Neurology Flashcards

Question

Epidemiology of epilepsy

Answer 1

- Epilepsy is a common neurological disorder that affects > 70 million people globally. - The lifetime risk of having a seizure is approximately 1 in 10. - Incidence is age-dependent, it is highest at the extremes of life with most cases starting before 20yrs or after the age of 60yrs

Answer 2

- **Cerebrovascular disease** - **Head trauma** - **Cerebral infections** - **Family history**: epilepsy or neurological illness - **Premature birth** - **Congenital malformations of the brain** - **Genetics conditions associated with epilepsy**

Answer 3

A seizure is a period where neurones in the brain are synchronously active - active at the same time, when they’re not supposed to be. The cause of epilepsy can be broadly divided into six groups: - **Genetic**: known or presumed genetic mutation that predisposes to recurrent seizures. Some patients with epilepsy seem to have fast or long-lasting activation of excitatory NMDA receptors and some patients seem to have genetic mutations in which their inhibitory GABA receptors are dysfunctional. - **Structural**: visible neurological abnormalities that predispose to seizures (e.g. chronic cerebrovascular disease, congenital malformation) - **Metabolic**: known or presumed metabolic disorder that predisposes to seizures - **Immune**: underlying immune disorder that predisposes to recurrent seizures - **Infectious**: chronic infection predisposing to seizures (e.g. HIV). This must be differentiated from seizures associated with an acute infection (e.g. meningitis) - **Unknown**: up to one third of patients. During a seizure, a clusters of neurones in the brain become temporarily impaired and start sending out a ton of excitatory signals - these are sometimes said to be paroxysmal. These paroxysmal electrical discharges are thought to happen due to either too much excitation, or too little inhibition. Whether it’s a decrease in inhibition or an increase in activation, when groups of neurones start firing simultaneously, it’s often noticed by others as obvious outward signs, like jerking, moving, and losing consciousness, but can also be subjective experiences that are only noticed by the person experiencing it, like fears or strange smells but can also involve jerking movements in specific muscle groups if the neurones controlling those muscles are affected. If the jerking activity starts in a specific muscle group, and spreads to surrounding muscle groups as more neurons are affected, it’s referred to as a Jacksonian march.

Answer 4

- **When the affected area is limited to one hemisphere - or one half of the brain - or sometimes even a smaller area like a single lobe, it is known as a focal seizure.** - Focal seizures start in temporal lobes. They affect hearing, speech, memory and emotions. There are various ways that focal seizures can present: - Hallucinations - Memory flashbacks - Déjà vu - Doing strange things on autopilot

Answer 5

- These are subcategorised as either without impaired awareness or with impaired awareness. - Those without impaired awareness typically affect a small area of the brain, and can involve the person experiencing strange sensations, but can also involve jerking movements in specific muscle groups if the neurones controlling those muscles are affected. Typically, the person is awake and alert and will usually know that something is happening and will remember the seizure afterwards - Those with impaired awareness, involve having some sort of loss of awareness and responsiveness, so they might not remember the seizure.

Answer 6

the muscles become stiff and flexed, which can cause the patient to fall, usually backwards

Answer 7

aka drop attacks. The muscles suddenly relax and become floppy, which can cause the patient to fall, usually forward. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome.

Answer 8

violent muscle contractions (convulsions).

Answer 9

- there is loss of consciousness and tonic (muscle tensing) and clonic (muscle jerking) episodes. Typically the tonic phase comes before the clonic phase. There may be associated tongue biting, incontinence, groaning and irregular breathing. After the seizure there is a prolonged post-ictal period where the person is confused, drowsy and feels irritable or depressed.

Answer 10

short muscle twitches. 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.

Answer 11

aka petit mal seizures, impaired awareness or responsiveness. Patient becomes blank and stares into space before returning to normal. Motor abnormalities are either absent or very minor e.g. eyelid flutters or repetitive lip smacking. Common in children. Most patients (> 90%) stop having absence seizures as they get older.

Answer 12

This is also known as West syndrome. It is a rare (1 in 4000) disorder starting in infancy at around 6 months of age. It is characterised by clusters of full body spasms. There is a poor prognosis: 1/3 die by age 25, however 1/3 are seizure free.

Answer 13

Confusion, irritability or mood disturbances

Answer 14

Aura: warning felt before a seizure. These can include sensory, cognitive, emotional or behaviour changes.

Answer 15

Will vary depending on seizure type

Answer 16

Confused, drowsy and irritable during recovery

Answer 17

A diagnosis of epilepsy is made if any of the following three criteria apply: - **Criteria 1**: ≥2 unprovoked (or reflex) seizures occurring more than 24 hours apart - **Criteria 2**: 1 unprovoked (or reflex) seizure with a probability of further seizures felt to be at a similar recurrence risk to patients with ≥2 unprovoked seizures over the next 10 years. - **Criteria 3**: A diagnosed epilepsy syndrome

Answer 18

- **Electroencephalogram** (**EEG**): can show typical patterns in different forms of epilepsy and support the diagnosis. - **MRI brain:** used to visualise the structure of the brain. Can diagnose structural problems that may be associated with seizures and other pathology such as tumours. - **CT:** alternative to MRI - **Arterial or venous blood gas:** metabolic acidosis with raised lactate - **ECG:** exclude problems in the heart. - **Blood electrolytes** including sodium, potassium, calcium and magnesium (electrolyte derangement can cause seizures) - **Blood glucose** for hypoglycaemia and diabetes (glucose derangement can cause seizures)

Answer 19

- **Syncope and anoxic seizures**: transient loss of consciousness from impaired cerebral blood flow. - **Behavioural, psychological and psychiatric**: non-epileptic seizures (i.e. pseudoseizures) - **Sleep-related conditions** - **Paroxysmal movement disorders** - **Migraine associated disorders** - **Other**

Answer 20

- **Sodium Valproate** - Works by increasing the activity of GABA, which has a relaxing effect on the brain. - Notable side effects: - Teratogenic so patients need careful advice about contraception - Liver damage and hepatitis - Hair loss - Tremor

Answer 21

- Sodium channel blocker; prevents repetitive and sustained firing of action potentials. - Notable side effects are: - Agranulocytosis - Aplastic anaemia - Induces the P450 system so there are many drug interactions

Answer 22

- Causes voltage-dependent block of voltage gated sodium channels. This blocks sustained high frequency repetitive firing of action potentials. - Notable side effects: - Folate and vitamin D deficiency - Megaloblastic anaemia (folate deficiency) - Osteomalacia (vitamin D deficiency)

Answer 23

- Partial antagonism of T-type calcium channels of the thalamic neurons, leading to a decrease in burst firing of thalamocortical neurons - Notable side effects: - Night terrors - Rashes

Answer 24

- Inhibits sodium currents and suppresses the release of the excitatory amino acid, glutamate. - Notable side effects: - Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes. - Leukopenia

Answer 25

- **Generalised tonic-clonic seizures** - First line: **sodium valproate** - Second line: **lamotrigine** or **carbamazepine**

Answer 26

- **Focal seizures** - First line: **carbamazepine** or **lamotrigine** - Second line: **sodium valproate** or **levetiracetam**

Answer 27

First line: sodium valproate or ethosuximide

Answer 28

- First line: **sodium valproate** - Second line: **lamotrigine**

Answer 29

- First line: **sodium valproate** - Other options: **lamotrigine**, **levetiracetam** or **topiramate**

Answer 30

- **Prednisolone** - **Vigabatrin**

Answer 31

- **Epilepsy surgery:** removal of cause of seizure e.g. specific part of the brain or tumour. - **Nerve stimulation:** certain nerves e.g. the vagus nerve are stimulated, which is thought to control seizures by influencing neurotransmitter release.

Answer 32

- **How to manage seizures** - Put the patient in a safe position (e.g. on a carpeted floor) - Place in the recovery position if possible - Put something soft under their head to protect against head injury - Remove obstacles that could lead to injury - Make a note of the time at the start and end of the seizure - Call an ambulance if lasting more than 5 minutes or this is their first seizure - **Other advice** - Take showers rather than baths - Be very cautious with swimming unless seizures are well controlled and they are closely supervised - Be cautious with heights - Be cautious with traffic - Be cautious with any heavy, hot or electrical equipment - Avoid driving

Answer 33

- **Todd's paralysis:** paralysis that affects the arms or the legs, usually just limited to one side of the body. Usually it subsides by itself completely after 2 days. Thought to be the result of temporary but severe suppression of activity of the area in the brain affected by the seizure. - **Status epilepticus:** prolonged seizure without regaining consciousness - **Sudden unexplained death in epilepsy (SUDEP)**

Answer 34

Assess GCS, Blood culture, Broad spectrum antibiotic (ceftriaxone or cefotaxime) then steroid e.g. Dexamethasone

Answer 35

Lumbar puncture and send to micro lab

Answer 36

Abnormal clotting, Petechial rash, Raised intercranial pressure

Answer 37

Neisseria meningitidis, Strep pneumoniae, Listeria species, Group B strep, Haemophilius influenzae B, E.coli

Answer 38

Meningitis describes inflammation of the leptomeninges (the arachnoid and pia mater) and usually occurs due to a bacterial, viral, or fungal infection.

Answer 39

The annual incidence of acute bacterial meningitis in developed countries is estimated to be 2–5 per 100,000 population

Answer 40

- *N. meningitidis and S. pneumoniae are the commonest causes of bacterial meningitis in the UK, whilst enteroviruses such as coxsackievirus are the most common cause of viral meningitis.* - **Bacterial:** - **Neonatal:** group B streptococcus, *E. coli*, *Listeria monocytogenes* - **Children:** *N. meningitidis*, *S. pneumoniae*, *H. influenzae* - **Adults:** *S. pneumoniae*, *N. meningitidis* - **Immunocompromised:** *Listeria monocytogenes, M. tuberculosis* - **Viral:** - **Enteroviruses**: coxsackievirus and echovirus - **Herpes simplex virus (HSV):** HSV-2 meningitis is more common than HSV-1 - **Varicella-zoster virus (VZV)** - **Fungal:** - **Cryptococcus neoformans** - **Candida** - It can also be caused by autoimmune disease, trauma, cancer, or drugs.

Answer 41

- **Immunocompromised**: numerous causes including **extremes of age** (children and the elderly), **infection** (such as HIV) and **medication** (such as chemotherapy) - **Non-immunised**: at risk of *H. influenza*, pneumococcal and meningococcal meningitis - **Crowded environment**: students living in halls of residence are a commonly affected demographic

Answer 42

There are two routes that an infection can take to reach the CSF and leptomeninges. - **Direct spread:** Pathogen gets inside the skull or spinal column, and then penetrates the meninges, eventually ending up in the CSF. Sometimes the pathogen will have come through the overlying skin or up through the nose, but it’s more likely that there’s an anatomical defect to blame e.g. congenital defect like spina bifida, or acquired defect like a skull fracture - **Haematogenous spread:** Pathogen enters the bloodstream and moves through the endothelial cells in the blood vessels making up the blood-brain barrier and gets into the CSF. Once the pathogen finds a way into the CSF it starts multiplying. The white blood cells surveilling the CSF identify the pathogen and release cytokines to recruit additional immune cells. Over time, a microliter of CSF might go on to contain up to thousands of white blood cells, but any more than five usually defines meningitis. The additional immune cells attract more fluid to the area and start causing local destruction as they try to control the infection. As a result the CSF pressure typically rises above 200 mm of H2O. The immune reaction also causes the glucose concentration in the CSF to fall, to below two thirds of the concentration in the blood, and makes the protein levels increase to over 50 mg per decilitre. When it comes to the causes of meningitis, viruses and bacteria usually cause **acute meningitis**, whereas fungi usually cause **chronic meningitis.**

Answer 43

- **Kernig’s sign:** when the hip is flexed and the knee is at 90°, extension of the knee results in pain - **Brudzinski sign:** severe neck stiffness causes the hips and knees to flex when the neck is flexed - **Petechial or purpuric non-blanching rash:** associated with meningococcal disease (N. meningitidis) - **Pyrexia** - **Reduced GCS**

Answer 44

- **Meningism** - **Headache** - **Photophobia** - **Neck stiffness** - **Fever** - **Nausea and vomiting** - **Seizures**

Answer 45

- **FBC:** leukocytosis - **CRP:** raised inflammatory markers - **Coagulation screen**: required prior to lumbar puncture (LP) - **Blood glucose**: required in all patients and for comparison with CSF glucose - **Blood culture:** positive in the case of bacterial infection - **Whole-blood PCR for *N meningitidis*** - **Lumbar puncture and CSF analysis:** - **CSF gram stain: *S. pneumoniae*** (gram-positive cocci in chains); ***N. meningitidis*** (gram-negative diplococci) - **CSF culture** - **CSF PCR:** useful for viruses such as HSV and VZV

Answer 46

- **Neurological:** - Abscess - Cerebral oedema - Hydrocephalus and brain herniation - Seizures - Sensorineural hearing loss - Memory loss - Cerebral palsy - Long-term cognitive and behaviour deficit - **Endocrine:** - Waterhouse-Friderichsen syndrome: adrenal gland failure to haemorrhage. This is typically caused by *Neisseria meningitidis* - **Other:** - Sepsis

Answer 47

For bacterial meningitis, the prognosis is good if patients are treated early. Mortality in children can reach up to 10%, whilst 15% of children will develop severe sequelae such as sensorineural hearing loss or seizures. Amongst adults, meningococcal meningitis has a 10% mortality, whilst pneumococcal meningitis has a 22% mortality. Viral meningitis is generally self-limiting, and most patients recover with support management within 7 to 10 days.

Answer 48

Metronidazole, Vaccine, Immunoglobulin to mop up toxin, Muscle relaxants and paracetamol

Answer 49

Prophylaxis, Management with sedatives (palliative) once symptomatic

Answer 50

A transient ischaemic attack (TIA) is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction. It usually resolves spontaneously within 24 hours.

Answer 51

- It is estimated that approximately 15% of patients have at least one TIA prior to a stroke. - M>F

Answer 52

- **Increasing age** - **Hypertension** - **Smoking** - **Obesity** - **Diabetes** - **Hypercholesterolaemia** - **Atrial fibrillation** - **Carotid stenosis** - **Thrombophilic disorders e.g. antiphospholipid syndrome** - **Sickle cell disease**

Answer 53

Transient ischaemic attack (TIA) refers to a period of transient cerebral ischaemia resulting in a self-resolving neurological deficit within 24 hours, whereas the features of a stroke last beyond 24 hours. The ‘tissue-based’ definition (as opposed to the 'time based' definition) of a TIA is: “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction”. **The aetiology of a TIA is similar to that of ischaemic stroke:** Ischaemia refers to the absence of blood flow to an organ, which deprives it of oxygen. Cerebral ischaemia may be due to in situ thrombosis, emboli, or rarely, dissection. - **Thrombosis**: local blockage of a vessel due to atherosclerosis. Precipitated by cardiovascular risk factors (e.g. hypertension, smoking) or small vessel disease (e.g. vasculitis, sickle cell). - **Emboli**: propagation of a blood clot that leads to acute obstruction and ischaemia. Typically due to atrial fibrillation or carotid artery disease. - **Dissection**: a rare cause of cerebral ischaemia from tearing of the intimal layer of an artery (typically carotid). This leads to an intramural haematoma that compromises cerebral blood flow. May be spontaneous or secondary to trauma.

Answer 54

- **Focal neurology:** on examination - **Irregular pulse:** suggests atrial fibrillation as an underlying cause - **Carotid bruit:** suggests carotid artery stenosis - **Hypertension**

Answer 55

- **Contralateral sensory/ motor deficits** - **Facial weakness** - **Limb weakness** - **Dysphasia:** slurred speech - **Ataxia, vertigo, or incoordination** - **Homonymous hemianopia:** visual field loss on the same side of both eyes - **Amaurosis fugax:** a painless temporary loss of vision, usually in one eye

Answer 56

- **The Face Arm Speech Time Test (FAST test):** check for/ ask about facial weakness, arm weakness, speech difficulty - **ECG:** rule out AF as an underlying cause - **Auscultation:** listen for carotid bruit - **Bloods:** - Screen for risk factors with bloods including Hba1c, lipids, clotting screen and rule out TIA mimics such as hypoglycemia and hyponatraemia - **TIA clinic:** - If the suspected TIA occurred less than a week ago: urgent assessment within 24 hours - If the suspected TIA occurred more than a week ago: urgent assessment within 7 days - At TIA clinic, a specialist assessment is conducted and further imaging is arranged, such as an **MRI head and carotid doppler**

Answer 57

- **Toxic/metabolic**: hypoglycaemia, drug and alcohol consumption - **Neurological**: seizure, Todds paralysis, migraine, Bell’s palsy - **Space occupying lesion**: tumour, haematoma - **Infection**: meningitis/encephalitis, systemic infection with ‘decompensation’ of old stroke - **Syncope**

Answer 58

- **Toxic/metabolic**: hypoglycaemia, drug and alcohol consumption - **Neurological**: seizure, Todds paralysis, migraine, Bell’s palsy - **Space occupying lesion**: tumour, haematoma - **Infection**: meningitis/encephalitis, systemic infection with ‘decompensation’ of old stroke - **Syncope**

Answer 59

- **Clopidogrel 75 mg** daily is first-line - Offer **aspirin** 75 mg daily with **MR dipyridamole** if clopidogrel is contraindicated - Offer **MR dipyridamole alone** if both aspirin and clopidogrel are contraindicated - **High-dose statin**: for lipid modification e.g. atorvastatin 20-80mg - **Manage hypertension, diabetes, smoking and other cardiovascular risk factors** - **Lifestyle advice:** increase physical activity, smoking cessation, diet optimisation and advice on alcohol intake

Answer 60

- **Stroke:** TIA is a medical emergency as the risk of recurrent stroke is up to 10% in the next week - **Myocardial infarction**: TIA represents underlying atherosclerotic disease, thus increasing the risk of acute coronary syndrome

Answer 61

Over 10% of TIA patients seen in the emergency department will have a stroke within 3 months. Additionally, a TIA is a marker of underlying atherosclerotic disease, therefore these patients are at risk for ischaemic heart disease.

Answer 62

**Intracerebral haemorrhage describes bleeding within the cerebrum.** Haemorrhagic strokes can be split into two types: an intracerebral haemorrhage which is when bleeding occurs within the cerebrum, and a subarachnoid haemorrhage which is when bleeding occurs between the pia mater and arachnoid mater of the meninges. An intracerebral haemorrhage that involves just the brain tissue is called an **intraparenchymal haemorrhage,** whereas if the blood extends into the ventricles of the brain which store cerebrospinal fluid, it’s called an **intraventricular haemorrhage.**

Answer 63

**Rupture due to:** - **Hypertension**, causing: - **Arteriosclerosis:** stiffening of vessels - **Microaneurysms**: called Charcot-Bouchard aneurysms, most likely to be found on small arteries - **Arteriovenous malformations:** blood vessels that directly connect an artery to a vein. Over time these abnormal vessels dilate and can rupture - **Vasculitis** - **Vascular tumours** - **Cerebral amyloid angiopathy:** a degenerative disease where abnormal protein deposits in the walls of arterioles making them less compliant - **Secondary to ischaemic stroke:** ischaemia causes brain tissue death. If there is reperfusion, there’s an increased chance that the damaged blood vessel might rupture. Bleeding into dead tissue is called haemorrhagic conversion.

Answer 64

- **Head injury** - **Hypertension** - **Aneurysms** - **Ischaemic stroke can progress to haemorrhage** - **Brain tumours** - **Anticoagulants such as warfarin**

Answer 65

Once there’s an intracerebral haemorrhage, blood starts to spew out from a damaged blood vessel creating a pool of blood which increases pressure in the skull and puts direct pressure on nearby tissue cells and blood vessels. This can occur anywhere, e.g. - Lobar intracerebral haemorrhage - Deep intracerebral haemorrhage - Intraventricular haemorrhage - Basal ganglia haemorrhage - Cerebellar haemorrhage Haemorrhage also means that less blood is flowing downstream to the cells that need it, which leaves the downstream tissue deprived of oxygen-rich blood. Healthy tissue can die from both the direct pressure and the lack of oxygen within a few hours. Increased pressure within the skull can also lead to brain herniation, which is when the brain moves across structures in the skull.

Answer 66

- **Headache** - **Weakness** - **Seizures** - **Vomiting** - **Reduced consciousness** Specific stroke symptoms depend on part of brain affected e.g. - Anterior or middle cerebral artery stroke: **numbness and sudden muscle weakness.** - Broca’s area or Wernicke’s area stroke: **slurred speech or difficulty understanding speech, respectively.** - Posterior cerebral artery stroke: **vision disturbances.**

Answer 67

- **CT/ MRI:** to confirm size and location of haemorrhage - **Angiography:** visualise the exact location of haemorrhage - **Check FBC and clotting**

Answer 68

- **Consider intubation, ventilation and ICU care if they have reduced consciousness** - **Correct any clotting abnormality** - **Correct severe hypertension but avoid hypotension** - Drugs to relieve intracranial pressure e.g. **Mannitol** - **Craniotomy:** part of the skull bone is removed to drain any accumulated blood and relieve pressure. Good for if the bleed is close to the surface of the skull - **Stereotactic aspiration:** aspirate off blood and relieve intracranial pressure, guided by CT scanner. Good for bleeding that is located deeper in brain tissue

Answer 69

Subarachnoid haemorrhage (SAH) is a type of intracranial haemorrhage characterised by blood within the subarachnoid space.

Answer 70

- The incidence of SAH in most populations is between 6-8 cases out of 100,000 per year - Most commonly presents in people age 45-70 - F>M - More common in Black patients

Answer 71

- **Trauma** - **Atraumatic** cases are referred to as **spontaneous** SAH and are caused by the following: - **Berry aneurysm**: saccular aneurysm is the most common cause of spontaneous SAH (80% of spontaneous SAH) - Arise at points of arterial bifurcation within the Circle of Willis; the junction between the anterior communicating and anterior cerebral arteries is the most common location - Associated with adult polycystic kidney disease, coarctation of the aorta and Ehlers-Danlos/ Marfan's syndrome - **Arteriovenous malformation** (AVM) - abnormal connections between artery and vein can dilate and cause rupture - **Perimesencephalic**: venous bleeding with normal CT and excellent prognosis - **Mycotic aneurysm**: due to bacterial infection e.g. secondary to emboli from infective endocarditis - **Vertebral artery dissection** - **Pituitary apoplexy**: bleeding into the pituitary gland, often associated with a tumour

Answer 72

- **Increasing age**: most commonly presents in people > 50 years old - **Hypertension** - **Smoking** - **Alcohol excess**: there is a significantly increased risk with current alcohol abuse - **Cocaine use** - **Family history** - **Polycystic kidney disease** (PKD): 5 times more common in autosomal dominant PKD - **Connective tissue disorders:** such as Marfan syndrome or Ehlers-Danlos - **Neurofibromatosis:** tumours form on your nerve tissues

Answer 73

- Subarachnoid haemorrhages can lead to a pool of blood under the arachnoid mater that increases the intracranial pressure. This puts direct pressure on nearby tissue cells and blood vessels as well as preventing more blood from flowing into the brain. - Healthy tissue can die from both the direct pressure and the lack of oxygen within a few hours. - Blood vessels that are “bathing” in a pool of blood can start to intermittently vasoconstrict - **vasospasm.** If the vasospasm affects arteries in the circle of Willis, it will reduce the supply of blood flow to the brain, causing further ischaemic injury. - Over time, blood in the subarachnoid space can irritate the meninges and cause inflammation which leads to scarring of the surrounding tissue. The scar tissue can obstruct the normal outflow of cerebrospinal fluid, causing fluid build up which dilates the ventricles at the centre of the brain. This is referred to as **hydrocephalus.**

Answer 74

- **3rd nerve palsy** - An aneurysm arising from the posterior communicating artery will press on the 3rd nerve, causing a **palsy** with a **fixed dilated pupil** - **6th nerve palsy** - A non-specific sign which indicates raised intracranial pressure - **Reduced GCS**

Answer 75

- **Headache** - Severe, sudden onset - Occipital - ‘Thunderclap’ headache - **Meningism: photophobia and neck stiffness** - **Vision changes** - **Nausea and vomiting** - **Speech changes** - **Seizures** - **Weakness** - **Confusion** - **Coma**

Answer 76

- **FBC** - **Serum glucose** - **Clotting screen** - **Urgent non-contrast CT head:** - Diagnostic (but can be negative in a minority of patients) - CT imaging typically shows blood in the basal cisterns - **ECG**: should be requested for all patients and may demonstrate arrhythmias, ischaemia and ST-elevation

Answer 77

- **Lumbar puncture (LP):** perform if CT head is negative and clinical suspicion remains - Findings - RBCs or xanthochromia (yellow pigmentation due to degradation of haemoglobin to bilirubin) with normal or raised opening pressure - **CT angiogram or digital subtraction angiography (DSA):** after spontaneous SAH has been confirmed, further imaging may be conducted to find the source, such as an aneurysm or AVM

Answer 78

- **Nimodipine:** calcium channel blocker that is used to prevent vasospasm - **Intervention**: first-line is **endovascular coiling** of the aneurysm; second-line is **surgical clipping** via craniotomy - **If features of raised intracranial pressure**: consider intubation with hyperventilation, head elevation (30°) and IV mannitol - **Conservative:** - **Bed rest** - **Antitussive (anti-cough) agent and stool softeners**: prevents straining and therefore reduce the risk of rebleeding

Answer 79

- **Rebleeding**: 22% risk at 1 month - **Vasospasm**: accounts for 23% of deaths; at highest risk for the first 2-3 weeks after SAH; treated with (induced) **h**ypertension, **h**ypervolaemia and **h**aemodilution (triple-H therapy). - **Hydrocephalus**: acutely managed with external ventricular drain (CSF drainage into an external bag) or a long-term ventriculoperitoneal shunt, if required - **Seizures**: seizure-prophylaxis is often administered (e.g. Keppra) - **Hyponatraemia**: commonly due to syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Answer 80

At 6 months, 25% of patients are dead and 50% are moderately to severely disabled. Important predictors of 30-day mortality include age, level of consciousness on admission and the amount of blood visible on CT. Causes of mortality include medical complications (23%), vasospasm (23%), rebleeding (22%) and initial haemorrhage (19%)

Answer 81

Bleeding below the dura mater

Answer 82

Occurs more frequently in the elderly or alcoholics

Answer 83

**Rupture of bridging veins, usually caused by:** - **Brain atrophy:** in the elderly the brain shrinks in size which means that the bridging veins are stretched across a wider space where they are largely unsupported - **Alcohol abuse:** caused the wall of the veins to thin out, and make them more likely to break. - **Trauma/ injury** e.g. - Falls - Shaken baby syndrome - Acceleration-deceleration injury: speeding on the road and then suddenly slamming the brakes. Causes damage to the front of the brain as the body jerks forward, and then the back of the brain as the body moves backwards.

Answer 84

- **Head injury** - **Brain atrophy** - **Alcohol abuse** - **Hypertension** - **Aneurysms** - **Ischaemic stroke can progress to haemorrhage** - **Brain tumours** - **Anticoagulants such as warfarin**

Answer 85

- The main cause of a subdural haemorrhage is a rupture of the bridging veins located in the subdural space. This can be due to trauma or without trauma e.g. reduced intracranial pressure or dural metastases - When there is active bleeding, it’s called a haemorrhage, and the collection of blood that results is called a haematoma. - As the damaged bridging veins are under low pressure, the bleeding can be slow causing delayed onset of symptoms which might develop over the course of days to weeks as the haematoma gradually expands. - An acute subdural haematoma causes symptoms within 2 days, a subacute subdural haematoma causes symptoms between 3 and 14 days, and a chronic subdural haematoma causes symptoms after 15 days. - The haematoma can compress the brain and cause increased intracranial pressure. A large subdural haematoma on one side of the skull can cause a midline shift which is a displacement of the whole brain towards the opposite side of the skull. The increased intracranial pressure can also cause the brain to herniate.

Answer 86

- **Reduced GCS**: loss of consciousness right after the injury or in the ensuing days to weeks as the haematoma increases in size. - **Headaches** - **Vomiting** - **Seizures** - Sometimes there can be focal neurological symptoms e.g. **muscle weakness, unequal pupils, hemiparesis or sensory problems**

Answer 87

- **Immediate CT head** to establish the diagnosis. Shows clot and midline shift. Findings: - Acute subdural haematoma: hyperdense mass = looks “more white” than the surrounding healthy brain tissue - Chronic subdural haematoma: hypodense masses = “less white” than the surrounding brain tissue. - Acute on chronic bleeding: combination of hyperdense and hypodense, seen in individuals who have a rebleed in the bridging veins after a chronic haematoma has already formed. - Bleeding is between the dura and arachnoid so subdural haematomas follow the contour of the brain and form a crescent-shape and cross suture lines. This is different to an epidural haemorrhage - **Check FBC and clotting**

Answer 88

- **Stroke** - **Dementia** - **CNS masses e.g. tumours or abscesses** - **Subarachnoid haemorrhage** - **Epidural haemorrhage**

Answer 89

- **Consider intubation, ventilation and ICU care if they have reduced consciousness** - **Correct any clotting abnormality** - **Correct severe hypertension but avoid hypotension** - **Mannitol:** used to reduce ICP - **Drainage:** - Small subdural haematomas are drained via **burr hole washout** - by placing a small tube called a catheter, through a drilled hole in the skull. - Large subdural haematomas require a **craniotomy,** which is when part of the skull bone is removed in order to remove accumulated blood below - **Address cause of trauma/ injury**

Answer 90

- Increased intracranial pressure can also cause the brain to herniate, these can be lethal: - **Supratentorial herniation:** cerebrum is pushed against the skull or the tentorium, can compress the arteries that nourish the brain leading to an ischaemic stroke - **Infratentorial herniation:** cerebellum is pushed against the brainstem, can compress the vital area in the brainstem that control consciousness, respiration, and heart rate - **Coma** - **Stroke** - **Neurological deficits** - **Epilepsy related to trauma**

Answer 91

Bleeding above the dura mater

Answer 92

Usually occurs in young adults (rare < 2 and > 60)

Answer 93

- **Head injury** - **Hypertension** - **Aneurysms** - **Ischaemic stroke can progress to haemorrhage** - **Brain tumours** - **Anticoagulants such as warfarin**

Answer 94

The most common cause of epidural haemorrhage is a head trauma. The meningeal arteries are protected by the skull but can be damaged by a serious head trauma. The most common site is at the pterion which is the spot where the frontal, parietal, temporal and sphenoid bones join together. This section of the skull is relatively thin and it’s located right above the middle meningeal artery. When there’s active bleeding, it’s called a haemorrhage, and the collection of blood that results is called a haematoma. Once a meningeal artery is torn, blood will pool between the skull and the external layer of the dura mater, separating it from the inner surface of the skull. The blood builds up between the skull and the outer layer of the dura mater but cannot cross the suture lines where the dura mater adheres more tightly. If blood accumulates slowly, there may be a lucid interval which is when several hours pass before the onset of symptoms. A large epidural haematoma on one side of the skull can cause a midline shift which is a displacement of the whole brain towards the opposite side of the skull. A large epidural haematoma can also cause an increase in intracranial pressure, and that can cause the brain to shift or herniate.

Answer 95

- **Reduced GCS:** loss of consciousness after the trauma due to concussion - There might be a **lucid interval** after initial trauma if there is a slower bleed. This is followed by rapid decline. - **Headaches** - **Vomiting** - **Confusion** - **Seizures** - **Pupil dilation** if bleeding continues - May be focal neurological symptoms e.g. **muscle weakness, hemiparesis, abnormal plantar reflex (upgoing plantar) or sensory problems**

Answer 96

- **CT scan** Findings: - Hyperdense mass = looks “more white” than the surrounding healthy brain tissue - Epidural haemorrhages cause blood to build up between the outer layer of the dura mater and the skull so epidural haematomas don’t cross suture lines and they push on the brain forming a biconvex shape. This is not the case with subdural haematomas. - **Check FBC and clotting** - **Skull X-ray:** may show fracture

Answer 97

- **Epilepsy** - **Carotid dissection** - **Carbon monoxide poisoning** - **Subdural haematoma** - **Subarachnoid haemorrhage**

Answer 98

- **Consider intubation, ventilation and ICU care if they have reduced consciousness** - **Correct any clotting abnormality** - **Correct severe hypertension but avoid hypotension** - **Mannitol:** to reduce ICP - **Clot evacuation** - **Craniotomy**: part of the skull bone is removed in order to remove accumulated blood below. - Followed by **ligation of the vessel.**

Answer 99

- Increased intracranial pressure can also cause the brain to herniate, these can be lethal: - **Supratentorial herniation:** cerebrum is pushed against the skull or the tentorium, can compress the arteries that nourish the brain leading to an ischaemic stroke - **Infratentorial herniation:** cerebellum is pushed against the brainstem, can compress the vital area in the brainstem that control consciousness, respiration, and heart rate. - Patients present with deep irregular breathing, high BP, low HR - **Coma**

Answer 100

Prognosis is good if diagnosed and operated on early. Poor prognosis if coma, pupil abnormalities or decerebrate rigidity are present pre-op.

Answer 101

Bradykinesia, Tremor (at rest), Rigidity (pain)

Answer 102

Small, stepped gait with stooped posture, reduced arm swing, L>R Increased tone = rigidity Rest tremor - often asymmetrical Decreasing amplitude/accuracy of repetetive movements - Much better at beginning gradual weakening

Answer 103

Substantia nigra damage from the midbrain

Answer 104

Lewy bodies

Answer 105

Parkinson’s Disease (PD) is a neurodegenerative disorder characterised by loss of dopaminergic neurones within the substantia nigra pars compacta (SNPC) of the basal ganglia (nigrostriatal pathway).

Answer 106

- Parkinson’s Disease is the second most common neurodegenerative disease (after Alzheimer’s Disease) - It’s progressive, adult-onset disease, and it gets more common with age - Prevalence of 1% in those aged 60-70 and up to 1-3% in those ≥80 years old - M>F

Answer 107

- **Age:** prevalence of 1% in those aged 60-70 and up to 1-3% in those ≥80 years old - **Gender:** males are 1.5 times more likely than females to develop PD - **Family History**

Answer 108

- Parkinson’s disease is a condition where there is a progressive reduction of dopamine in the basal ganglia of the brain, leading to disorders of movement. - PD is idiopathic and the aetiology is not well understood. Some key genes implicated include those which code for α-synuclein and the ubiquitin-protease system. Ultimately, the result is a loss of transmission between the basal ganglia, thalamus, and motor cortex, resulting in impaired control of voluntary movements. The histological hallmark of PD is eosinophilic inclusion bodies consisting of misfolded α-synuclein in the dopaminergic neurones of the SNPC called Lewy bodies. The significance of these inclusion bodies remains uncertain but it has been postulated that misfolded α-synuclein may spread to neighbouring brain regions in a prion-like fashion. - PD results in a constellation of symptoms known as parkinsonism which consists of: - Bradykinesia - Tremor - Rigidity - Postural instability - Non-motor brain functions can be affected as well, leading to additional non-motor symptoms. These are thought to come about because of dysfunction in dopaminergic signalling in other parts of the brain beyond the substantia nigra. - Parkinsons can be associated with other conditions e.g. lewy body dementia, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration

Answer 109

- **Bradykinesia**: - Slow movements - Difficulty initiating movement - Shuffling gait with reduced arm swing and turning en bloc - **Tremor**: - Resting ‘pill-rolling’ (4-6 Hz) tremor - More pronounced when resting and improves on voluntary movement - **Rigidity**: - Cogwheel rigidity occurs due to a tremor superimposed on a rigid movement - Lead-pipe rigidity describes stiffness throughout the entire movement - **Other features** - Micrographia (abnormally small, cramped handwriting) - Hypomimia (reduced degree of facial expression) - Postural instability

Answer 110

- **Anosmia** (smell blindness) - **Sleep disturbance**: REM sleep is impaired - Psychiatric symptoms - **Depression** - **Anxiety** - **Dementia:** usually develops after motor symptoms, unlike in Lewy-body dementia - **Constipation**

Answer 111

- PD is a **clinical diagnosis:** it should be suspected in a patient who has bradykinesia and at least one of the following: - Tremor - Rigidity - Postural instability - Investigations to consider - **MRI brain:** may help exclude other causes of neurological disease but should not be used to diagnose PD - **SPECT (DaT scan):** single-photon emission computed tomography (SPECT) will show reduced dopamine uptake in the basal ganglia

Answer 112

Benign essential tremour: -Symmetrical, Improves at rest, Worse with intentional movement, No other Parkinsons symptoms, Improves with alcohol

Answer 113

Motor symptoms affecting quality of life: - **Levodopa + decarboxylase inhibitor** - Co-benyldopa (levodopa and benserazide) - Co-careldopa (levodopa and carbidopa) - *Boosts dopamine levels and decarboxylase inhibitor prevents levodopa breakdown before it reaches the brain* Motor symptoms not affecting quality of life: A choice of one of the following: - **Dopamine agonist** (non-ergot derived) - Pramipexole, ropinirole - Ergot derived medications (e.g. bromocriptine) should be avoided as they are associated with cardiac and pulmonary fibrosis - **Monoamine oxidase B inhibitor** - Selegiline, rasagiline - Stop breakdown of circulating dopamine - **Levodopa + decarboxylase inhibitor**

Answer 114

COMT inhibitors e.g. Entacapone - reduces breakdown of levadopa peripherally so that more reaches the brain - indicated for those with motor fluctuations or dyskinesia despite optimal levadopa therapy

Answer 115

Dispersible (morning kick start), Standard release (day) or slow release (night)

Answer 116

**Motor complications:** these are usually related to the use of anti-parkinsonian medication - **Motor fluctuations:** symptoms are initially well-controlled (on period) but then re-emerge prior to the next dose (off period). The off period gets longer and more unpredictable as PD advances - **Freezing:** sudden stoppage of movement - **Dyskinesia:** excessive involuntary movements related to levodopa use (excess dopamine) - **Dystonia**: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements. - **Chorea**: These are abnormal involuntary movements that can be jerking and random. - **Athetosis**: These are involuntary twisting or writhing movements usually in the fingers, hands or feet. **Non-motor complications:** - **Psychiatric:** impulse control disorders, depression, anxiety, dementia - **Autonomic:** postural hypotension, constipation

Answer 117

PD is a chronic and progressive condition with no cure. Overall, life expectancy is reduced with the mortality being 2-5 times higher for those aged 70-89 years old. Also, the risk of dementia is up to 6 times higher in PD patients.

Answer 118

The **Glasgow Coma Scale** (**GCS**) is a universal assessment tool for assessing the level of consciousness. It is scored based on **eyes**, **verbal** response and **motor** response. The maximum score is 15/15, minimum is 3/15. When someone has a score of 8/15 or below then you need to consider securing their airway as there is a risk they are not able to maintaining it on their own.

Answer 119

**Eyes** - Spontaneous = 4 - Speech = 3 - Pain = 2 - None = 1 **Verbal response** - Orientated = 5 - Confused conversation = 4 - Inappropriate words = 3 - Incomprehensible sounds = 2 - None = 1 **Motor response** - Obeys commands = 6 - Localises pain = 5 - Normal flexion = 4 - Abnormal flexion = 3 - Extends = 2 - None = 1

Answer 120

A seizure is hypersynchronous, abnormal neuronal activity occurring in the brain. Status epilepticus (SE) is a single, continuous seizure lasting more than five minutes or two or more seizures within a five-minute period without regaining consciousness in between. It is a **medical emergency**.

Answer 121

The incidence of SE peaks in children and the elderly, with febrile seizures and strokes as its main aetiologies within these age groups, respectively

Answer 122

- **Epilepsy** - **Poor compliance with anti-epileptic medication** - **Alcoholism** - **Recreational drugs**: such as cocaine - **Previous neuronal injury**: head trauma, stroke, haemorrhage, brain tumours, central nervous system infections - **Electrolyte imbalance**: particularly hyponatraemia and hypocalcemia - **Various factors that can reduce the seizure threshold:** medications (e.g. bupropion, tramadol, theophylline and certain antibiotics), sleep deprivation, fever and malnutrition.

Answer 123

- Loss of consciousness - **Post-ictal:** confusion and altered state of consciousness after an epileptic seizure

Answer 124

- **Tonic-clonic seizure:** muscles stiffen and jerking of limbs occurs - Non-convulsive status is possible, such as absence status, but is less common - **Tongue biting** - **Urinary incontinence**

Answer 125

- **ECG:** cardiac arrhythmias can precipitate seizures - **Arterial or venous blood gas:** metabolic acidosis with raised lactate - **Metabolic screen:** electrolyte and glucose derangement can cause seizures - **FBC, U&Es and LFTs** - **Inflammatory markers:** identify possible infection

Answer 126

- **ABCDE approach** - **Secure the airway** - **Give high-concentration oxygen** - **Assess cardiac and respiratory function** - **Check blood glucose levels** - **Gain intravenous access (insert a cannula)** - Patients with a known history of alcohol excess may also benefit from IV **Pabrinex** or **glucose** - **Benzodiazepines:** help enhance the effect of the inhibitory neurotransmitter GABA. - **IV** **lorazepam**, repeated after 10 minutes if the seizure continues - If the seizures persist: infusion of IV **phenobarbital** or **phenytoin**. At this point **intubation and ventilation to secure the airway needs to be considered,** along with transfer to the intensive care unit if appropriate. Medical options in the community: - **Buccal midazolam** - **Rectal diazepam**

Answer 127

- **Cardiac**: arrhythmias and cardiac arrest - **Pulmonary**: respiratory failure and aspiration pneumonia - **Metabolic**: hyperkalaemia and hypoglycaemia - **Neurological**: increased seizure frequency, memory impairment, cerebral oedema and raised intracranial pressure

Answer 128

The mortality associated with SE is approximately 3%. Poor prognostic factors include older age, longer duration of SE, a large number of co-morbidities, use of mechanical ventilation and hypoxic brain injury

Answer 129

- Bradykinesia - Tremor - Rigidity - Postural instability

Answer 130

Parkinsons, Multiple system atrophy (Shy-Drager syndrome), Progressive supranuclear palsy, Corticobasal degeneration, Lewy body dementia, Wilsons disease, Antipsychotic meds (Haliperidol), Meoclorpramide, Domperidone, Lithium, MTPT, Carbon monoxide, CNS infection, Trauma,

Answer 131

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes significant deterioration in mental performance.

Answer 132

- Alzheimer’s disease is the most common cause of dementia (50-75%) - In the UK, it is estimated that > 500,000 people have a diagnosis of AD - The prevalence of dementia increases with age. The estimated prevalence at 60-64 years is 0.9% compared to 41.1% in those aged 95 years and over. - F>M

Answer 133

- **Age**: older age is a major risk for AD - **Genetics**: most cases of AD are sporadic. Small number of inherited causes exist (<5%, autosomal dominant inheritance). Inherited causes suggested by early-onset disease. Mutations in the amyloid precursor protein (*APP*) and presenilin genes (*PSEN1, PSEN2*) have been identified. Certain alleles of apolipoprotein E (APOE) have also been identified as a risk factor. Down's syndrome may also be associated with an increased risk. - **Cardiovascular disease**: smoking and diabetes increase risk. Exercise decreases risk. - **Depression** - **Low educational attainment** - **Low social engagement and support** - **Others**: head trauma, learning difficulties

Answer 134

The exact cause of AD is unknown Pathological changes that occur in AD leads to interruption of key neuronal process including communication, metabolism and repair. This ultimately leads to neuronal cell death. The two key pathological changes in AD are senile plaques and neurofibrillary tangles: - **Senile plaques (SP)**: deposits of beta-amyloid (aggregation of protein with a beta-sheet secondary structure). Dense, insoluble. Occur outside of neurons (i.e. extracellular). - **Neurofibrillary tangles (NFT)**: aggregations of hyperphosphorylated tau proteins. Typically occur in areas of the brain involved in memory. Promote neuronal cell death. Form inside neurons (i.e. intracellular) Neurones with tangles and non-functioning microtubules can’t signal as well, and sometimes end up undergoing apoptosis. As neurones die, the brain starts to atrophy.

Answer 135

- **Poor memory** - **Language problems**: receptive and expressive dysphasia - **Problems with executive functioning**: planning and problem solving - **Disorientation**

Answer 136

- **Agitation and emotional lability** - **Depression and anxiety** - **Sleep cycle disturbance** - **Disinhibition**: social or sexually inappropriate behaviour - **Withdrawal/apathy** - **Motor disturbance**: wandering is a typical feature of dementia - **Psychosis**

Answer 137

- **Loss of independence**: increasing reliance on others for assistance with personal and domestic activities - **Early stages**: problems with higher level function (e.g. managing finances, difficulties at work) - **Later stages**: problems with basic personal care (e.g. washing, eating, toileting) and motor function (e.g. walking, transferring)

Answer 138

- **Cognitive assessment:** e.g. mini mental state examination (MMSE)/ Montreal cognitive assessment scale (MoCA); assess different areas of higher cortical functioning e.g. - **Attention and concentration** - **Recent and remote memory** - **Language** - **Praxis**: planned motor movement (e.g. perform a task) - **Executive function** - **Visuospatial function** - **Bloods and other investigations e.g. ECG, virology, chest x-ray:** exclude other pathologies - Imaging - **CT/MRI:** exclude other diagnosis and can help determine type of dementia; will show medial temporal lobe atrophy - Definitive diagnosis of AD is made by performing **a brain biopsy after autopsy.**

Answer 139

There is a diagnostic criteria for dementia based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-V): - **Functional ability**: inability to carry out normal functions. Represents a decline from previous functional level - **Cognitive domains**: impairment involving ≥2 cognitive domains - **Differentials excluded**: clinical features cannot be explained by another cause (esp. psychiatric disorders and delirium)

Answer 140

- **Other dementia's** - **Depression** - **Delirium**

Answer 141

- **Non-pharmacological:** programmes to improve/maintain cognitive function (e.g. structured group cognitive stimulation programmes). Also exercise, aromatherapy, therapeutic use of music/dancing, massage. - **Pharmacological:** - **Mild-to-moderate AD**: acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine). - **Moderate-to-severe AD**: N-methyl-D-aspartic acid receptor antagonist (e.g. memantine). May be used in combination with acetylcholinesterase inhibitors. - **Advanced care planning** - **End of life care**

Answer 142

There is no cure for dementia and it is considered a life-limiting condition It is estimated that one in three people over the age of 65 will die with dementia and the estimated median survival after diagnosis is 3-9 years (variable). Progression of dementia has been estimated by WHO, which is based on each stage of severity. Development of delirium on a background of dementia is associated with more rapid progression. - **Mild**: first 2 years - **Moderate**: next 2-4 years - **Severe**: 4-5 years onwards

Answer 143

Migraine is a chronic, genetically determined, episodic neurological disorder that usually presents in early-to-mid life.

Answer 144

- Second most common primary headache - Migraine is a common condition with a global prevalence of 14.7% - F>M - In 90% onset is before 40yrs

Answer 145

- **Family history** - **Female gender**: migraines are three times more common in women - **Obesity** - **Triggers**: CHOCOLATE - **Ch**ocolate - **O**ral **C**ontraceptive - Alcoh**ol** - **A**nxiety - **T**ravel - **E**xercise - **Other important triggers** include tiredness, lack of food, dehydration, menstruation, red wine and bright lights

Answer 146

There are several types of migraine: - **Migraine without aura** - **Migraine with aura** - **Silent migraine** (migraine with aura but without a headache) - **Hemiplegic migraine** Migraine is a primary headache which is usually episodic. ‘Classic' migraines are preceded by an aura, however, these only occur in one-third of patients. *Initial theory: aura was due to cerebral vasoconstriction, whilst the subsequent headache occurred due to reflex vasodilatation.* The headache now is thought to be due to neuronal hyperexcitability. This leads to trigeminal nerves initiating an inflammatory response with subsequent dilation of meningeal blood vessels, and sensitisation of surrounding nerve fibres leading to pain The aura is thought to occur due to cortical spreading depression, which is a propagating wave of depolarisation across the cerebral cortex causing the brain to become hypersensitive to certain stimuli **5 stages:** - **Premonitory** or **prodromal** stage (can begin 3 days before the headache) - **Aura** (lasting up to 60 minutes) - **Headache** stage (lasts 4-72 hours) - **Resolution** stage (the headache can fade away or be relieved completely by vomiting or sleeping) - **Postdromal** or **recovery** phase

Answer 147

- **Severe, unilateral, pulsating headache** lasting up to 72 hours - In children, migraines are more commonly **bilateral, shorter-lasting and associated with gastrointestinal symptoms** such as abdominal pain - **Nausea and vomiting** - **Photophobia and phonophobia** - **Typical aura**: develops over 5 minutes, lasts 5-60 minutes and is fully reversible - **Visual symptoms** e.g. distortion, lines, dots, zigzag lines, scotoma - **Paresthesia** - **Speech disturbance** - **Atypical aura**: may last more than 60 minutes - **Motor weakness** (e.g. hemiplegic migraine - dysarthria, ataxia, ophthalmoplegia, hemiparesis) - **Diplopia** - **Visual symptoms affecting one eye** - **Poor balance** (e.g. vestibular migraine) - **Decreased level of consciousness**

Answer 148

- Migraine is a **clinical diagnosis** - Investigations to rule out other pathology: - **CT or MRI head**: rule out the cause of a secondary headache, such as a subarachnoid haemorrhage - **ESR:** exclude giant cell arteritis

Answer 149

- **Stroke:** hemiplegic migraines can mimic strokes - Primary headaches - **Migraines** - **Trigeminal autonomic cephalalgias** - **Other primary headache disorders** - Secondary headaches - **Trauma** - **Idiopathic intracranial hypertension** - **Subarachnoid haemorrhage** - **Space occupying lesion** - **Giant cell arteritis** - **Infection** - **Drugs and medications** - **Venous sinus thrombosis** - **Malignant hypertension** - **Temporomandibular disorder**

Answer 150

- **Analgesia** - **Ibuprofen or aspirin or paracetamol** - **Oral triptan** alone +/- paracetamol or an NSAID - Oral sumatriptan is the first choice triptan (5-HT receptor agonist - mimic serotonin to cause vasoconstriction) - Consider a nasal triptan over an oral triptan in people aged 12 to 17 years old - **Antiemetic:** consider metoclopramide or prochlorperazine - **Avoid opiates:** due to the risk of medication-overuse headache, dependence, and worsening nausea

Answer 151

- **Headache diary:** document headache frequency to illicit triggers - **Avoid triggers** - **Prophylaxis (pharmacological):** - **Propranolol** is considered first-line - **Topiramate**: contraindicated in pregnancy as it is teratogenic and reduces oral contraceptive efficacy - **Amitriptyline:** low-dose may be considered - **Frovatriptan** or **zolmitriptan**: for predictable menstrual migraines - **Prophylaxis (non-pharmacological)**: - **Mindfulness:** alternatives include meditation and CBT - **Acupuncture**: if both propranolol and topiramate are ineffective or unsuitable - **Riboflavin (vitamin B2)**: **may be effective in some people, but avoid in pregnancy

Answer 152

- **Depression** - **Status migrainosus:** a severe, debilitating migraine lasting for more than 72 hours that may warrant admission

Answer 153

The prognosis associated with episodic migraine is generally good with treatment, whilst the frequency of headaches is thought to decrease with age.

Answer 154

Tension-type headaches is a common primary headache disorder and can be either episodic or chronic.

Answer 155

- Very common: most common primary headache - Onset tends to be in a patients' 20's - Most common between ages of 20-39 - Gradually becomes less common with advancing age

Answer 156

- Increased muscle tenderness - Combination of genetic and environmental factors

Answer 157

- **Stress** - **Bad posture** - **Sleep deprivation** - **Eye strain** - **Depression** - **Alcohol** - **Skipping meals** - **Dehydration**

Answer 158

May be due to muscle ache in the frontalis, temporalis and occipitalis muscles. - Increased tenderness of pericranial myofascial structures leads to activation of vasculature-surrounding nociceptors leading to episodic tension headaches - Prolonged nociceptor stimulation leads to pain pathway sensitisation with hyperalgesia causing chronic tension headaches

Answer 159

- **Bilateral with a pressing/tight sensation of mild-moderate intensity** - Frequency varies depending on type of headache: chronic or episodic - Other associated symptoms: - **Nausea or vomiting** - **Photophobia** - **Phonophobia**

Answer 160

- It is a **clinical diagnosis** based on criteria outlined by the International Headache Society - **Infrequent episodic tension-type headache** **Frequency:** At least 10 episodes of headache occurring on <1 day/month on average (<12 days/year) **Time:** 30 minutes to 7 days **Characteristics:** At least two of the following: 1. Bilateral location 2. Pressing or tightening (non-pulsating) quality 3. Mild or moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing stairs **Both of:** 1. No nausea or vomiting 2. No more than one of photophobia or phonophobia - **Frequent episodic tension-type headache** **Frequency:** At least 10 episodes of headache occurring on 1-14 days/month on average for >3 months (≥12 and <180 days/year) **Time:** 30 minutes to 7 days **Characteristics:** At least two of the following: 1. Bilateral location 2. Pressing or tightening (non-pulsating) quality 3. Mild or moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing stairs **Both of:** 1. No nausea or vomiting 2. No more than one of photophobia or phonophobia - **Chronic tension-type headache** **Frequency:** Headache occurring on ≥15 days/month on average for >3 months (≥180 days/year) **Time:** Hours to days, may be unremitting **Characteristics:** At least two of the following: 1. Bilateral location 2. Pressing or tightening (non-pulsating) quality 3. Mild or moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing stairs **Both of:** 1. No more than one of photophobia, phonophobia or nausea 2. Neither moderate or severe nausea or vomiting

Answer 161

- Patient's advised to keep a **headache diary** - Other investigations to rule out other pathology: - **CT or MRI head**: rule out the cause of a secondary headache, such as a subarachnoid haemorrhage - **ESR:** exclude giant cell arteritis

Answer 162

Primary headaches - **Migraines** - **Trigeminal autonomic cephalalgias** - **Other primary headache disorders** Secondary headaches - **Trauma** - **Idiopathic intracranial hypertension** - **Subarachnoid haemorrhage** - **Space occupying lesion** - **Giant cell arteritis** - **Infection** - **Drugs and medications** - **Venous sinus thrombosis** - **Malignant hypertension** - **Temporomandibular disorder**

Answer 163

- **Analgesia:** Simple painkillers e.g. paracetamol or NSAIDs to be taken when headache occurs. - Limit the use of analgesia to no more than 6 days a month to reduce chance of medication-overuse headache - **Hot towels to local area** - **Lifestyle:** Evaluate and offer help with possible precipitants. Consider sources of stress, depression/anxiety, sleep disorder and chronic illnesses. Some patients find regular exercise helps.

Answer 164

- **Acupuncture/ massage** - **Prophylaxis:** consider low dose amitriptyline - **Lifestyle:** Evaluate and offer help with possible precipitants. Consider sources of stress, depression/anxiety, sleep disorder and chronic illnesses. Some patients find regular exercise helps. - **Referral:** If there is no improvement or diagnostic uncertainty refer to neurology.

Answer 165

Tension headaches comes on and resolve gradually and don’t produce visual changes

Answer 166

Cluster headaches are intensely painful, unilateral, periorbital headaches with associated autonomic dysfunction.

Answer 167

- The estimated annual incidence of cluster headaches is 53 per 100,000 in the Western population - Peak onset of 20 to 40 years old - M>F

Answer 168

- **Male**: 3 times more common in males - **Family history** - Autosomal dominant gene has a role - **Smoking** - **Alcohol excess**

Answer 169

Cluster headaches are classified as a trigeminal autonomic cephalgia (TAC) and are thought to occur due to hypersensitivity of the trigeminal-autonomic reflex arc, resulting in vascular dilation and trigeminal nerve stimulation. *Two other important types of TAC include:* - *Paroxysmal hemicranial* - *Short-lived unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT)* Furthermore, histamine release, an increase in mast cells and activation of the autonomic nervous system may also be involved. Common precipitants of a cluster headache include alcohol, volatile smells, warm temperatures and sleep - Can be episodic (clusters followed by remission periods) or chronic (no substantial remission period)

Answer 170

- Clusters usually last 2 weeks to 3 months, separated by remission periods lasting at least 3 month - Patients experience 1 to 8 attacks per day - Clusters typically occur 1 to 2 times per year

Answer 171

- Signs - **Autonomic signs** - Symptoms - **Unilateral, periorbital or temporal headaches** lasting 15 minutes to 3 hours - Ipsilateral **autonomic** symptoms: - **Lacrimation** (teary eye) - **Conjunctival injection** (red eye due to enlargement of conjunctival vessels) - **Nasal congestion** - **Rhinorrhoea** (nasal discharge) - **Ptosis** (eyelid drooping) - **Miosis** (excessive constriction of the pupil of the eye) - **Facial sweating** - **Nausea and vomiting** - **Photophobia, with agitation and restlessness**

Answer 172

- Diagnosis is predominantly based on **clinical presentation** - At least 5 headache attacks fulfilling the symptomatic criteria - Investigations to rule out other pathology: - **CT or MRI Brain:** to rule out an underlying cause such as a space-occupying lesion or pituitary adenoma - **ESR:** to exclude giant cell arteritis

Answer 173

Primary headaches - **Migraines** - **Trigeminal autonomic cephalalgias** - **Other primary headache disorders** Secondary headaches - **Trauma** - **Idiopathic intracranial hypertension** - **Subarachnoid haemorrhage** - **Space occupying lesion** - **Giant cell arteritis** - **Infection** - **Drugs and medications** - **Venous sinus thrombosis** - **Malignant hypertension** - **Temporomandibular disorder**

Answer 174

- **Triptans**: triptans are 5HT 1B/D agonists. Subcutaneous or intranasal sumatriptan provides symptomatic relief within 15 minutes in 75% of patients. - **High flow oxygen**: 100% oxygen at 12-15L/minute via a non-rebreather mask for 15-20 minutes; provides symptomatic relief within 15 minutes in 70% of patients - **Avoid triggers** - The following drugs should be **avoided**: paracetamol, NSAIDs, opioids, ergots, and oral triptans

Answer 175

- **Verapamil**: first-line preventative management - **Lithium** - **Prednisolone:** a short course for 2-3 weeks to break the cycle during clusters

Answer 176

- **Mental illness:** depression, anxiety, self-harm and suicide - **Auto-enucleation:** individuals attempting to remove the affected eye due to a belief that the pain will subside

Answer 177

The prognosis is variable and difficult to predict. Patients with episodic headaches may develop chronic headaches, and vice versa. There is evidence to suggest that headaches remit with increasing age, with less frequent episodes and prolonged periods of remission between attacks.

Answer 178

Overuse of medication causing headaches

Answer 179

- Medication overuse headache is estimated to occur in 1-2% of the general population worldwide - The third most common cause of headache after migraine and tension headache - It can occur at any age but is most common in people in their 30s and 40s. - F>M

Answer 180

An analgesic headache is a headache caused by long term analgesia use. They are secondary to continuous or excessive use of analgesia. e.g. ergotamine, triptans, opioids, nonsteroidal anti-inflammatories (including aspirin), and paracetamol. Overuse is a common reason for episodic headache becoming chronic daily headache. - *It is only seen if overuse of analgesia related to an already existing headache, rather than analgesia for other conditions*

Answer 181

It gives similar non-specific features to a tension headache.

Answer 182

- Headache occurring on 15 or more days per month in a person with a pre-existing headache disorder *and* - Regular overuse for more than 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache. - For ergotamine, triptans, opioids and combination analgesics intake must be 10 days or more per month to be considered overuse. - For simple analgesics such as nonsteroidal anti-inflammatories (including aspirin) and paracetamol intake must be 15 days or more per month to be considered overuse. - Headache must not be better accounted for by another headache diagnosis.

Answer 183

Trigeminal neuralgia is a pain syndrome which describes severe unilateral pain in the distribution of one or more trigeminal branches

Answer 184

- The estimated prevalence of trigeminal neuralgia ranges from 0.03% to 0.3% - Rare in people younger than 40 years of age. Peak incidence between 50-60yrs - F>M

Answer 185

- **Advancing age**: rare in people younger than 40 years of age - **Female gender:** more common in women - **Demyelinating disease**: trigeminal neuralgia is 20 times more common in patients with multiple sclerosis

Answer 186

- It is estimated that up to 90% of patients with trigeminal neuralgia have **compression of the nerve by a vascular loop** near the nerve’s root entry zone, typically by the superior cerebellar artery. - Other causes include: - **Demyelinating disease** - **Posterior fossa masses** - **Brainstem infarcts.** The pathophysiology involves **aberrant conduction along the trigeminal nerve resulting in neuropathic pain.** Specific triggers include light touch, such as washing, shaving, and talking, and brushing the teeth as well as cold weather, spicy food, caffeine and citrus fruits.

Answer 187

Pain may be provoked by touch on examination

Answer 188

- **Facial pain:** comes on spontaneously and last anywhere between a few seconds to hours. - **Trigeminal distribution** - **Severe** - **Unilateral** (but minority of cases are bilateral) - **Electric shock-like sensation** - **Episodic** - **Provoked, e.g. touch or cold** - Some patients experience autonomic symptoms e.g. - **Lacrimation** - **Facial swelling** - **Rhinorrhoea** - **Ptosis**

Answer 189

- **Age of onset before 40 years** - **Pain only in the ophthalmic division (eye socket, forehead, and nose), or bilaterally** - **Sensory changes** - **Deafness or other ear problems** - **History of skin or oral lesions that could spread perineurally** - **Optic neuritis** - **Family history of multiple sclerosis**

Answer 190

- Trigeminal neuralgia is a **clinical diagnosis** - Investigations to rule out other pathology - **MRI brain:** imaging may be used if a sinister cause is suspected, such as a space-occupying lesion or demyelination, or if the patient is refractory to medical treatment and surgical intervention is being considered

Answer 191

- **Medical: carbamazepine** is first-line. The dose is titrated upwards every two weeks until the pain is relieved. - Other medication may be used but only under specialist guidance - **Refer to neurology**: ****if there is severe pain or pain that significantly affects daily function, as well as patients refractory to treatment or with atypical symptoms (e.g. age < 50 years)

Answer 192

Depression and anxiety

Answer 193

Trigeminal neuralgia is a chronic pain condition, meaning that patients often have a relapsing and remitting course throughout their life. Medical and ablative procedures are associated with partial relief of symptoms in the majority of patients. However, over time, patients often become less responsive to conventional treatments and relapse.

Answer 194

Subarachnoid haemorrage

Answer 195

Temporal arteritis or space occupying lesion

Answer 196

Space-occupying lesion and subdural haematoma

Answer 197

Subdural haematoma

Answer 198

Raised intracranial pressure e.g. space occupying lesion, Chairi 1 malformation

Answer 199

Raised intracranial pressure

Answer 200

Carbon monoxide poisoning

Answer 201

Meningitis or Encephalitis

Answer 202

Raised intracranial pressure, Venous sinus thrombosis

Answer 203

Raised intracranial pressure, Stroke

Answer 204

Acute closure glaucoma, temporal arteritis

Answer 205

Raised intracranial pressure, Brain abscess, Carbon monoxide poisoning

Answer 206

Cerebral infection and malignancy

Answer 207

Cerebral metastases

Answer 208

Pre-eclampsia

Answer 209

Multiple sclerosis (MS) is an autoimmune, cell-mediated demyelinating disease of the central nervous system.

Answer 210

- The estimated prevalence of MS in England and Wales is 180 per 100,000 - F>M - Most commonly diagnosed in 20-40 year olds - More common in white populations - More common in northern latitudes

Answer 211

- **Age**: most commonly diagnosed in 20-40 year olds - **Female gender**: MS is 3 times more common in females - **Smoking** - **Obesity** - **Vitamin D deficiency** - **Northern latitudes** - **Family history**: HLA-DR2 is implicated; 30% monozygotic twin concordance - **Autoimmunity**: patients often have a family history of other autoimmune disorders - **EBV infection**: the virus with the greatest link to MS

Answer 212

**Myelin:** Myelin is the protective sheath that surrounds the axons of neurons, allowing them to quickly send electrical impulses. This myelin is produced by oligodendrocytes in the CNS and by schwann cells in the peripheral nervous system **Pathology:** In multiple sclerosis, demyelination happens when the immune system inappropriately attacks and destroys the myelin. T-cells manage to get through the blood brain barrier and is activated by myelin. The T-cell then changes the blood brain barrier for it to express more receptors which allow more immune cells to get into the brain. MS is a type IV hypersensitivity reaction: T-cells release cytokines. These can recruit more immune cells as well as directly damaging the oligodendrocytes. B-cell make antibodies and macrophages can use these antibodies to attack the oligodendrocytes, ultimately destroying the myelin. This leaves behind areas of plaque/ sclera. These attacks usually happen in bouts, as regulatory T-cells can inhibit other immune cells. At first there may be remyelination but over time there is permanent damage. A characteristic features of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time. **Pathogenesis:** The pathogenesis of MS is not well understood, although it is thought to occur due to environmental triggers in genetically susceptible individuals, comprising an inflammatory and degenerative component. - **Relapsing-remitting**: - The most common pattern (85% of cases) - Episodic flare-ups (may last days, weeks or months), separated by periods of remission. There isn't full recovery after the flare-ups, so disability increases over time - 60% of patients develop secondary progressive MS within 15 years - **Secondary progressive:** - Initially, the disease starts with a relapsing-remitting course, but then symptoms get progressively worse with no periods of remission - **Primary progressive:** - Symptoms get progressively worse from disease onset with no periods of remission - Accounts for 10% of cases and is more common in older patients - **Progressive relapsing:** - One constant attack but there are bouts superimposed during which the disability increases even faster

Answer 213

- **Visual:** - Optic neuritis (demyelination of the optic nerve) - Loss of vision in one eye - Pain on eye movement - Pale optic disk and inability to see red - Relative afferent pupillary defect - Double vision: lesions with the sixth cranial nerve - Internuclear ophthalmoplegia and conjugate lateral gaze disorder - Demyelination of the medial longitudinal fasciculus (MLF) - Can be unilateral or bilateral - For example, with right sided INO, i.e. a right MLF lesion, the patient cannot adduct their right eye when looking left - **Upper motor neuron signs** with spastic paraparesis are common - **Cerebellar signs:** such as ataxia and tremor - **Sensory loss:** due to demyelination of spinothalamic or dorsal columns - **Trigeminal neuralgia:** stimulation to face causes pain

Answer 214

- **Blurred vision and red desaturation** - **Numbness, tingling and other strange sensations:** plaques in the sensory pathways - **Weakness** - **Bowel and bladder dysfunction:** plaques involve the autonomic nervous system - **Lhermitte’s phenomenon:** electric shock sensation on neck flexion, caused by stretching the demyelinated dorsal column. - **Uhtoff’s phenomenon:** worsening of symptoms following a rise in temperature, such as a hot bath

Answer 215

- **MRI brain and spine:** - **Demyelinating plaques**: periventricular plaques are called Dawson’s fingers - **High signal T2 lesions** - **Old lesions will not enhance with contrast, whereas newer lesions will.** This provides evidence of dissemination of lesions in time and space which is required for a diagnosis of MS - **Lumbar puncture for CSF:** oligoclonal bands found in the CSF and **not** in the serum, increased IgG - **Visual evoked potentials:** responses recorded to visual stimulus using electrodes; ****delayed velocity but a normal amplitude

Answer 216

The McDonald criteria is used to diagnose MS. In brief, the criteria can be described as **symptoms/signs which demonstrate dissemination in space (i.e. different parts of the CNS affected) and time**. The main diagnostic criteria: **Diagnosis is based on:** - 2 or more relapses **AND EITHER** - Objective clinical evidence of 2 or more lesions **OR** - Objective clinical evidence of one lesion **WITH** a reasonable history of a previous relapse - ‘Objective evidence’ is defined as an abnormality on neurological exam, MRI or visual evoked potentials

Answer 217

- **Steroids:** - Oral or IV methylprednisolone is first-line - Steroids reduce relapse duration by 13 days - **Plasma exchange**: to remove disease-causing antibodies

Answer 218

- **Disease-modifying drugs**: - **Beta-interferon**: decreases the level of inflammatory cytokines - **Monoclonal antibodies** e.g. alemtuzumab (anti-CD52) and natalizumab (anti-α4𝛃1-integrin) - **Glatiramer acetate**: immunomodulator drug which acts as a ‘decoy’ - **Fingolimod**: a sphingosine-1-phosphate receptor modulator that keeps lymphocytes in lymph nodes so they can’t cause inflammation

Answer 219

- **Spasticity**: physiotherapy, avoid triggers, baclofen or gabapentin are first-line - Alternatives include dantrolene and diazepam - **Neuropathic pain**: consider amitriptyline or gabapentin - **Bladder dysfunction**: perform a bladder ultrasound - Insignificant residual volume: consider an anticholinergic (e.g. oxybutynin) - Significant residual volume: intermittent self-catheterisation - **Depression:** SSRIs - **Fatigue:** investigate other causes (e.g. anaemia), CBT and consider amantadine

Answer 220

- **Genitourinary:** urinary tract infections, urinary retention and incontinence - **Constipation** - **Depression**: offer mental health support if required - **Visual impairment** - **Mobility impairment**: offer physiotherapy, orthotics and other mobility aids - **Erectile dysfunction**

Answer 221

Given the varying disease course, the prognosis varies significantly between patients. Most patients will still be ambulant at 15 years post-diagnosis, whilst the life expectancy for people with MS is around 5 to 10 years lower than average. Fortunately, the most common presentation of MS has good prognostic features. Other good prognostic features include: - Sensory symptoms alone - Complete recovery between relapses - A long period between the first two relapses

Answer 222

Motor neurone disease is an umbrella term that encompasses a variety of specific diagnoses. It is a cluster of degenerative disease characterised by axonal degeneration of neurones in the motor cortex, cranial nerve nuclei and anterior horn cells.

Answer 223

Various patterns of disease exist, with amyotrophic lateral sclerosis (ALS) being the most common (50% of cases). - **Amyotrophic lateral sclerosis: UMN + LMN** - The familial form is associated with mutations in superoxide dismutase (SOD1) - UMN signs: predominantly affects the corticospinal tracts - LMN signs: also affects anterior horn cells - Overall, mixed UMN/LMN signs may be seen - **Progressive muscular atrophy: LMN only** - Primarily the muscles of talking and swallowing - LMN signs: predominantly affects the anterior horn cells - Best prognosis - **Primary lateral sclerosis: UMN only** - Least common - Loss of Betz cells in motor cortex - UMN signs: predominantly affects the corticospinal tracts - **Progressive bulbar palsy: LMN only** - Affects the suprabulbar nuclei and cranial nerves, producing speech and swallow issues - Worst prognosis

Answer 224

Relapsing-remitting, Secondary progressive, Primary progressive and Progressive-relapsing

Answer 225

- Rarely presents before 40 years old. The average age of onset of MND is 60 years old - M>F - Often fatal in 2-4yrs

Answer 226

- **Advancing age** - **Male gender**: 1.2 to 1.8 times more likely to develop MND - **Family history**: familial in 5% of cases and the SOD1 mutation is implicated - **Smoking**: currently a ‘probable’ risk factor for MND - **Exposure to heavy metals and certain pesticides**

Answer 227

Motor neurone disease is a progressive, ultimately fatal condition where the motor neurones (both upper and lower) stop functioning. There is no effect on the sensory neurones and patients should not experience any sensory symptoms. The exact cause is unclear although several mechanisms have been considered. There is a genetic component and many genes have been linked with an increased risk of developing the condition.

Answer 228

- **Mixed UMN and LMN signs** - **Spastic paraparesis with brisk reflexes** - **Upgoing plantar responses** - **Fasciculations (twitches in the muscles)** especially on the tongue - **Dysarthria and dysphagia:** particularly in progressive bulbar palsy - **Muscle wasting:** particularly of small hand muscles and tibialis anterior - **Reduced tone**

Answer 229

- **Progressive weakness** often first noticed in the upper limbs - **Clumsiness** - **Fatigue** - **Falls** - **Speech and swallow issues:** particularly in progressive bulbar palsy

Answer 230

No sensory abnormalities such as sphincter dysfunction, No extraocular involvement (E.g abdo reflexes are usually preserved), no cerebellar involvement

Answer 231

- Investigations to rule out other pathology: - **Electromyography:** in MND there will be evidence of fibrillation potentials - **Nerve conduction studies:** may show modest reductions in amplitude - **MRI spine:** imaging can help exclude spinal pathology which may mimic MND, such as cervical cord compression and myelopathy - **Lumbar puncture:** to exclude inflammatory causes - **Pulmonary function tests:** patients with MND are at risk of respiratory failure MND is a clinical diagnosis

Answer 232

- **Multiple sclerosis** - **Polyneuropathies** - **Myasthenia gravis** - **Diabetic amyotrophy** - **Guillain-Barre syndrome** - **Spinal cord tumours**

Answer 233

- **Riluzole:** prolongs survival by 2-4 months; it is thought to protect motor neurons from glutamate-induced damage - **Respiratory support:** patients with reduced FVC can use non-invasive ventilation at home, usually BiPAP; prolongs survival by 7 months - **Supportive treatment:** - **Antispasmodics:** such as baclofen - **Analgesia** - **Feeding support:** many patients require nutritional support, often with PEG tube - **Speech and language therapy** - **Physiotherapy** - **Advanced directives** to document the patients wishes as the disease progresses - **End of life care** planning

Answer 234

- **Aspiration pneumonia** and **bronchopneumonia** - **Respiratory failure**: often occurs in advanced disease when respiratory muscles have been affected

Answer 235

Prognosis is variable and depends on the pattern of disease, with progressive bulbar palsy associated with the worst prognosis. Most patients die within 3 years from the onset of their symptoms. Poor prognostic factors include progressive bulbar palsy, old age and poor respiratory function. The majority of patients die from respiratory complications.

Answer 236

Encephalitis describes inflammation of the brain parenchyma. It mostly affects frontal and temporal lobes.

Answer 237

The estimated incidence of encephalitis worldwide (excluding epidemics) is 1.5-7 per 100,000 person-years

Answer 238

- The most common cause of encephalitis is **herpes simplex virus-1** (HSV-1; 95% of cases), which causes temporal and inferior frontal lobe encephalitis - **Viral:** - Herpesviruses - HSV-1 and HSV-2 - Varicella-zoster virus - Epstein-Barr virus (EBV) - Cytomegalovirus (CMV) - Enteroviruses - Coxsackievirus - Poliovirus - Flaviviruses - Japanese encephalitis virus - West Nile virus - Retroviruses - HIV - **Bacterial:** - Neisseria meningitidis - Tuberculosis - Syphilis - **Fungal:** - Cryptococcus - **Parasitic:** - Toxoplasmosis - Cysticercosis - **Paraneoplastic:** - Anti-NMDA - Anti-voltage gated potassium channel - **Non-infective:** - Antibodies created against brain tissue

Answer 239

- **Immunocompromise** - **Blood/fluid exposure**: HIV and West Nile virus - **Mosquito bite**: West Nile virus - **Transfusion and transplantation**: CMV, EBV, HIV - **Close contact with cats**: toxoplasmosis

Answer 240

- Encephalitis is an immune response to the invasion of a pathogen, causing inflammation of the brain parenchyma. - **Primary infection:** first infection with HSV - **Recurrent infection:** reactivated infection from sensory neurones - HSV gets into the sensory ganglia by travelling retrograde from skin and recurrent infection happens when it travels anterograde back to the skin. If it travels to the CNS, it leads to encephalitis. This is usually along olfactory or trigeminal nerves. - Can also be haematogenous spread

Answer 241

- **Pyrexia** - **Reduced GCS** - Focal neurological deficit, such as: - **Aphasia** - **Hemiparesis** - **Cerebellar signs** - **May also have signs of meningitis:** meningo-encephalitis

Answer 242

- **Fever** - **Headache** - **Fatigue** - **Confusion** - **Seizures** - Behavioural changes: - **Memory disturbance** - **Psychotic behaviour** - **Withdrawal or change in personality**

Answer 243

- **Blood tests:** FBC, CRP, U&Es and blood culture - **Throat swab:** culture for viral organisms - **HIV serology**: now routinely tested in the emergency department - **CT or MRI head:** MRI is preferred and will show evidence of inflammation in the medial temporal and inferior frontal lobes in HSV encephalitis; CT is normal in ⅓ of cases - **Lumbar puncture and CSF investigations**: - **Analysis:** lymphocytosis with raised protein in the case of viral aetiology - **PCR:** assays for common viral infections including HSV should be carried out - **Culture:** useful for bacterial causes - **Serology:** antibodies against specific viral antigens

Answer 244

- **Meningitis** - **Encephalopathy** - **Status epilepticus** - **CNS vasculitis**

Answer 245

- **Antiviral medication:** - **Aciclovir** should be commenced empirically in all patients with suspected encephalitis - **Ganciclovir** may be preferred in other herpesvirus infections, such as HHV-6 - A combination of **ganciclovir and foscarnet** is usually used in CMV - Further management options will depend on the underlying organism

Answer 246

- **Seizures** - **Ischaemic stroke** - **Hydrocephalus:** accumulation of cerebrospinal fluid (CSF) within the brain - **Lasting fatigue and prolonged recovery** - **Aphasia** - **Change in personality or mood** - **Changes to memory and cognition** - **Learning disability** - **Headaches** - **Chronic pain** - **Movement disorders** - **Sensory disturbance** - **Hormonal imbalance**

Answer 247

Untreated HSV encephalitis is associated with a 70% mortality. This is significantly reduced with early antiviral therapy. Survivors often have neurological sequelae such as short-term memory impairment and behavioural changes

Answer 248

Herpes zoster (HZ) (shingles) is caused by reactivation of varicella-zoster virus (VZV) that was acquired during a primary varicella infection, and is characterised by dermatomal pain and papular rash.

Answer 249

- 90% of children have been exposed to chicken pox (varicella zoster) before they are aged 16 - The annual incidence of HZ in the UK is estimated between 1.85 and 3.9 cases per 1000 population - Herpes zoster can effect all ages but seen as a disease of the elderly - F>M

Answer 250

- **Increasing age** - **Immunocompromise**

Answer 251

- **Herpes zoster (shingles):** Some remaining varicella zoster virus remains latent in the ganglion. If the immune system weakens, due to ageing, stress, or immunosuppressive therapy, the virus can be reactivated. It can then travel back up through the sensory nerve, anterogradely to the skin and cause an infection in the innervated dermatome, most commonly in lower thoracic dermatomes and ophthalmic division of trigeminal nerve.

Answer 252

- **Macular-vesicular rash in dermatomal distribution** - Usually in a single stripe of vesicles around either the left or the right side of the body or on one side of the face. - Crust formation and drying occurs over the next week with resolution in 2-3 weeks - **Pain, itching, or tingling** in the area where the rash is - **Malaise, myalgia, headache and fever can be present** - **Disseminated infection may occur,** if immunosuppressed

Answer 253

- Shingles are usually diagnosed based on **clinical presentation** of the skin lesions - Diagnosis confirmed with: **viral PCR, culture, immunohistochemistry** - Tzanck test: look for multinucleated giant cells in the fluid of the vesicles - Look for varicella zoster antibodies or viral DNA.

Answer 254

- **Oral aciclovir/ valaciclovir** - **IV aciclovir** if pregnant, immunosuppressed or severe/ disseminated infection - **Topical antibiotic treatment** for secondary bacterial infection - **Oral/ topical analgesics** - **Prevention:** - **Zoster vaccine can be used to reduce zoster -** not routine, but given at age 70 to prevent shingles - **VZV immunoglobulin:** given if non-immune exposure in imunosuppression, pregnancy, neonates

Answer 255

- **Secondary bacterial infection** of the lesions e.g. hepatitis, pneumonia, encephalomeningitis - **Postherpetic neuralgia:** pain in the affected dermatome which lasts for more than 90 days. Affects nerve fibers and skin, causing burning pain that lasts long after the rash and blisters of shingles disappear. - **Ramsay-hunt syndrome**: neurological disorder characterised by paralysis of the facial nerve (facial palsy) and a rash affecting the ear or mouth. Ear abnormalities such as ringing in the ears (tinnitus) and hearing loss may also be present. - **Herpes zoster ophthalmicus:** reactivation of a varicella-zoster virus infection (shingles) involving the eye. - Can cause **chickenpox in people who have close contact**

Answer 256

Herpes zoster rarely causes fatalities in patients who are immunocompetent, but it can be life-threatening in immunocompromised patients. Ocular complications occur in 50% to 90% of the cases, resulting in either temporary or permanently decreased visual acuity or blindness if untreated.

Answer 257

A brain tumour is an abnormal growth occurring in any tissue contained within the cranium, including the brain, cranial nerves, meninges, skull, pituitary gland, and pineal gland. There are many different types of brain tumours. They vary from benign tumours (e.g. meningiomas) to highly malignant (e.g. glioblastomas).

Answer 258

- Primary brain tumour incidence is around 8 per 100,000 (secondary brain tumours are more common) - Accounts for less than 2% of all malignant tumours but 20% of childhood cases - In adults, the majority are supratentorial

Answer 259

Severity is classified by the World Health Organisation’s (WHO) scale. The scale goes from I to IV based on the morphologic and functional features of the tumour cells; a grade IV tumour being the most abnormal looking cells that also tend to be the most aggressive.

Answer 260

Tumours of the glial cells in the brain or spinal cord Gliomas are graded from 1-4. Grade 1 are most benign (possibly curable with surgery). Given enough time, most gliomas will progress to become Glioblastoma Multiforme (GBM)

Answer 261

Astrocytoma, Oligodendroglioma, Ependymoma

Answer 262

- **Glioblastoma multiforme** is the most common - Most commonly found in cerebral hemisphere - Histologically has pseudo-palisading pattern - peripheral tumour cells lined up around necrotic centre - Grade IV (most malignant)

Answer 263

- Most common in 40s-50s - Adult oligodendrogliomas typically form in the frontal lobes of the cerebral cortex because those neurones are the most heavily myelinated. - Categorised as grade II or III, with an overall tendency to be relatively slow-growing tumours, though they still have the ability to become malignant. - Histologically, prominent features can vary from fairly small, round nuclei, surrounded by well-defined “halos” or thick white borders of cytoplasm giving them a “fried egg” appearance in grade II tumours; to having a “chicken wired” pattern of nearby blood vessels with areas of calcifications in grade III tumours.

Answer 264

Arise from ependymal cells (form the epithelial lining of the ventricles in the brain and the central canal of the spinal cord)

Answer 265

- More common in older people and women - Grow from cells found in the arachnoid mater of the meninges, called arachnoid cap cells. - They are usually benign, however they take up space and this mass effect can lead to raised intracranial pressure and neurological symptoms. - They are graded I through III and tend to be relatively slow growing. - Histologically, they form nests of cells or a multinuclear syncytium of fused cells. - These tumours may also cause the formation of calcifications called psammoma bodies.

Answer 266

- Pituitary tumours tend to be benign. - If they grow large enough they can press on the optic chiasm causing bitemporal hemianopia. This causes loss of the outer half of the visual fields in both eyes. - They have the potential to cause hormone deficiencies (hypopituitarism) or to release excessive hormones leading to: - Acromegaly - Hyperprolactinaemia - Cushing’s disease - Thyrotoxicosis - They are classified by the hormone that’s released and by the size of the tumour; rather than using the standard WHO classifications.

Answer 267

- Derived from cells with blood vessel origins - Can develop anywhere in the brain they are most often found in the cerebellum, especially in a middle-aged person. - They are slow-growing tumors and are typically grade I. - Histologically, there are often thin-walled capillaries that are arranged close to one another.

Answer 268

- Tumours of the Schwann cells surrounding the auditory nerve that innervates the inner ear. - They occur around the “cerebellopontine angle” and are sometimes referred to as cerebellopontine angle tumours. - They are slow-growing but eventually grow large enough to produce symptoms and become dangerous. - Acoustic neuromas are usually unilateral. Bilateral acoustic neuromas are associated with neurofibromatosis type 2. - Classic symptoms of an acoustic neuroma are: - Hearing loss - Tinnitus - Balance problems - They can also be associated with a facial nerve palsy.

Answer 269

- **More common in affluent groups** - **Ionising radiation** - **Vinyl chloride** - **Immunosuppression** - **Family history - genetics**

Answer 270

- Signs and symptoms of **raised intracranial pressure** - **Headache:** worse on waking, coughing and bending - **Vomiting** - **Altered mental state** - **Visual field defects** - **Seizures** (particularly focal) - **Unilateral ptosis** - **Third and sixth nerve palsies** - **Papilloedema** (on fundoscopy) - **Symptoms associated with individual types e.g.** - **Excess hormone from pituitary tumours** e.g. amenorrhea in women due to prolactin secretion - **Vestibular schwannoma:** hearing loss, tinnitus, balance problems

Answer 271

- **Temporal lobe:** dysphasia, amnesia - **Frontal lobe:** hemiparesis, personality change, Broca’s dysphasia, lack of initiative, unable to plan tasks - **Parietal lobe**: hemisensory loss, reduction in 2-point discrimination, dysphasia, astereognosis (unable to recognise object from touch alone) - **Occipital lobe:** contralateral visual defects - **Cerebellum:** DASHING - Dysdiadochokinesis (impaired rapidly alternating movement), Ataxia, Slurred speech (dysarthria), Hypotonia, Intention tremor, Nystagmus, Gait abnormality

Answer 272

- **CT/ MRI** - **Blood tests** e.g. FBC, U&Es, LFT’s, B12 - **Tissue biopsy:** to determine cancer grade and guide management

Answer 273

- **Aneurysm** - **Abscess** - **Cyst** - **Haemorrhage** - **Idiopathic intracranial hypertension**

Answer 274

- **Steroids e.g. IV Dexamethasone:** to reduce oedema/ inflammation - **Surgery** (dependent on the grade and behaviour of the brain tumour) - **Chemotherapy** - **Radiotherapy** - **Palliative care**

Answer 275

- **Trans-sphenoidal surgery** - **Radiotherapy** - **Bromocriptine:** to block prolactin-secreting tumours - **Somatostatin analogues (e.g. ocreotide)** to block growth hormone-secreting tumours

Answer 276

- **Hydrocephalus:** as the tumour grows it can compress nearby cells and structures e.g. as meningiomas enlarge they can compress the ventricles and block CSF flow causing hydrocephalus - **Midline shift and herniations through foramen magnum:** due to rising pressures

Answer 277

- Brain metastasis affects up to 40% of patients with cancer - 10 times more common than primary brain tumours

Answer 278

- Common metastases: - **Lung: non small cell and small cell** - **Breast** - **Melanoma** - **Renal cell** - **GI**

Answer 279

- **Headache:** worse in morning, when coughing or bending - **Focal neurological signs** - **Ataxia** - **Fits** - **Nausea** - **Vomiting** - **Papilloedema** (on fundoscopy)

Answer 280

- **Steroids e.g. dexamethasone:** reduce cerebral oedema - **Stereotactic radiotherapy/ chemotherapy** - **Surgery if <75 years** - **Palliative care**

Answer 281

Poor prognosis Median survival 1-2 months

Answer 282

Giant cell arteritis (GCA), also known as temporal arteritis, is a vasculitis of medium and large arteries. It is the most common form of systemic vasculitis that affects adults, and usually affects branches of the carotid artery.

Answer 283

- GCA is rare with an estimated prevalence of approximately 0.5% - Associated with polymyalgia rheumatica (PMR) in 50% - Common in elderly >55 years. - F>M - The patients at higher risk are white females over 50

Answer 284

- **Age:** usually affects those over 50 - **Female** - **Caucasians** - **Polymyalgia rheumatica (PMR):** individuals who suffer from PMR are at increased risk of developing GCA - **Family history**

Answer 285

Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries. Arteries become inflamed, thickened and can obstruct blood flow. Cerebral arteries affected in particular e.g. temporal artery Examples of common arterial distributions affected include: - **Superficial temporal artery:** headache and scalp tenderness - **Mandibular artery:** jaw claudication - **Ophthalmic artery:** visual loss (retinal ischaemia) Granulomatous inflammation along the vessel wall occurs segmentally. The result is intimal thickening and a narrowed vascular lumen. It is not known why these arteries become inflamed, however, it is thought to occur due to a subtle interplay between genetic and environmental factors.

Answer 286

- **Superficial temporal artery tenderness** - **Absent temporal artery pulse** - **Reduced visual acuity** - **Pallor of the optic disc**

Answer 287

- **Severe unilateral persistent headache** - **Blurred vision or amaurosis fugax:** painless sight loss can occur rapidly - **Scalp pain:** classically described as pain when combing hair - **Jaw claudication** - **Symptoms of PMR:** shoulder and hip pain - Systemic symptoms: - **Fever** - **Muscle aches** - **Fatigue** - **Weight loss** - **Loss of appetite** - **Peripheral oedema**

Answer 288

- **ESR**: ****a value ≥ 50mm/h makes up 1 of the 5 diagnostic criteria for GCA - **Temporal artery biopsy**: definitive test for diagnosis - A positive biopsy is defined as the presence of multinucleated giant cells (granulomas) - Intimal thickening and a narrowed vascular lumen may be seen - Negative biopsies are possible due to the presence of “skip lesions” along the artery; a negative result does **not** rule out GCA - **Fundoscopy**: may reveal pallor and oedema of the optic disc due to ischaemia of the optic nerve

Answer 289

- **Full blood count:** may show a **normocytic anaemia** and **thrombocytosis** (raised platelets) - **Liver function tests:** can show a raised **alkaline phosphatase** - **C reactive protein:** usually raised - **Temporal artery ultrasound:** performed if biopsy is not available and may demonstrate wall thickening (halo sign), stenosis or occlusion

Answer 290

Meet 3 or more of these: - Age over 50 - New onset headache - Temporal artery abnormality: e.g. tenderness on palpation or decreased pulsation - Elevated ESR of 50 mm/h or above - Abnormal temporal artery biopsy

Answer 291

- **Corticosteroid**: 40mg-60mg prednisolone daily if there are **no** visual symptoms. IV methylprednisolone is required for visual symptoms - Corticosteroid must be started immediately if there is suspicion of GCA - Patients may require low doses for a number of years - **Oral aspirin**: 75mg daily. May protect against ischaemic cranial complications, such as visual loss or cerebrovascular accident - **Urgent ophthalmology review:** if there is evidence of visual compromise

Answer 292

Specialist referral: if not responding to prednisolone within 48 hours then seek specialist advice from a rheumatologist

Answer 293

- **Ischaemic cranial complications:** visual loss and cerebrovascular accidents - **Aortic aneurysms:** patients with GCA are at an increased risk of developing aortic aneurysms, with a recommendation of 2-yearly thoracic imaging - **Glucocorticoid toxicity:** gastritis, osteoporosis, diabetes, HTN

Answer 294

Prevalence of a GCA relapse is not well understood, with some population studies claiming rates as high as 65%. Disease relapse should be suspected in patients with a return of symptoms of GCA, ischaemic complications, or unexplained constitutional or polymyalgic symptoms.

Answer 295

- Polymyalgia rheumatica is a condition that causes pain, stiffness and inflammation in the muscles around the shoulders, neck and hips. - Frequently occurs alongside GCA - Pathogenesis unknown - Age >50 years, F>M - Subacute onset >2 weeks of bilateral aching, tenderness and morning stiffness in shoulders, hips and proximal limbs. - Fatigue, fever, weight loss, anorexia and depression. - Sometimes associated with polyarthritis, tenosynovitis and carpal tunnel syndrome. - Investigations: elevated ESR and CRP, raised ALP. - Management: prednisolone

Answer 296

A classical syndrome of painless short-lived monocular blindness. It is a term usually reserved for transient visual loss of ischaemic origin. Management will depend on cause.

Answer 297

- Occurs due to the temporary reduction in the retinal, ophthalmic or ciliary blood flow leading to temporary retinal hypoxia. - The principle cause of amaurosis fugax is transient obstruction e.g. due to emboli, of the ophthalmic artery, which is a branch of the internal carotid artery. - However, other ischaemic causes to consider include giant cell arteritis (i.e. temporal arteritis) and central retinal artery occlusion.

Answer 298

- Often described as a black curtain coming across the vision.

Answer 299

Migraine: can cause transient visual loss

Answer 300

Spinal cord compression (SCC) results from processes that compress or displace arterial, venous, and cerebrospinal fluid spaces, as well as the cord itself. This is a medical emergency as it can lead to paralysis.

Answer 301

It is estimated that 5-10% of patients with cancer will develop metastatic lesions that affect the spinal cord

Answer 302

- **Vertebral body neoplasms** (most common cause) - Collapse or compression of the vertebral body due to metastases - Metastasis most commonly from lung, breast, prostate, thyroid, kidney, myeloma, lymphoma - Most commonly affects thoracic spine: 60% of cases occur in the thoracic spine, 30% in the lumbar spine and 10% within the cervical spine. - Rarer causes - **Spinal pathology** - **Disc herniation** - When centre of disc (nucleus pulposus) has moved out through the annulus (outer part of disc) resulting in pressure on nerve root and pain - **Disc prolapse** - When nucleus pulposus moves and presses against the annulus but it doesn't escape outside the annulus - Can produce a bulge in the disc which, sometimes, can result in pressure (less pressure than herniation) on nerve root resulting in pain - **Primary spinal cord tumour** e.g. glioma, neurofibroma - **Infection** e.g. epidural abscess - **Haematoma**

Answer 303

**Onset may be acute (hours to days) or chronic (weeks to months) depending on cause** - **Back pain**: radicular pain (spinal/ root pain) may precede weakness and sensory loss - **Progressive weakness of legs** (typically symmetrical) with UMN signs e.g. contralateral spasticity and hyperreflexia - **Sensory loss 1-2 cord segments below level of lesion** - **UMN signs below the level of lesion** - **LMN signs at level of lesion** - Signs dependent on level of lesion e.g. - L5/S1 lesion = sciatica (sensory loss and pain in back of thigh/ leg/ lateral aspect of little toe) - L4/L5 lesion = L5 nerve root compression (sensory loss/pain in lateral thigh/lateral leg & medial side of big toe) - **Bladder and anal sphincter involvement:** a late sign; hesitancy, frequency and painless retention

Answer 304

**Do not delay investigations** - **MRI:** gold standard; identifies cause and site of compression - **Biopsy/surgical exploration** may be required to identify the nature of any mass - **Screening blood tests**: FBC, ESR, B12, U&E’s, syphilis serology, LFT, PSA - **Chest x-ray:** to check for TB or lung malignancy

Answer 305

- **Transverse myelitis** - **Multiple sclerosis** - **Carcinomatous meningitis** - **Cord vasculitis** - **Spinal artery thrombosis/ aneurysm** - **Trauma** - **Guillain-Barre syndrome**

Answer 306

**Do not delay treatment** General: - **Epidural steroid injections:** effective for leg pain - **Surgical decompression** - **Laminectomy:** removal of the lamina/spongy tissue between discs to relieve pressure - **Microdiscectomy:** removal of herniated tissue from disc Treatment will depend on cause e.g. If malignancy: - **Steroids** e.g. IV dexamethasone: reduces inflammation/ oedema around malignancy and improves outcome - **Radiotherapy** - **Surgical decompression** If epidural abscess: - **Surgical decompression** - **Antibiotics**

Answer 307

Prognosis depends on the cause and the level of symptoms when patient first presents. Rapid investigations and treatment is needed to prevent permanent damage!

Answer 308

Cauda equina syndrome (CES) is a neurosurgical emergency which occurs when the bundle of nerves below the end of the spinal cord are compressed.

Answer 309

CES is a relatively rare condition, with an incidence of 1 in 33,000 to 1 in 100,000

Answer 310

Compression/ damage of the cauda equina due to: - **Lumbar disc herniation**: the most common cause of CES - **Trauma** - **Spinal tumour** - **Lumbar spinal stenosis**: narrowing of the spinal cord may result in CES. This can be congenital or acquired e.g. spinal osteoarthritis (spondylosis), rheumatoid arthritis, and a slipped vertebra (spondylolisthesis) - **Epidural abscess or haematoma**

Answer 311

- **Bilateral lower limb weakness and/or reduced sensation** - **Decreased or absent lower limb reflexes** - **Reduced perianal sensation (S2-S4) and anal tone** on examination - **Palpable bladder** due to urinary retention

Answer 312

- **Lower back pain and sciatica** (97%) - **‘Saddle anaesthesia’:** numbness in the peri-anal region, groin and inner thighs (93%) - **Bladder and bowel dysfunction:** urinary retention or incontinence (92%), or rarely faecal incontinence - **Leg weakness and difficulty walking/ paralysis of the legs** - Leg weakness if flaccid and hyporeflexic/ areflexic (lower motor neuron signs) - **Erectile dysfunction**

Answer 313

- **Examinations:** PR exam, knee reflexes, ankle reflexes etc - **MRI spine**: gold-standard investigation and must be requested urgently - **Bladder ultrasound**: to determine whether urinary retention is present; do not delay an MRI to do a bladder scan if there is a high clinical suspicion of CES

Answer 314

CT myelography: imaging investigation of choice if there are contraindications to MRI

Answer 315

- **Conus medullaris syndrome** - **Vertebral fracture** - **Peripheral neuropathy** - **Mechanical lower back pain**

Answer 316

- **Emergency decompressive laminectomy**: surgery should be performed within 24-48 hours of symptom onset - All patients with suspected CES should be urgently referred to neurosurgery - Early treatment reduces the risk of permanent neurological deficit - **Antibiotics** are also needed for abscesses - **Corticosteroids or radiotherapy**: may be considered in certain patients with CES secondary to malignancy

Answer 317

- **Complications of delayed presentation or decompression**: permanent leg weakness, sexual dysfunction, urinary dysfunction or chronic pain - **Deep vein thrombosis (DVT)**: the incidence of thromboemboli in patients with CES is remarkably high, therefore patients require adequate thromboprophylaxis - **Post-operative complications**: autonomic dysfunction, recurrent herniation, soft tissue infection or an epidural haematoma are key complications

Answer 318

The most important factors influencing the prognosis of patients with CES are the severity and duration of compression upon the damaged nerve(s). 75% of patients who are treated within 48 hours of symptom onset have acceptable post-operative urological function, but often have ongoing back pain and some motor or sensory deficit. 20% will have a poor outcome and require ongoing treatment, such as management of sexual dysfunction, self-catheterisation or a colostomy

Answer 319

Pathology: CMS: Damage to the spinal cord at vertebral level T12-L2 CES: Damage to the spinal cord at vertebral level L1-5 Features: CMS: UMN signs (Hyperreflexia and hypertonia) CES: LMN signs (e.g. hyporeflexia and hypotonia)

Answer 320

- Schwann cell damage leads to myelin sheath disruption - Results in marked slowing of conduction seen e.g. in Guillain-Barre syndrome

Answer 321

- Conduction speed remains normal, and the axon tends to die off peripherally first, then more proximally. - Surviving axons often strive to re-innervate affected areas - Axonal degeneration typically occurs in toxic neuropathies

Answer 322

- Focal demyelination at the point of compression causes disruption of conduction - Typically occurs in entrapment neuropathies e.g. carpal tunnel syndrome

Answer 323

- Process that results when a nerve fibre is cut or crash and the distal part of the axon that is separated from the neurone’s cell body degenerates - Both the axon and the myelin sheath will degenerate over several weeks after the incident

Answer 324

- Micro-infarction of vasa nervorum occurs in diabetes and arteritis such as polyarteritis nodosa and eosinophilic granulomatosis with polyangiitis - There will also be wallerian degeneration distal to the infarct

Answer 325

Infiltration occurs by inflammatory cells in leprosy and granulomas such as sarcoid and by neoplastic cells (cancer)

Answer 326

- **Remyelination –** more likely to occur than axonal regrowth - **Axonal regrowth –** this can occur at a rate of up to 1mm per day

Answer 327

The pneumonic ***DAVID*** can be used: - **D –** Diabetes - **A –** Alcoholism - **V –** Vitamin Deficiency – B12 - **I –** Infective / inherited – Guillian-Barre / Charcot-Marie-Tooth - **D –** Drugs – e.g. isoniazid

Answer 328

- **Numbness and tingling in the feet or hands** - **Burning, stabbing or shooting pain in affected areas** - **Loss of balance and co-ordination** - **Muscle weakness, especially in the feet**

Answer 329

- **Treat underlying cause** e.g. diabetes - **Neuropathic pain agents**

Answer 330

- **Neuropathy:** a pathological process affecting a peripheral nerve or nerves - **Mononeuropathy:** a process affecting a single nerve - **Mononeuritis multiplex**: usually describes a condition that affects several nerves, but in no discernible pattern, and no underlying unifying condition. i.e. the nerves have been individually damaged. - **Polyneuropathy:** many nerves involved. Usually describes a symmetrical disease, and it usually begins distally. Can be sensory, motor or mixed. Classified into demyelinating, or axonal types. Loads of different types and different classifications. Often widespread loss of tendon reflexes is typical, with distal weakness and distal sensory loss

Answer 331

Sympathetic and parasympathetic neuropathies may be isolated or part of a generalised sensorimotor peripheral neuropathy

Answer 332

- **Diabetes mellitus** - **Amyloidosis** - **Guillain-Barre & Sjogren’s syndrome** - **HIV** - **Leprosy** - **SLE** - **Paraneoplastic syndromes**

Answer 333

- **Postural hypotension** - **Reduced sweating** - **Ejaculatory failure** - **Horner's syndrome**

Answer 334

- **Erectile dysfunction** - **Constipation** - **Nocturnal diarrhoea** - **Urine retention** - **Holmes-Adie pupil**

Answer 335

- Lesions of individual peripheral or cranial nerves - Causes are usually local e.g. trauma or entrapment (e.g. tumour)

Answer 336

- C6-T1 - The nerve of precision grip - Muscles involved = LOAF - 2 Lumbricals - Opponens pollicis - Abductor pollicis brevis - Flexor pollicis brevis

Answer 337

Depends on location - **Wrist:** carpal tunnel syndrome; weakness of abductor pollicis brevis; sensory loss over the radial 3 1/2 fingers and palm - **Anterior interosseous nerve lesions:** weakness of flexion of the distal phalanx of the thumb and index finger - **Proximal lesions:** may show combined effects

Answer 338

- **Weakness/ wasting of:** - Medial wrist flexors - Interossei: cannot cross fingers in the good luck sign - Medial two lumbricals: claw hand - **Wasting of hypothenar eminence** - **Weak 5th digit abduction** - **Weak 4th and 5th DIP joint flexion** - **Sensory loss over medial 1 1/2 fingers and ulnar side of the hand**

Answer 339

- **Rest and avoid pressure on nerve** - **Night time soft elbow splinting** may be required - **Surgery for decompression** may be an option

Answer 340

- C5-T1 - Nerve for opening the fist

Answer 341

May be damaged by compression against the humerus

Answer 342

- **Test for wrist and finger drop** with elbow flexed and arm pronated - **Sensory loss is variable:** dorsal aspect of the root of the thumb most affected - **Muscles involved** = BEAST - Brachioradialis - Extensors - Abductor pollicis longus - Supinator - Triceps

Answer 343

- **Trauma** - **Radiotherapy** - **Prolonged wearing of heavy rucksack** - **Cervical rib** - **Thoracic outlet compression** - **Neuralgic amyotrophy**

Answer 344

Pain/ paraesthesia and weakness in the affected arm in a variable distribution

Answer 345

C3-C5, keeps the diaphragm alive

Answer 346

- **Lung cancer** - **TB** - **Paraneoplastic syndrome** - **Myeloma** - **Thymoma** - **Cervical spondylosis/ trauma** - **Thoracic surgery** - **Infections e.g. HZV, HIV, Lyme disease** - **Muscular dystrophy**

Answer 347

- **Orthopnoea** - **Raised hemi-diaphragm** on chest x-ray

Answer 348

- L2-L3 - Cause: entrapment under the inguinal ligament

Answer 349

Meralgia paraesthetica: anterolateral burning thigh pain

Answer 350

Causes: damage by pelvic tumours or fractures to the pelvis or femur

Answer 351

Affect hamstrings and all muscles below the knee (foot drop), with loss of sensation below the knee, laterally

Answer 352

- L4-S1 - Originates from the sciatic nerve just above the knee

Answer 353

often damaged as it winds around the fibular head (trauma, sitting cross-legged)

Answer 354

- **Foot drop** - **Weak ankle dorsiflexion/ eversion** - **Sensory loss over dorsal foot**

Answer 355

- L4-S3 - Originates from the sciatic nerve just above the knee

Answer 356

- **Inability to** - Stand on tiptoes (plantarflexion) - Invert the foot - Flex the toes - **Sensory loss over the sole**

Answer 357

- Involvement of two or more peripheral nerves - Causes tend to be systemic: diabetes mellitus, connective tissue disorders, vasculitis, sarcoidosis, amyloidosis, leprosy - Electromyography helps define the anatomic site of lesion

Answer 358

Carpal tunnel syndrome (CTS) is a collection of symptoms and signs caused by compression of the median nerve in the carpal tunnel.

Answer 359

- Most common mononeuropathy and entrapment neuropathy - F>M: smaller wrists but same sized tendons as men - Usually in those over 30 years

Answer 360

- Compression or swelling caused by: - **Repetitive stress injury e.g. typing** - **Enforced flexion – e.g. Colles’ splint** - **Obesity** - **Pregnancy** - **Underlying inflammatory conditions e.g. rheumatoid arthritis** - **Myxoedema** - **Diabetic neuropathy** - **Acromegaly** - **Neoplasms e.g. myeloma** - **Benign tumours e.g. lipomas, ganglia** - **Amyloidosis** - **Sarcoidosis**

Answer 361

Carpal tunnel syndrome is caused by compression of the median nerve. This typically happens as a result of inflammation of the nearby tendons and tissues, which creates local oedema or swelling which increases the amount of fluid in a very tight space, and essentially puts pressure on the median nerve. The median nerve and the nine tendons compete for space. Initially that pressure can cause a dull ache or discomfort in any of the areas of the hand that are innervated by the median nerve. Eventually this discomfort can lead to paraesthesia, which can extend up the forearm. The areas that are affected include the thumb, index finger, middle finger, and the thumb side of the ring finger, as they are the areas of skin innervated by the median nerve. People might also have muscle weakness which can cause clumsiness. In severe situations, the thenar muscles at the base of the thumb, and the abductor pollicus brevis can start to waste away. This happens because these muscles are innervated by the recurrent branch of the median nerve which arises from the median nerve after it passes through the carpal tunnel. So compression of the medial nerve will affect anything downstream of it. The little finger isn't affected as it is supplied by the ulnar nerve, while the back of the hand is supplied by the radial nerve. The palm is also unaffected as this is supplied by a superficial palmar branch of the medial nerve that is upstream of the carpal tunnel, rather than downstream.

Answer 362

- **Pain:** worse at night after a day's use of hands - **Numbness** - **Paraesthesia:** relieved by hanging hand over bed and shaking it (wake and shake) - **Muscle weakness in the hands** - **Tinels, Phalens and Durkans sign: +ve** - **Light touch, 2-point discrimination and sweating can be impaired**

Answer 363

- **Clinical diagnosis based on presentation** - **Examination:** - **Phalen’s maneuver:** flex the wrists are far as possible and hold that position for a minute, this results in numbness in the areas of the hand innervated by the median nerve in people with carpal tunnel syndrome - **Tinel’s sign:** tap the transverse carpal ligament, this reproduces the symptoms of tingling or feelings of pins and needles in areas of the hand served by the median nerve - **Durkan’s test:** manually compressing the carpal tunnel with the thumb for 30 second, to reproduce symptoms of carpal tunnel - **Neurophysiology testing (electromyography):** confirm lesion site and severity; can see slowing of conduction velocity in the median sensory nerves across the carpal tunnel

Answer 364

- **Behaviour modification** e.g. changing position of hand when typing, using wrist supports etc - **Physical therapy** e.g. stretching and isometric exercises to help relieve symptoms - **Non-surgical:** splinting or corticosteroid injection - **Surgical:** definitive management with decompression surgery; division of the transverse carpal ligament to help open up the carpal tunnel and relieve the pressure

Answer 365

- Reduced taste and smell - Ammonia taste remains as it stimulates the pain fibres carried in the trigeminal nerve

Answer 366

- Trauma - Frontal lobe tumour - Meningitis

Answer 367

- Visual field defects - Start as small areas of visual loss (scotomas). - Monocular severe sight impairment: lesions of one eye or optic nerve - Bilateral severe sight impairment - Bitemporal hemianopia - Homonymous hemianopia: loss of the same half (left or right) of the visual field of both eyes, on the opposite side to the lesion (eg, a right side lesion causes loss of the left side of the visual field of both eyes). - Pupillary abnormalities - Optic neuritis - Pain on moving the eye - Loss of central vision - Afferent pupillary defect - Papilloedema - Optic atrophy - Pale optic discs - Reduced acuity

Answer 368

Visual field defects: - MS, giant cell arteritis *(Monocular severe sight impairment)* - Methyl alcohol, tobacco ambylopia, neurosyphylis *(bilateral severe sight impairment)* - Optic chiasm compression e.g. internal carotid artery aneurysm, pituitary adenoma or craniopharyngioma *(bitemporal hemianopia)* - Lesions lie behind the optic chiasm in the optic tract, lateral geniculate nucleus, optic radiations or the occipital cortex e.g. stroke, abscess, tumour *(homonymous hemianopia)* Optic neuritis: - Demyelination - Rare causes: - Sinusitis - Syphilis - Collagen vascular disorders Optic atrophy: - MS - Frontal tumours - Friedrich's ataxia - Retinitis pigmentosa - Syphilis - Glaucoma - Leber's optic atrophy - Optic nerve compression Papilloedema: - Raised ICP (tumour, abscess, encephalitis, hydrocephalus, benign intracranial hypertension) - Retro-orbital lesion (e.g. cavernous sinus thrombosis) - Inflammation (e.g. optic neuritis) - Ischaemia (e.g. accelerated hypertension)

Answer 369

- Fixed dilated pupil which doesn't accommodate - Ptosis - Complete internal ophthalmoplegia - Unopposed lateral rectus causes outward deviation of the eye - If the ocular sympathetic fibres are also affected behind the orbit, the pupil will be fixed but not dilated.

Answer 370

- Diabetes mellitus - Giant cell arteritis - Syphilis - Posterior communicating artery aneurysm - Idiopathic - Raised ICP (if uncal herniation through the tentorium - this compresses the nerve)

Answer 371

- Diplopia due to weakness of downward and inward eye movement (pure vertical diplopia) - Compensation by tilting the head away from the affected side

Answer 372

- Trauma to the orbit - Diabetes - Infarction secondary to hypertension

Answer 373

- Reduced sensation or dysasthesia over the affected area - Weakness of jaw clenching and side-to-side movement. - If LMN lesion, the jaw deviates to the weak side when the mouth is opened - May be fasciculation of temporalis and masseter

Answer 374

Sensory: - Trigeminal neuralgia - Herpes zoster - Nasopharyngeal carcinoma Motor: - Bulbar palsy - Acoustic neuroma

Answer 375

- Inability to look laterally - Eye is deviated medially because of unopposed action of the medial rectus muscle

Answer 376

- MS - Pontine CVA

Answer 377

- Facial weakness - LMN lesion: - Forehead is paralysed - the final common pathway to the muscles is destroyed - UMN lesion: - Upper facial muscles are partially spared because of alternative pathways in the brainstem

Answer 378

LMN: - Bell's palsy - Polio - Otitis media - Skull fracture - Cerebellopontine angle tumours - Parotid tumours - Herpes zoster (Ramsay Hunt syndrome) - Lyme disease UMN: - Stroke - Tumour

Answer 379

- Unilateral sensorineural deafness - Tinnitus - Slow-growing lesions seldom present with vestibular symptoms as compensation has time to occur

Answer 380

- Loud noise - Paget's disease of bone - Ménière's disease - Herpes zoster - Neurofibroma - Acoustic neuroma - Brainstem CVA - Lead - Aminoglycosides - Furosemide - Aspirin

Answer 381

- Unilateral lesions do not cause any deficit because of bilateral corticobulbar connections - Bilateral lesions result in pseudobulbar palsy

Answer 382

- Trauma - Brainstem lesions - Cerebellopontine angle and neck tumours - Polio - Guillain-Barre syndrome (GBS)

Answer 383

- Palatal weakness: - Nasal speech - Nasal regurgitation of food - Palate moves asymmetrically when the patient says 'ahh' - Recurrent nerve palsy: - Hoarseness - Loss of volume - Bovine cough

Answer 384

- Trauma - Brainstem lesions - Tumours in the cerebellopontine angle, jugular foramen and neck - Polio - GBS

Answer 385

Weakness and wasting of these muscles

Answer 386

- Trauma - Brainstem lesions - Tumours in the cerebellopontine angle, jugular foramen and neck - Polio - GBS

Answer 387

- LMN lesion: - Wasting of the ipsilateral side of the tongue, with fasciculation - Attempted protrusion of tongue causes deviation towards the affected side

Answer 388

- Polio - Syringomyelia tuberculosis - Median branch thrombosis of the vertebral artery

Answer 389

- Diabetes mellitus - Stroke - MS - Tumours - Sarcoid - Vasculitis (e.g. polyarteritis nodosa) - Systemic lupus erythematosus (SLE) - Syphilis - Chronic meningitis (malignant, TB, or fungal)

Answer 390

I – test ability of each nostril to distinguish familiar smells e.g. lemon, grass II – test visual acuity, visual fields, pupils, ophthalmoscopy III, IV & VI – ask patient to keep head still and follow finger with eye as you draw a H V1 – assess light touch and pinprick sensation of forehead V2 – asses light touch and pinprick sensation of cheek V3 - assess light touch and pinprick sensation of jaw; ask patient to clench teeth and inspect masseter and temporalis for any wasting; ask patient to open their mouth against resistance VII – ask patient to smile, raise eyebrows, show teeth, puff out cheeks etc; test taste with salt/ sweet solutions VIII – ask them to repeat whispered number while blocking one ear at a time; Weber's and Rinne's test (tuning fork test); check balance and vertigo IX & X – ask the patient to say 'ahh'; ask them to take a sip of water; touch back of throat with stick XI – shake head and shrug shoulders XII – stick out tongue

Answer 391

Motor and/or sensory disorder of multiple peripheral or cranial nerves Usually symmetrical, widespread and worse distally (glove and stocking distribution)

Answer 392

Chronicity (e.g. acute or chronic) , Function (e.g. sensory, motor, autonomic or mixed), Pathology (e.g. demyelination, axonal degeneration or both)

Answer 393

- **Mostly motor e.g.** - Guillain-Barre syndrome - Lead poisoning - Charcot-Marie-Tooth syndrome - **Mostly sensory e.g.** - Diabetes mellitus - Renal failure - Leprosy

Answer 394

- **Metabolic:** diabetes mellitus, renal failure, hypothyroidism, hypoglycaemia, mitochondrial disorders - **Vasculitides:** polyarteritis nodosa, rheumatoid arthritis, GPA - **Malignancy:** paraneoplastic syndromes, polycythaemia rubra vera - **Inflammatory:** Guillain-Barre syndrome, sarcoidosis - **Infections:** leprosy, HIV, syphilis, lyme disease - **Nutritional:** decreased; vit B12, B1, B6, E - **Inherited syndromes:** Charcot-marie-tooth, porphyria, leucodystrophy - **Drugs/toxins:** lead, arsenic, alcohol, vincristine, cisplatin, metronidazole, isoniazid, phenytoin, nitrofurantoin - **Other:** paraproteinaemias, amyloidosis

Answer 395

- **Sensory neuropathy:** - Numbness, pins & needles, paraesthesiae - Glove & stocking distribution - Difficulty handling small objects - Signs of trauma e.g. finger burns or joint deformation may indicate sensory loss - Diabetic and alcoholic neuropathies are typically painful

Answer 396

- **Motor neuropathy:** - Often progressive, may be rapid - Weak or clumsy hands - Difficulty in walking e.g. falls and stumbling - Difficulty in breathing e.g. reduced vital capacity - LMN lesion: - Wasting and weakness is most marked in the distal muscle of the hands and feet e.g. foot or wrist drop - Reflexes are reduced or absent

Answer 397

- **Cranial nerves:** - Swallowing difficulty - Speaking difficulty - Diplopia

Answer 398

- **History:** time course, nature of symptoms, preceding or associated events (e.g. diarrhoea and vomiting before Guillain-Barre syndrome, weight loss in cancer, arthralgia from connective tissue disease), travel, alcohol and drug use, sexual infections, family history Examine other systems for clues to causes e.g. alcoholic liver disease

Answer 399

- FBC, ESR, glucose, U&E, LFT, TSH, B12 - ANA, ANCA, anti-CCP - CXR - Urinalysis - Lumbar puncture and specific genetic testing for inherited neuropathies e.g. Charcot-Marie-Tooth - Nerve conduction studies

Answer 400

- **Treat the cause** - **Involve physio and OT** - **Foot care and show choice** important in sensory neuropathies to minimise trauma - **Splinting of joints** helps to prevent contractures (shortening & hardening of muscles and tendons) in prolonged paralysis - Guillain-Barre syndrome and CIDP: **IV immunoglobulins** - Vasculitic causes: **steroids/immunosuppressants may help** - Treat neuropathic pain with: **amitriptyline, duloxetine, gabapentin or pregabalin**

Answer 401

Myasthenia gravis is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction of skeletal muscle.

Answer 402

- Myasthenia gravis is a rare disease with an estimated worldwide prevalence of 200 people per million - Symptoms peak in women during their 20s or 30s, and in men in their 50s or 60s

Answer 403

- **Female gender**: twice as common in women - **Family** **history** - **Autoimmunity**: either a personal or family history of autoimmune disorders such as rheumatoid arthritis and SLE - **Thymoma or thymic hyperplasia**: 10-15% of patients have a thymoma, whilst up to 70% have thymic hyperplasia

Answer 404

**Pathology:** - Myasthenia gravis occurs due to circulating autoantibodies against the nicotinic acetylcholine receptor (AChR). Ultimately, this causes fewer available binding sites for acetylcholine (Ach) at the postsynaptic membrane, resulting in weakness. As the receptors are used more during muscle activity, more of them become blocked up. This leads to less effective stimulation of the muscle with increased activity. - These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane. This further worsens the symptoms. - A small proportion of patients also have antibodies against muscle-specific kinase (MuSK) and antibodies against low-density lipoprotein receptor-related protein 4 (LRP4). MuSK and LRP4 are important proteins for the creation and organisation of the acetylcholine receptor. Destruction of these proteins by autoantibodies leads to inadequate acetylcholine receptors. - In very rare cases, myasthenia gravis can present as a paraneoplastic syndrome - an underlying cancer like bronchogenic carcinoma or thymoma generates an immune response which results in generation of autoantibodies.

Answer 405

- **Proximal muscle weakness with fatigability:** often affecting the face and neck - **Ptosis (drooping eyelid) exacerbated on upward gaze:** may be bilateral or unilateral - **Complex ophthalmoplegia:** cannot be isolated to one cranial nerve - **Head drop:** a rare sign due to weakness of cervical extensor muscles - **Myasthenic snarl:** a ‘snarling’ expression when attempting to smile

Answer 406

- **Lethargy** - **Muscle weakness:** worsens throughout the day, can improve with rest - **Diplopia:** double vision due to effects on eye muscles - **Slurred speech** - **Dysphagia:** difficulty swallowing - **Fatigue in jaw when chewing** - **Shortness of breath:** may suggest a myasthenic crisis

Answer 407

- **Antibodies:** AchR antibodies are first-line, whilst anti-MuSK and anti-LRP4 can also be tested in patients who are AchR antibody negative - **Electrophysiological studies:** repetitive nerve stimulation shows a decremental muscle response - **CT thorax:** all patients should have a CT chest to exclude a thymoma; **MRI** is an alternative - **Thyroid function:** all patients require thyroid function tests, as there is a higher prevalence of autoimmune thyroiditis

Answer 408

- **Lambert-eaton myasthenic syndrome** - **Botulism** - **Penicillamine-induced myasthenia gravis** - **Primary myopathies**

Answer 409

- **First-line: pyridostigmine**; an acetylcholinesterase inhibitor - **Second-line: prednisolone** (to dampen down immune system) on alternate days is offered if symptomatic despite pyridostigmine - **Third-line: azathioprine** is offered if symptoms are not controlled on prednisolone - **Other**: if symptoms remain uncontrolled, consider alternatives such as **methotrexate** or **rituximab** - **Thymectomy:** indicated if a thymoma is present on imaging, **or** in patients aged < 45 years old with positive serology; thymectomy may help to induce remission

Answer 410

- **IV immunoglobulin or plasmapheresis** - **Intubation**: ****if severe respiratory compromise - **Corticosteroids** may be used as an adjunct

Answer 411

- **Myasthenic crisis:** weakening of the respiratory muscles and is often provoked by infections or medications. Patients present with increasing shortness of breath, which can deteriorate into respiratory failure. - **Respiratory failure** - **Aspiration pneumonia:** dysphagia increases the risk of aspiration

Answer 412

The goal of therapy is to induce clinical remission. Myasthenia gravis is associated with a reasonably good prognosis and patients who undergo thymectomy tend to have a better prognosis. However, it is estimated that as many as 10 to 20% of patients may experience at least one myasthenic crisis, and the annual risk of a myasthenic crisis is approximately 2 to 3%.

Answer 413

Aminoglycosides, Fluoroquinolones, Macrolides, Tetracyclines, Quinolones, Neuromuscular blocking agents, Magnesium sulfate, Penicillamine, Use cardiac drugs such as Beta blockers and Procainamide with caution, litium and phenytoin

Answer 414

Syncope is the term used to describe the event of temporarily losing consciousness due to a disruption of blood flow to the brain, often leading to a fall. Syncopal episodes are also known as vasovagal episodes, or simply fainting. *Presyncope: near loss of consciousness with lightheadedness, muscular weakness, blurred vision, and feeling faint without actually fainting.*

Answer 415

- Dehydration - Missed meals - Extended standing in a warm environment, such as a school assembly - A vasovagal response to a stimuli, such as sudden surprise, pain or the sight of blood

Answer 416

- Hypoglycaemia - Anaemia - Hypovolaemia e.g. due to haemorrhage, GI bleeding, ruptured aortic aneurysm - Infection - Anaphylaxis - Arrhythmias - Valvular heart disease - Hypertrophic obstructive cardiomyopathy - Pulmonary embolism: causing hypoxia

Answer 417

- **Elderly** - **Pregnant women** - **Certain medications that** - Block vasoconstriction e.g. calcium channel blockers, beta blockers, alpha blockers, and nitrates - Affect the volume status e.g. diuretics - That prolong the QT interval e.g. antipsychotics and antiemetics - **Anxiety and panic disorders** - **Alcohol abuse** - **Drug abuse**

Answer 418

- A **vasovagal episode** (neurocardiogenic syncope) is caused by a problem with the autonomic nervous system regulating blood flow to the brain. When the vagus nerve receives a strong stimulus, such as an emotional event, painful sensation or change in temperature it can stimulate the parasympathetic nervous system. Parasympathetic activation counteracts the sympathetic nervous system, which keeps the smooth muscles in blood vessels constricted. As the blood vessels delivering blood to the brain relax, the blood pressure in the cerebral circulation drops, leading to hypoperfusion of brain tissue. This causes the patient to lose consciousness and “faint”. - **Carotid sinus hypersensitivity** is a variant of neurocardiogenic syncope. This occurs when mild external pressure on the carotid bodies in the neck is enough to induce this reflex response. Mild pressure could be due to shaving, neck turning, tight collar etc - Another common cause is **orthostatic hypotension,** which is defined by either a drop in blood pressure of more than 20 mmHg or a reflex tachycardia of more than 20 beats per minute, when a person goes abruptly from lying down or sitting to standing up. It occurs when there’s a delay in constriction of the lower body veins, which is needed to maintain an adequate blood pressure when changing position to standing. As a result, blood pools in the veins of the legs for longer and less is returned to the heart, leading to a reduced cardiac output.

Answer 419

- **Hot or clammy** - **Sweaty** - **Heavy** - **Dizzy or lightheaded** - **Vision going blurry or dark** - **Headache**

Answer 420

- **Loss of consciousness,** described as: - Suddenly losing consciousness and falling to the ground - Unconscious on the ground for a few seconds to a minute as blood returns to their brain - Twitching, shaking or convulsion activity, which can be confused with a seizure - Patients may feel **groggy** after fainting - May be **incontinence**

Answer 421

- Features that distinguish a syncopal episode from a seizure - After exercise? Syncope after exercise is more likely to be secondary to an underlying condition. - Triggers? - Concurrent illness? Do they have a fever or signs of infection? - Injury secondary to the faint? Do they have a head injury? - Associated cardiac symptoms, such as palpitations or chest pain? - Associated neurological symptoms? - Seizure activity? - Family history, particularly cardiac problems or sudden death?

Answer 422

- Check for: - Physical injuries as a result of the faint e.g. head injury - Concurrent illness e.g. an infection or gastroenteritis? - Neurological examination - Cardiac examination, specifically assessing pulses, heart rate, rhythm and murmurs - Lying and standing blood pressure; tilt table test

Answer 423

- **ECG**, particularly assessing for arrhythmia and the QT interval for long QT syndrome - **24 hour ECG** if paroxysmal arrhythmias are suspected - **Echocardiogram** if structural heart disease is suspected - **Bloods**, including a **full blood count** (anaemia), **electrolytes** (arrhythmias and seizures) and **blood glucose** (diabetes)

Answer 424

Syncope: Prolonged upright position prior to event, Lightheaded before event, sweating before event, blurring or clouding of vision before event , reduced tone during episode, return to consciousness shortly after falling, no prolonged post-ictal period Seizure: Epilepsy aura prior to event, head turning or abnormal limb position, tonic clinic activity, tongue biting, cyanosis, lasts more than five minutes, prolonged post-ictal period

Answer 425

Seizure, Stroke, Sleep disturbance, accidental falls with head injury

Answer 426

- Patient's will **recover spontaneously** - If simple syncope, advise patient - **Avoid dehydration** - **Avoid missing meals** - **Avoid standing still for long periods** - **When experiencing prodromal symptoms such as sweating and dizziness, sit or lie down, have some water or something to eat and wait until feeling better** - It is important to **rule out other pathology.** If found, it should be appropriately managed

Answer 427

Huntington’s chorea is an autosomal dominant genetic neurodegenerative condition that causes a progressive deterioration in the nervous system.

Answer 428

- HD is estimated to have a prevalence of 2-5 per 100,000 worldwide - Usually presents in middle age - It appears to be less common in asian populations where the normal number of CAG trinucleotide repeats is lower.

Answer 429

Huntington’s chorea is a “trinucleotide repeat disorder” that involves a genetic mutation in the HTT gene on chromosome 4. The CAG repeat usually goes on x36. CAG usually codes for glutamine, so patients have 36 or more glutamines in a row in the huntingtin protein. These mutated proteins aggregate within the neuronal cells of the caudate and putamen (dorsal striatum) of the basal ganglia causing neuronal cell death. Over time, if enough of the neurones die, then it can cause actual loss of brain tissue volume in that area and expansion of the lateral ventricles. These areas play an important role in movement, so damage leads to chorea. There is specifically loss of the corpus striatum GABAergic and cholinergic neurones which results in decreased ACh and GABA synthesis. Without this, levels of dopamine increase leading to excessive movement **Anticipation:** Huntington’s chorea displays something called genetic “anticipation”. Anticipation is a feature of trinucleotide repeat disorders. The expanded CAG repeats not only affect the huntingtin protein – they affect DNA replication itself. When copying the HTT gene, DNA polymerase can lose track of which CAG it’s on and so add extra CAGs. This is called repeat expansion and happens more frequently in the production of sperm than egg. Anticipation is where successive generations have more repeats in the gene, resulting in: - Earlier age of onset - Increased severity of disease

Answer 430

Patients are usually asymptomatic until symptoms begin around aged 30 to 50. It presents with an insidious, progressive worsening of symptoms. - Typically begins with prodromal phase: **cognitive, psychiatric or mood problems.** - **Chorea** (involuntary, abnormal movements) - **Eye movement disorders** - **Dysarthria:** speech difficulties - **Dysphagia:** swallowing difficulties - **Dementia**

Answer 431

- Diagnosis is made in a specialist genetic centre using a **genetic test for the faulty gene and identification of the number of CAG repeats**. - This involves pre-test and post-test counselling regarding the implications of the results.

Answer 432

- **Post-test counselling:** to help patients cope with diagnosis - **Genetic counselling** regarding relatives, pregnancy and children - Involvement of **MDT** in supporting and maintaining their quality of life (e.g. occupational therapy, physiotherapy and psychology) - **Speech and language therapy** where there are speech and swallowing difficulties - **Advanced directives** to document the patients wishes as the disease progresses - **End of life** care planning - Medical treatment is for symptomatic relief: - For disordered movements - **Antipsychotics (e.g. olanzapine)** - **Benzodiazepines (e.g. diazepam)** - **Dopamine-depleting agents (e.g. tetrabenazine)** - For depression - **Antidepressants**

Answer 433

Huntington’s chorea is a progressive condition. Life expectancy is around 15-20 years after the onset of symptoms. As the disease progresses patients become more susceptible and less able to fight off illnesses. Death is often due to respiratory disease (e.g. pneumonia). Suicide is a more common cause of death than in the general population.

Answer 434

- **Huntington disease:** CAG repeat - **Myotonic dystrophy:** CTG repeat - **Friedreich ataxia:** GAA repeat - **Fragile X syndrome:** CGG repeat

Answer 435

Guillain-Barré syndrome is an acute paralytic polyneuropathy. It is an autoimmune, rapidly progressive demyelinating condition of the peripheral nervous system, often triggered by infection

Answer 436

- GBS is a rare condition. - M>F - Peak incidence between 15-35 years old and 50-75 years old - A key risk factor is an infection in the preceding 6 weeks, with 60% of cases being linked to a prior infection as the trigger.

Answer 437

- **Male:** slightly more common in males than females (1.8:1) - **Age:** peak incidence between 15-35 years old and 50-75 years old - **Infections:** typically gastrointestinal or respiratory: - **Bacterial:** e.g. Campylobacter jejuni (30%) and mycoplasma pneumoniae - **Viral:** e.g. Zika virus, influenza, Epstein-Barr virus and cytomegalovirus - **Malignancies:** lymphoma may increase the risk of GBS - **Vaccines:** association with the influenza vaccination (uncommon)

Answer 438

**GBS is believed to be caused by ‘molecular mimicry’** - A pathogenic antigen (e.g. *Campylobacter jejuni*) resembles myelin gangliosides in the peripheral nervous system - The immune system targets the antigen and attacks the myelin sheath of sensory and motor nerves - This autoimmune process involves the production of anti-ganglioside antibodies (anti-GMI is positive in 25% of patients) - The demyelination occurs in patches along the length of the axon, so it’s called segmental demyelination - Early on, there is remyelination but over time, there's irreversible damage **There are different subtypes of GBS, based on which type of nerves are demyelinated:** - Acute inflammatory demyelinating **polyneuropathy (ADIP): ~90% of cases - Acute motor axonal neuropathy (AMAN) - Acute motor and sensory axonal neuropathy (AMSAN) - Miller-Fisher Syndrome (MFS): - Classic triad: ataxia, areflexia, and ophthalmoplegia - Eye muscles are typically affected first - Usually causes descending (rather than ascending) paralysis and anti-Gq1b antibodies are present in 90% of cases

Answer 439

- **Reduced sensation in affected limbs:** sensory findings on examination are usually mild - **Symmetrical weakness** in lower extremities first, progressing to the upper limbs: proximal muscles often affected earlier than distal muscles - **Ataxia with hyporeflexia** (or areflexia) in affected limbs - **Autonomic dysfunction:** e.g. tachycardia, hypertension, postural hypotension, urinary retention (in severe disease) - **Respiratory distress:** shortness of breath, respiratory muscle weakness requiring mechanical ventilation in severe cases - **Cranial nerve involvement and bulbar dysfunction:** e.g. diplopia or facial droop

Answer 440

- **Tingling and numbness in hands and feet:** often precedes muscle weakness - **Symmetrical, progressive, ascending weakness** - **Unsteady when walking** - **Back and leg pain:** common at some point in disease course - **Shortness of breath** - **Facial weakness and speech problems**

Answer 441

Predominantly a **clinical diagnosis** evidenced by progressive weakness and areflexia (or hyporeflexia) in the weaker limbs. The **Brighton criteria** is used for diagnosis. - Primary investigations - **Bloods:** exclude other causes - **U&Es**: electrolyte abnormalities resulting in neuropathic symptoms - **B12 and folate**: deficiency associated with neurological features - **TFTs**: to exclude hypothyroidism as a cause of weakness - **LFTs**: elevation of hepatic enzymes is associated with more severe disease - **Anti-ganglioside antibodies**: can be used to differentiate GBS variants, e.g. anti-GQ1b antibody in Miller-Fisher syndrome - **Cultures:** stool or sputum sample if there are ongoing infective features, e.g. gastroenteritis - **Lumbar puncture for CSF**: **raised protein** with **normal WBC count** is typical, although an initial normal protein level does not exclude GBS - **Spirometry**: to monitor respiratory function as 20% of patients require mechanical ventilation at some stage

Answer 442

- **Transverse myelitis** - **Myasthenia gravis** - **Lambert-eaton myasthenic syndrome** - **Botulism** - **Polymyositis** - **Vasculitic neuropathy**

Answer 443

- **IV immunoglobulins (IVIg):** 5 day treatment course commenced within the first 2 weeks of symptom onset, **OR** - **Plasma exchange**: 5 treatments of 2-3L over 2 weeks commenced within the first 4 weeks of symptom onset

Answer 444

- **Type 2 respiratory failure:** if respiratory muscles are affected; may require mechanical ventilation in intensive care - **Impaired mobility:** may persist for months to years after the initial onset of GBS - **Pulmonary complications:** including infections due to intubation, or pulmonary emboli due to immobility and a pro-inflammatory state - **Autonomic dysfunction:** dysfunction of the bowel (ileus) and bladder (retention) may occur, as may arrhythmias, and variations in heart rate and blood pressure - **Psychiatric impact:** depression, post-traumatic stress disorder and anxiety are all associated with GBS

Answer 445

The mortality rate can vary between 3-7%. This is typically a result of ventilatory failure, pulmonary complications (such as infection) or autonomic failure (arrhythmias). There is often a prolonged recovery phase (months to years), with 20% of patients still unable to walk unaided 6 months after disease onset. Poorer prognostic factors include: - Advanced age (≥40 years old) - Rapid initial progression of symptoms - Preceding diarrhoea - Prolonged ventilatory needs

Answer 446

Inflammation of a blood vessel (arteries or veins), which is characterised by the presence of an inflammatory infiltrate and destruction of the vessel wall. - Vessel wall destruction leads to aneurysm, rupture and stenosis: resulting in perforation and haemorrhage into tissues - Endothelial injury: resulting in thrombosis + ischaemia/infarction of dependent tissues

Answer 447

They are categorised based on whether they affect small vessels, medium sized vessels or large vessels: **Types of Vasculitis Affecting The Large Vessels:** arteries and major tributaries - Giant cell arteritis - Takayasu’s arteritis **Types of Vasculitis Affecting The Medium Sized Vessels:** small arteries and arterioles - Polyarteritis nodosa - Kawasaki Disease **Types of Vasculitis Affecting The Small Vessels:** small arteries, arterioles, venuoles and capillaries ANCA +ve: - Microscopic polyangiitis - Granulomatosis with polyangiitis (Wegener’s granulomatosis) - Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome) ANCA -ve: - Henoch-Schonlein purpura

Answer 448

May be primary (this may be due to direct or indirect damage of endothelial cells of the vessel) or secondary to other conditions such as RA, SLE, hepatitis B & C, HIV, polymyositis and some allergic drug reactions.

Answer 449

Typically, vasculitis is due to an autoimmune disease, where the immune system confuses a part of normal body as a foreign invader, and there are a couple of ways this might happen. - Sometimes the body confuses the innermost layer of the blood vessel, which is the endothelial layer, with a foreign pathogen and directly attacks it. The white blood cells mix up the normal antigens on the endothelial cells with the antigens of foreign invaders like bacteria - due to molecular mimicry. This autoimmune confusion is thought to be the cause of several types of medium-vessel and large-vessel vasculitides. - Other times the immune system attacks healthy cells that are near the vascular endothelium, and the endothelial cells are only getting indirectly damaged. This is the situation in many small-vessel vasculitides, where the immune system attacks white blood cell enzymes or other non-endothelial cell targets. Once the endothelium is damaged either directly or indirectly, almost all vasculitis diseases progress in a similar way. The damaged endothelium exposes the underlying collagen and tissue factor, and these exposed materials increase the chance of blood coagulation. The blood vessel walls themselves get weaker as they’re more damaged, making aneurysms more likely. And finally, as the vessel wall heals, it becomes harder and stiffer because fibrin is deposited into the vessel walls as part of the healing process. The presentation depends on the vessel affected and the corresponding organ (which may experience ischaemia due to the lack of blood flow). - Blood cells clump onto the exposed tissue factor and collagen on the inside of blood vessels forming blood clots that can restrict blood flow. - As fibrin is deposited in the vessel wall, the walls become thicker and bulge into the vessel, reducing the diameter of the vessel lumen, and restricting blood flow.

Answer 450

- Fatigue - Fever - Weight loss - Anorexia (loss of appetite) - Anaemia

Answer 451

- Joint and muscle pain - Peripheral neuropathy - vessels to the head are affected - Anterior uveitis and scleritis - vessels to the head affected, causing ischaemia of the eye - Gastrointestinal disturbance (diarrhoea, abdominal pain and bleeding) - Renal impairment - Hypertension - Purpura. These are purple-coloured non-blanching spots caused by blood leaking from the vessels under the skin.

Answer 452

- Elevated ESR and CRP - Anti neutrophil cytoplasmic antibodies (ANCA) - positive in most small vessel vasculitis - 2 types: P-ANCA are also called anti-MPO antibodies. C-ANCA are also called anti-PR3 antibodies.

Answer 453

- **Steroid** - Oral (i.e. prednisolone) - Intravenous (i.e. hydrocortisone) - Nasal sprays for nasal symptoms - Inhaled for lung involvement (e.g. Churg-Strauss syndrome) - **Immunosuppressants** that are used include: - Cyclophosphamide - Methotrexate - Azathioprine - Rituximab and other monoclonal antibodies

Answer 454

Frontotemporal dementia is a neurodegenerative disorder characterised by focal degeneration of the frontal & temporal lobes. FTD is a heterogeneous condition with various subtypes e.g. Pick's disease

Answer 455

- It is an uncommon cause of dementia (2% of dementias) - Typically affects patients at a younger age (< 65 years) - The mean age of onset is 58 years old. The onset before 40 years old and after 75 years old is uncommon.

Answer 456

Frontal and temporal atrophy with loss of over 70% of spindle neurons

Answer 457

- Family history: strong genetic predisposition. Genes include: - **Microtubule associated protein tau** (MAPT): found on chromosome 17. Multiple identified mutations. Leads to a propensity of tau to form neurotoxic aggregates. - **Granulin precursor** (GRN): found on chromosome 17. Multiple identified mutations. - **C9ORF72 gene**: found on chromosome 9. Most common genetic cause of inherited FTD. Also implicated in hereditary motor neuron disease.

Answer 458

- Frontal lobe effects: personality and behavior changes - **Disinhibition** (e.g. socially inappropriate behaviour) - **Loss of empathy** - **Apathy** (losing interest and/or motivation) - **Hyperorality** (e.g. dietary changes, attempt to consume non-edible products, eat beyond satiety) - **Compulsive behaviour** (e.g. cleaning, checking, hoarding)

Answer 459

- Temporal lobe effects: language problems - **Effortful speech** - **Halting speech** - **Speech-sound errors** - **Speech apraxia** (i.e. difficulty in articulation) - **Word-finding difficulty** - **Surface dyslexia or dysgraphia**: mispronouncing difficult words (e.g. yacht)

Answer 460

- As atrophy progresses - **Memory loss** - **Lack of concentration** - **Inability to learn new things**

Answer 461

- Diagnosis based on **cognitive assessment** - Imaging: - **MRI:** exclude other pathology; indicates changes in the frontal and temporal lobes - Definitive diagnosis: **brain biopsy** after a person has died

Answer 462

- No cure and no way to slow down frontotemporal dementia - **Non-pharmacological:** exercise, physiotherapy, speech and language therapy, behaviour modification - **Pharmacological** - **Serotonin reuptake inhibitors (SSRI)**: used for difficult behavioural symptoms. Have been shown to decrease disinhibition, anxiety, impulsivity and repetitive behaviours. - **Atypical anti-psychotics**: can help with agitation and behavioural symptoms.

Answer 463

Overall survival is 8-10 years from symptoms onset.

Answer 464

Lewy body dementia is a neurodegenerative disease. It is a type of dementia characterised by fluctuating cognitive impairment, visual hallucinations and parkinsonism.

Answer 465

Make up around 15-25% of dementia's

Answer 466

- **Older age** - **Male sex** - **Family history**

Answer 467

Normally, neurones contain a protein called alpha synuclein, and in Lewy body dementia, this protein gets misfolded within the neurones. The misfolded alpha-synuclein aggregates to form Lewy bodies that deposit inside neurones, particularly in the cortex and the substantia nigra. As the disease progresses, more and more neurones accumulate Lewy bodies and die. Lewy bodies are also seen in other diseases like Parkinson’s disease and multiple system atrophy.

Answer 468

- Early symptoms are typically cognitive ones (Alzheimer's-like) - **Difficulty focusing** - **Poor memory** - **Visual hallucinations** - **Disorganized speech** - **Depression** - Later symptoms are typically motor ones (Parkinson's-like) - **Resting tremors** - **Stiff and slow movements** - **Reduced facial expressions** - Some patients may have **sleep disorders** e.g. sleep walking or talking in their sleep

Answer 469

- Diagnosis of Lewy body dementia is **based on the pattern of symptoms.** - **FBC, U&E, LFT, MSU, ESR, serum B12, folate, TSH, glucose, thiamine, Ca2+:** exclude other causes of symptoms - **Imaging e.g. CT/MRI:** identify other pathologies - Diagnosis can only be confirmed with a **brain autopsy** that shows Lewy bodies in neurones. Under a microscope, Lewy bodies look like dark, eosinophilic inclusions in brainstem and neocortex.

Answer 470

- **Alzheimer's** - **Parkinson's** - **Frontotemporal dementia** - **Vascular dementia**

Answer 471

- **Dopamine analogue e.g. levodopa:** for Parkinson's like motor symptoms - **Cholinesterase inhibitors e.g. donepezil:** increases acetylcholine availability, used for Alzheimer's-like cognitive symptoms Avoid using antipsychotics as there is increased risk of side effects

Answer 472

Treatment is symptomatic and is unlikely to entirely prevent cognitive and behavioural disturbance. The course of disease is progressive, and a steady decline in functioning leads to eventual institutionalisation, loss of independence, and death.

Answer 473

Vascular dementia is a chronic progressive disease of the brain bringing about cognitive impairment. It is a common form of dementia caused by cerebrovascular disease.

Answer 474

- Makes up 20% of the dementias - It is the second most common form of dementia in the UK affecting around 150,000 people. - It is commonly part of 'mixed dementia' a combination of Alzheimer's disease and vascular dementia. - Dementia is a disease of older adults

Answer 475

- Vascular brain injury or dysfunction as a result of conditions that impair cerebral blood flow - **Ischaemic stroke**: any cause (e.g. atrial fibrillation with emboli, carotid artery disease) - **Small vessel disease**: atherosclerosis due to traditional cardiovascular risk factors (hypertension, diabetes, hypercholesterolaemia, smoking) - **Haemorrhage**: intracerebral, subarachnoid - **Other**: cerebral amyloid, which is a cause of small vessel disease. Deposition of amyloid in small arteries. CADASIL, which is due to mutation in the NOTCH3 gene and leads to arterial thickening and occlusion.

Answer 476

- Vascular dementia is a progressive loss of brain function caused by long term poor blood flow to the brain, typically because of a series of strokes. - Vascular dementia develops in some individuals, when atherosclerosis starts to form in the arteries. - When this process affects the arteries supplying the brain, it leads to a gradual decrease in blood flow to the brain - chronic ischaemia. Sometimes, small parts of the plaques can embolise and block a smaller artery, completely stopping the blood supply to that part of the brain. Other times, the tiny perforating arteries are affected by atherosclerosis and can get completely blocked off by plaque growing within them. - Regardless of the cause, once blood supply to the brain falls below the demands of the tissue, it’s considered an ischaemic stroke. The tissue damage from an ischaemic stroke is usually permanent, because the tissue gets damaged and the dead tissue liquefies in a process called liquefactive necrosis. - Brain tissue necrosis leads to a loss of mental functions governed by that area. - The final result is dementia, a persistent loss of mental functions that is severe enough to affect a person’s daily functioning.

Answer 477

- Symptoms of dementia appear suddenly and brain function decline is step-wise (e.g. decreases with each stroke) - Symptoms of vascular dementia vary depending on which region of the brain is damaged

Answer 478

- **Poor memory** - **Language problems**: receptive and expressive dysphasia - **Problems with executive functioning**: planning and problem solving - **Disorientation**

Answer 479

- **Agitation and emotional lability** - **Depression and anxiety** - **Sleep cycle disturbance** - **Disinhibition**: social or sexually inappropriate behaviour - **Withdrawal/apathy** - **Motor disturbance**: wandering is a typical feature of dementia - **Psychosis**

Answer 480

- **Early stages**: problems with higher level function (e.g. managing finances, difficulties at work) - **Later stages**: problems with basic personal care (e.g. washing, eating, toileting) and motor function (e.g. walking, transferring)

Answer 481

- **Neuropsychological tests:** e.g. mini mental state exam, used to confirm loss of brain function - **Blood tests and other examinations e.g. ECG, virology, chest x-ray:** exclude other pathologies - **Imaging** - **CT/MRI:** exclude other pathologies; shows multiple cortical and subcortical infarcts and changes e.g. atrophy of the brain cortex, confirming ischaemia

Answer 482

- No cure or medication to help specifically with [](https://www.osmosis.org/learn/Vascular_dementia)vascular dementia. Treatment focuses on reducing the risk of repeated strokes - **Management of risk factors** e.g. high BP, high cholesterol, diabetes, smoking. - **Acetylcholinesterase inhibitors e.g. donepezil:** only used if mixed dementia as may have some benefit - **Non-pharmacological:** programmes to improve/maintain cognitive function (e.g. structured group cognitive stimulation programmes), exercise, aromatherapy, therapeutic use of music/dancing, massage - **Advanced care planning** - **End of life care**

Answer 483

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction in the peripheral nervous system. It may occur as a paraneoplastic disorder in association with cancer, usually a small cell carcinoma of the lung, or may occur without cancer, as part of a more general autoimmune state.

Answer 484

- Can be **paraneoplastic:** associated with malignancies, especially small cell lung cancer - OR **autoimmune**

Answer 485

Can be associated with other autoimmune diseases e.g. Hashimoto’s thyroiditis or diabetes mellitus type 1

Answer 486

Lambert-Eaton syndrome is a result of antibodies produced by the immune system against voltage-gated calcium channels in the presynaptic terminals of the neuromuscular junction where motor nerves communicate with muscle cells. It mostly affects the somatic nervous system, but also the parasympathetic part of the autonomic nervous system. It is a type II hypersensitivity reaction - the body produces antibodies against its own proteins. In this case, B cells inappropriately make antibodies that recognise, bind to and block voltage-gated calcium channels on the motor neurones, which leaves only a few unbound channels that are available to open and allow calcium in. When only a few of the channels are working, they can only generate a low level of calcium within the neurone, and it’s insufficient to trigger the release of acetylcholine into the neuromuscular junction. The majority of Lambert-Eaton cases are associated with small cell lung cancer, because the small cell lung cancer cells express the same calcium channels that are found on motor neurones. When B cells generate antibodies against the cancer cells, the antibodies can mistakenly attack the voltage-gated calcium channels on the motor neurones. Lambert-Eaton myasthenic syndrome has a similar set of features to myasthenia gravis. It causes progressive muscle weakness, **but** symptoms may improve with movement. The symptoms tend to be more insidious and less pronounced than in myasthenia gravis.

Answer 487

The symptoms of Lambert-Eaton syndrome tend to develop slowly. Gait difficulties occur **BEFORE** eye signs - **Symmetrical proximal muscle weakness,** especially proximal leg muscle weakness - **Diplopia:** double vision due to effect on intraocular muscles - **Ptosis:** drooping of eyelids due to effect on levator muscles - **Slurred speech:** due to effect on oropharyngeal muscles - **Dysphagia:** due to effect on oropharyngeal muscles - **Reduced tendon reflexes** - **Post-tetanic potentiation:** reflexes become temporarily normal for a short period following a period of strong muscle contraction due to buildup of neurotransmitter in the synaptic cleft - Autonomic dysfunction: - **Dry mouth** - **Constipation** - **Urinary problems** - **Blurred vision** - **Impotence** - **Dizziness and fainting**

Answer 488

- **Test for autoantibodies** against voltage-gated calcium channels - **Electromyography:** measures the electrical activity of muscles, lowered amplitude (similar to myasthenia gravis) but amplitude increases post exercise - **Chest X-ray/ CT scan:** investigate for small cell lung cancer

Answer 489

- Botulism - Myasthenia gravis - Myopathy - Chronic inflammatory demyelinating neuropathy - Guillain-Barre syndrome

Answer 490

- **Manage underlying malignancy** - **Pyridostigmine/ amifampridine:** allows more acetylcholine to be released in the neuromuscular junction synapses - **Immunosuppressants** (e.g. prednisolone or azathioprine) - **IV immunoglobulins:** bind and neutralise the autoantibodies. - **Plasmapheresis:** to remove damaging antibodies

Answer 491

- **Respiratory failure:** when respiratory muscles are affected - **Aspiration:** due to impaired swallowing - **Amifampridine related seizures** - **Osteoporosis:** related to corticosteroid use

Answer 492

Charcot-Marie-Tooth disease is a group of inherited diseases that affects the peripheral motor and sensory nerves.

Answer 493

Symptoms usually start to appear before the age of 10 years but the onset of symptoms can be delayed until 40 or later.

Answer 494

- **Pes cavus:** high foot arches - **Hammer toes:** the middle joint of a toe bends upwards - Distal muscle wasting causing **inverted champagne bottle legs** - Hand and arm muscle wasting causing **claw hand** - **Thickened palpable nerves** e.g. common peroneal

Answer 495

- **Weakness in the lower legs, particularly loss of ankle dorsiflexion** - **Foot drop** - **High-stepped gait** - **Weakness in the hands** - **Reduced tendon reflexes** - **Reduced muscle tone** - **Peripheral sensory loss** - **Tingling and burning sensations in the hands and feet** - **May be neuropathic pain**

Answer 496

- **Nerve conduction studies:** measures ability of nerves to conduct impulses, conduction speed will be lowered. - **Neurologists** and **geneticists** to make the diagnosis: look for mutations

Answer 497

- **Diabetic neuropathy** - **Chronic inflammatory demyelinating polyneuropathy** - **Acquired peripheral neuropathy** - **Hereditary spastic paraplegia** - **Spinocerebellar degeneration**

Answer 498

**Supportive:** - **Physiotherapists** to maintain muscle strength and joint range of motion - **Occupational therapists** to assist with activities of living - **Podiatrists** to help with foot symptoms and suggest insoles and other orthoses to improve symptoms - **Orthopaedic surgeons** to correct disabling joint deformities

Answer 499

- **Osteoarthritis** - **Pain**

Answer 500

- Quality of life is good - Total incapacity is rare

Answer 501

**Wernicke's encephalopathy** is a neurological emergency resulting from thiamine deficiency with varied neurocognitive manifestations. **Wernicke–Korsakoff** syndrome is the combined presence of Wernicke encephalopathy and alcoholic Korsakoff syndrome.

Answer 502

Thiamine (vitamin B1) deficiency

Answer 503

- **Wernicke's encephalopathy** - **Ophthalmoplegia:** weakness or paralysis of the eye muscles, nystagmus; lateral rectus; conjugate gate palsies - **Ataxia or unsteady gait** - Changes in mental state e.g. **confusion, apathy, and difficulty concentrating** May also present with hypotension, hypothermia and reduced consciousness.

Answer 504

- **Wernicke-Korsakoff syndrome** - Mainly targets the limbic system, causing severe memory impairment: - **Anterograde amnesia:** inability to create new memories - **Retrograde amnesia:** inability to recall previous memories. - **Confabulation:** creating stories to fill in the gaps in their memory which they believe to be true. - **Behavioural changes**

Answer 505

- Diagnosis is typically made **based on clinical presentation** - **Bloods including LFTs**: measure thiamine levels, measure blood alcohol levels, liver function may be deranged in alcoholism

Answer 506

- **Alcohol intoxication** - **Alcohol withdrawal** - **Encephalitis** - **Miller-Fisher syndrome**

Answer 507

- **Infusion of thiamine** over a few days to get rid of the deficiency, followed by oral supplementation - **Usually given alongside glucose, if hyperglycaemic:** it’s important to normalise the thiamine levels first, because without thiamine pyrophosphate, most of the glucose will become lactic acid and that can lead to metabolic acidosis.

Answer 508

Muscular dystrophy is an umbrella term for genetic conditions that cause gradual weakening and wasting of muscles. The main type of muscular dystrophy is Duchennes muscular dystrophy.

Answer 509

- **Duchennes muscular dystrophy** - **Beckers muscular dystrophy** - **Myotonic dystrophy** - **Facioscapulohumeral muscular dystrophy** - **Oculopharyngeal muscular dystrophy** - **Limb-girdle muscular dystrophy** - **Emery-Dreifuss muscular dystrophy**

Answer 510

- **M>F:** due to condition being X-linked - **Duchennes:** 3/1000 male births

Answer 511

- Usually presents around 3 – 5 years - Weakness in the muscles around pelvis. The weakness tends to be progressive and eventually all muscles will be affected. - Children start walking later than average - Waddling gait - Tend to develop calf pseudohypertrophy: visibly enlarged calves which are large because of fat and fibrotic tissue rather than muscle tissue. - Usually wheelchair bound by their teenager years - Gowers sign: children with proximal muscle weakness use a specific technique to stand up from a lying position. To stand up, they get onto their hands and knees, then push their hips up and backwards like the “downward dog” yoga pose. They then shift their weight backwards and transfer their hands to their knees. Whilst keeping their legs mostly straight they walk their hands up their legs to get their upper body erect. This is because the muscles around the pelvis are not strong enough to get their upper body erect without the help of their arms.

Answer 512

- **High creatine kinase level** - **Genetic testing:** diagnosis can be confirmed by looking for mutations in dystrophin - **Muscle biopsy:** staining for dystrophin - **Electromyogram:** distinguish between neuropathic and myopathic pathology

Answer 513

No curative treatment for muscular dystrophy. Management is aimed at allowing the person to have the highest quality of life for the longest time possible. - **Occupational therapy** - **Physiotherapy** - **Medical appliances** (such as wheelchairs and braces) - **Surgical and medical management of complications** e.g. spinal scoliosis and heart failure. - **Oral steroids** have been shown to slow the progression of muscle weakness - **Creatine supplementation** can give a slight improvement in muscle strength - **Genetic counselling** for patients who want to have children

Answer 514

- **Respiratory failure** because of a weak diaphragm - **Scoliosis** - **Dilated cardiomyopathy and arrhythmias:** dystrophin protein is also expressed in heart muscle.

Answer 515

Duchenne's muscular dystrophy: patients have a life expectancy of around 25 – 35 years with good management of the cardiac and respiratory complications.

Neurology Flashcards

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