low blood levels of uric acid, and high levels of sulphite, xanthine, and uric acid in urine. Additionally, the disease produces characteristic MRI images infants may also experience increased or decreased muscle tone, difficulty feeding, abnormally high fussiness, exaggerated startle, microcephaly, coarse facial features, and eye lens dislocation glut1 deficiency is an autosomal dominant genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier; characterized by an array of signs and symptoms including mental and motor developmental delays, infantile seizures refractory to anticonvulsants that often begin between 3mo and 6mo, ataxia, dystonia, dysarthria, opsoclonus, spasticity, other paroxysmal neurologic phenomena and sometimes deceleration of head growth also known as microcephaly A low glucose value in CSF (<2.2 mmol/L) or lowered CSF/plasma glucose ratio (<0.4)are indicative of GLUT1 deficiency. A genetic mutation in the SLC2A1 gene confirms the diagnosis; ketogenic diet can control seizures pyridoxine dependent seizures characterized by intractable seizures in the prenatal and neonatal period which do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of vitamin B6 and remission from seizures are often maintained on daily therapeutic doses. can do two trials with EEG monitoring to check for seizure remission. intellectual disability is frequently seen in patients with PDE. Because the affected enzyme antiquitin is involved in the cerebral lysine degradation pathway, lysine restriction as an additional treatment modality has recently been explored. diagnosis of PDE-ALDH7A1 is suspected in a proband with seizures responsive to pyridoxine administration and increased concentration of alpha-aminoadipic semialdehyde (α-AASA) in urine and/or plasma. The diagnosis is established in a proband with suggestive clinical findings and biallelic pathogenic (or likely pathogenic) variants in ALDH7A1 identified by molecular genetic testing Pyridox(am)ine 5'-Phosphate Oxidase Deficiency - In classic PNPO deficiency, seizures (including status epilepticus) often begin on the first day of life and typically before age two weeks. In both classic and late-onset untreated PNPO deficiency, seizure semiology varies from myoclonic to clonic or tonic seizures, and seizures are typically resistant to common anti-seizure medications. Independent of age of onset, seizures respond to life-long treatment with a B6 vitamer: pyridoxal 5'-phosphate (PLP) in about 60% of affected individuals and pyridoxine (PN) in about 40%. diagnosis of PNPO deficiency is established in a proband with suggestive findings (i.e., infantile onset of a wide range of seizure types resistant to common anti-seizure medications and a positive standardized vitamin B6 trial) and (most commonly) biallelic pathogenic variants in PNPO identified by molecular genetic testing or deficient PNPO enzyme activity. Lifelong oral vit B6 Biotin deficiency A B vitamin complex (B7) that acts as a coenzyme for 4 carboxylation reactions Inefficient pyruvate carboxylase results in a buildup of lactic acid and alanine Propionate, 3-OH propionate, and methyl citrate become increased in the body due to deficient propionyl-CoA carboxylase 3-methylcrotonylglycine and 3-hydroxyisovalerate accumulate as a result of inefficient 3-methylcrotonyl-CoA carboxylase Acetyl-CoA carboxylase deficiency leads to the accumulation of acetyl-CoA Symptoms of untreated profound biotinidase deficiency (<10% mean normal serum biotinidase activity) usually appear between ages one week and ten years, typically with optic atrophy, hypotonia, seizures, hair loss, and skin rash. Affected children often have ataxia and developmental delay. Individuals with partial biotinidase deficiency (10%-30% of mean normal serum biotinidase activity) may develop symptoms only when stressed, such as during infection. Some symptoms, such as feeding issues, cutaneous manifestations, and respiratory issues, usually resolve with biotin therapy, whereas other manifestations presenting prior to biotin treatment, such as optic atrophy, hearing loss, and developmental delay, may improve but are usually not completely reversible diagnosis of biotinidase deficiency is established in a proband whose newborn screening or biochemical findings indicate multiple carboxylase deficiency based on EITHER of the following: Detection of deficient biotinidase enzyme activity in serum/plasma Identification of biallelic pathogenic variants in BTD on molecular genetic testing when the results of enzymatic testing are ambiguous should be treated with oral biotin in the free form as opposed to the protein-bound form; biotin therapy is lifelong creatine synthesis disorders are inborn errors of creatine metabolism with dev delay, hypotonia, refractory epilepsy, dystonia or chorea, behavioural problems; 3 types and biochem findings are: GAMT deficiency. Elevated guanidinoacetate (GAA) levels in urine, plasma, or cerebrospinal fluid (CSF) and low or low-normal creatine and creatinine levels in urine, plasma, or CSF AGAT deficiency. Low GAA levels in urine, plasma, or CSF and low or low-normal creatine and creatinine levels in urine, plasma, or CSF CRTR deficiency. Elevated creatine-to-creatinine ratio in urine in males. Females can have normal or mildly elevated creatine-to-creatinine ratio in urine. Diagnosis of a CDD is established in a proband with suggestive clinical findings by identification of biallelic pathogenic (or likely pathogenic) variants in GAMT or GATM or of a hemizygous or heterozygous pathogenic (or likely pathogenic) variant in SLC6A8 on molecular genetic testing

Answer 356

Non-ketotic hyperglycinaemia (NKH), called glycine encephalopathy, is an autosomal recessive IEM glycine metabolism disorder characterized by an abnormal accumulation of glycine in all bodily tissues, including the CNS. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. glycine accumulation in the brain changes the MAPK signalling pathways, which injures neurons and activates NMDAr leading to intracellular Ca accumulation, endonuclease activation, and cell death typically presents as a severe encephalopathy with myoclonic and apnoeic seizures, is rapidly progressive and eventually results in respiratory arrest. Standard evaluation for inborn errors of metabolism and other causes of this presentation does not reveal any abnormality (no acidosis, no hypoglycaemia, or hyperammonaemia and no other organ affected). Pronounced and sustained hiccups in an encephalopathic infant have been described as a typical observation but note 3 varying severities: most patients have the life-threatening neonatal form and present mild to severe disease manifestations starting within a few days of birth including lethargy or even coma, hypotonia, hiccups, myoclonic jerks, and breathing/swallowing disorders, with subsequent intellectual deficit, spasticity and intractable seizures. A smaller proportion of patients show developmental delay and generally mild seizures in the infantile period, while others do not develop symptoms until late infancy or adulthood Differential diagnosis includes organic acidemias that may present hyperglycinemia such as D-glyceric acidemia, propionic acidemia, methylmalonic acidemia, isovaleric acidemia - these other forms are sometimes referred to as ketotic hyperglycinemias

Answer 357

lip biting, head banging, fingertip biting usually seen in lead poisoning, familial dysautonomia, leprosy, congenital sensory neuropathy, lesch-nyhan syndrome usually in setting of global dev delay so eg isolated head banging rarely cause for neuro concern

Answer 358

leigh syndrome, also known as subacute necrotizing encephalomyelopathy, is the most frequent presentation of mitochondrial disease in childhood; features are a characteristic clinical course (including neurodevelopmental regression and symptoms and signs related to basal ganglia and/or brainstem dysfunction), elevated lactate levels in blood or cerebrospinal fluid (CSF) or other evidence of mitochondrial dysfunction (e.g. PDH or OXPHOS deficiency) and characteristic neuroimaging features of bilateral symmetrical T2 signal hyperintensity variably involving the basal ganglia, midbrain and brainstem structures alpers syndrome onset is typically in infancy or early childhood with initially focal motor seizures that evolve to bilateral convulsive seizures and often to epilepsia partialis continua and status epilepticus. The prognosis is extremely poor; most cases have a rapidly progressive course leading to death from status epilepticus or hepatic failure within a few months of presentation; most commonly caused by POLG mutation leading to mtDNA depletion MELAS stroke-like episodes may be heralded by migraine headache, homonymous hemianopia or quadrantanopia and seizures, which are often focal but may subsequently generalize as the stroke-like episode progresses. The first seizure or stroke-like episode occurred at a mean of 13.7 years in those with childhood onset; other sx include short stature, cognitive decline, exercise intolerance, SNHL, ptosis, optic atrophy, GI dysmotility and diabetes mellitus; in MELAS there are typically parieto-occipital stroke-like lesions not corresponding to vascular territories Myoclonus epilepsy with ragged-red fibres (MERRF) frequently presents in childhood with an insidious onset that may include ataxia, SNHL and endocrine disturbance; Myoclonus may not be apparent initially and may present later, with additional seizure types. Other clinical features of MERRF include cognitive impairment, multiple lipomatosis, ptosis/PEO, myopathy, peripheral neuropathy and cardiomyopathy; overlap with MELAS Leber hereditary optic neuropathy (LHON) most frequently presents in the second or third decade of life, with a median age of onset of ~20 years with painless subacute central visual loss typically affects both eyes sequentially; Most affected individuals have isolated ophthalmological symptoms, but there may be other clinical features such as dystonia or cardiac conduction problems (Wolff–Parkinson–White); overlap with leigh syndrome and MELAS clinical presentations that should arouse suspicion of an underlying mitochondrial disorder include stroke-like episodes, acquired ptosis and/or ophthalmoplegia, sideroblastic anaemia and epilepsia partialis continua. However, it is frequently the combination of disease pathologies affecting multiple seemingly unrelated organs that triggers the clinical recognition of a mitochondrial disorder

Answer 359

AD mild dwarfing, delay in ossification of fontanelles and sutures so bossing of frontal bone, small nasal bridge and shallow orbits giving pseudoexophthalmos narrow thoracic cavity and absent lat clavicles (maybe bring shoulder to front of chest) late eruption of (oft deformed) teeth, narrow pelvis (risk for obstructed labour later in life), no mental retardation, live to average age

Answer 360

don't focus on one modality, associate them; simpler secondary cortex like V2 allows diff components of one modality (eg vision) to be processed together; then higher areas more complex eg sound/vision/touch combined in parietal-temporal-occipital area, with wernickes area also found here (usually on left side); brocas area adjacent to PMC; PFC and limbic association areas essential for cognitive processes

Answer 361

strip of white matter lying on surface is fimbria - an output tract, the other being the subiculum; fimbria forms fornix on each side which leave temporal lobe and merge to form one fornix following inf aspect of corpus callosum to hypothalamus; subiculum lies between hippocampus and PHG; all 3 of those plus dentate gyrus are contiguous; plays role in episodic memory though CA2 recently implicated in social memory in animals; vulnerable to hypoxia and sensitive to corticoids like cortisol and thus to stress; major input from PHG through PHG carrying info from neocortex, esp sensory association areas; output through fimbria-fornix to mammillary bodies of hypothalamus/diencephalic memory system of thalamus; second back to entorhinal cortex then on to neocortex; fibres exchange between two sides in fornical commisure so two hippocampi linked; fornix splits on ant commisure before running to MBs

Answer 362

cingulate gyrus lies above corpus callosum, and is continuous posteriorly with parahippocampal gyrus with functions including olfaction (ant PHG), recognition memory (post PHG entorhinal cortex) and emotion (ACG); diff parts implicated in memory and self-awareness (inc pain); deep brain stim into subgenual cortex to treat intractable depression; most output fibres into PHG with cingulum a white matter tract linking them; ant PHG is pyriform cortex - uncus and POC and post is entorhinal cortex with many projections from cerebral cortex, esp parts dealing with highly processed sensory info (PTO cortex)

Answer 363

subregions have specialised roles (like the visual cortex) eg damage to ventrolateral PFC shows defects in attentional control; orbitofrontal cortex on ventral part above orbits, with damage associated with change in emotional/social behaviour; input to OFC from all neocortical association areas, as well as amygdala, hippocampus, hypothalamus and projects to all areas it receives from with esp close contact with cingulate cortex, amygdala, hypothalamus, and one main output pathway is to nucleus accumbens via which it can influence action

Answer 364

frontal: VL/VA, medial dorsal nuclei for motor, planning and cognition and with subcortical connections to BG and cerebellum; parietal: VP and pulvinar for somatosensation and multimodal integration with main subcortical area the sup colliculus; temporal: pulvinar and anterior for recognition, memory and emotion with subcortical amygdala and hippocampal formation; occipital: LG and pulvinar for vision and visual association with subcortical sup colliculus

Answer 365

hypothalamus: MBs posteriorly, optic chiasm ant, 3rd ventricle in midline, understand its nuclei for eating disorders, fertility problems; nucleus accumbens (techincally low forebrain) associated with schizophrenia and drug addictions; forebrain cholinergic system arises close to septal nuclei and basal forebrain, projects throughout cortex with roles in learning/memory and cholinergic deficits in AD; midbrain dopaminergic systems of substantia nigra (into BG for initiating movement, problems in PD) and ventral tegmental area (into nucleus accumbens for motivation); midbrain/pontine NA from locus coeruleus for overall attention; medullary serototinergic form raphe nuclei to modulate emotional behaviour (OCD and impulsive behaviour)

Answer 366

clinical syndrome of deterioration in mental function which interferes with activities of daily living (ADLs). It affects more than one cognitive domain (for example memory, language, orientation, or judgement) and social behaviour (for example, emotional control or motivation). Early (or young) onset dementia is generally defined as dementia that develops before 65 years of age. Mild cognitive impairment is cognitive impairment that does not fulfil the diagnostic criteria for dementia — for example, only one cognitive domain is affected, or ADLs are not significantly affected. The most common subtypes of dementia include: Alzheimer's disease (50–75%) which often co-exists with vascular dementia. Vascular dementia (up to 20%). Dementia with Lewy bodies (10–15%). Frontotemporal dementia (2%). Symptoms related to specific subtypes of dementia include: For Alzheimer’s disease: Early impairment of episodic memory — this may include memory loss for recent events, repeated questioning, and difficulty learning new information. For vascular dementia: Stepwise increases in the severity of symptoms — subcortical ischaemic vascular dementia may present insidiously with gait and attention problems and changes in personality. Focal neurological signs (such as hemiparesis or visual field defects) may be present. For dementia with Lewy bodies: Repeated falls, syncope or transient loss of consciousness, severe sensitivity to antipsychotics, delusions, and hallucinations may be present. Memory impairment may not be apparent in early stages. Parkinsonian motor features (such as shuffling gait, rigidity, slow movement [bradykinesia], and loss of spontaneous movement) and autonomic dysfunction (such as postural hypotension, difficulty in swallowing, and incontinence or constipation) may be present. For frontotemporal dementia (FTD): Personality change and behavioural disturbance (such as apathy or social/sexual disinhibition) may develop insidiously. Other cognitive functions (such as memory and perception) may be relatively preserved. When dementia is diagnosed, the person is legally required to inform the Driver and Vehicle Licensing Agency (DVLA) [DVLA, 2016]. The DVLA states that for dementia and/or any organic syndrome affecting cognitive functioning: Group 1 (car and motorcycle) license holders may be able to drive but must notify the DVLA, the decision on licensing is usually based on medical reports. Poor short-term memory, disorientation, and lack of insight and judgement almost certainly mean no fitness to drive. The variable presentation and rate of progression is acknowledged. Disorders of attention will also cause impairment. In early dementia, when sufficient skills are retained and progression is slow, a licence may be issued subject to annual review. A formal driving assessment may be necessary. Group 2 (bus and lorry) — license holders must not drive and must notify the DVLA. Licensing will be refused or revoked. MCI no need to report to DVLA

Answer 367

Four drugs are currently licensed for the treatment of cognitive deficits in dementia - Donepezil, Galantamine, Rivastigmine and Memantine. Donepezil, Galantamine and Rivastigmine are acetylcholinesterase inhibitors (AChEI). Their mode of action and development is based on the observation that cholinergic projections from the nucleus basalis of Meynert are reduced in Alzheimer’s disease. They are currently licensed for use in mild to moderate Alzheimer’s disease. Treatment with AChEI should only be initiated by specialists in the care of patients with dementia (psychiatrists, neurologists and geriatricians) and patients on these medication should be reviewed every 6 months with MMSE score and global, functional, and behavioural assessment. Carers’ views should be sought each time. Memantine is an NMDA receptor antagonist and is designed to stop excitatory cell death in Alzheimer’s and vascular dementia. for achei beware: GI side effects. Seizure Sinoatrial and atrioventricular blocks. Caution with concomitant cytochrome enzymes inducers and inhibitors for memantine beware confusion, hallucination - these drugs can worsen FTD, but good for AD and DWLB

Answer 368

Alzheimer’s disease Episodic Memory – “what happened when” Disorientation (But not momentary attentional lapses) Dementia with Lewy bodies fluctuations, visual hallucinations (±parkinsonism) Vascular dementia Attention, apathy, processing speed slow, modest memory and language problems Frontotemporal dementia personality change aphasia Anticholinergics worsen cognition in Alzheimer’s and increase risk of dementia (biochemical opposites of Donepezil etc)

Answer 369

assessment with PMH, life questionnaire, behavioural info, bedside cognitive test eg ACE-R; which domain? is it progressive, stepwise etc working or long term, implicit (procedural), explicit (semantic, episodic); attention/orientation tends to affect working memory (isolated impairment here likely delirium rather than dementia), problems here might affect other tests though other fields: memory, fluency, language, visuospatial dementia bloods: FBC, U&Es, Ca++, random glucose, LFTs, TFTs, B12/folate; midstream urine if delirium a possibility; if dementia not well established and subtype clear then imaging to rule out reversible causes and assist with subtype diagnosis - dont exclude AD based on scans MRI generally best for dementia clinics but CT gives all the needed info too; reversible organic types eg normal pressure hydroceph, chronic subdural bleed etc; peripheral microbleeds, amyloid angiopathy, AD; subcortical microbleeds, hypertension, vasc dementia MRI also tells you general cortical atrophy degree; assess focal atrophy eg medial temporal lobe/HC still uncertain diagnosis, FDG-pet or csf analysis for tau and amyloid beta 1-42, may get false pos as person gets older on histo: loss of neurons, gliosis, but no lymphocytic infilitration, protein inclusions; may see amyloid angiopathy; neurofib tangles and amyloid plaques; small vessel disease often co-existant REM sleep behaviour disorder - act out during dreaming (lose sleep atonia, may vocalise or kick/punch/cry out); usually PD or LWD; PD can develop dementia: parkinsons disease dementia if dev dementia after 1yr plus of symptoms, DWL/LWD if dev dementia within a year of parkinsonism PD will have depigmentation of substantia nigra, preservation of eg striatum, HC etc; histo see loss of neurons, lewy bodies that stain for alpha synuclein FTD common presenile dementia, see behavioural or semantic features, oft pos FH; macropath see severe atropy of frontal lobe, sparing of other areas (relative); pick cells and pick bodies under histo

Answer 370

Anticholinergic Syndrome: is a state of confusion with characteristic features related to dysfunction of the autonomic parasympathetic (cholinergic) nervous system. Symptoms classified into systemic and CNS manifestations: o Systemic (peripheral) symptoms: Blurred vision, photophobia, non-reactive mydriasis, loss of accommodation response, flushed and dry skin, dry mouth, tachycardia, hypertension and fever. Gastrointestinal and urinary motility are frequently reduced o CNS symptoms: Delirium, agitation, disorientation, and visual hallucinations. Ataxia, choreoathetosis, myoclonus and seizures may also occur without peripheral symptoms. Medication Issues: several commonly prescribed medications that may not be thought of as anticholinergic have significant anticholinergic effects, which when taken with known anticholinergic medication can increase the risk of adverse effects. Many medication groups e.g. antihistamines, tricyclic antidepressants, drugs for asthma and COPD, cold preparations, hyoscine have varying degrees of anticholinergic activity and have the potential to cause Anticholinergic Syndrome >65yos become increasingly sensitive due to fewer cholinergic neurons or receptors in the brain of older individuals. In addition, the liver and kidney have less ability to break down and excrete medications

Answer 371

consciousness determined by activity from reticular formation, content of consciousness determined by cortex; so reduced consciousness reflects derangement of brainstem where retic formation lies; content may be impaired by cortical damage; brainstem reflexes may be helpful for large reductions of consciousness FLAIR is T2 with csf suppressed so you can see pathological fluid; grey matter bright on T2/flair, white matter bright on T1 meningitis may get obstructive hydroceph, vasculitis giving infarction,subdural empyema; thickened subarachnoid space with neutrophils gram stain may show bacti; n meningitidis septicaemia can give necrosis of adrenals (waterhouse-friederichsen) giving adrenocort insuff TB meningitis gives white non purulent meningitis, bumpy looking ventriculitis; cortical tuberculomas abscess has dark surrounding, bright middle on T2, T1 dark middle with avid enhancement of wall; high signal in abscess on DWI; brain abscesses more common right-left shunt eg VSD HSV1 enceph, HSV2 meningitis usually; HSV1 enceph - altered conscious, confusion, seizures, fever, often inc'd intensity in temp lobe or insula on T2 or flair; iv aciclovir; necrotising destruction of temp lobe on macrohist, also insula; may see viral inclusions on histo high signal in BG and orbital pole plus frontal/parietal lobes on DWI/maybe T2 suggests global hypoxic ischaemic enceph; dark grey, necrotic cortex worst at watershed areas CT venogram can be used to show a bleed is superficial to venous sinuses ie extradural if youre unsure; one risk from EDH/SDH is uncal or transtent herniation; big clot sat on brain in EDH macropath hypoglycaemia (maybe diabetics whove had alcohol) or hypoglyc agent, insulinoma, addisons, post gastric surg; sweating, anxiety, hunger; maybe focal neurology, fits, coma; DKA, hepatic/wernickes enceph, ethanol/methanol/ethylene glycol toxcity (these for collapse w low gcs and suspicion of drinking); also infective causes (men/enceph as above, abscess bleed etc too); give thiamine asap if clinical suspect wernike on path see brown discolouration and petechial H+ in mamm bodies and maybe dorsal brainstem eg floor of 4th ventricle, pag other causes of metabolic coma: TCA/opiate overdose, hypothyroid, addisons, uraemia, hypo/hypernat/cal, met/resp acidosis, inborn EM -> U&Es, LFTs (inc PT), bone profile (ca/mg/phos - low of these last 2 also cause), glucose, TFTs, cortisol (short synacthen test); ABG, toxicology, serum/urine ketones; osmolar gap can be useful so coma: diffuse think metabolic, toxic, infective (men/enceph), or nonconvulsive status epi; if focal signs think structural eg EDH/SDH, hydroceph, abscess/empyema, parencyhmal/subarachnoid h+, stroke

Answer 372

neuro causes: stroke, bleed, tumour, infection, abscess, oedema, hydrocephalus, anoxic brain injury, PRES metabo causes: hypo/hyperglyc, hypo/hypernat, hypercalc, addisonian crisis, hypothyroid, uraemia, hypercapnia, septic or hepatic encehalopathy (ammonaemia) other: seizures inc NCSE, alcohol, opioid, other drug, hypothermia, neuroleptic malig syndrome, serotonin syndrome, psychogenic immobilise c-spine if trauma poss, intubate if GCS <8 measure BM (correct if abnormal), examine pupils (naloxone), calculate GCS, consider pabrinex A-E assessment, urgent CT scan (if unclear diagnosis, evidence of trauma or focal neuro deficit); should attempt neuro exam, and look for bruises or other evidence of possible anticoag; assess breathing (depressed? kussmaul (acidosis), ataxic/Biots (lower pons lesion), neurogenic hyperventilation (pons/midbrain), cheyne-stokes obtain collateral history, send bloods (inc FBC, glucose, U&Es, LFTs, bone profile, clotting screen, toxicology inc BAC, ABG, ammonia, cultures if suspect sepsis), get CXR and ECG, consider resus status and liaise with CCOT if still unclear after all this then consider MRI, LP, EEG for NCSE

Answer 373

ant temp lobe, rostral to hippocampus, adjacent o olfactory cortex, in end wall of inf horn of lat ventricle; 3 basic subdivisions: cortico-medial, receiving olfactory info (and other stuff) and is route used by pheromones to influence behaviour; central nucleus controls ANS, endocrine system, and simple reflexes with afferents coming from NTS and efferents to hypothalamus and brainstem; basolateral receives input from higher order sensory regions and projects for regions involved in planning/action including prefrontal cortex and ventral striatum, either directly or via mediodorsal nucleus of thalamus; 2 main efferent pathways: ventral amygdalofugal is diffuse, courses across temporal stem; stria terminalis is fibre bundle running around lat ventricle in groove between caudate tail and thalamus male rats work to obtain light associated with female, POA lesion unable to mount but still press lever, basolateral amygdala lesion can mount but don't press lever, has steroid receptors and eg testosterone may act to promote appetitive behaviours, with intact amygdala but castration still no lever press; same loss of light processing if light associated with food, and amygdala active in humans (PET scanner) when selecting from menus, with higher activity from greater incentive value of items; thus amygdala necessary for appetitive behaviour elicited by cues in environment predictive of primary rewards, so it asses motivational significance of environmental cues and drives automatic (ANS etc) and voluntary (prefrontal, striatum) responses identifies stimulus associated with learned desirable outcome; projects to ventral striatum (nucleus accumbens and ventral caudate/putamen) to influence motor systems of BG; ventral striatum also has dopaminergic input from A10 groups of neurons in ventral tegmental area, medial to A9 (substantia nigra) - also projects to amygdala and prefrontal cortex (ie other parts of brain to do with motivation)

Answer 374

damage to LH (aphagia) also damaged mfb which had fibres for dopamine projection to striatum; DA one of several NT specific pathways in ascending activating system of reticular formation (also noradrenergic, cholinergic and serotonergic); some LH lesion deficits could be fixed by dopamine agonists and lesions of DA projections in mfb by neurotoxin 6-hydroxydopamine caused aphagia, adipsia and akinesia with first two mirroring LH syndrome; akinesia from loss of nigrostriatal DA projections (as in PD); DA projections to ventral striatum concerned wit appetitive response so mediate incentive motivation: DA released in nucleus accumbens in presence of reward like food, sex, and also in presence of stimuli associated with them like mcdonalds sign with lesions stopping the appetitive behaviour but not the consummatory; so stimulus (noise, sign whatever), appetitive behaviour initiated, thus more likely to get goal; orexin neurons send projections to nucleus accumbens and its DA innervation (A10 - thus also to amygdala/prefrontal cortex) which increase motivation to eat when hungry (ie food looks more appetising); so DA lesions to ventral striatum opposite to hypothalamus, same as amygdala; DA projections to ventral striatum = mesolimbic pathway

Answer 375

continuous caudally with intermediate grey of spinal cord and rostrally with hypothalamus (lateral) and subthalamic region; medial in brainstem and composed of loose aggregates of different neurons mingling with fibres heading in different directions; many functions including integrating basic, stereotyped responses (pattern generation for posture, walking, chewing, swallowing, vomiting, sneezing etc and regulating resp cycle and cardio system), and regulating level of activity of brain via ascending activation system: stimulating here leads to widespread cortical activation and desynchronisation of ECG; reticular neurons are part of isodendritic core and project to cortex directly by mfb and indirectly by intralaminar nuclei of thalamus (in turn project to striatum/cortex); note EEG prob most from summed EPSPs/IPSPs as cortical APs too rapid to sum together unless epilepeptic seizure rf can be fractionated into discrete, chemically defined components: DA, NA, 5HT, ACh; isodendritic core also has cholinergic neurons of basal forebrain and histaminergic neurons of post hypothalamus; each group has diffuse but discrete projections, differing not just between each other but also between one cortical/subcortical region and the next; DA activates appetitive and consummatory behaviours; NA may play role in attention as activating locus coeruleus increases signal to noise ratio, enhancing inhib effect of meaningless tone on hippocampus and exciting meaningul tone (eg food etc) on hippocampus, this may form basis of attention and esp important in stress when LC maximally activated serotonin less well understood, can affect processes to do with behavioural inhibition, esp in aversive situations; so impulsive and obsessive compulsive behaviours linked to reduced 5HT in forebrain and drugs that increase it used to treat those, as well as anxiety and depressive states; ACh related to learning and memory both from experiments and also loss of cholinergic neurons gives memory loss in eg AD (only forebrain ones lost, not pedunculopontine); most psychiatric drugs interact with one of the monoaminergic systems

Answer 376

active process, with behavioural definition based on loss of consciousness and electrophysiological based on eeg brain waves; sleep and wakefullness change based on circadian rhythms; when awake, high freq (15-60Hz)low amp beta activity when eyes open, signalling active cortex, and lower freq (8-13Hz) alpha activity associated with quiet waking states; 4 sleep stages; 1 is drowsy period with 4-9Hz inc amplitude theta waves, then stage 2 (light sleep) even lower freq/higher amp plus intermittent clusters of high freq spikes called spindles (generated by thalamic nuclei, extensive learning of declarative memory tasks increases density of spindles) and occasionally steep up/down deflections called k complexes; stage 3 is moderate to deep and stage 4 deep with very low freq high amplitude delta waves, following this is REM sleep where eeg looks like awake state several cycles between rem and non-rem sleep; latter have decreased muscle tone, heart/metabolic/breathing rate, and blood pressure; rem has blood pressure, heart/metabolic rates increase almost to waking levels, also rolling eye movements and paralysis of large muscles; some cortical regions equally active during awake and rem states, but extrastriate cortex and certain limbic structures much more active during rem and prefrontal less; PVC and some areas less active during rem than non-rem but extrastirate cortex more; debate on functions of sleep with proposals like restoring body/mental functions, brain dev (in children), memory consolidation; sleep is critical to life

Answer 377

2 major contributors are brainstem modulators and the thalamus; stimulating thalamus in awake animal with low freq pulses produce slow wave sleep; ACh/NA shift cells in cortex/thalamus from intrinsic burst firing to single spiking which may well underlie transition from non-rem to waking; in intrinsic burst firing, thalamus and cortex become synchronised which disconnects cortex from outside world with maximal disconnect in delta sleep; during rem sleep, NA and 5HT neurons decrease activity even further but pedunclopontine cholinergic neurons increase activity, with the former two increasing again just before rem offset ventrolateral preoptic area of hypothalamus important for providing switch; VLPA has inhibitory innervation on ascending arousal system, and they have inhibitory input on VLPA, this set up allowing sharp boundaries between sleep and awake; VLPA lesions reduce sleep time by >50% with such animals showing normal circadian cycle but waking up more often during sleep and falling asleep more often in wake cycle; many other hypothalamic region feed into these pathways with excitatory orexin containing neurons and inhibitory MCH containing neurons for example; adenosine accumuates in VLPA during awake time to promote sleep; parafacial zone within medulla helps initiate slow wave sleep by GABA input to ascending activating system; NA/ACh inhibits all triangular multipolar neurons in VLPA, serotonin and adenosine excite type 2 which send inhib GABA to ascending activating system (and these accumulate during wakefulness)

Answer 378

short term insomnia from stress, jetlag, too much coffee; more serious from psychiatric disorders like depression which upset the balance of neuromodulatory transmitter systems; one of best understood is narcolespy, with frequent rem sleep attacks during day with possible cataplexy (temp loss of muscle control), genetic with mutation in orexin receptor 2 (in dogs at least, though many familial cases in humans linked to low levels of orexin, possibly autoimmune in nature); orexin neurons sens excitatory input to reticular formation inc NA and 5HT systems and increase activity in those arousal pathways, favouring flip flop towards waking state: an their absence, switch is weakened and switching becomes more frequent; one reason why people/animals sleep after a big meal - orexin neurons stimulated when hungry; food availability can shape sleep-wakefullness cycles with nocturnal animals becoming diurnal if can only find food during day sleep-wake cycle has clear 24hr circadian rhythm with animals tending to be nocturnal or diurnal, but without external cues, can still show 24hr cycle give or take half an hour; in mammals, principal clock is paired SCN in ant hypothalamus, above optic chiasm and on each side of third ventricle; in absence of light/dark will free run with period of 24hrish with individual SCN neurons seemingly coupled to make a pacemaker and without SCN, biological rhythmicity is lost; it gets info via retinohypothalamic tract from melanopsin containing GCs (esp sensitive to blue); SCN then controls physiological and psychological rhythmicity via conncetions to nuclear groups in hypothalamus, prominently the dorsomedial nucleus, and other diencephalic sites including midline thalamus and bed nucleus of stria terminalis; these then influence endocrine and autonomic output as well as mood and emotional state; SCN regulates VLPA via DMN; mood disorders (anxiety, depression) and neurodegenrative disorders (Huntingtons/AD) disrupt the clock, with AD patients wandering at night - restoring this would allow home care for longer; SCN projects to pineal gland which releases melatonin to promote sleep; independent circadian rhythms may be seen in liver, pancreas, spleen and other, but main one is SCN; as well as sleep, body temp and cortisol vary in cycle, and others too

Answer 379

administration of exogenous melatonin has a rapid, transient, mild sleep inducing effect and it lowers alertness, body temperature and performance for about 3 to 4 hours of value for treating sleep onset insomnia and delayed sleep phase syndrome in children with conditions such as visual impairment, cerebral palsy, attention deficit hyperactivity disorder, autism spectrum disorder, and learning difficulties it is important to note, in children/ adolescents with neurodevelopmental difficulties response to Melatonin can be variable sleep disorder diagnosed where: Symptoms of sleep disturbance have been present for at least six months or sleep disturbance is so severe that it is causing significant family disturbance Sleep hygiene / behavioural measures, have been tried and either did not work and/ or had limited benefit Melatonin IR initially 2 mg daily. Increase every 1-2 weeks based on response to 4-6mg daily For children waking during the night, the same dose or a smaller dose can be repeated during the night Studies have found melatonin very well tolerated with a side effect profile as of the placebo and so symptoms are likely to be a coincidence.

Answer 380

sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror; affects up to 20% of ppl with narcolepsy, but can occur without narcolepsy more rarely may range from a barely perceptible slackening of the facial muscles to complete muscle paralysis with postural collapse, and attacks last seconds to mins; as in REM sleep, the person continues to breathe and is able to control eye movements secondary when it is due to specific lesions in the brain (primarily in the lateral and posterior hypothalamus) that cause a depletion of the hypocretin neurotransmitter; Some of the tumors include astrocytoma, glioblastoma, glioma, and subependymoma.; also MS, ischaemic events, head injury, encephalitis, niemann pick, KCNMA1 problems etc; may also occur transiently or permanently due to lesions of the hypothalamus that were caused by surgery, especially in difficult tumor resections

Answer 381

KCNMA1-linked channelopathy is an emerging neurological disorder characterized by heterogeneous and overlapping combinations of movement disorder, seizure, developmental delay, and intellectual disability; gene encodes the α subunit of the BK (“Big K+”) large conductance voltage and Ca2+-dependent K+ channel, which conducts outward K+ currents in response to changes in intracellular Ca2+ and membrane depolarization Episodic symptoms can be particularly difficult to delineate, as they can resemble paroxysmal dyskinesia, tonic or atonic seizures, and cataplexy; may cause seizures of various kinda, episodic myoclonus, dystonia, cataplexy; contant ataxia, tremor, dystonia, hypotonia

Answer 382

benign, underdiagnosed sensory parasomnia. It is the sensation of hearing a loud sound during sleep-wake/wake-sleep transitions generally last <1s, accompanied by flashes of light and patient distress, but there is no significant associated pain sounds have most commonly been described as explosions, gunshots, or thunder but can be almost any loud noise; may be prolonged remission between episodes MRI will be normal, polysomnography shows normal sleep but may have abnorm during an episode mx with education/reassurance; try to identify and remove triggers dd: Nocturnal epilepsy: Occurs during NREM sleep, but unlike EHS, patients with nocturnal epilepsy have no memory of the events Hypnic headaches: These are recurrent headaches during sleep leading to awakening. They are associated with pain that lasts from 15 minutes to four hours. These headaches can be unilateral or bilateral and occur for more than ten days a month, for more than three months Post-traumatic stress disorder (PTSD) and nightmare disorder: There is no specific dream content that patients will be able to recall with EHS good prognosis. There are no sequelae reported; freq and intensity of eps may decrease with reassurance and it can resolve completely

Answer 383

overt attention is eg moving eyes to look at something, covert is more internal; usually they align but can covertly pay attention to something without overtly looking at it; can also be voluntary or reflexive cherry's dichotic listening observation that play two different messages, one in each ear, and get person to repeat one - they can, but dont notice much about the other; proposed attention was like a filter, acting before sensory info reaches memory, however if message being listened to is switched to other ear, subject switches which ear theyre paying attention to so suggests attention follows filter-attenuation model, with broadbent's model that selective filtering occurs at bottlenecks where processing capacity is limited; cherry also found subjects own name could be identified in ignored stream and wright/anderson/stenman found words associated with electric shock led to skin galvanisation even when on ignored side thus v important info can overwhelm the attenuation on them; so attention attenuates some aspects of info and enhances others, seen in fMRI of human visual cortex (motion perception in V5) can study covert attention through effects on performance and physiological measures; cherry's expt was dichotic listening; attention can be shifted by endogenous cues, like arrow pointing in direction where target will appear, so subject shifts attention voluntarily, reacting faster if where attention is focused; attention modulates cortical processing in human brain; (extra that i found): saalman et al found that firing of neurons in medial temporal area and parietal lobe synchronised when macaques selectively attended a location in visual matching task, with parietal cortex leading the MT, so they think parietal neurons selectively increase activity in earlier sensory areas to enable spatially focused attention in top-down feedback attention selects objects rather than a region of space; egly's 'cueing paradigm' with bigger responses to targets on same object as cue than target same distance away from cue but on different object; read about multiple object tracking

Answer 384

common and may consist of abnormal movements, behaviours, emotions, and autonomic activity during transitions between sleep states, from sleep to wakefulness, or during arousals from sleep; Most paediatric parasomnias are benign, self-limited, and generally do not persist into adulthood Non-rapid eye movement (NREM) parasomnias include sleepwalking, night terrors, and confusional arousals, that occur most commonly in the first half of the night. Rapid eye movement (REM) parasomnias occur later during the night and consist of experiences such as nightmares, recurrent isolated sleep paralysis, and REM sleep behaviour disorder (RBD) aka acting out dreams. The latter is extremely rare in children and is associated with PD. three most common modifiable triggers for parasomnias in children include sleep deprivation, restless legs syndrome, and obstructive sleep apnoea. Treatment of these disorders may significantly reduce or resolve parasomnias and you should screen for all 3 diagnosis usually clinical, Ordinarily, a sleep study (diagnostic polysomnogram) is not necessary to establish the diagnosis. However, this test may be ordered when other comorbid primary sleep disorders, such as sleep apnoea, are suspected, and it is required for the diagnosis of RBD Management usually consists of treatment of the underlying cause of the parasomnia, reassurance, modification of the sleep environment, and, in adolescents, avoidance of substances such as caffeine and alcohol. When parasomnias become frequent and more problematic, occasionally pharmacological agents may be helpful confusional arousals - tend to occur immediately after sleep-onset or early mornings and are associated with a transient confusion in thought process after awakening, resolve by 5yo normally night terrors - associated with inconsolable crying (consoling usually delays recovery from the event) and heightened autonomic system activity, severe may need scheduled awakenings or benzos like clonazepam sleep walking - make sure getting enough sleep nightmares - normally resolve by 6yo, persistent symptoms beyond this age may require further evaluation to rule out underlying anxiety disorders, affective distress, or trauma exposure (and probable PTSD) home environment needs to be modified to increase safety. This includes removal of any potentially dangerous items and sharp objects, locking doors, arranging for a sleeping space on the ground floor, and installation of door alarms note nightmare vs night terror: REM vs NREM, full waking vs partial waking, last half of night vs first third of night, remember bad dream and can tell you about it vs don't remember what happened, respond to comfort vs don't (as asleep still) night terror might also be confused with seizures: han sleep terrors: * Child is school-age rather than preschool-age. * Episodes typically include stereotypic movement. * Some patients experience a nonspecific aura of somatosensory, sensory, psychic or autonomic symptoms. * Patient may recall episodes. * Patient has a history of daytime sleepiness, daytime seizures, or neurodevelopmental disabilities or has a family history of epilepsy. When some of these factors are present, using the Frontal Lobe Epilepsy (FLEP) scale can be helpful. For typical parasomnias such as sleep terrors, the FLEP score will be less than zero. For NFLE, the score will be greater than zero Differentiating between nocturnal seizures and NREM parasomnias can be challenging, especially in regards to nocturnal frontal lobe epilepsy (NLFE) because of the typically unusual, bizarre presentation of NLFE seizures, along with its common association with a normal EEG. Features supporting an epileptic etiology of paroxysmal events are: (1) stereotyped nature of the spells; (2) high frequency and tendency to cluster; (3) timing of the events (NREM parasomnias usually emerge from slow wave sleep, which typically occurs within 2 h of sleep onset, whereas frontal lobe seizures may occur during any sleep stage, but are common shortly after falling asleep); (4) semiology of events (although frontal lobe seizures may have variable manifestations, the occurrence of prominent unilateral tonic stiffening favors an epileptic origin rather than a parasomnia); (5) duration of events (parasomnias are usually relatively prolonged events, whereas epileptic seizures, especially frontal lobe seizures, tend to be very brief, lasting < 2 min on average); and (6) presenting age

Answer 385

encompass sleep myoclonus of infancy, rhythmic movement disorder, periodic limb movement disorder (PLMD), and restless legs syndrome (RLS). Sleep myoclonus of infancy is typically associated with clusters of myoclonic jerks that involve the whole body, trunk, or limbs. They are usually considered to be benign phenomena and gradually disappear after six months of age note children may also be observed to show hypnic jerks In rhythmic movement disorder (RMD), a child exhibits repetitive and stereotyped motor behaviors involving large muscle groups and are predominantly sleep related. RMD can also be associated with significant daytime impairments and/or associated with self-inflicted bodily injuries; treatment encompasses ensuring safety of the child during sleep and reassuring parents that RMD should gradually resolve by five years of age. Persistent symptoms beyond five years of age can be seen in children with developmental disorders; video polysomnography can be used if unsure, and severe cases can respond to benzo like clonazepam Periodic limb movements in sleep (PLMS) are brief jerks (movements) during sleep that can last up to five seconds in duration occurring at 20- to 40-second intervals (periodicity) and occur more commonly in the lower extremities than upper extremities. Patients are usually unaware of these symptoms, but bed partners like siblings and parents are affected by these movements restless legs syndrome: criteria for RLS are as follows: 1) An urge to move the legs, 2) the urge to move begins or worsens when sitting or lying down, 3) the urge to move is partially or totally relieved by movement, and 4) the urge to move is worse in the evening or night than during the day or only occurs in the evening or night. Typically in children less than 2 years of age, diagnosis of RLS needs further support by a child's own age-appropriate descriptors of sensorimotor symptoms, such as “spiders crawling” or “tickles in my legs” sleep-onset and sleep maintenance insomnia can be a common occurrence in children with underlying RLS Behavioral treatment options for RLS and associated sleep disturbances in children and adolescents include enforcing strict routines for bedtime and wake-up time, reducing environmental stimulation prior to/at bedtime (e.g., limiting TV and video games), and encouraging daily physical exercise. It is helpful to ascertain the child's current serum iron status through measurement of serum ferritin levels as symptoms of RLS and PLMS have been shown to be associated with low serum ferritin levels Dopamine pathways have been implicated as the common pathophysiological link in comorbid RLS and ADHD. Low serum iron stores can affect levels of dopamine since iron is the cofactor for tyrosine hydroxylase, a rate-limiting enzyme, during production of dopamine. Iron supplementation has been shown to be effective in reducing symptoms of RLS and PLMD; thoroughly assess for symptoms of ADHD in patients with RLS and vice versa Fe and vit C supplementation can help; pramipexole and ropinirole in adults, evidence and us in children is less common; clonidine or clonazepam may help; so do behavioural interventions, Fe supplementation if needed, and then if severe look into medications, esp if co-morbid ADHD

Answer 386

unilateral neglect syndrome causes neglect of space opposite lesion ie will ignore food on left if lesion on right; anosognosia is shown - unaware of the deficit; line bisection tests reveal: if most of line is on left hand side, their attempt to bisect will be far to the right, german artist who neglected left side of canvas and himself in portrait, became better as recovered from stroke; also neglect visual memory eg bisiach et al ask people to describe a piazza as if standing outside cathedral, neglect left side in description but include previously left out stuff if imagine facing other way; parietal lesions to both hemispheres cause balints syndrome, where you cannot attend to two objects simultaneously (simultanagnosia) or shift attention rapidly between objects, ocular apraxia (hard to do saccades) and optic ataxia (hard to guide hand to object); unilateral extinction similar lesions to those that cause neglect, closely related and often get both, you can perceive a single object presented to left or right side but if two presented, one each side, can only see the one on the side of the lesion (so mild simultanagnosia for brief stimuli); more than just space neglected as struggle to tell difference between left side of objects even if part of that side is in right of space, so additive effect of left of object or left in space; neglect/extinction from disorders of right parietal lobe, esp temporo-parietal junction (though also damage to frontal and some subcortical areas)

Answer 387

short term memory retained for seconds to minutes including sensory memory, working memory, and short term (knowledge of world); atkinson and shiffrin; sensory stores (hold info briefly that you aren't aware of) consist of iconic store which briefly stores visual info with subjects able to repeat letters shown to them if delay between removal of prompt and request <1s, so suggests stored in iconic store for 1s; echoic store is analogous but for auditory info, decay after ~2s (message in one, ask to repeat and ignore 2nd played in other ear, only noticed that 2nd was identical to 1st if played within 2 secs of each other); if attention paid and decay didnt happen, on to short term store short term: miller showed subjects could generally recall 7 +/- 2 digits, similar for letters, words etc so suggested short term memory holds ~7 chunks of info at a time; you can retain this info by rehearsing it (aloud or subvocally) which sends it to a long term store; short term memory decays within seconds, due to interference from new information rather than the passage of time; a criticism of multistore model is short term memory processing required for long term storage but patient KF had defective short term memory but preserved long term and recall, also KF has worse short term memory for auditory info than vision which suggests different short term memory for diff kinds of material; EE also had preserved long term but lost short term (eg remembering abstract verbal material) working memory model: address above limitations, consists of auditory-verbal phonological loop for short term storage of speech based info, visuo-spatial skecthpad for storing that info short term, and modality free central executive that selects and initiates cognitive processing routines; used for retaining info longer than short term to perform mental operations eg doing mental maths

Answer 388

along with sketch pad make working memory, remember letters as sounds not shapes eg when recalling list more likely to swap T for G than Q for G; phonological similarity effect, recall of list of words that sound similar worse than recall of distinct sounding words suggesting words stored in speech based system, and recall requires differentiating between memory traces which is harder for words that sound similar; word length effect shows recall of long words worse than short words; phonological store perceives speech, and articulatory control process links phonological store to speech production: PSE from confusion between similar representations in PS and WLE from time taken to rehearse longer words in ACP; WLE has implications for digit span across cultures: chinese remember more digits than english speakers (9.9 vs 6.8) and welsh less (5.8) temporary storage/manipulation of spatial and visual info; participants learn something either orally or visually, if also tracking moving image then visual learning effected but not oral; then see effect of bright light (visual) vs pointing at moving pendulum (blindfolded with guiding auditory tone - spatial) and latter had more effect on visual learning; so visual cache (passive store about visual form/colour subject to decay etc) and inner scribe, processing spatial info and allowing active rehearsal of images in visual cache and passing info to central executive - right hemisphere more activated for spatial and left for visual), supported by patients like NL who had fine percpeption but couldnt describe scene from memory

Answer 389

if given a list of words to remember, you usually recall first and last few the best (primacy and recency effects); recency effect from items in short term store and can be eliminated if patients count backwards prior to recall; this doesnt eliminate primacy effect, though it can be affected by word familiarity, presentation rate, age or participant - all implicating long term memory; also eg patient HM who had impaired long term memory but normal digit span (medial temporal damage) vs KF who had opposite (and parietooccipital lobe lesion); fMRI also implicates medial temporal lobe when patients encoding/retrieving info, and when using short term activity is in inf frontal and parietal cortex ebbinghaus found retention decreased with longer retention interval, but rate of forgetting slowed down after first hour or so; capacity of long term theoretically unlimited (except by number of neurons/synapses in brain - 10^15), with expts trying to find limit using pictures showing people can remember >10,000; lindauer suggested limit could come from rate of acquisition, with humans able to learn ~100 stimuli a min for 3 billlion stimuli over 70yr life; ebbinghaus's studies suggest forgetting most rapid over first hour, then decreasing logarithmically; believed forgetting primarily due to interference from other experienced events: proactive interference is where previous learning affects later learning and retroactive interference is the opposite; latter can be shown by questioning affecting eye witness testimony, former by the more nonsense syllable lists a person learns, the more forgetting they show after 24hrs declarative/explicit/conscious is memory for facts that HM had impaired, subdivided into episodic/personal and semantic/facts; and nondeclarative/implicit/not conscious, which was not impaired in HM, subdivided into perceptual/priming (learned behaviours) and procedural/motor skills + conditioning; explicit usually needs conscious recollection; diff tasks to study diff systems eg explicit might be recall and implicit word stem completion; deeper levels of processing improve explicit memory but not implicit eg amnesiacs with medial temporal lobe damage can get better at motor tasks despite not remembering doing them; patients with opposite are much rarer but eg MS (occipital cortex lesion) performed as well as controls at explicit memory tasks but implicit task was very impaired; diff anatomical sites suggests they are functionally separate systems semantic memory is knowledge you know without awareness of where/when you learned it eg knowing breakfast is the meal at the start of the day; episodic is unique to each person whereas semantic can be culturally shared to some extent; diff levels of processing improve episodic memory but not semantic, and reading a word out of context improves semantic memory, learning the context then generating the word for yourself improves episodic memory; HM (med temp lobe damage) was impaired at episodic tasks but could remember names of everyday objects etc and children with hippocampal damage could recall vocab (semantic) but were poor at episodic tasks; early AD have medial temporal lobe atrophy and have impaired episodic but good semantic, people with semantic dementia have atrophy in lat temporal lobe and have impaired semantic and preserved episodic

Answer 390

2 major forms: retrograde (forget events prior to trauma) from eg closed head injury, electroconvulsive shock therapy with temporal gradient of forgetting often diminishing over time; anterograde where cannot retain new material ie learn; can occur together; causes include anoxia, ischaemia, encephalitis, alcoholism (korsakoffs syndrome), surgery (to relieve epilepsy) and is early part of AD where hippocampus and entorhinal cortex struck; studying amnesia in patients after surgery helped with understanding of memory medial temporal lobe amnesia: HM had resection of temporal lobes (inc hippocampus/amygdala) to relieve epilepsy, giving profound and polymodal anterograde amnesia for verbal and non-verbal stuff so couldn't learn anything new, or remember things in the few years prior to operation but could have convo, do maths, and remember distant things; his short term memory and iq were preserved; unilateral right lesions tend to produce nonverbal deficits and left lesions verbal memory deficits diencephalic: NA got anterograde after lesion to mediodorsal thalamic nucleus; korsakoff patients have lesion to medial thalamus, fornix, mammillary bodies; not known is these depend on same circuit as medial temporal lobe amnesia, suggested it is as hippocampus involved in both though korsakoff patients have greater retrograde amnesia than MTL selective loss of short term memory: post cortex, usually temporal-parietal lobe junction, can consolidate knowledge into long term memory and are conduction aphasics, so short term memory deficits don't have to lead to anterograde amnesia, instead this form of short term memory evolved to help follow convos maybe?; loss in other modalities (like visual) may be due to lesion of association area of modality in question special knowledge systems: some aphasias, apraxias, and agnosias are loss of highly specific, long term, semantic memories, usually due to damage of specific bits of association cortex; some associative and apperceptive agnosias are weird eg can recognise inanimate objects but not living ones (associative) procedural and declarative memories: anterograde amnesiacs can learn skill like drawing in mirror even though no recall of daily testing sessions, and korsakoffs patients learn to mirror read as fast as controls but cant remember what words they read (in contrast, huntingtons patients cant dev skill as well but can recall the words); declarative knowledge is facts and procedural is knowledge gained through practice, this latter system older and reliant perhaps on cerebellum and BG instead of temporal lobe and diencephalon

Answer 391

impairments to recognition memory associated with damage to rhinal cortex (peri and ento) so eg projections into this from inferotemporal cortex crucial for visual recognition memory; relevant to associative agnosias and possibly part of larger system within temporal lobes for storing info about objects, analogous to semantic knowledge, and assessed using DNMS monkey test and controls plus lesions to rhinal cortex, amygalda + hipocampus, middle group doing worst and last group close to control; damage to amygdala impairs emotional/motivational memory so people/animals with lesions here no longer respond to fearful/pleasurable stimuli: can recognise a stimulus and recall previous interactions with it, just with no emotional component; route for recognition memory is association cortices to perirhinal and parahippocampal cortex to entorhinal cortex to hippocampus most medial section of temporal cortex is hippocampus and dentate gyrus which are 3-layered allocortex; between these and temporal neocortex lie subiculum and parahippocampal cortex; during dev, hippocampus invaginates into lat ventricle to form ridge called Ammons horn; hippocampus divided into 3 longitudinal areas CA1/2/3 based on connections/cell types and all have output pyramidal cells with dentate gyrus having input granule cells; the formation is hippocampus, dentate gyrus, and subiculum aff: major association cortices all project to entorhinal cortex (including polymodal processing areas like prefontal cortex) and neurons here send afferents to dentate gyrus granule cells (perforant pathway as perforate hippocampal fissure to reach destination), subcortical structures include septum ant thalamus and amygdala and these are second afferent input, and third is from non-specific arousal systems (cholinergic, serotonoergic, noradrenergic) intrinsic: trisynpatic circuitry; perforant pathway to dendrities of granule cells and apical dendrites of CA3 pyramidal cells; granule cells project via mossy fibres to CA3 cells; these project via Schaffer collaterals to CA1 cells which then project to subiculum; 2 sets of eff connections: from subiculum/entorhinal cortex to neocortex, and from CA3 and subiculum through fimbria-fornix to hypothalamus, mammilary bodies, ant thalamus, nucleus accumbens; projections from mam bodies to an thalamus, thence to cingulate cortex before back to entorhinal cortex forming classic Papez's circuit

Answer 392

CA1 degeneration in humans causes episodic memory defects; also clear from animal studies that HC important for spatial memories with lesions to fimbria-fornix or HC itself causing impairment of learning placement of objects in environment: eg for rats Morris water maze where rats trained to escape pool by swimming to submerged platform with HC lesions affecting learning and retention of this info; much weaker deficit if task trained before lesion on retention tests post lesion (retention test based on how long rat spends searching for platform if it's removed), suggesting HC important for laying down but not recalling spatial memories; human HC is active during navigation and is larger in london taxi drivers; possible that spatial memory just one component of HC role in encoding context (what/where/when) where memories take place, thus binding together disparate elements of a memory and distilling them into coherent trace; transient global amnesia where stress in people >50 deprives CA1 of blood giving anterograde amnesia which passes within a few days; fMRI shows HC active when new memories being encoded; HC in recall of semantic memories but not sensory: inc bloodflow (fMRI) between true and closely related false words from a list (semantically related) and less for new false words how learning might take place: seem to be various stages where interactions between diff sets of inputs can occur in matrix like manner with eg rows of perforant axons and columns of granule cell dendrites; synapses modifible with activity increased if afferent axon synapses on already strongly activated granule cell with diff input pattern activating diff output neurons and inhibitory interneurons between output neurons mediating mutual inhib; so typical sequence would be: in response to stimulus, strengthening of synapses between active afferents and strongly activated output cells so next time stimulus presented, output neuron responds more and more inhib between pathways; unlike cerebellum no teacher (ie climbing fibre) to correct errors, thus is an unsupervised learning system; non-specific arousal pathways may influence rate of learning eg memories with emotional impact more easily remembered; proposed that projections of hippocampus to neocortex allows it to supervise laying down of long term memories

Answer 393

temporary, anterograde amnesia with an acute onset that usually occurs in middle-aged and older individuals often precipitated by particularly strenuous activity, high-stress events, or coitus, but it can be seen with migraines thought to arise from the hippocampus, particularly the CA-1 and Sommer sector, and mediobasal temporal lobe. The hippocampal region noted is a watershed area of the brain that is especially subject to impact from various metabolic stresses present with acute onset of several hours of memory loss. They will display repetitive questioning and have no recall of how they got where they are or what they did in the time immediately preceding the onset. Often, the person(s) accompanying the patient will report recent activity such as vigorous exertion, coitus, or severe stress. They will not report a loss of consciousness. They do not lose their self-identity ability. There are no accompanying neurological deficits or other cognitive deficits. There will be no history of trauma, and the symptoms will resolve within 24 hours of onset. The presence of active seizures excludes TGA, whether new-onset or chronic oxicology screen, alcohol level, and basic labs including glucose and electrolytes should be reviewed. Vitals, including oxygen saturation, should be checked. Because of the possibility of similar presentation with Wernicke encephalopathy, consider administering thiamine. If there are features suggestive of repetitive or seizure-like etiology, EEG could be considered, but it is not routinely recommended. MRI with diffusion-weighted imaging is needed to rule out ischemic stroke, which can have a similar presentation in some cases it is ultimately a diagnosis of exclusion ddx includes intoxication on substance, Wernicke encephalopathy, ischemic stroke, epileptic disorder, transient ischemic attack, toxic encephalopathy, hypoxia, or head injury. However, the confusion is more global in many of these cases and it is not limited to memory loss or there are other presenting symptoms. In seizure-related memory loss, there is usually seizure-like activity prior to the onset, and the memory loss is almost purely retrograde; this differs from TGA which involves anterograde amnesia presenting with minimal retrograde amnesia confined to events surrounding the onset

Answer 394

long term change in efficiency of synaptic transmission; brief trains of tetanic stimulation to dentate gyrus caused increased amplitude in electrically evoked responses, and subsequently this was also shown in HC itself; the enhanced firing can last many days; LTP is useful synaptic model of learning/memory because it is rapidly induced, long lasting, synapse specific, can be associative in nature (weak + strong stimulus, both strengthened - ie behavioural conditioning) although in C3 it is non-associative (strong stimuli only), and it (along with LTD) is seen in many neocortical areas and other structures perforant, mossy fibre and schaffer collaterals all use glutamate with kainate and AMPA (quisqualate) receptors mediating fast transmission and NMDA (agonist for NMDA only has no effect, antagonist AP5 can block LTP in CA1-CA3 pathway); there are however many forms of LTP dependent on diff kinds of activity and with diff underlying mechanisms, not all using NMDAr, not all associative, not all dependent on post-synaptic activity infuse AP5 into ventricles over long time at slow rate, near hippocampus, impairs learning of the water maze task; thus NMDAr involved in LTP and spatial learning; this supports (but doesnt prove) LTP in spatial learning (with recent evidence even throwing doubt on this link); (not related to title but nice summary) say someone burns hand on oven, imagine lesion just before/after to diff bits of brain: hippocampus they will feel anxious next time they see oven but not know why, amygdala will remember burning themselves but wont feel anxious, temporal cortex may not recognise it as oven or say what it is used for; cool memory diagram: memory: short/sensory/working, and long: implicit (cerebellum, BG, association cortex) and explicit (MTL, diencephalon, neocortex)

Answer 395

brocas: laboured, slow speech with impaired articulation but can usually communicate as select correct words (nouns more so than verbs and conjunctions, which may even be missing); comprehend words/sentences but struggle to repeat complex ones; in severest form patient can say almost no words; damage is to broca's area (brodman's 44/45), the surrounding frontal field, white matter, and the insula and BG, and if damage restricted to Brocas area get less severe + transient aphasia; can understand sentence if can piece together meaning by knowledge of individual words but not when grammar complex - in other words when short term memory needed to link gramatical ideas (they do understand grammar rules) wernickes: lesions on left hemisphere sup temporal lobe; speech pattern is effortless, melodic and at normal rate but content unintelligible due to frequent wrong words and phonemes; patients also have trouble comprehending sentences; damage specifically to post part of left auditory association cortex (brodmanns 22), and in severe cases also middle temporal gyrus and underlying white matter

Answer 396

split brain patients have corpus callosum and anterior commissure severed to treat epileptic seizures: can name object in right hand (processed in left hemisphere) but not object in left hand - only rudimentary description eg ball = round thing (also they couldnt see what they were holding), left hemisphere can respond to written commands whereas right responds to non-verbal or rudimentary written commands; right half's role is in prosody (emotional and tonal colouring of language) such as intonation to indicate a question; ant right hemisphere damage can cause inappropriate intonation, post right hemisphere damage leads to problems identifying emotion in other's speech, understanding jokes, working in social settings, and incorporating sentences into coherent narrative

Answer 397

transcortical motor aphasia (damage ant to broca's area) similar to broca's but without impaired repetition, and transcortical sensory aphasia from damage to cortex near parietal/occipital/temporal lobe junction, and similar to wernicke's but without impaired repetition; TMA speak non fluenty but can repeat even very long sentences, TSA show poor comprehension but repeat v long sentences and even correct grammar of sentence they dont understand; wernicke's model doesn't explain these, lichtheim suggests these due to disconnect of language centres (auditory/wernickes and motor/brocas) from concept centres wernicke-geschine model: extend lichtheim and suggest distinct routes: spoken word to area 41/42 then wernicke's, then on to be recognised and 'heard'; written through area 17, then 18/19, then area 39 (angular gyrus), then wernicke's, then perceived (so written word translated in head into spoken); cognition to wernicke's to brocas to motor cortex regions for face, along cranial nerves and muscles move/you speak but problems: when reading, info from visual cortex doesnt go through angular gyrus or wernicke's area so must take alternate route to ant speech areas; also much overlap between speech production and word comprehension so these abilities not independent; also category specific naming deficits (anomias eg can name animals but not tools) and modality specific deficits (define names of animals worse than define pics of them) so no single comprehension system (neuroimaging backs this up) (also anomias arent associate visual agnosias); model doesnt include subcortical areas known to play role like BG; can remove cortico-cortical connections from sensory to speech, and arcuate fasciculus, without causing aphasia good model accounting for these criticisms: written processed in striate cortex, then recognition in extrastriate cortex, on to semantic association in inf frontal cortex, and premotor coding in SMA and other areas near sylvian fissure (also from semantic association to premotor coding); auditory processing of spoken word in primary auditory cortex, then recognised in temporoparietal cortex (angular gyrus) and ant sup temporal cortex, on to semantic association and premotor coding; both can go from premotor coding to motor control of speech in PMC, then speech produced neuroimaging of language: study activity when passively viewing words, listening, speaking, generating words, and at rest; first activates striate and extra-striate cortex, second primary/secondary auditory cortex including wernicke's (non-word stimuli didnt activate these specific parts of visual/auditory cortex); when repeating written/spoken word, same areas of cortex activated as when perceiving word, plus activity in PMC/SMA/broca's area; when generating new words, activity in frontal/temporal cortices thought to be related to word association task

Answer 398

apraxias: motor disorders of voluntary movement: limb, oral (speech), agraphic (writing), constructional (copying visual/mental pictures); many are ideomotor ie can do movements spontaneously but not on command or to imitate; also often impairments in learning new sequences of actions; associated with damage to post parietal cortex, frontal premotor areas, and connections between them; generally deficits in recognition and execution of movement (eg constructional) from parietal damage, execution but not recognition with premotor damage posterior parietal cortex: areas 5/7 with rostral part integrating somatosensory/proprioceptive info relating body part position to movement, posterior part integrates visual info about events in external info so role in motor eg reaching outwards; lesions in monkeys impair sequential reaching movements (removing polo mints from bent wire); single unit recordings in monkeys show neurons in area 7 which fire when monkey detects visual target, increasing firing as arm projects towards it and decreasing once arm reaches it, and manipulation neurons which fire when target is manipulated; this region has reciprocal connections to lateral and medial premotor areas of frontal lobes lPMC and SMA: both connect to motor and post parietal cortices; LPC also with cerebellum more and SMA basal ganglia more; both output to subcortical motor systems and corticospinal tract via PMC; both areas involved in selecting appropriate movements, sequential ordering of the movements, and optimising conditions eg posture, inhib of irrelevant movements; SMA esp important for bimanual movement and internal generation of action (movement when no external cues) whereas LPC more when have to use external cues to direct action; ventral regions of LPC contain mirror neurons (also in inf parietal cortex, maybe involved in detecting intention of others) ablation of SMA gives deficit in bimanual coordination, orientation of fingers/hands when approaching food, failure to raise hands in absence of external cues to get peanut reward; SMA pathology may give alien hand syndrome with movements outside your control; SMA far more active when performing learned sequence of finger movements rather than following cues to do novel movements (along with hippocampus and occipital regions); ablation of PM in monkeys gives deficit in hand actions directed by external cues; PET studies show when doing new externally directed movement, PM, lat prefrontal, parietal, and cerebellum are more active; damage to premotor areas can release suppressed reflexes (sucking, rooting, grasping) with these possibly residing in parietal lobe and under inhib from frontal

Answer 399

lesion to prefrontal cortex causes loss of inhibition eg in wisconsin card sort test which shows failure to inhib previously relevant rules governing behaviour so in test learn to sort cards according to colour, unable to switch to sorting by shape, continuing to sort by colour; mainly associated with damage to lat pfc; monkeys with prefrontal damage also show behavioural inflexibility/perseverance eg after having learned one object is associated with a reward, find it hard to switch responding to other object when that one gives reward instead PET shows it is part of distributed neural network involved in spatial/feature detection with subjects asked to attend to either colour, shape, or movement lesions of various pfc regions impair delayed response task where monkeys have to remember spatial/object/proprioceptive info for brief delay with sample stage (eg peanut hidden in object, shown an object, or required to press a lever 1 or five times) then brief delay, then choice stage; lesions dont impair monkey's ability if there's no delay; similar impairments in spatial responses seen in humans with damage to dorsal pfc; some neurons in lat regions of pfc in monkeys shown to fire during delay in spatial response task; thus pfc appears necessary for attending selectively to stimuli when in external world and maintaining attention to stimuli in mind when no longer in outside world orbital regions of pfc have large reciprocal connections with limbic system; damaging this region in humans/monkeys disrupts emotional and social behaviour eg submission/solictation shown by female monkeys when males approach replaced by indifference or aggression and indifference to own offspring, and patient EVR who was unable to maintain enduring attachment to sexual partner or function as a responsible parent; impaired social behaviour accompanied by impaired autonomic activity to emotion provoking pictures but not to loud noises; proposed orbital pfc enables emotions to contribute to complex decision making (aka the 'gut' feeling); orbitofrontal may be involved in selecting which of many positive/negative reinforces at any one time should be goal and dorsolateral regions involved in learning/planning higher order strategies to achieve goal; ultimately planning action requires: hold info in mind, filter out irrelevant info, choose goal, select responses to achieve goal, inhib inappropriate responses

Answer 400

former view emergence of cognitive skills as consequence of genetically preprogrammed cognitive mechanisms; some like face processing visible at birth and others emerge; assert that brain areas act as modules which process specific inputs like faces which seems plausible eg lesion of fusiform gyrus results in prosopagnosia with no other losses; evidence more complex than just modules present from birth though; latter assert newborn mind is blank slate with sensory images becoming connected if associated however problem in eg language acquisition where children develop sophisticated syntax at young age despite parents rarely correcting grammar piaget constructivism argued against both of the above with argument that cognitive development from primitive knowledge states (schemas, such as knowing how to grasp) which are innate but change as baby interacts with the world: by holding object baby learns they can stop objects falling, thus that they have agency, a precursor to learning that other people have agency too but this criticised for various reasons neoconstructivism postulates that innate biases to certain stimuli like faces allow general information processes (memory, attention, learning) and constructive processes (action on objects) to increase knowledge, giving specialisation of function; neonates will track moving faces more than other objects but this disappears around 4-6 weeks, then at 2-3months will look more at stationary face than another object; by 5 months, babies show no preference between face and other object (so dev doesnt occur in linear fashion); brain imaging studies show face processing areas dont dev fully until adolescence

Answer 401

fact that face processing areas show such extended dev suggests mechanisms involved in understanding others is long/complex; key mechanism is theory of mind: developing a guess of what other people are thinking; argued this doesnt develop until 4 based on what kids do in false belief test (eg sally ann task); might not be because they dont have a theory of mind, may just have not developed executive inhibition of pre-potent response to indicate location of where the doll etc is now; strong evidence for this from windows task (sweet hidden in cup, if child points at cup without sweet under it then they get it, even with no opponent and window into cup they point at one with sweet in so dont get it); by 4 years, children pass the falsebelief and windows tasks at 8 years children show greater prefrontal activation than adults when doing go-no go task (eg press button if x, dont if y), and adolescents also find some difficulty with this (although this may be due to different dev state of reward system and prefrontal cortex in teens, with enhanced activity of nucleus accumbens (reward) relative to orbitofrontal cortex (not in adults or kids) which may explain risk taking and impulsivity of teens; subtle dev of prefrontal cortex may also contribute to this)

Answer 402

wakefulness and awareness are two main components; awake consciousness is max of both, types of sleep to general anaesthesia and then coma is descending line to origin (min of both) for coma, and vegetative state is high wakefulness but low alertness; thus stages of consciousness can be plotted on graph; can add a third axis to represent behaviour; blindsight, from spared elements of primary visual pathway, subcortical etc cerebral metabolic activity highest in normal waking, then REM, then deep sleep, coma, GA, vegetative state; vegetative patients can hear, and speech can be perceived under some anaesthesias and classical conditioning can take place

Answer 403

psychosocial disturbances - impaired feeding or sleeping, poor school performance, aggression, regression to earlier dev stage, phobia or psychosomatic illness; usually response to family problems, poor parenting style, stress, injury, separation or bereavement, child abuse; multifactorial origins habit disorders - nail biting, breath holding, hair pulling, thumb sucking, body rocking, head banging, hitting or biting self; may reduce physical or emotional stress, eg tics (different from dyskinesia as absent during sleep); may provide comfort when alone, or reduce felt tension 6-7% children dev anxiety disorders; family therapy, parental training, treat psychiatry, liaise with school depression in children - as young as 5, up to 18; if mild then watchful waiting, if no change after 2 weeks group or individual CBT or ITP; after 2-3mo CAMHS referral; self help and lifestyle advice if moderate then CAMHS review; fluoxetine following CAP psych review, consultant may use sert or cital if severe; TCAs not used

Answer 404

may be normal variation eg girls tend to dev faster, consider referral if: no double syllable babble by 12mo, persistent drooling or fewer than 6 words by 18mo, no 2-3 word sentences by 2.5yrs, speech unintelligible by 4yrs primary delay, or sec due to physical problems (cleft lip, tongue tie, cerebral palsy), conductive or sensorineural deafness, learning disabilities, environmental deprivation, autism, dysarthria, selective mutism, apraxia of speech, stammer history, observe child play and interact with parent, ask them questions, assess general motor and social skills, examine mouth and ears; audiologist, speech and language therapy assessments; management dependent on cause, speech therapy may be needed

Answer 405

suspect in preschool child if: language delay or regression, or unusual characteristics eg monotone or echolalia; reduced or negative response to others eg delay or ignore their name being called, reject cuddles from parents, reduced tolerance of others in personal space, preference to play alone, reduced imitation of others actions; repetitive movements or play, overly focused interests, distress at changes, over or underreaction to sensory experiences; distinguish from dev delay and reaction to maltreatment in prim school kids may also see unusual skill profile eg social and motor skills poor but reading and vocab very good in secondary school may see excessive discussion of their interests or very limited speech; talking at others; reduced imagination and lack of flexible social play and creativity, though maybe reenacting scenes from eg TV; strong adherence to rules consider learning disability, global or specific dev delay, ADHD and other psych conditions, OCD, rett syndrome (girls motor regression, hand wringing, ataxia), hearing or visual impairment, selective mutism, maltreatment

Answer 406

is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors Neuropathologic studies are limited, but have revealed differences in cerebellar architecture and connectivity, limbic system abnormalities, and frontal and temporal lobe cortical alterations, along with other subtle malformations; genetic factors play a role in ASD susceptibility; Prenatal exposure to thalidomide and valproic acid have been reported to increase risk, while studies suggest that prenatal supplements of folic acid in patients exposed to antiepileptic drugs may reduce risk; Advanced maternal and paternal age have both been shown to have an increased risk of having a child with ASD; Maternal infection or immune activation during pregnancy is another area of interest and may be a potential risk factor according to recent investigations; Infants born prematurely have been demonstrated to carry a higher risk for ASD in addition to other neurodevelopmental disorders behavioral or psychiatric co-occurring conditions in ASD include anxiety, attention deficit/hyperactivity disorder (ADHD - 25-81% in studies), obsessive compulsive disorder, and mood disorders or other disruptive behavior disorders diagnosis is made based on fulfillment of descriptive criteria: Avoids or does not keep eye contact Does not respond to name by 9 months of age Does not show facial expressions like happy, sad, angry, and surprised by 9 months of age Does not play simple interactive games like pat-a-cake by 12 months of age Uses few or no gestures by 12 months of age (for example, does not wave goodbye) Does not share interests with others by 15 months of age (for example, shows you an object that they like) Does not point to show you something interesting by 18 months of age Does not notice when others are hurt or upset by 24 months of age Does not notice other children and join them in play by 36 months of age Does not pretend to be something else, like a teacher or superhero, during play by 48 months of age Does not sing, dance, or act for you by 60 months of age Lines up toys or other objects and gets upset when order is changed Repeats words or phrases over and over (called echolalia) Plays with toys the same way every time Is focused on parts of objects (for example, wheels) Gets upset by minor changes Has obsessive interests Must follow certain routines Flaps hands, rocks body, or spins self in circles Has unusual reactions to the way things sound, smell, taste, look, or feel Delayed language skills Delayed movement skills Delayed cognitive or learning skills Hyperactive, impulsive, and/or inattentive behavior Epilepsy or seizure disorder Unusual eating and sleeping habits Gastrointestinal issues (for example, constipation) Unusual mood or emotional reactions Anxiety, stress, or excessive worry Lack of fear or more fear than expected

Answer 407

Age Milestone 3 months Quietens to parents voice Turns towards sound Squeals 6 months Double syllables 'adah', 'erleh' 9 months Says 'mama' and 'dada' Understands 'no' 12 months Knows and responds to own name 12-15 months Knows about 2-6 words (Refer at 18 months) Understands simple commands - 'give it to mummy' 2 years Combine two words Points to parts of the body 2½ years Vocabulary of 200 words 3 years Talks in short sentences (e.g. 3-5 words) Asks 'what' and 'who' questions Identifies colours Counts to 10 (little appreciation of numbers though) 4 years Asks 'why', 'when' and 'how' questions

Answer 408

present at birth: moro reflex - gone by 2-4mo rooting reflex - gone by 3-4mo palmar grasp - gone by 5-6mo ATNR - gone by 6mo spinal gallant reflex - gone by 3-9mo appears later: landau reflex appears at 4-5mo and gone by 12mo STNR appears by 6-9mo and gone by 9-11mo

Answer 409

Two months At around two months you can expect your child to be able to do the following: Physical Whilst laying on tummy, baby turns their head to the side Whilst laying on back, baby waves arms, legs and wiggles/squirms Briefly holds a toy when you place it in their hand Follows an object or person with both eyes Communication Be able to make cooing sounds such as ‘aaah’, ‘gah’, ‘ooo’ Baby smiles when spoken to When you talk to your baby, they make sounds back to you Cries when wet, hungry tired or wants to be held Eye to eye contact is deliberately maintained Turns to voices Four months At around four months you can expect your child to be able to do the following: Physical When laying on tummy, baby will hold their head straight up and look around When in a sitting position, baby will hold their head steady, without support Whilst laying on back, baby will bring hands together over the chest, touching their fingers When in a sitting position, baby should start to reach for a toy close by When baby has a toy in their hand, they will hold it whilst looking at it, waving it about and attempting to chew it Communication When in front of a mirror, baby should smile or ‘coo’ at themselves Baby will be able to chuckle softly and/or laugh After you have been out of sight, baby will smile or get excited when they see you Baby will make sounds when looking at toys or people Baby will be able to make high pitched squeals Six months At around six months you can expect your child to be able to do the following: Physical Baby will roll from their back to their tummy Baby will be able to sit up with support Baby will be able to get into a crawling position Be able to grasp a toy using both hands at once Reach a small object using their finger and pick it up using their thumb and all fingers Be able to pick up a small toy with one hand and pass it to the other Plays with feet when laying on back Communication Holds hands up to be lifted Makes sounds like ‘Da’, ‘ga’, ‘ka’ Squeals and laughs Likes to look at themselves in a mirror Nine months At around nine months you can expect your child to be able to do the following: Physical Sits without support Can get into sitting position from lying down Will pull to stand and take weight on feet May crawl Rolls over both ways Communication Copy simple sounds Babbles making different sounds e.g. mamma Baby will when asked ‘Give it to me’ or ‘Put it back’ Recognises family members Clingy to familiar adults Has a favourite toy Twelve months At around twelve months you can expect your child to be able to do the following: Physical Sits well and gets into sitting position alone Pulls to stand from sitting position and can sit down again Walks around furniture May crawl or bottom shuffle May stand alone Help turn the pages of a book Throw a small ball Be able to pick up a piece of string with first finger and thumb Communication Points at objects Responds to own name When dressing, will hold out arm or foot to help Makes more meaningful sounds e.g. Mamma, Dadda Eighteen months At around eighteen months you can expect your child to be able to do the following: Physical Walks well Can walk upstairs holding an adults hand Can stack blocks on top of each other Turn the page of a book Put a small in their mouth, right side up Communication Says several single words Recognises and points to parts of the body Enjoys nursery rhymes and tries to join in Obeys simple commands, such as ‘bring me your shoes’ Two years old At around two years old you can expect your child to be able to do the following: Physical Tries to kick a ball Runs well Jumps with both feet leaving the floor at the same time Holds pencil by using thumb and first two fingers Can string small items such as beads, pasta onto a string Drinks from a cup with no lid Communication Likes to pretend and role play Can name well known objects Correctly uses words like ‘I’, ‘Mine’ and ‘You’ Will correctly put two – three words together Three years old At around three years old you can expect your child to be able to do the following: Physical Will walk on tip toes when shown Walks upstairs with alternate feet, still puts both feet on each step when coming down Catches a large ball Pedals a tricycle Climbs walls Communication Can say own name, age and sex Can say numbers up to 10 Pretend play is more vivid Plays with other children and takes turns Understands and uses ‘You’, ‘Me’, ‘I’ Four years old At around four years old you can expect your child to be able to do the following: Physical Walks up and down stairs using alternate feet Good on a tricycle Hops and stands on one foot Can throw, catch and kick well Draws a person with recognisable body parts eg head, arms and legs Uses a fork and spoon well Communication Knows own first and last name Can sing several nursery rhymes Likes to listen to longer stories and will tell own stories Continues to ask lots of questions Takes turns and shares Shows sympathy to friends when hurt or upset Five years old At around five years old you can expect your child to be able to do the following: Physical Can balance and stand on one foot for about 10 seconds Hops Dances Swings and climbs Slides down a slide Can now get dressed and undressed by self Communication Speech is very clear Knows name, address and age Likes listening and telling stories May have best friend Sense of humour increasing Uses more imagination Shows more independence

Answer 410

coma - unrousable unresponsiveness; a gcs <8, altered consciousness if gcs 9-14 hypoglycaemia, sometimes rarely hyperglycaemia, can result in altered consciousness; bedside glucose test so must do this for any pt with altered consciousness, confusion, coma, or focal neuro deficit commonest cause of altered consciousness is excess alcohol; opiates, bzds, tcas, certain street drugs also affect consciousness; opiate excess is dep cons, dep resp rate, pin point pupils, needlestick trackmarks or prescribed opioid - if suspect this then give naloxone; tca overdose is common cause of coma and will also see dry skin/mouth, urinary retention, tachy, ataxia, jerky limbs, divergent squint intracranial h+ also poss: sudden onset headache, altered cons, focal neuro signs; can present as sah or intra parenchymal h+; stroke doesnt alter conc level (big diff between this and the bleeds), but may appear that way due to altered communication, esp in locked in syndrome from brainstem infarction systemic or intracranial infection: often preceded by meningism, systemic infection signs, raised icp (vomiting, irritability, fits) coma also in post-ictal state but usually resolves in 30-60 mins, bleeding from tongue bite or urine from incontinence support diagnosis; look for ongoing seizure as status epilepticus poss psychogenic in <2% cases, must rule out everything else first; signs that it might be inc intact blink response, closing eyes when opened, bell's phenomenon, actively holding eyes closed head trauma is common cause of coma intacerebral sol by mass effect or anatomical position may cause coma, and inc tumour, cerebral abscess, cyst, granuloma; usually these will be slowly progressing symptoms but can get acute come from h+ into sol CO poisoning from smoke or fume inhalation can cause, usually multiple members of household would be affected hydrocephalus and vertebral a dissection hypoxia, hypercapnia, hypo/hypercalc, hypo/hypernat, uraemia, hepatic enceph, addisons, cushing, hypo/hyperthy, hypopitu

Answer 411

consider if speech and language dev normal but between age 3 and 10 abrupt deterioration to point becomes mute 70% cases will have partial or generalised seizures and eeg aids diagnosis -> post-temp and parietal continuous spikes, slow waves in sleep; behavioural and psychomotor dev problems anticonvulsants not that good, steroids used in short term

Answer 412

psychiatric illness, deafness, neurodegen disease, autism - younger age than L-K, fragile X, landau-kleffner

Answer 413

failing to meet or maybe regressing may also see personality changes, dementia, weakness, spasticity, ataxia, peripheral neuropathy, dysphasia, convulsions if grey matter involvement (poliodystrophy) and cortical blindness if white matter (leucodystrophy) causes inc metabolic (metachromatic leucodystrophy, adrenal leucodystrophy; tay-sachs, niemann-pick, gaucher [all poliodystrophies]; mucopolysaccharidoses; wilson disease, menkes syndrome; lesch-nyhan syndrome; lead poisoning) infection (HIV, encephalopathy, SSPE) immunological (ataxia telangiectasia) misc (huntington, rett syndrome, batten disease) fundoscopy may reveal CMV retinitis if HIV, optic atrophy w accentuated vessels and inc'd pigmentation in Batten disease, cherry red spot in tay-sachs and niemann-pick, papilloedema in lead poisoning urine should be sent for glycosaminoglycans hexosaminidase levels (tay-sachs), uric acid (lesch-nyhan), caeruloplasmin (wilsons), carnitine (fatty acid ox defects) also skin fibroblast culture for enzyme deficiencies, muscle biopsy, EEG and MRI

Answer 414

aka neuronal ceroid lipofuscinoses - group of rare inherited lysosomal neurodegenerative disorders that most often begin in childhood, most commonly 5-10yo; ceroid lipofuscin builds up in neurons leading to cell death; commonest cause of paediatric neurodegeneration People with NCL may experience the following symptoms: Progressive vision loss leading to blindness Seizures Cognitive decline and dementia with developmental regression Problems with movement Personality and behaviour changes Shortened lifespan Children with Batten disease may appear healthy and develop normally for the first few years of life before they begin to show symptoms, but infantile forms also exist enzymatic functional assay and genetic testing if suspect; Tissue biopsy and electron microscopy can show reliable and characteristic findings but they may not be present in every case

Answer 415

cranial: anencephaly, encephalocele (meningocele), spinal: spina bifida, meningocele inadequate folate, sod val, carbamazepine, FH are risk factors anencephaly - cranial vault absent, prenatal diagnosis, termination; otherwise 75% stillborn, rest die shortly after cephalocele - brain matter deviates through defect in skull eg meninges in meningocele, brain matter too in encephalocele; seizures. intellectual impairment, or other disturbance spinal meningocele: meninges outside spinal canal, normal exam, 5% cases spina bifida cystica myelomeningocele: 80-90% spina bifida cystica cases, disturbed bladder/bowel control inc obstruction + chronic pyeloneph, sensory loss to level of lesion, motor weakness below lesion, hydrocephalus, chiari malformation chiaria II malformation - medulla below foramen magnum to overlap spinal cord giving palsies and central apnoea spina bifida occulta -often incidental finding but if naevus, hairy patch, sinus then MRI spine indicated; may give asym lower motor neuron weakness, diminished reflexes and tone; can get spasticity and impaired bladder control keep newborn warm, defect covered with sterile saline dressing in prone position, close defect promptly; shunt for hydroceph if myelomeningocele; post fossa decompression for CM if sympt; physio, occupational therapy, wheelchairs or walking aids etc usually picked up on anomaly scan (18-21 weeks)

Answer 416

rapid onset of symptoms including headache, seizures, altered consciousness, and visual disturbance often but not always associated with acute hypertension PRES patients often have CKD or AKI -> renal disease and rapidly progressing neuro sx consider PRES in dd besides renal can be drug induced htn, autonomic following eg GBS etc also linked to autoimmune diseases like TTP or SLE, and to malignancy esp leukaemia visual disturbance can manifest as blurred vision, homonymous hemianopsia, or even cortical blindness; confusion varies from mild to comatose; status can occur, non-convulsive status more common (staring, eye blinking, head turning, or a prolonged postictal state lasting for more than a few hours) cause of PRES remains controversial, but the most popular theory is that severe hypertension causes interruption to brain autoregulation Breakdown in autoregulation occurs above a mean (two thirds diastolic, plus one third systolic) arterial blood pressure of 150 - 160 mmHg; in chronic hypertension, it occurs at higher pressures; Uncontrolled hypertension leads to hyperperfusion and cerebral vessel damage, resulting in interstitial extravasation of proteins and fluids, causing vasogenic edema however BP in PRES often not higher than upper limit of autoreg, PRES can occur in absence of HTN, and oedema isnt direclty linked to BP level alt theory is PRES due to systemic inflam giving endothelial dysfunction (such inflam could be autoimmune, infection, transplantation) and then vasoconstriction due to HTN exacerbates giving downstream hypoxia and oedema; but some cases theres no inflam state -> more research needed CT acutely to rule out other causes, but oft normal in PRES -> MRI shows bilateral white-matter abnormalities in vascular watershed areas in the posterior regions of both cerebral hemispheres, affecting mostly the occipital and parietal lobes but atypical features common mx is to control BP, AEDs if seizing, PRES normally resolves within a week MRI changes normally resolved within a month, but in 30-40% some changes persist, these usually resolved by 20 months

Answer 417

CVST, or SDH/SAH/intracerebral bleed an all present with headache, seizures, reduced consciousness, and focal neurologic signs. Infective encephalitis or meningitis, particularly herpes simplex encephalitis can too, and rapidly starting abx/aciclovir initially is good idea while pursuing diagnosis also consider posterior circulation stroke, central nrevous system vasculitis, autoimmune encephalitis and metabolic encephalopathies such as deranged serum glucose, sodium (including central pontine myelinolysis), uremia, or drug toxicity also consider ICU delirium

Answer 418

prevalence of delirium reported in medical and surgical ICU cohort studies has varied from 20% to 80% terms intensive care unit (ICU) syndrome and ICU psychosis have been used interchangeably to describe a cluster of psychiatric symptoms that are unique to the ICU environment. It is often postulated that aspects of the ICU, such as sleep deprivation and sensory overload or monotony, are causes of the syndrome suggested hallmark signs are a fluctuating level of consciousness, poor orientation, delusions and hallucinations, and behavioral anomalies, such as aggression or passivity; rapid onset, lasts 24-48 hours however has been argued term ICU syndrome is not helpful and potentially dangerous, since it implies that some causes that are not organic are responsible, which may discourage thorough investigation and treatment of the medical causes

Answer 419

aka complex motor stereotypies (note can also affect lower limbs or whole body); simple stereotypies inc thumb sucking and nail biting these movements include recurrent raising and lowering of the arms, internal and external twisting of the upper extremities, flapping, waving, rotating motions at the wrists, and rapid finger wiggling. The recognition that similar movements can be seen in children with autism, mental retardation, and sensory deprivation compounds medical interpretation and often leads to erroneous diagnoses, incorrect counseling, and unnecessary laboratory investigations Motor stereotypies, clinically defined by their involuntary, patterned, coordinated, repetitive, rhythmic, and nonreflexive features, typically last for seconds to minutes, tend to occur in clusters, appear many times per day, and are associated with periods of excitement, stress, fatigue, or boredom. These movements are readily suppressed by sensory stimuli or distraction and are of little concern to the patient onset before 2yo often, before 3yo almost always, but oft not seen until 5yo+ ADHD and learning disabilities are common, and there is an increased familial history of stereotypies or tic disorders; appear to persist for many years best managed through distraction rather than suppression which can cause anxiety - teachers at school could eg ask them to do a task like handing out books Reassurance and psychoeducation are usually appropriate for stereotypies, but in some patients they can reduce quality of life, and in these patients, behavioral therapies such as habit-reversal training or response interruption and redirection can reduce the severity and frequency of stereotypies, while pharmacotherapy is usually not effective

Answer 420

differential diagnosis in developmentally normal children with complex stereotypies includes complex motor tics, compulsions, and paroxysmal dyskinesias. Complex tics, defined as abrupt movements that involve either a cluster of simple motor tics or a more coordinated sequence of movements, have several features in common with stereotypies (eg, intermittent and precipitated by excitement). A variety of clinical characteristics, however, can assist in distinguishing them (1) stereotypies have onset at an earlier age (<2 years) than do tics (mean onset, 6-7 years); (2) they are more constant and fixed in pattern compared with the more variable action of tics; (3) they involve arms, hands, or the entire body rather than eye blinks, facial grimaces, head twists, or shoulder shrugs; (4) they are more rhythmic, with flapping and waving, than tics, which tend to be rapid and random; (5) they are generally more continuous and prolonged in duration; (6) they are not associated with premonitory urges or desires to reduce an inner tension; (7) although both might occur during periods of excitement or stress, stereotypic movements often occur when the child is engrossed in an activity (eg, computer games or at a game arcade); and (8) stereotypies can be stopped by distraction, but the child rarely makes a conscious effort to control the movements, whereas tics can be voluntarily suppressed for brief periods Compulsions differ from stereotypies by their association with an attempt to prevent or reduce distress or some dreaded event or situation. They are also frequently driven by an obsessive thought or by intrinsic rules that must be applied rigidly. Finally, paroxysmal dyskinesias include episodic bouts of chorea, athetosis, or dystonia, which are frequently precipitated by sudden (kinesigenic) movements

Answer 421

characterized by sudden, rapid, recurrent, nonrhythmic movement or vocalization, and are the most common movement disorders in children. Their onset is usually in childhood and tics often will diminish within one year. However, some of the tics can persist and cause various problems such as social embarrassment, physical discomfort, or emotional impairments, which could interfere with daily activities and school performance. Furthermore, tic disorders are frequently associated with comorbid neuropsychiatric symptoms Conventionally, movement disorders are divided into two categories. The first category is hyperkinetic movement disorders, associated with an excess of movement (e.g., excessive, unnatural, and involuntary movement). These include tics, stereotypies, chorea, myoclonus, dystonia, and tremor; he second group is hypokinetic movement disorders, with a paucity of movement (e.g., decreased amplitude, decreased speed, or loss of movement), including bradykinesia, akinesia, and rigidity Simple motor tics are brief, abrupt, repetitive, and seemingly non-purposeful movements, and involve only one muscle group or body part (e.g., face, neck, shoulders, or hands); otor tics most frequently involve the eyes and mouth, followed by the neck and limbs; feet and midline axial structures are the least frequently involved; Examples of motor tics include blinking, eye rolling, wide opening of the eyes or mouth, tilting the neck, raising the shoulders, and shaking the hands. Based on their phenomenology, simple motor tics are subdivided into three groups: clonic, dystonic, and tonic tics complex motor tics are caused by several muscle groups and sometimes appear to be purposeful, coordinated, or orchestrated patterns of movement. Examples include touching, tapping, waving, kicking, jumping, echopraxia (mimicking others’ gestures), and copropraxia (performing obscene or forbidden gestures or inappropriate touching) Simple vocal tics are meaningless sounds made by moving air through the nose, mouth, or throat. Vocal tics are often referred to as “phonic tics,” because the sound may be produced not only by contraction of the vocal cords but also by contraction of the nasal, oral, laryngeal, pharyngeal, and respiratory muscles. Examples include coughing, throat clearing, grunting, mimicking animal noises, and tongue clicking. Complex vocal tics involve several muscle groups and are characterized by words, phrases, or sentences. Examples include shouting and yelling, echolalia (repeating another person’s words), and coprolalia (uttering socially inappropriate expressions) neurological examination is normal in children with a tic disorder, except for the tics themselves Tics usually begin between 3 and 8 years of age. The first tic symptoms are usually simple motor tics involving the face, head, or neck. Tics then spread in the rostro-caudal direction over time If tics persist for more than one year, the severity usually peaks around 8–12 years of age and most patients with tics experience significant improvement or complete resolution by early adulthood Tics usually follow a waxing and waning pattern in severity and frequency, with a mixture of old and new tics. Although the onset of TS does not seem to be associated with life events, exacerbations and fluctuating severity of tics are related to environmental factors Tics may be temporarily exacerbated by psychological strains (e.g., stress, anxiety, excitement, anger), physical strains (e.g., fatigue, sleep deprivation, and infections), and environmental changes. This exacerbation is usually transient and subsides after the cause resolves. Individuals with tics often experience an unpleasant sensation preceding the tics, referred to as a premonitory urge, which is temporarily relieved by the execution of the tics Currently, tic disorders and TS are considered to be polygenic inherited disorders involving a large number of different genes Tourette syndrome is frequently comorbid with other psychiatric symptoms, such as ADHD, OCD, autistic spectrum disorder, depression, anxiety disorder, sleep disorders, migraine, and self-injurious behavior Adequate education for patients, family members, and schools is sufficient. If tics are severe and bothersome enough to affect quality of life, activities, or self-esteem, or cause significant social, emotional, and physical impairments, it is appropriate to refer the patient to specialists To assess the frequency and severity of tic symptoms, the Yale Global Tic Severity Scale (YGTSS) is often used in clinics behavioural therapy is first line mx pharmacological if these fail or severe/vilent tics needing immediate treatment; first choice alpha-2-adrenergic agonists such as clonidine; keppra, topiramate, clonazepam, baclofen have worked too; second line are DAr blockers (aka antipsychotics)

Answer 422

Various movements may resemble tics, from the common (e.g., habits, stereotypies, and mannerisms) to the abnormal (e.g., compulsion, chorea, dystonia, and myoclonus). To distinguish such movements from tics, one can confirm the presence of the premonitory urge, suppressibility, and suggestibility, as well as the phenomenology and timing of the movements vs stereotypies: Stereotypies usually begin before the age of 3 years, which is earlier than the onset of tics, and they tend to improve during childhood, stereotypies are longer in duration, rhythmic, and less variable in type, location, and severity over time, premonitory urge is not seen in patients with stereotypies. Stereotypies often provide a comforting, enjoyable, and pleasing experience for children, in contrast to the discomfort and distress of tics some complex motor tics such as touching, tapping, and knocking resemble compulsions. Clinically, compulsions are associated with specific, sometimes ritualistic rules, or are performed in response to an obsession to reduce anxiety, distress, or discomfort; do not experience premonitory sensations. Compulsions and complex tics may both occur in patients but distinguishing between them can be important to guiding treatment of the most bothersome symptoms. Compulsions improve with treatments for OCD, such as behavior therapy or serotonin reuptake inhibitors chorea is characterized by brief, abrupt, irregular, unpredictable, purposeless, non-stereotyped movements flowing randomly from one part of the body to another; Damage or dysfunction of the interconnection between the motor cortical areas and the basal ganglia, including the caudate nucleus, putamen, globus pallidus interna and externa, and associated structures such as the subthalamic nucleus and substantia nigra, leads to deficient inhibition to the thalamus and excessive thalamocortical motor facilitation, resulting in chorea movements etiologies of acute chorea include autoimmune disease, infection, vascular disease, mitochondrial disease, toxins, and functional disease and those of chronic chorea include genetic, metabolic, and vascular diseases unlike tics, patients with chorea do not have premonitory urges. Compared to chorea, tic movements are usually more patterned and are repeated in a predictable and stereotypical manner Dystonia is a movement disorder characterized by involuntary sustained muscle contractions that produce abnormal postures or repetitive movements; most distinctive features of dystonia are sustained twisting movements, a sensory phenomenon called sensory trick (i.e., an internally generated, specific voluntary movement aimed at ameliorating the dystonia), task specificity, and directionality (e.g., alternates between quick jerking movements in one direction and slower movements in the opposite direction); dystonia is not preceded by premonitory urges myoclonus: brief, sudden, involuntary muscle jerks. It arises from all levels of the nervous system, including the cortical and subcortical areas, brainstem, spinal cord, and peripheral areas, and causes muscle contractions (positive myoclonus) or brief inhibition during sustained posture (negative myoclonus); Tics and myoclonus may be visibly indistinguishable, but some clinical features are useful to distinguish them. Myoclonus is very brief (traditionally <200 ms on EMG), is non-suppressible, may be unpredictable in terms of location and timing, and is not associated with a premonitory urge

Answer 423

diagnosis of Tics and Tourettes is a clinical one A child or young person must: have multiple motor and one or more vocal tics that happen regularly although not necessarily at the same time have tics occurring many times a day or on and off for longer than one year. There should not have been a tic-free period of more than three months be distressed about the tics or they have a significant effect on home life, social life and schooling be less than 18 years old not have any other conditions that could cause the tics Examples of physical tics include: blinking eye rolling grimacing shoulder shrugging jerking of the head or limbs jumping twirling touching objects and other people Examples of vocal tics include: grunting throat clearing whistling coughing tongue clicking animal sounds saying random words and phrases repeating a sound, word or phrase swearing aka copralalia (only 10% of pts) Tics may be preceded by premonitory feeling that can feel like the urge you get before sneezing or eg itchy throat before grunting or sore eyes before blinking; can control tics sometimes, but often have to release them later Tics do not always need to be treated if they're mild and will often go away or improve significantly after a few years more severe tics can cause issues such as difficulties at school or social problems. Initial treatment is self-directed and there are some general principles that can be shared – avoid stress, anxiety and boredom. Aim for good sleep. Reassure the child and ensure that attention is not drawn to the Tics and that they aren’t told off for them Those with ADHD (commonest co-morbidity) should be referred to the school SENCO and Community Paediatrics Those with anxiety, depression, OCD, severe mental disorder should be referred to CAMHS then therapy - habit reversal training or exposure with response prevention guanfacine or clonidine can be useful if tics and ADHD present for severe resistant tics, haloperidol, risperidone, and aripiprazole can be used

Answer 424

dystonia is a neurologic disorder characterized by sustained or intermittent contractions causing abnormal, often repetitive movements, postures, or both; focal dystonia affects muscle groups in single body region 55% of patients with LD report gradual symptom development, whereas the other half (45%) experience a sudden onset, often associated with stress or upper respiratory infection task specific: selective impairment of speaking, singing, or inspiration depending on which muscle affected. Patients with adductor dystonia exhibit worse symptoms on voiced phonemes during counting from 80 to 90, whereas patients with abductor dystonia have more difficulties with voiceless phonemes during counting from 60 to 70. In addition, shouting may differentiate between LD subtypes as it is more challenging for those with adductor dystonia due to increased effort for voice projection. Conversely, whispered speech, overt emotional speech, innate vocalizations (e.g., crying, laughing, and yawning), and other upper respiratory behaviors (e.g., coughing and sniffing) remain intact Neuroimaging studies determined that LD pathophysiology involves widespread alterations of network function and structure, which comprise not only the basal ganglia but also higher-order motor and associative cortical regions, thalamus and cerebellum. Alterations of premotor and parietal cortices are of critical importance as they are influenced by external and polygenic risk factors, likely triggering symptoms in susceptible individuals Altered brain plasticity and neurotransmission in LD points to other mechanisms in dystonia pathophysiology, including abnormal dopaminergic and GABAergic function and maladaptive plasticity botulinum injection clinical choice for temporary symptom management of LD. However, the benefits are limited, with more than 40% of patients remaining untreated

Answer 425

Stiff person syndrome (SPS) is a rare disorder of the central nervous system characterized by rigidity and stimulus triggered painful muscle spasms of predominantly axial and proximal limb muscles it is an autoimmune condition associated with high titres of autoantibodies to various components of inhibitory synapses, which leads to their impaired functioning; the production of anti-GAD65 antibodies is a hallmark; often get with other autoimmune diseases, and pts often have or develop anxiety or depression leading to condition being termed FND paraneoplastic form accounts for 5% to 10% of all cases, associated with breast, colon, small cell, and others usually starts with rigidity and stiffness of the trunk muscles, specifically in the thoracolumbar region, due to continuous contraction of both abdominal and paraspinal muscles. Patients describe difficulties bending and turning, feeling that they walk like a “tin-man.” Later, the rigidity spreads to proximal upper and lower extremities. then abnormal posturing and joint deformities, get gait disturbance and falls painful spasms and exaggerated startle responses; worsens with stress so diurnal and linked to eg cold, infection partial form may be isolated limb, resembling dystonia, or else just trunk current diagnostic criteria for classic SPS include: Stiffness in the limb and axial muscles, prominent in the abdomen and thoracolumbar region Painful spasms precipitated by unexpected tactile and auditory stimuli Evidence of the continuous motor unit activity in agonist and antagonist muscles demonstrated by EMG Absence of other neurological impairments that could support an alternative diagnosis Positive serology for anti-GAD65 or anti-amphiphysin autoantibodies Clinical response to therapy with benzodiazepines/baclofen IVIG and rituximab also used, steroids controversial

Answer 426

dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive opisthotonus, risus sardonicus, and trismus are found in tetanus other causes inc meningitis, encephalitis, orther cerebral infection eg malaria or syphillis, poisoning with various drugs, intracranial bleed of any kind, hydrocephalus, HH or wilsons, PD, neurometabolic disorders like maple syrup urine disease, glutaric aciduria, Lesch Nehan syndrome, dopa-responsive dystonias, anoxic injury, psychogenic, dandy-walker malformation in babies: Cerebral palsy, Krabbe disease, hyperbilirubinemia, and kernicterus, Gaucher disease, adenylosuccinate lyase deficiency, infant alcohol withdrawal syndrome typical posture occurs due to the simultaneous mass contraction of agonist and antagonist muscle groups along with increased tone. There is an imbalance between facilitatory and inhibitory neurologic pathways innervating the muscle groups involved. It is possible that the secretion of inhibitory neurotransmitters, such as glycine and gamma-aminobutyric acid, plays a role. Consequently, there is uncontrolled activity of alfa and gamma motor neurons. The segmental reflex loop keeps active, perpetuating a sustained state of muscle contraction. In tetanus, the toxin blocks the presynaptic spinal inhibitory neurons treat the underlying condition

Answer 427

symptoms begin at a young age and usually include lack of attention, lack of concentration, disorganization, difficulty completing tasks, being forgetful, and losing things. These symptoms should be present before the age of 12, have lasted six months, and interfere with daily life activities in order to be labeled as 'ADHD.' This must be present in more than one setting (i.e., at home and school, or school and after-school activities) one of the most heritable conditions in terms of psychiatric disorders The anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) are found to be small in individuals who are suffering from ADHD. It is thought that these changes account for the deficits in goal-directed behavior. Moreover, activity in the frontostriatal region is also reduced in these individuals as measured by fMRI; but ADHD is a clinical diagnosis ADHD is diagnosed in children based upon their history, where the children face difficulty in at least 6 of the 9 symptoms as mentioned in DSM 5. Inattentive symptoms include: not paying close attention to tasks, missing small details, rushing through tasks, not seeming to listen when spoken to, difficulty organizing things, not finishing work, dislikes or avoids tasks that take sustained mental effort, losing thins, or being forgetful. Hyperactive symptoms include: fidgeting, feeling like an "internal motor" is always going, leaving their seat, climbing on things, being loud, blurting out answers, talking excessively or out of turn, having trouble waiting their turn, interrupts, or intrudes on others. These symptoms must be present in multiple settings Pharmacological therapy remains the mainstay of treatment for patients who have ADHD. It is divided into two major categories, which fall into stimulants or non-stimulants. Stimulants are further broken into amphetamines and methylphenidates. Both types of stimulants block the reuptake of dopamine at the presynaptic membranes and postsynaptic membranes. Amphetamines also directly release dopamine. Stimulants are the mainstay of treatment for ADHD. They are effective in about 70% of patients recent studies showed that stimulant use for ADHD is safe in epilepsy can be an increase in the frequency of tics in patients with ADHD and Tic disorders. Adding alpha agonists may help to reduce tics. However, these are associated with multiple cardiovascular effects like lowering blood pressure, sedation (clonidine more than guanfacine), weight gain, dizziness, SNRIs can be used in children who don't tolerate stimulants or have anxiety

Answer 428

Preceding symptoms: ? Gradual onset vs. immediate? Headache, fever? Abnormal movements/seizure? Weakness / focal deficits? Last known normal. History of substance or EtOH use. med/neuro/psych history if you can get it, plus any med changes Pupil size & reactivity. Eye position & Doll's Eyes reflex. Corneal reflex. Response to TMJ, sternal, & limb stimulation (all 4). -> localise/abnormal posturing Cough reflex (if intubated). Patellar reflex, ? ankle clonus. Babinski sign. Nuchal rigidity. from this you get GCS STAT fingerstick glucose. Electrolytes including Ca/Mg/Phos. CBC with differential. Coagulation studies (INR, PTT). Liver function tests & ammonia. TSH (thyroid stimulating hormone). Blood gas ?hypercapnia CK tox screen as appropriate: Serum salicylate & paracetamol levels. Carboxyhemoglobin level (from the gas) Serum ethanol level. cultures, CXR, urine dip non-contrast CTH; CTA and perfusion if ?stroke, CTV if ?CVST MRI if above workup NAD LP if suspect meningitis, encephalitis, or above ix have found nothing EEG (may be NCSE), esp if seizure history, Clinical indications of possible nonconvulsive status, for example: Focal twitching of the hands or face, nystagmus, eye blinking, or chewing movements. Recurrent pupillary hippus (pupils dilating/constricting spontaneously), pupillary dilation. Focal neurologic findings despite a normal CT scan (e.g., gaze deviation), or elevated lactate IV dex if glucose low, IV thiamine unless you know theyre nutritionally replete, naloxone (careful if pt on opioids for pain), hold sedating meds, maintain adequate MAP, gentle BP reduction if >180/120mmHg or pt has eg PRES Maintain normothermia COnsider empiric abx +/-antivirals+/-dex (following culture but before CTH) Load on keppra if suspect seizures/NCSE Control ICP, correct electrolytes Intubate if airway threatened, dialysis if needed sedating meds: Opioids. Alcohols (ethanol, methanol, ethylene glycol). Sedatives, including baclofen. Serotonin syndrome. Malignant catatonia, including neuroleptic malignant syndrome. Sympathomimetic intoxication. Salicylate poisoning. Lithium. Anticholinergics, including tricyclics. Carbon monoxide. most common kind of stroke to cause coma is basilar CVST causes through 2 means: straight sinus can cause b/ thalamic dysfunction, or if large or multiple then can get diffuse cerebral oedema Coma results from disruption of pathways from the ascending Reticular Activating System. This system originates in the tegmentum of the upper pons and midbrain, projects via the central tegmental tract to the bilateral reticular nuclei of the thalami, and subsequently diverges widely throughout the bilateral cortexes For a lesion to cause coma, it must have one of the following locations: (1) Dorsolateral upper-mid pontine lesion (2) Paramedian upper midbrain lesion (3) Bilateral thalamic injury (e.g., artery of Percheron occlusion, or vein of Galen thrombosis). (4) Diffuse bihemispheric damage Coma cannot be attributed to a unilateral cortical lesion alone.(33218655) For example, in order for a unilateral cortical lesion to cause coma it must cause a herniation syndrome that results in damage to the upper midbrain.

Answer 429

Locked-in syndrome is caused by a lesion in the anterior (ventral) pons which damages the bilateral corticobulbar and corticospinal tracts. This eliminates nearly all afferent motor activity from the brain. Sensory pathways and the reticular activating system in the posterior pons are preserved, so the patient is awake and has preserved sensation. Vertical eye movements and blinking are usually spared (since these are controlled by the midbrain tegmentum). abulia/akinetic mutism Profound failure of executive function (potentially including failure to speak, move, or eat). Patients may respond to questions, but only in a very delayed fashion. Visual tracking may occur, with conjugate eye movements. Often reflects damage to the medial frontal lobe(s). - generally ACA territory infarct hypokinetic catatonia Common symptoms include immobility, mutism, and staring. Less commonly rigidity and posturing may be seen. Other distinctive features of catatonia may be useful if observed (e.g., cataplexy, waxy flexibility). May be incontinent, or retain Rarely, this may progress to malignant catatonia wherein autonomic instability occurs (e.g., hyperthermia, diaphoresis, labile blood pressures, and tachypnea). Functional unresponsiveness Time-limited state that resembles stupor or coma, with impaired responsiveness to external stimuli such as pain, lasting longer than 30 minutes. Unequivocal evidence that brain function is analogous to a waking state during this time. Experienced by the patient as a genuine and involuntary problem (this is not factitious/malingering). Not better explained by catatonia. Common triggers may include psychological stress, or procedures involving anesthesia. Malingering Malingering refers to intentionally faking a coma for the purpose of secondary gain (e.g., avoiding an uncomfortable situation). Neurological examination may appear similar to functional unconsciousness (as above). A clue may be that patients look around or move when they think nobody is paying attention.

Answer 430

dissociative seizures can be explained as problem with way neurons wire to each other, as opposed to problem with their electrophysiology or synaptic activity, and so treatment is to rewire them more appropriately - medication can't do this, but brain can rewire itself as in learning, eg with conditioning after an aversive stimulus like food/drink making you sick; formal way to help brain re-wire is through cognitive techniques performed by psychologists; likewise for other functional sx like paralysis ask patients if they're engaging with health influencers and ask if they will try a "social media cleanse" - some symptoms spread via social contagion (give examples like tiktok tics, yawning, feeling hungry after seeing food commercials) and tell them some patients show improvement with a social media break. Using the wellness "cleanse" language can resonate pretty well

Answer 431

plagiocephaly - normal, corrects in weeks, no pressure on brain etc, often linked to a preference for turning head in one direction dislike of tummy time - important to build strength for crawling, sitting, getting rounded head shape; do as often as possible when baby awake and happy, they might not like to start with but you need to encourage them and they will start to like it delayed sitting - should be able to within 4-9mo, will be delayed if don't have enough tummy time so try to do more (give leaflet on tips for this) bottom shuffling - builds less muscle than crawling on hands/knees, so can delay walking until 24-30mo - so encourage hand/knee crawling if possible w sitting - sitting with bottom, knees, feet all on ground and knees outside feet; discourage as leads to weak core, in-toeing, delayed motor development and back/hip pain as adults delayed walking - if prefers to bottom shuffle, commando crawl, bear walk, or if using baby walker may have weaker muscles and so delayed walking to 18-24mo normal gait variations that kids grow out of: in-toeing, flat feet (all children have as arch doesn't form until 3yo, if not symptomatic don't need treatment), crossed toes (no PT needed if walking okay and toes flexible), knock knees (normal and corrects by 6-7yo) and bow legs (normal and corrects by 4yo, associated with obesity and early walking), tip-toe walking is normal in early stages and should self-resolve quickly, frequent falls (>17 times an hour in some studies, help build strength and balance, will reduce in frequency over time)

Answer 432

exclude confound from: depressant drugs, neuromusc blocking drugs, hypothermia, metabolic or endocrine disturbance, c-spine injury causing apnoea check pupil response, corneal reflex, eye movement on caloric testing, face motor response to stimulation of face limbs and trunk, gag reflex, cough reflex, apnoea testing, absence of respiratory movements Reflex movements of the limbs and torso may still occur in the presence of irreversible cessation of brain-stem function, and should be explained this is due to spinal reflexes and don't represent higher function of the brain apnoea testing should be last to be performed and should not be performed if any of the preceding tests confirm the presence of brain-stem reflexes the procedure recommended to induce moderate hypercarbia and mild acidaemia is as follows: * Increase the patient’s FiO2 to 1.0 * Check arterial blood gases to confirm that the measured PaCO2 and SaO2 correlate with the monitored values * With oxygen saturation greater than 95%, reduce minute volume ventilation by lowering the respiratory rate to allow a slow rise in ETCO2 * Once ETCO2 rises above 6.0KPa, check arterial blood gases to confirm that PaCO2 is at least 6.0KPa and that the pH is less than 7.40 If cardiovascular stability is maintained, the patient should then be disconnected from the ventilator and attached to an oxygen flow of 5L/min via an endotracheal catheter and observed for five minutes * If the maintenance of adequate oxygenation proves difficult, then CPAP (and possibly a prior recruitment manoeuvre) may be used * If, after five minutes, there has been no spontaneous respiratory response, a presumption of no respiratory centre activity will be documented and a further confirmatory arterial blood gas sample obtained to ensure that the PaCO2 has increased from the starting level by more than 0.5KPa * The ventilator should be reconnected and the minute volume adjusted to allow a gradual return of the blood gas concentrations to the levels set prior to the commencement of testing. if all above support diagnosis then neurological death can be confirmed after repeating (so all tests carried out twice, by 2 doctors each time one of whom must be consultant) modified criteria in infants <2mo, as above but: In post-asphyxiated infants, or those receiving intensive care after resuscitation, whether or not they have undergone therapeutic hypothermia, there should be a period of at least 24 hours of observation during which the preconditions necessary for assessment for DNC should be present before clinical testing for DNC. A stronger hypercarbic stimulus is used to establish respiratory unresponsiveness. Specifically, there should be a clear rise in PaCO2 levels of >2.7 kPa (>20 mm Hg) above a baseline of at least 5.3 kPa (40 mm Hg) to >8.0 kPa (60 mm Hg) with no respiratory response at that level.

Answer 433

derived from precursor cells of the sympathetic nervous system, and found at various points along the SNS, most commonly in the adrenal gland Fatigue, loss of appetite, fever, and joint pain are common Abdominal mass: The most common presentation of neuroblastoma. Abdominal distention: May occur with respiratory compromise in infants because of massive liver metastases. Bone pain: Occurs in association with metastatic disease. Pancytopenia: May result from extensive bone marrow metastasis. Paralysis: Neuroblastoma originating in paraspinal ganglia may invade through neural foramina and compress the spinal cord extradurally. Immediate treatment is given for symptomatic spinal cord compression Watery diarrhea: On rare occasions, children may have severe, watery diarrhea caused by the secretion of vasoactive intestinal peptide by the tumor, or they may have protein-losing enteropathy with intestinal lymphangiectasia. Presence of Horner syndrome: Characterized by miosis, ptosis, and anhidrosis. It may be caused by neuroblastoma in the stellate ganglion. Subcutaneous skin nodules: Subcutaneous metastases of neuroblastoma often have bluish discoloration of the overlying skin; usually seen only in infants. most common clinical presentation of orbital neuroblastoma metastases in patients less than two years old is unilateral or bilateral periorbital or eyelid ecchymosis, typically called “raccoon eyes" which can be confused for trauma may also see proptosis, strabismus Paraneoplastic neurological findings include cerebellar ataxia or opsoclonus/myoclonus - these often have neuroblastoma with favorable biological features and have excellent survival rates; treatment with adrenocorticotropic hormones or corticosteroids can be effective for acute symptoms, and tumour needs to be removed over half of all neuroblastoma patients having hematogenous spread at diagnosis, the disease can involve the bone and bone marrow, followed by lymph nodes, and lungs Imaging of the primary tumor mass with CT or MRI Metaiodobenzylguanidine (MIBG) scanning is a critical part of the standard diagnostic evaluation of neuroblastoma, for both the primary tumor and sites of metastases and to assess response to therapy Urinary excretion of the catecholamine metabolites VMA and HVA per milligram of excreted creatinine is measured before therapy - if remain elevated suggest disease persistence There is an absolute requirement for tissue biopsy to determine the International Neuroblastoma Pathology Classification Risk stratification: INGRS staging: Stage L1 The tumor hasn’t spread beyond its original site and no image-defined risk factors are found on imaging, such as CT scans or MRI. Stage L2 It’s the same as stage L1, but image-defined risk factors are found on imaging. Stage M The tumor has spread to other body parts except those in stage MS. Stage MS The tumor has spread to skin, liver, and/or bone marrow in an infant under 18 months. Lower risk/more likely regression <18mo Differentiated tumour cells Near triploid number of chromosomes. No MYCN amplification. No loss of chromosome 1p low risk get observation or resection intermediate chemo then resection high risk hemotherapy, surgery, radiation therapy, myeloablative therapy and hematopoietic stem cell transplant (HSCT), isotretinoin, and immunotherapy Observation with biopsy (for infants aged <12 months with stage 4S disease without hepatomegaly and MYCN-nonamplified tumors; infants aged <12 months with localized disease, favorable histology and genomics, and MYCN-nonamplified tumors with no segmental chromosomal aberrations)