Neurology Flashcards

Question

What is Juvenile Myoclonic Epilepsy (JME? - give an overview

Answer 1

* Commonest form of primary generalized epilepsy 3-12% all epilepsy * Juvenile onset, probably lifelong * Early morning myoclonic jerks (ask) * Photosensitive, sleep deprivation triggers * +/- absences * generalized tonic-clonic seizures – occur without warning

Answer 2

- sudden onset without warning in primary generalised epilepsy * Tonic phase * continuous muscle spasm, fall, cyanosis, tongue biting, incontinence * Clonic phase * rhythmic jerking slows and gets larger in amplitude as the attack progresses * Ends; the duration is typically 1-3 minutes * Post-ictal (post-seizure) phase * coma, drowsiness, confusion, headache * muscle aching * red/blue, wakes in ambulance/A&E

Answer 3

* Abrupt, short, 5-20 seconds * Multiple times/day, can lead to learning difficulties * Unresponsive, amnesia for the gap, rapid recovery * Tone preserved (or mildly reduced) * If absences only, tend to remit in adulthood (childhood absence epilepsy)

Answer 4

* a simple partial seizure where the patient is aware (used to be an aura) * focal seizure with awareness * a complex partial seizure- aura/warning with a level of reduced awareness * focal seizure with reduced awareness

Answer 5

* Temporal lobe - 70% * Frontal lobe - 25% * Occipital lobe - 4% * Parietal lobe - 1%

Answer 6

* Hippocampal sclerosis: 50% * have a history of febrile convulsion * Tumour: 18% * Birth Hypoxia: 10% * Vascular: 10% * Post Traumatic: 8% * Other: 4%

Answer 7

* hallucinations of taste, speech and /or smell, visual distortion; memory déjà vu and jamais vu * epigastric rising sensation (over humpback bridge) * fear, elation, low mood * pallor/ flushing/ heart rate changes (can mimic panic/hyperventilation attacks) * automatisms- semi-purposeful limb movements * Oral automatisms- lip-smacking, chewing movements * dystonic posturing (limb rises) * speech disturbance (dominant hemisphere onset) last 1-3 minutes typically

Answer 8

* brief 10-30 seconds, rapid recovery, frequent * predominantly nocturnal * forced head /eye deviation to the contralateral side * motor activity often bizarre, thrashing * often misdiagnosed as non-epileptic * ictal EEG (during the seizure) is often normal * Jacksonian spread with Todd’s paresis * automatisms, dystonic posturing for example * a fencing posture (overlap TLE)

Answer 9

* positive sensory symptoms (unlike TIA/stroke) * tingling, pain * distortion of body shape/image * Jacksonian march of positive sensory symptoms

Answer 10

* typically simple visual hallucinations -balls of coloured or flashing lights * amaurosis (blackout or whiteout) at onset -25%

Answer 11

* Phenytoin * treats tonic-clonic seizures * safe to use in status epilepticus (when a seizure lasts more than 5 minutes or are close together) * Carbamazepine, * Gabapentin, * Pregabalin

Answer 12

* Jacksonian motor or sensory seizures * Patients with focal neurological deficit (including a temporary unilateral Todds paresis) * Alcohol withdrawal seizure; only scan if subdural haematoma suspected fall, hit head, found on the floor, bruising on head

Answer 13

* Epilepsy represents a hyperexcitation or a failure of inhibitory regulation, either focally (e.g. motor cortex, temporal cortex) or generally (whole cortex at once)

Answer 14

* Na+ channel inactivation too slow in excitatory neurons * Reduced number of functional Na+ channels in inhibitory neurons * Reduced number of functional K+ channels in excitatory neurons * Mutated ion channels: voltage-gated and ligand-gated ion channels

Answer 15

_Na+ channel inactivation too slow in excitatory neurons_ * e.g., generalized epilepsy with febrile seizures plus (GEFS+) * a point mutation in part of Na+ channel (β subunit) --\> abnormally slow inactivation * _action potential repolarization impaired_ _Reduced number of functional Na+ channels in inhibitory neurons_ * e.g., generalized epilepsy with febrile seizures plus (GEFS+) * missense mutations or truncated protein results in reduction or loss of Na+ channel function * **action potential generation impaired**

Answer 16

_Reduced number of functional K+ channels in excitatory neurons_ * e.g., benign familial neonatal convulsions * defect in KCNQ2 or KCNQ3 K+ channel subunit --\> impaired activation * action potential repolarization impaired

Answer 17

* synchronized ‘**paroxysmal depolarizing shift**’ (PDS, 20 to 40 mV, lasting 50 to 200 ms) _overcomes inhibition_ * **increased extracellular K+** _due to neuronal damage_ or _reduced uptake by the astrocytes_ as well as _glutamate release from neurons or astrocytes contribute to PDS_ * during the PDS trains of action, potentials occur * _hippocampal neurons have similar responses under normal conditions_, making t**he hippocampus more prone to seizures than the neocortex** * Focal seizures may spread to other brain regions along the normal neuronal pathways and may also _show **secondary generalization** if the activity spreads to the thalamus (tonic clonic seizure)_

Answer 18

* Primary generalized seizures _reach the cerebral cortex_ via normal neuronal pathways _from the thalamus_ * e.g. tonic clonic seizure; absence; juvenile myoclonic epilepsy * pathways originate in the brainstem and are normally involved in regulating the sleep/wake cycle and arousal of the cerebral cortex * **Ca2+ channels** and inhibitory **GABA receptors** in thalamic neurons have been implicated in ‘spike and wave’ seizures, showing that inhibition (the wave) is preserved

Answer 19

* work to inhibit Glutamate * this is an excitatory molecule in the brain * work to increase GABA activity * this is an inhibitory molecule in the brain

Answer 20

* Phenytoin, Carbama/ Oxcarba-zepine, Eslicarbazepine acetate, Lamotrigine, Lacos/ Zonis-amide * inhibits voltage-gated Na+ ion channel * Ethosuximide * inhibits Ca2++ entry into postsynaptic neuron * Retigabine * increases excite of K+ from the postsynaptic neuron * Perampanel * inhibits the AMPA receptor which glutamate binds to and allows NA+ into the postsynaptic neuron

Answer 21

* Levetiracetam * increases activity of SV2A- regulates action potential-dependent neurotransmitter release * Retigabine * increases the activity of KCNQ K+ channels in the pre and postsynaptic neuron * Gabapentin, Pregabalin * inhibit alpha-2-beta-subunit of Ca2+ channels in the presynaptic neuron * Tiagabine * Inhibits GAT-1 in presynaptic neurons and on glial cells * Benzodiazepines, Barbiturates * increases activity of GABA_A more Cl- moved into the postsynaptic neuron

Answer 22

* non-competitive blockade of AMPA glutamate receptor * release of glutamate cannot overcome the block * reduce spread/generalisation of seizure * can also affect behaviour and mood

Answer 23

* Focal epilepsy characterised by intermittent high amplitude discharges at site of epileptic focus during inter-ictal (seizure) periods. * Two phases: * synchronous depolarisation (caused by strong excitatory inputs to the region of the focus), * followed by a period of hyperpolarisation, (activation of GABA inhibition) * Transition from inter-ictal discharges to full-blown seizure is a decrease in the hyper-polarisation phase * failure of inhibition to kick in, therefore treating with GABA stimulants helps control the seizure

Answer 24

* sodium valproate (sodium channels) * benzodiazepines (clobazam, lorazepam) * barbiturates/ primidone pro drug * tiagabine (inhibits GABA re-uptake) * vigabatrin (inhibits GABA –T breakdown)

Answer 25

* high-affinity synaptic vesicle protein-2A ligand that modulates glutamate neurotransmitter release * rapidly up titrated and is effective * IV formulation; no drug-drug interactions * keeps patients alert but causes mood lowering/agitation side-effects * brivaracetam second-generation version

Answer 26

_First line_ * Sodium valproate * Lamotrigine _Second line_ * levetiracetam, topiramate, zonisamide, benzodiazepines

Answer 27

_First line_ * Carbamazepine * Lamotrigine - all other AEDs have efficacy

Answer 28

_Dose related (acute)_ * Drowsiness * Ataxia * Hyperactivity * cognitive impairment _Long term_ * Tolerance/ Dependence

Answer 29

_Dose-related (acute)_ * Ataxia * Diplopia * Nystagmus _Long-term_ * Gingival hyperplasia * Osteomalacia * Cerebellar atrophy

Answer 30

_Dose-related_ _(acute)_ * Sedation * Tremor _Long-term_ * Hair thinning * Weight gain * Menstrual irregularities * Encephalopathy * Parkinsonism (**is an enzyme inhibitor**)

Answer 31

* High for strategy: Association areas of Neocortex and basal ganglia * Medium for tactics: Motor Cortex and Cerebellum * Low for execution: Brainstem and Spinal Cord

Answer 32

* predominentley innervates the flexor muscles in the upper limb

Answer 33

* originates in the vestibular nuclei of the medulla which relay sensory information from the vestibular labyrinth in the inner ear * Medial Vestibulospinal pathway activates the cervical spinal circuits that control neck and back muscle guides * guides head movements * helps keep eyes stable as the body moves * Lateral vestibulospinal projects ipsilaterally far down the lumbar spinal cord * helos maintain an upright and balanced posture * facilitates the extensor motor neurons of the legs

Answer 34

* Originates in the superior colliculus in the midbrain * The superior colliculus receives information from the retina and the visual cortex used to construct the map of the world around us * allows the direction of the head and eyes so that the appropriate point of space is imagined on the fovea * The neurons decussate immediately and lie close to the midline into the cervical region of the spinal cord * help control muscles of the neck, upper trunk and shoulder

Answer 35

* Reticulospinal tract descends in two separate pathways * Pontine (medial) * Medullary (lateral) * both facilitate the extension of the limbs * the pathway runs from the brainstem, the reticular formation is under the cerebral aqueduct and fourth ventricle

Answer 36

* Tectospinal and medial vestibulospinal * Control head and neck movements. * Lateral vestibulospinal and reticulospinal * Activate extensor muscles in arms and legs. * Rubrospinal * Activates flexor muscles in arms.

Answer 37

* **Decorticate posturing:** the lesion is above the red nucleus * the rubrospinal neurons are disinhibited and therefore facilitate flexors in the upper limbs _(lesions above the red nucleus)_ * **Decerebrate posturing:** the rubrospinal neurons are disrupted and therefore upper limbs are extended _(lesions below the red nucleus)_ * _Noxious stimuli_ allow us to understand where the lesion is * supraorbital pressure * nail bed stimulation * sternal stimulation

Answer 38

* Typical Posture * some preserved upper limb flexion * lower limb extension * Increased tone (spasticity), * Brisk Reflexes: * Extensor Plantar/Babinski reflex: abnormal extension of toes (up till age 2 is normal) * Clonus - Patient maintains a posture

Answer 39

* Anterior Cerebral artery --\> Frontal * Middle Cerebral Artery --\> Temporal and Parietal * Posterior Cerebral Artery --\> Occipital * Anterior choroidal artery + Branch of Internal Carotid --\> centre of the brain

Answer 40

* a Proximal lesion would affect the internal capsule * leading to complete hemiparesis * a Distal lesion may spare the leg area of the motor cortex * (secondary swelling and ischaemia may compromise function)

Answer 41

* this supplies the medial part of the frontal lobes including leg area of the motor cortex * leg (crural) paresis * frontal sing e.g *abulia: loss or impairment of the ability to make decisions or act independently*

Answer 42

* partial onset of a simple motor seizure becoming secondarily generalised * strongly associated with a structural abnormality in or close to the motor cortex

Answer 43

* Area 5- somatosensory afferents * Area 7- visual pathway afferents * Mental body/ environment image * Damage results in neglect (can perceive but do not attend) * Exploratory movements * Eg turning object in hand (looking and feeling)

Answer 44

* Visual, Auditory, Somatosensory, Vestibular, Gustatory all feed into the Heteronodal which allows for motor planning * the prefrontal cortex plans for movement after receiving information from the other cortices in the brain

Answer 45

* Importance in control of visually guided movements * origination of the hand in relation to the object to be grasped (prehension) * *Damage:* may cause perseveration of motor activity despite lack of success * receives input from the cerebellum is involved in planning movements based on visual cues, mostly involved in * **control of postural and proximal limb muscles** * lesions in the PMA disrupts response to visual cues

Answer 46

**_Inability to carry out purposeful movements in the absence of paralysis or paresis. There is great difficulty in the sequencing and execution of movements_** * **Ideational (Parietal) apraxia**: unable to report sequence * show me how to make a peanut butter sandwich * **Ideomotor (SMA) apraxia:** unable to use the tool * show me how to hold and use a pair of scissors

Answer 47

**_Sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions. If only occurs with certain actions, said to be ‘task specific’._** * though manifestation is motor, the primary abnormality is likely to be disrupted sensory processing mediated by the basal ganglia

Answer 48

implicated in empathy, impulse control, emotion, and decision-making

Answer 49

Positive feedback loop with the cortex to select wanted movements and deselect unwanted movements.

Answer 50

* Coordination of muscles in order to make smooth movements. * Balance * Motor learning * Cognitive functions

Answer 51

* Spinocerebellum * Vermis, * Fastiguel & Interposed nuclei: motor execution * Cerebrocerebelllum * Dentate nucleus: motor planning * Vestibulocerbellum * Flocculus, Nodulus * Vestibular nuclei: balance and eye movements

Answer 52

* functions in the control of muscle tone/posture * takes in information via the spinocerebellar tracts from the midbrain * the cerebellum puts out information through efferent neurons * from the **reticular formation** down the **reticulo** and **vestibulospinal tracts**

Answer 53

* Planning movements * afferent fibres from the cortex travel through the corticopontine tract synapse and continue on the pontocerebellar tract * efferent fibres go back to the cortex from the Dentate cerebellar nuclei to the thalamus then the cortex

Answer 54

* involved in balance and eye movements * information from the ear from the vestibular nerve to the flocculondular lobe * efferent fibres synapse and decussate at the vestibular nuclei. travel down the vestibulospinal tract down the spine and up to the extraocular muscle nuclei in the midbrain

Answer 55

_Superior cerebellar peduncle_ * Dentate nuclei: to thalamus and * Interposed nuclei: to red nucleus * Fastigial nucleus: to vestibular nuclei _Middle Cerebellar peduncle_ * Descending Corticospinal fibres synapse at the pons and enter the cerebellum _Inferior cerebellar peduncles_ * Ascending fibres from the inferior olive and proprioceptive information from eh spinocerebellar tract

Answer 56

* **Dysmetria**: movement is not stopped in time (overshoot) * **Dsynergia**: decomposition of complex movements * **Dysdiadochokinesia**: reduced ability to perform rapidly alternating movements * **Intentional tremor**: tremor arising when trying to perform a goal-directed movement * **Dysarthria** – articulation inco.ordination: incoordination in the respiratory muscles, muscles of the larynx, etc. Uneven speech strength and velocity.

Answer 57

* Nystagmus- involuntary, rhythmical, repeated oscillations of one or both eyes, in any or all directions of view * movement of the eyes minimises the ability to focus the eyes on one point (fixation).

Answer 58

* Gait ataxia (unsteadiness of walking), and disturbance of limb tone (hypotonia) and posture

Answer 59

* MPG-W * Molecular: Stellate cell, Parallel fibre * Purkinje: Purkinje cell, Basket cell * Granular: Granule cell, Golgi cell, Mossy fibre, climbing fibre from the inferior olive, Purkinje cell axon * White matter: Mossy fibre, climbing fibre from the inferior olive

Answer 60

* the release of DAG and IP₃ causes increased intracellular Ca2+ and activation of PKC * this triggers clatherin-dependent internalization of postsynaptic AMPA receptors * this weakens the parallel fibre synapse

Answer 61

* Frederich’s ataxia * Spinocerebellar degeneration * (Ataxia may occur if major connections disrupted) * Ataxia-telengiectasia * Von Hippel Lindau

Answer 62

Cerebellar atrophy * Alcohol * Metabolic (B12/Thyroid/Coeliac) * Drugs (eg phenytoin) * Degenerative (familial, MSA) * Immune (paraneoplastic)

Answer 63

* Metastasis * PICA (Posterior inferior cerebellar artery) territory stroke * MS

Answer 64

* the endolymph in the chochlear duct is continuous with he endolymph on the apical surface of the vestibular hair cells

Answer 65

* they are sensory cells in the otolith organs (sacculus and utriculus cells) are embedded in a gelatinous sheet covered with crystals of calcium carbonate * they sense linear and gravitational accelerations of the head * the four otolith organs are not exactly perpendicular to enable them to resolve and tilt * the six semicircular canals are oriented at right angles to one another to detect head rotation in all directions

Answer 66

* Type II vestibular hair cells * receive afferent and efferent information * appear to be more sensitive * Type I vestibular hair cells * surrounded by an afferent nerve calyx and are not directly contacted by efferent nerve fibres

Answer 67

* they detect rotation of the head *

Answer 68

* Slow eye movements followed by fast ones during continued head rotation - _the fast phase defines the direction of the nystagmus_ * physiological nystagmus occurs in the head rotation due to the vestibulo-ocular reflex * **Spontaneous nystagmus** is when the eyes move rhythmically from side to side in the absence of any head movements * this occurs when one of the canals is damage * no firing takes place instead of the reduced firing that would happen in physiological nystagmus

Answer 69

* water is used to test the function of the brainstem in an unconscious patient - uses ocular reflexes * using slightly warmer or colder warmer than body temp generates currents in the canal that mimics endolymph movement induced by turning the head * affects the firing rates of the associated vestibular nerve * warmer water = higher frequency * cooler water = decreased rate * the net difference generates an eye movement

Answer 70

* Ear infection * Head injury * Whiplash * Ageing * certain drugs: AMinoglycoside antibiotics (gentamicin)

Answer 71

* Patient complains of “dizziness” * Light-headed à check cardiovascular * Vertigo (spinning) à check vestibular * Trauma * Esp. CN VIII, e.g. motorcycle accident * Benign paroxysmal positional vertigo (BPPV) * vertigo caused by changes in head position * Ménière's disease * Progressive disease * episodes of vertigo, tinnitus and progressive hearing loss, usually in one ear * Excess fluid in inner ear

Answer 72

* ciliated receptor cells send their own afferent axons to the brain * olfactory information is coded by the pattern of stimulation that the brain learns to interpret

Answer 73

* Olfactory transduction depends on a second messenger process, with cAMP being activated in response to an odorant molecule * This leads to opening of cAMP-dependent ligand-gated ion channels * non-selective cation channels, permeable to Na+ and Ca2+ * Na+ and Ca2+ influx (inward current in the figure) depolarizes the olfactory receptor cells, signalling the binding of an odorant molecule, and leading to action potentials * The Ca2+ influx indirectly opens Cl- channels which, due to the unusually high intracellular Cl- concentration of the olfactory receptors, contributes to the depolarization

Answer 74

* reduced or increased olfaction- very common * Causes: * upper resp. tract infection * older age * nasal polyps * diabetes mellitus * head trauma, high dose radiation at nasal epithelium, some drugs

Answer 75

* _Salt sensation_ depends on the equilibrium potential for Na+ ions across the taste receptors * _Sour sensation_ depends on pH (acidity), with H+ ions (protons) closing K+ channels either directly or indirectly via a cAMP as a second messenger. * his leads to depolarization of the taste receptors * _Sweet sensation_ comes about via a second messenger system that closes K+ channels, leading to depolarization of the taste receptors * _Bitter and umami sensation_ are due to a second-messenger induced increase in intracellular Ca2+ in the receptors. The Ca2+ increase leads to neurotransmitter release

Answer 76

* Taste is signalled by cranial nerves VII (front 2/3 of the tongue), IX and X (both rear 1/3 of the tongue) to the nucleus of the solitary tract in the brainstem. * Fibres (red lines) from second-order taste neurons project ipsilaterally to the ventral posterior nucleus of the thalamus. * Thalamic efferents (green lines) then project to the insula, defining the primary gustatory cortex which, in turn, projects (black lines) to the orbitofrontal cortex, sometimes defined as a secondary cortical taste area. * The parabrachial nuclei of the pons are shown in orange. The parabrachial nuclei have a dorsal thalamocortical projection and also a ventral projection that terminates in amygdalar and hypothalamic nuclei, among others.

Answer 77

* 80% of taste disorders are smell disorders True taste disorders * prior upper respiratory tract infection * head injury * poor oral hygiene less obvious daignosis

Answer 78

* Early symptoms * Asymmetric hand weakness → dropping of objects * Cramping of upper extremities * Dysarthria, dysphagia, dysphonia develop later * Atrophy → decreased strength, decreased muscle bulk, abnormal tone causing fasiculations * weakness → inability to ambulate leads to wheelchair use * Late symptoms * resp[iratory weakness → dyspnoea → respiratory infection * Recurrent bouts of cough, fever chill → pneumonia

Answer 79

* progressive degenerative motor neurone disease with upper and lower motor neuron signs * Protein aggregation → neuronal injury, death → retrograde neuronal degeneration → gliosis (change in glial cells) * *Supreoxide dismutase 1 (SOD1):* antioxidant protein encoded on chromosome 9 is seen in 20% of familial ALS * gain of function mutation → misfolding → protein aggregation → direct neuronal injury, unfolded protein response → death * interference with: organelle autophagy, proteasome function, axonal transport, mitochondrial function * C9orf72 proteins is involved in some way * Hexanucleotide repeat expansion involved in dead neurons * TDP-43, FUS: an RNA binding genes cause abnormal RNA accumulation \_\> abnormal protein accumulation → neuronal injury

Answer 80

* raised creatine kinase due to muscle atrophy * heavy-metal levels and Lyme disease tests negative * EL Escorial criteria * Family history

Answer 81

* Evidence of lower motor neuron disease by clinical/ electrophysiological/ neuropathic examination * Evidence of upper motor neuron disease by clinical examination * Progressive spread of signs/s and symptoms within/ outside of body region as determined by history/ examination All three are required to make a diagnosis of ALS

Answer 82

* CPN compression/trauma * Sciatic n. compression/trauma * L5 radiculopathy * L4 radiculopathy * Diabetes, vasculitis, leprosy, other inflammatory neuropathies, malignant infiltration, Charcot- Marie-Tooth

Answer 83

* Distal muscular dystrophy * Inclusion body myopathy

Answer 84

* Spinal cord lesions (esp. conus) * Para-saggital meningiomas

Answer 85

Ends at L1 / L2 interspace Cervical spine: cord levels correspond to vertebrae Thoracic spine: the cord level (clinical) lower than vertebral level T12/L1 disc will compress the conus (sacral cord segments)

Answer 86

* High cervical spine compression * Clumsy slow fingers * Quadriplegia * Respiratory problems * Bladder & bowel dysfunction * Thoracic spine disease * Paraplegia * Sensory level * Bladder & bowel dysfunction * Traps for the unwary * Triple flexion response to pain * Gait ataxia may be the only feature

Answer 87

* Cauda Equina syndrome is a sacral **sensory** & sphincter syndrome * If weakness occurs, it often only affects ankle and toe plantar flexion (S1/S2) with accompanying loss of ankle reflexes * It may be painless * Decompression undertaken later than 48 hours after **clinical presentation yields** very poor results

Answer 88

Inflammation of the meninges and subarachnoid space – classic triad of symptoms: _headache, fever and neck stiffness_ — and pleocytosis (an increased cell count, particularly of leukocytes) in the CSF

Answer 89

Inflammation of the brain cortex parenchyma - behavioural changes, focal neurological abnormalities and impairment of consciousness

Answer 90

Central nervous system infection with clinical features of both meningeal and parenchymal disease.

Answer 91

- inflammation of the meninges not due to pyogenic bacteria

Answer 92

* Bacterial meningitis is associated with high mortality and morbidity worldwide, with an estimated 16 million cases in 2013, causing 1.6 million years lived with disability each year * Incidence rates of community-acquired bacterial meningitis in high-income areas (such as Europe, the United States and Australia) are 1–3 per 100,000 population per year * Reported case fatality rates are high and vary with patient age, causative pathogen and country income * Meningitis caused by *_Streptococcus pneumoniae_* _has the highest case fatality rates: 20–37%_ in high-income countries and up to 51% in low-income countries. Case fatality rates for meningococcal meningitis are distinctly lower, in the range of 3–10% worldwide

Answer 93

* Bacterial meningitis is associated with high mortality and morbidity worldwide, with an estimated 16 million cases in 2013, causing 1.6 million years lived with disability each year * Incidence rates of community-acquired bacterial meningitis in high-income areas (such as Europe, the United States and Australia) are 1–3 per 100,000 population per year * Reported case fatality rates are high and vary with patient age, causative pathogen and country income * Meningitis caused by *_Streptococcus pneumoniae_* _has the highest case fatality rates: 20–37%_ in high-income countries and up to 51% in low-income countries. Case fatality rates for meningococcal meningitis are distinctly lower, in the range of 3–10% worldwide

Answer 94

* Causative pathogens depend on the **age** of the patient and **predisposing factors** * _Neonates_: early (first week of life – vertical transmission) *vs.* late (second to sixth week of life) - *Streptococcus agalactiae* (group B streptococcus, GBS) and *Escherichia coli* * _Children_: Vaccination against *Haemophilus influenzae* type b, *Neisseria meningitidis* serogroup C and 7-, 10- and 13-valent pneumococcal conjugate vaccines has reduced the incidence of bacterial meningitis in children - currently *N. meningitidis* serogroup B causes most cases in both children and adults

Answer 95

* reduces the incidence of bacterial infections

Answer 96

* _Neonates_: nonspecific symptoms: irritability, poor feeding, respiratory distress, pale or marble skin and hyper- or hypotonia (low diagnostic accuracy – low threshold to perform a LP) * _Children_: fever, chills, vomiting, photophobia and severe headache; the younger the patient with bacterial meningitis, the more subtle and atypical are the symptoms * Some signs or symptoms are associated with specific pathogens: petechial and purpuric rash are usually signs of meningococcal disease, although a rash has also been described in pneumococcal meningitis * In all children with suspected bacterial meningitis CSF examination should be performed, unless contraindications for LP are present

Answer 97

_Adults_: headache, fever, neck stiffness and altered mental status are common signs and symptoms at admission A petechial rash is identified in 20–52% of patients and is indicative of meningococcal infection in over 90% of patients

Answer 98

* _CSF_ * A positive CSF culture is diagnostic for bacterial meningitis and enables in vitro testing of the antimicrobial susceptibility patterns, after which antibiotic treatment can be optimized * Gram staining, latex agglutination, immunochromatographic antigen testing and PCR could provide additional information, especially when the CSF culture is negative * Classic abnormalities of CSF composition in bacterial meningitis are a _pleocytosis_ of mainly _polymorphic leukocytes_, _low glucose concentration_, _low CSF to blood glucose ratio_ and _elevated protein levels_ * The CSF lactate concentration is a widely available, cheap and rapid diagnostic test

Answer 99

* _Serum_ * Serum concentrations of C-reactive protein (CRP) and pro-calcitonin are highly discriminatory between paediatric bacterial and viral meningitis * Blood cultures are valuable for detection of the causative organism and establish susceptibility patterns if CSF cultures are negative or unavailable

Answer 100

* Viral pathogens are the most common aetiology of aseptic meningitis * Non-infectious causes: * drug-induced (e.g., amoxicillin, nonsteroidal anti-inflammatory medications or trimethoprim-sulfamethoxazole) * neoplastic, * neurosarcoidosis, * rheumatoid arthritis, systemic lupus erythematosus, or * vasculitis (e.g., Kawasaki disease)

Answer 101

* Viral meningitis exhibits a summer-to-fall seasonality in temperate climates and a year-round incidence in tropical and subtropical areas * _Non-polio human enteroviruses (NPEV) are the leading recognizable cause of viral meningitis (_*_Picornaviridae_*_)_ * NPEV have a worldwide distribution and humans as the only natural reservoir * The majority of meningitis cases are due to _Enterovirus species B,_ Echovirus A71 (species A), and Coxsackievirus A9 and B5 (species B) * Herpes Simplex viruses (HSV, *Herpesviridae*) account for 0.5 - 17% of viral meningitis cases * Mups cirus * Causative pathogens are primarily transmitted through the faecal-oral route, and less commonly via respiratory secretions

Answer 102

Herpes simplex viruses (HSV) (*Herpesviridae*), account for approximately 0.5% to 18% of viral meningitis cases HSV type 1 (HSV-1) is the most commonly identified cause of sporadic encephalitis worldwide HSV type 2 (HSV-2) is associated with benign recurrent aseptic meningitis and recurrent benign lymphocytic meningitis (RBLM)

Answer 103

* _Fever_ * _Headache_ * _Neck stiffness_ * Arthralgia/myalgia * Nausea/ vomiting * Photophobia (mainly non-polio human enteroviruses)

Answer 104

* Kernig's sign – With the patient's hips and knees flexed, a positive sign is when the patient resists extension of the knee. The test was originally performed with a patient seated on the edge of the bed and feet dangling over the side * Brudzinski's sign – Flexion of the supine patient's neck causes the patient to flex both hips and knees; therefore, retracting the legs toward the chest * Nuchal rigidity – Neck stiffness denoting involuntary resistance to passive neck flexion

Answer 105

* WBC (cells/mm³) normal CSF \<5 * in NPEV 9–2590 *raised* * Lymphocytes (%) normal CSF 0–30 * in NPEV 24–100 *raised* * Glucose (mg/dL) normal CSF 45–80 * in NPEV 45–80 *normal* * Protein (mg/dL) normal CSF 15–45 * in NPEV 277–1540 *raised*

Answer 106

* WBC (cells/mm³) normal CSF \<5 * in infection 46-1860 *raised* * Lymphocytes (%) normal CSF 0–30 * in infection 80–100 *raised* * Glucose (mg/dL) normal CSF 45–80 * in infection 32-80 *normal/ slightly low* * Protein (mg/dL) normal CSF 15–45 * in infection 404-3215 *very* *raised*

Answer 107

* WBC (cells/mm³) normal CSF \<5 * in infection 415-1715 *more likely to be raised* * Lymphocytes (%) normal CSF 0–30 * in infection 95–100 *more likely to be raised* * Glucose (mg/dL) normal CSF 45–80 * in infection 43-68 *normal but lower end of spectrum* * Protein (mg/dL) normal CSF 15–45 * in infection 128-240 *raised but not very high*

Answer 108

* WBC (cells/mm³) normal CSF \<5 * in infection 77-1600 *raised* * Lymphocytes (%) normal CSF 0–30 * in infection 77–100 *more likely to be raised* * Glucose (mg/dL) normal CSF 45–80 * in infection NR * Protein (mg/dL) normal CSF 15–45 * in infection 40-74 *barley raised*

Answer 109

The gold standard tool for the diagnosis of viral meningitis is the _polymerase chain reaction (PCR), which detects and quantifies viral DNA or RNA in the CSF_ Alternative specimens, such as blood, throat or nasal swabs, or stool samples might be used instead, particularly in cases of suspected NPEV infections Diagnosis of mumps virus, herpesvirus, arboviruses, and human immunodeficiency virus (HIV) infections can be achieved using serological assays, although the results might be negative at early stages of the disease

Answer 110

* Asian and Pacific regions * Cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, Japanese encephalitis B * Sub-Saharan Africa * Tuberculous meningitis, cryptococcal meningitis, cytomegalovirus, malaria * Europe and North America * Progressive Multifocal Leukoencephalopathy, toxoplasmic encephalitis, cryptococcal meningitis * South America * Cerebral toxoplasmosis, tuberculous meningitis, cryptococcal meningitis; Chagas disease is reported in southern US states and South America

Answer 111

* The measles virus is a non-segmented, negative-sense RNA virus and a member of the Morbillivirus genus in the family of *Paramyxoviridae* * The genome of about 16000 nucleotides encodes six structural proteins, the nucleoprotein, phosphoprotein, matrix, fusion, haemagglutinin, and large protein, and two non-structural proteins V and C encoded within the phosphoprotein gene

Answer 112

* Respiratory route of transmission - respiratory droplets and small particle aerosols that remain suspended in the air for up to 2 h * R₀ of 9-18 – high contagiousness * Incubation period: 12.5 days * The infectious period begins several days before and lasts for several days after the onset of rash, coinciding with peak levels of viraemia and when cough and coryza are most intense, facilitating transmission

Answer 113

* Fever and maculopapular rash * Cough, coryza, conjunctivitis * Koplik's spots appear on the buccal mucosa as small white papules and provide an opportunity to clinically diagnose measles a day or two before the rash * The rash appears 3–4 days after the onset of fever, * → first on the face and behind the ears → spreads to the trunk and extremities, coinciding with development of the adaptive immune response

Answer 114

Acute disseminated encephalomyelitis (**ADEM**) - a demyelinating autoimmune disease that is triggered by measles virus and occurs within days to weeks in approximately one in 1000 cases Measles inclusion body encephalitis (**MIBE**) - a progressive measles virus infection of the brain that results in neurological deterioration and death in individuals with impaired cellular immunity within months of the acute illness Subacute sclerosing panencephalitis (**SSPE**) - a delayed complication of measles that occurs in about 1:10 000 to 1:100 000 cases 5–10 years after the acute illness, caused by the host response to production of mutated virions with defective assembly and budding

Answer 115

* The differential diagnosis includes rubella, dengue fever, parvovirus B19 infection, human herpesvirus 6 infection ... * The most _common laboratory_ method for confirming measles is detection of _measles virus–specific IgM antibodies in a blood specimen_ * A real-time PCR assay for measles virus RNA in urine, blood, oral fluid, or nasopharyngeal specimens can identify infection with a sensitivity of 94% and a specificity of 99% before measles IgM antibodies are detectable, and it allows genotyping of the measles virus

Answer 116

Young infants, adults older than 20 years, pregnant women, and those who are immunocompromised or undernourished, particularly children with vitamin A deficiency are most at risk of complications * Pneumonia * Laryngotracheobronchitis (croup) and otitis media * Diarrhoea * Keratoconjunctivitis

Answer 117

* Primary headaches * Migraine * tension-type * Trigeminal autonomic cephalagis * other primary headache disorders * Secondary headaches

Answer 118

* Prodrome: few hours to days * Aura: 5- 60 minutes * Migraine attack: 4-72 hours * Postrdome: 24-48 hours can last days

Answer 119

* Fatigue/cognitive change: * Concentration difficulty, fatigue, memory impairment, depression, elation, irritability. * Homeostatic alterations: * Food cravings, thirst, frequency of urination, yawning, sleep disturbance * Sensory sensitivites/nonpainful migrainous symptoms: * Neck stiffness, photophobia, phonophobia, osmophobia, nausea.

Answer 120

* Dysfunction of the Orexinergic system involved in regulating *feeding*, *sleep/wake cycle, stress* *and motivation.* * Increased ADH secretion – *thirst/urination* * Increase sensitivity of TCC – *Neck stiffness.* * PET and functional MRI : show changes in the connectivity within the hypothalamus. The hypothalamus can often be viewed as the “generator”of migraine – homestatic alterations * Changes in connectivity with other regions of the brain – *fatigue/cognitive change* * Increased activity in the occipital lobe – *visual* *sensitivities* * Activation of brainstem – *nasuea* * Differences in thalamic and thalamo-cortical activity – *allodynia, aberrant sensory* *processing*

Answer 121

* Visual (most common) – Zig-zag lines, visual fortification * Speech – Dysphasia * Sensory disturbance – (negative and positive symptoms) → caused by where cortical spreading depression occurs → some people have aura without migraines and vice versa

Answer 122

Cortical spreading depression (CSD) is considered the **electrophysiological substrate of the migraine aura**. CSD is a spreading depolarization that tends to start in the occipital lobe and spreads forward over the cerebral hemisphere at a rate of about 2–4 mm/min.

Answer 123

* A: At least five attacks fulfilling criteria B-D * B: Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated)2;3 * C: Headache has at least two of the following four characteristics: * 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) * D: During headache at least one of the following: * 1. nausea and/or vomiting 2. photophobia and phonophobia * E: Not better accounted for by another ICHD-3 diagnosis

Answer 124

• Presenting headache – Constant or episodic – Site: Unilateral or bilateral/holocranic – Headache load: Frequency/duration/severity • Character of pain: Throbbing, stabbing etc • Precipitating factor • Previous history of headaches

Answer 125

* Sertonoing: low levels of serotonin are associated with migraines * Dopamine: dopamine hypersensitivity leads to associated symptoms of migraine: nausea vomiting yawning * CGRP (calcitonin gene-related peptide): CGRP is released from the C-fibres and acts on the CGRP receptors located on the A-delta fibres → this has a role in modulating pain transmission

Answer 126

Trigeminal C-fibres are activated which leads to CGRP release • CGRP release causes vasodilatation leading to release of proteins which results in neurogenic inflammation. • Neurogenic inflammation activates A-delta fibres which transmit signal back to the brainstem.

Answer 127

* migraines are more common in females and are more prevalent around menstruation and menopause due to a decrease in oestrogen * reduced during pregnancy due to an increase in oestrogen * the net effect of oestrogen is to increase serotonin levels therefore migraines are more likely when oestrogen levels decreased causing serotonin also decrease

Answer 128

* Oestrogen facilitates the glutaminergic system. * – Glutaminergic pathways are involved in the induction of Cortical spreading depression. – Therefore high oestrogen levels (as in pregnancy) is associated with a higher frequency of migraines with aura (NB overall migraine frequency is reduced) * Prostaglandin secretion is highest during menstruation which is involved in signalling pain. This contributes to menstrual migraines.

Answer 129

* avoidance of triggeers * hydrate, reduce caffeine, alcohol * regular meals * good sleep hygeine * excercise

Answer 130

* Abortive treatments: • Triptans – Decrease CGRP release • NSAIDs – Decrease prostaglandin secretion • Paracetamol • Antiemetics – Decrease Dopamine centrally * Preventatives: _Oral drugs_ • Anti-hypertensives: Propranolol (women of child bearing age) • Anti-epileptics: Topiramate • Antidepressants _Injectables_ • Botox – blocks release of neurotransmitters • CGRP antagonists – blocks CGRP pathway

Answer 131

***Ditans (Lasmiditan)*** • 5HT-1F receptor agonist • Inhibits peptide release • Does not affect 5HT-1B,D so no cardiovascular effects • Not contraindication in those with IHD/CVAA ***Gepants (Umbrogepant, Rimgepant)*** • CGRP receptor antagonist (small molecule) • Oral tablet • Abortive and preventative • Redefines concept of episodic vs chronic • No issue of overuse headache

Answer 132

* Pain \> 4 hours, noo migrainous features, often bilateral (band across the forehead) and prefer to be still * Caused by: stress, anxiety, depression, lack of sleep, poor posture * accumulate to reaching a threshold for triggering a headache

Answer 133

• Age: _Greater than 50 yrs_ • Onset: Thunderclap \< 5mins, NDPH • Severity: “worst headache of their life” • Progression: Rapid or developing associated features. • Triggers: Provoked by valsalva, exercise, sex, postural change. • Systemic symptoms: Rash, weight loss, fever, neck stiffness. • Risk factors: HIV, Suspected malignancy, surgery, shunt in situ, inflammatory disorders, recent head injury. • Neurological signs: optic nerve swelling, hemiparesis, altered consciousness, visual field defect, cranial nerve palsies, seizures. • Raised ICP features: N&V, Position dependent, Visual obscurations, pusalatile tinnitus, worse with Valsalva maneouvres

Answer 134

* Brain tumour * Brain haemorrhage * Giant cell arthritis: * Age \> 50 years Raised ESR, CRP Scalp tenderness Jaw claudication Associated with polymyalgia Rheumatica Can lead to blindness * Reversible Cerebral vasoconstriction Syndrome * sudden, intense headache, "thunderclap" headache * seen in postpartum, serotonergic medication and use of stimulants * Idiopathic intracranial hypertension * often occur in obese females, have visual changes * caused by impaired lymphatic drainage and increased venous sinus pressure * Low-pressure headache: headache worse on sitting/standing up, relieved by lying down * Hypertensive encephalopathy/PRES: acute rise in BP can cause high levels of hydrostatic pressure leading to increased interstitial fluid this can manifest in seizures * seen in later stages of pregnancy * Trigeminal neuralgia: Paroxzysmal pain typically in V2 and v3 dermatomes. Commonly shooting pain triggered by touch, wind talking and brushing teeth

Answer 135

Age \> 50 years Raised ESR, CRP Scalp tenderness Jaw claudication Associated with polymyalgia Rheumatica Can lead to blindness

Answer 136

Paroxysmal pain typically in V2 and V3 dermatomes of the cranial nerve 7. Commonly shooting pain triggered by touch, wind talking and brushing teeth

Answer 137

* sudden, intense headache, "thunderclap" headache * seen in postpartum, serotonergic medication and use of stimulants

Answer 138

Immune-mediated demyelination of the peripheral nervous system often triggered by infection - classically *Campylobacter jejuni* * cross-reaction of antibodies with gangliosides in the peripheral nervous system * correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated * anti-GM1 antibodies in 25% of patients

Answer 139

* cross-reaction of antibodies with gangliosides in the peripheral nervous system * correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated * anti-GM1 antibodies in 25% of patients

Answer 140

progressive symmetrical weakness of the limbs often in an ascending fashion this is in conjunction with diminished reflexes and normal sensation

Answer 141

* Damage to the posterior columns - loss of proprioception, light touch and vibration sense (sensory ataxia and a positive Romberg's test). * Damage to lateral columns - spastic weakness and upgoing plantars (UMN signs). * Damage to peripheral nerves - absent ankle and knee jerks (LMN signs). → caused by B12 deficiency, may present with macrocytic anaemia, b12 should be replaced before folate else it can precipitate combined degeneration of the cord

Answer 142

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

Answer 143

autoimmune disorder resulting in _insufficient functioning acetylcholine receptors._ _Antibodies to acetylcholine receptors are seen in 85-90% of cases_\*. Myasthenia is more common in women (2:1)

Answer 144

fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest: * extraocular muscle weakness: diplopia * proximal muscle weakness: face, neck, limb girdle * ptosis * dysphagia

Answer 145

* thymomas in 15% (thymic carcnioma) * autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE * thymic hyperplasia in 50-70%

Answer 146

* single fibre electromyography: high sensitivity (92-100%) * CT thorax to exclude thymoma * CK normal * autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies * Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used any more due to the risk of cardiac arrhythmia

Answer 147

* long-acting acetylcholinesterase inhibitors * ***Pyridostigmine*** is first-line * immunosuppression is usually not started at diagnosis, but the majority of patients eventually require it in addition to long-acting acetylcholinesterase inhibitors: * *Prednisolone* initially * *Azathioprine, Cyclosporine, Mycophenolate mofetil* may also be used * thymectomy

Answer 148

* **M**otor response 6. Obeys commands 5. Localises to pain 4. Withdraws from pain 3. Abnormal flexion to pain (decorticate posture) 2. Extending to pain 1. None * **V**erbal response 5. Orientated 4. Confused 3. Words 2. Sounds 1. None * **E**ye opening 4. Spontaneous 3. To speech 2. To pain 1. None

Answer 149

headaches that are very painful and typically occur in clusters lasting several weeks, and occur typically once a year they are common in men (3:1) and in smokers Alcohol may trigger an attack and there is some relation to nocturnal sleep

Answer 150

* pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours * clusters typically last 4-12 weeks * intense sharp, stabbing pain around one eye (recurrent attacks 'always' affect same side) * patient is restless and agitated during an attack * accompanied by redness, lacrimation, lid swelling * nasal stuffiness * miosis and ptosis in a minority

Answer 151

* acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75% response rate within 15 minutes) * prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisolone * NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging

Answer 152

* Ondansetron for chemotherapy-induced nausea * Haloperidol for intracranial causes (raised ICP, direct effect of tumour) * Prochlorperazine for vestibular causes * Metoclopramide for gastrointestinal causes

Answer 153

* ABC * airway adjunct * oxygen * check blood glucose * First-line drugs are IV benzodiazepines such as ***diazepam*** or ***lorazepam*** * in the prehospital setting PR diazepam or buccal midazolam may be given * in hospital IV lorazepam is generally used. This may be repeated once after 10-20 minutes * If ongoing (or 'established') status it is appropriate to start a second-line agent such as phenytoin or phenobarbital infusion * If no response ('refractory status') within 45 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia.

Answer 154

* a single seizure lasting \>5 minutes, or * \>= 2 seizures within a 5-minute period without the person returning to normal between them

Answer 155

* eye is deviated 'down and out' * ptosis * pupil may be dilated (sometimes called a 'surgical' third nerve palsy)

Answer 156

* diabetes mellitus * vasculitis e.g. temporal arteritis, SLE * false localizing sign\* due to uncal herniation through tentorium if raised ICP * posterior communicating artery aneurysm * pupil dilated * often associated pain * cavernous sinus thrombosis * Weber's syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes * other possible causes: amyloid, multiple sclerosis

Answer 157

* repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis) * in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease * limb-girdle weakness (affects lower limbs first) * hyporeflexia * autonomic symptoms: dry mouth, impotence, difficulty micturating * ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)

Answer 158

myasthenic syndrome is associated with small cell lung cancer and to a lesser extent breast and ovarian cancer it can also occur independently as an autoimmune disorder/ it is caused by antibodies directed against presynaptic voltage-gated calcium channels in the peripheral nervous system

Answer 159

* treatment of underlying cancer * immunosuppression, for example with *prednisolone* and/or *azathioprine* * *3,4-diaminopyridine* is currently being trialled * works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate * intravenous immunoglobulin therapy and plasma exchange may be beneficial