Neurology Flashcards

Question

How does natalizumab work?

Answer 1

Mab to alpha 4 integrin (VCAM1) Inhibits tissue migration of lymphocytes and monocytes into CNS. PML risk exist - risk factor being duration of exposure \>2 years, and previous exposure to an immunosuppressant, and JCV serology is positive.

Answer 2

S1P receptor modulator. S1P - sphingosine 1 phosphate. Fingolimod selectively retains circulating lymphocytes in the lymphoid organ, especially those involved in MS pathology. Well studied safety profile and known adverse events are manageable - transient bradycardia, small increase in blood pressure, asymptomatic LFT derangements.

Answer 3

Closes exposed potassium channels on demyelinated axons, by blocking specialized potassium channels, ALlows axonal impulse transmission again, even in demyelinated state. Improves walking speed in 25 foot walk test. Symptomatic management only Does not alter disability progression.

Answer 4

Blocks voltage dependent sodium channels Rash especially when used as an adjunct therapy with sodium valproate Interacts with CBZ and increases CBZ toxicity

Answer 5

Has multiple actions - blocks sodium channels, enhances GABAergic transmission etc 1. Neurotoxic - alteration in cognition and language at higher dose 2. Renal stones 3. Weight loss 4. Teratogenicity

Answer 6

Binds to synaptic vesicular protein (SV2A) which is involved in release of glutamate and GABA. Well tolerated - can make people grumpy 10% Useful in both focal and generalized epilepsy

Answer 7

HLAB1502 associated with SJS in carbamazepine use. Common in Han Chinese and SEA. OR of \>50. HLA-A31:01 associated with DRESS in carbamazepine use. OR 13.

Answer 8

OCP induce uridine glucosyl transferase which metabolizes lamotrigine. This causes increased lamotrigine clearance with risk of breakthrough seizures.

Answer 9

weakness of foot dorsiflexion weakness of foot eversion weakness of extensor hallucis longus sensory loss over the dorsum of the foot and the lower lateral part of the leg wasting of the anterior tibial and peroneal muscles

Answer 10

Stabilisation of the muscle fibre against the mechanical force of muscle contraction. Found on locus Xq21.2

Answer 11

NMDA receptor antagonist. Used in treatment of levodopa induced dyskinesias in Parkinson's disease. Stimulating medication therefore should NOT be given in the evenings or at night

Answer 12

Oligoclonal bands occurs in any disorders that disrupts the BBB or can also be caused by intrathecal production of IgG. Occurs in infection (CNS lyme disease), autoimmune disease, brain tumours, lymphoproliferative disease.

Answer 13

Innervates the posterior compartment of the thigh and the hamstring portion of the adductor magnus. Innervates all the muscles in the leg and the foot. Sensory innervation to the lateral aspect of the leg (antero, posterolateral) and the foot except the medial portion which is supplied by the saphenous nerve.

Answer 14

1. Agraphia 2. Acalculia 3. L/R dissociation 4. Finger agnosia 5. Constructional apraxia Lesions of the dominant parietal lobe (angular gyrus) - associated with posterior circulation event

Answer 15

Non disabling stroke/TIA of carotid artery territory with ipsilateral carotid artery stenosis 70-99% by a specialist surgeon with low rates of perioperative mortality/morbidity Can also be considered in milder stenosis (symptomatic 50-69%) or asymptomatic \>60%) at discretion of the surgeon only if low predicted peri-operative mortality/morbidity.

Answer 16

Tonically dilated pupil which reacts slowly to light but reacts well to accommodation. Caused by damage to the post ganglionic parasympathetic innervation of the eye Usually occurs in young women in association with decreased or absent lower limb reflexes and impaired sweating or other autonomic features. Caused by viral/bacterial infection causing inflammation and damage to the ciliary ganglion.

Answer 17

Major cause of autosomal dominant early onset Alzheimer's disease.

Answer 18

Remember LOAF: Lumbricals (1st and 2nd) Oppoonens pollicis Abductor pollicis brevis Flexor pollicis brevis

Answer 19

3rd and 4th lumbricals Flexor carpi ulnaris Adductor pollicis

Answer 20

Nausea, vomiting, leg swelling, postural hypotension, and other dyskinesias associated with dopamine

Answer 21

Demyelinating neurophaty directed against myelin-associated glycoprotein (MAG) characterized by distal to proximal sensory predominant neuropathy (more than motor) Profound sensory loss leads to sensory ataxia causing tremor and gait disorder.

Answer 22

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) Approximately 80% of patients with the clinical characteristics of MELAS syndrome have a heteroplasmic A-to-G point mutation in the dihydrouridine loop of the transfer RNA (tRNA)

Answer 23

Autosomal dominant, triplet nucleotide CTG disorder with anticipation. Mutation of the DMPK gene Commonest inherited neuromuscular disease in adults. Characterized by myotonia with distal\>proximal weakness, frontal balding, SCM and temporalis wasting, cataracts, intellectual disability with avoidant personality. Can develop diabetes, hypogonadism and hypopituitarism and respiratory/swallowing difficulties.

Answer 24

13% of DMD patients have exon 50 deletion which leads to truncated and unstable dystrophin protein. Eteplirsen is a morpholino antisense oligomer which triggers exision of exon 51 during pre-MRNA splicing of the dystrophin and allows formation of a smaller but still stable dystrophin gen with small deletion. Therefore restores funtional muscle fibre structure. Leads to sustained improvement in 6MWT over 3 years.

Answer 25

High specificity for inclusion body myositis. Common in IBM but not in PM or other myopathy disorders. Important as upto 20% of patients with IBM do not have classical rimmed vacuoles in the muscle biopsy and are often misdiagnosed as PM. Also prognostic - predicts more severe motor, bulbar and respiratory involvement.

Answer 26

Associated with autoimmune myopathy with statin exposure. Progresses despite discontinuing statins and often requires multiple immunosuppressants (third line often being IVIg). Not present in patients with self-limited statin nintolerance.

Answer 27

Increased cancer risk seen in DM but not PM/IBM. From highest incidence to lowest: 1. Ovarian 2. Lung 3. Pancreatic 4. NHL 5. Stomach 6. CRC 7. Breast

Answer 28

Dermatomyositis is strongly associated with cancer. Anti-p115 had reasonable specificity and sensitivty (89, 78%) with NPD of 95%. Could consider extensive cancer work up in patients with p115 positivity.

Answer 29

Showed that in generalized AChRAb+ myasthenia gravis WITHOUT thymoma, removal of thymectomy plus prednisone compared to prednisone alone was effective in lower disability score and lower average prednisone dose and less need for azathioprine maintenance therapy. Therefore remove the thymus gland in Ab + MG even if thymoma is not present.

Answer 30

Heliotrope rash around the eyes, gottron's papules around the fingers. Photosensitive eruptions around sun exposed areas. Quadriparesis involving proximal musculature Difficulty rising from a seated or supine position without support Extensor muscles often more affected than the flexor muscles Neck flexor muscle weakness Distal strength, sensation, and tendon reflexes maintained (unless the patient has severely weak and atrophic muscle)

Answer 31

Positive ANA, raised CK Anti–Mi-2 antibodies are highly specific for dermatomyositis, but sensitivity is low; only 25% of patients with dermatomyositis demonstrate these antibodies Anti–Jo-1 (antihistidyl transfer RNA [t-RNA] synthetase) antibodies are more common in patients with polymyositis, but may occur in patients with dermatomyositis Other MSAs include anti-signal recognition protein (anti-SRP), which is associated with severe myositis; anti–PM-Scl and anti-Ku, which are associated with overlapping features of myositis and scleroderma

Answer 32

For muscle disease: use prednisone with methotrexate/azathioprine (cyclophosphamide is not effective) Skin disease: sun protection, HCQ, and if HCQ fails, use MTX.

Answer 33

Symmetrical proximal muscle weakness +/- myalgia Systemic constitutional symptoms Dysphagia with risk of aspiration Weak neck extensors ILD in 5-30% of patients

Answer 34

Overlap syndrome where scleroderma have myositis (25% of scleroderma patients)

Answer 35

Positive for anti-Jo antibodies. Clinical features include: Idiopathic inflammatory myopathy, interstitial lung disease, arthritis, Raynaud phenomenon, fever, and/or mechanic's hands

Answer 36

Approximately 4% of patients with polymyositis have antibodies to signal recognition particles (SRPs), which are associated with acute onset of severe weakness, increased incidence of cardiac involvement, and higher mortality rates

Answer 37

Mainstay of treatment is prednisone. If steroid refractory or with poor prognostic features such as dysphagia or dysphonia, methotrexate is the second line agent. Rehabilitation during/following acute flare of disease to maintain muscle strength and to avoid contractures. General measures targeting other associated conditions such as osteoporosis, esophageal dysmotility and raynauds phenomenon.

Answer 38

Associated with MGUS, POEMS, waldenstroms Distal predominantly symmetrical sensorimotor neuropathy or polyradiculoneuropathy resembling CIDP especially in IgA/IgM Profound ataxia and tremors can occur with IgM On NCS, 1/3 will be demyelinating, 2/3 will be mixed axonal/demyelinating. TREATMENT 1. IgA/IgG demyelinating neuropathy respond to prednisone/IVIG/PLX just like CIDP 2. Could also consider PLX + IV cyclophosphamide or oral cyclsophosphamide and prednisone for 6 months IgM neuropathy responds poorly. Rituximab is of some benefit in some patients.

Answer 39

1. Predominantly proximal weakness without wasting (just like a myopathy) howevre secondary axonal degeneration is common late in the disease course 2. Mild symmetrical sensory symptoms only 3. Global areflexia

Answer 40

1. Immune/inflammatory - GBS syndromes, CIDP, paraproteinaemic, POEMS, HIV 2. Metabolic - storage disorders, mitochondrial 3. Drugs - myriads! (amiodarone, bortezomib, taxanes, platinum based, vincristine/blastine...)

Answer 41

1. Very slow conduction velocity 2. Conduction block - characterized by decay in amplitude with normal dispersion 3. Very prolonged distal latencies and F wave 4. Temporal dispersion of motor response. Reduced motor recruitment in clinically weak muscles in EMG.

Answer 42

1. Fabry's disease 2. Amyloidosis 3. Diabetes Will often present with pain and autonomic features.

Answer 43

1. Usually chronic with development of weeks to months 2. Predilection for large diameter, long nerve fibres (with exception of some diseases which prefer small diameter fibres) 3. Distal symmetric pattern with 'dying back' pattern - ascending involvement 4. Sensory \> Motor involvement 5. Areflexia initially locally then progresses

Answer 44

1. Low amplitude due to loss of axons, with relatively normal conduction velocities. EMG patterns differ depneding on timing. 7 days - 6 weeks: 1. Fibrillation potential and positvie sharp waves at rest 2. Surviving units give normal MUPs 3. Reduced interference pattern \>6weeks 1. Now no fibrillation potential (as all the muscles are connected) 2. Polyphasic MUPs with increased amplitude, unstable (shape varies with each discharge) 3. Reduced recruitment with suboptimal interference pattern

Answer 45

Usually responds to monotherapy Sodium valproate and levetiracetam are first line Other agents such as topiramate and lamotrigine are equally as effective. Phenytoin and carbamazepine may control some component of JME seizures however requires high dose and may potentiate to cause other types of seizures such as absence seizure.

Answer 46

Triad of nystagmus, ataxia and confusion Due to thiamine deficiency which is required for carbohydrate and lipid metabolism in the CNS Thiamine administration results in rapid improvement of ocular manifestations Only 40% recover fully from ataxia with remainder of the patients having variable deficits long term Only 20% who develop amnestic state will recover with treatment - amnesia is both antegrade (difficulty forming new memories) AND retrograde (gaps in previously formed memories) with confabultation.

Answer 47

TRAP: 1. Tremor 2. Rigidity 3. Akinesia - essential component, decrementing. Includes hypokinesia and bradykinesia 4. Postural instability - gait freezing (perform 360 degree test) or postural instability (perform pull test - unable to stop, need to tkae 5-7 steps backwards) Gait freezing occurs with walking forward (ie, automated gait) but not walking backwards which is intentional and coordinated movement!

Answer 48

1. REM sleep disturbances 2. Anosmia 3. Misperception

Answer 49

Age, not disease duration. Interval between onset of cogntive disability and death is around 3 years. Virtually all PD patients develop dementia within 20 years of disease duration.

Answer 50

Showed that L-dopa was better as an initial therapy than L Dopa sparing drugs such as DA/MAOB inhibitors (selegiline) However it was only a very small advantage and more dyskinesias associated with L-Dopa therapy at 3 years, but there was no difference in dyskinesia at 7 years regardless of which treatment was started first as an initiation therapy. MAOB is better than DA in terms of mobiity scores and less side effects. Therefore start any drug (except L dopa/entacapone) as an initiation therapy but don't be afraid of using L dopa if required as dyskinesia burden is same at 7 years.

Answer 51

1. L-Dopa fractionation - smaller doses more often 2. Drug infusions (eg: Apomorphine SC infusions or duodopa via PEJ) 3. Deep brain stimulation - involves constant delivery of electricity to STN. Early DBS usage when motor fluctuations are starting to occur is better than late DBS.

Answer 52

1. Remove medications in order: Anticholinergics \> MAOB \> Dopamine agonist 2. If above doesn't work, add antipsychotic agents such as quetiapine or clozapine.

Answer 53

1. First think whether depression could be an 'off' symptom - if so, manage dopamine fluctuations 2. Consider dopamine agonist 3. Anti-depressants - TCA have more evidence than SSRIs/SNRIs.

Answer 54

low dose clonazepam before sleep

Answer 55

A type of MSA in which autonomic failures dominate. Shy-Drager syndrome is a combination of parkinsonism with autonomic dysfunction (eg, orthostatic hypotension or hyperhidrosis). T2-weighted MRI of the brain in patients with MSA shows the hot cross bun sign in axial views of the pons (see slide 13). Selective degeneration of pontocerebellar tracts gives rise to a hyperintense cross

Answer 56

PSP (also known as Steele-Olszewski-Richardson disease) has features of idiopathic PD with marked postural instability, axial rigidity, vertical gaze dysfunction (especially of downgaze), and pseudobulbar palsy.[8] Patients with PSP respond poorly to antiparkinsonian treatment. They have a characteristic look, with masked facies, lid retraction, and axial rigidity yielding a startled appearance. The appearance of the brainstem on T1-weighted brain MRI (sagittal view) resembles that of a hummingbird (or, in the eyes of some viewers, a penguin). Atrophy of the midbrain is seen, with preservation of the pons.

Answer 57

Parkinson disease dementia (PDD) and Lewy body dementia. In PDD, the signs and symptoms of PD precede the onset of dementia by at least 1 year. In Lewy body dementia, the onset of dementia is almost simultaneous with the onset of parkinsonian features

Answer 58

C spine vertebrae ranges from C1-C7 Roots are C1-C8 Therefore Cervical roots emerge ABOVE the numbered spine (ie, C6 nerve root emerge at C5/6 spacce) Thoracic lumbar roots emerge BELOW (ie, L5 nerve root exit L5/S1 space)

Answer 59

1. Encephalopathy - drowsiness, coinfusion, headache, papiloedema 2. Multifocal lesions, randomly scattered (nerve roots, cranial nerves and spinal cords)

Answer 60

1. Demyelination (most common - MS, transverse myelitis etc) 2. Infection - viral, especially HSV-2, VZV, CMV, fungal, bacterial, schistosoma, neurocysticercosis 3. Vascular - ASA/PSA occlusion 4. Other inflammatory processes - vasculitis such as SLE, sjogrens, systemic sclerosis, neurosarcoidosis 5. Neoplastic/paraneoplastic 6. Surgical/compression Inflammatory CSF findings seen in demyelination, infection or inflammation. Usually normal in vascular/paraneoplastic.

Answer 61

Most common cause of acute myelitis. Bimodal distribution with incidence at 10-19, 30-39 Cord symptoms (sensorimotor/autonomic) evolving over hours to days. Bilateral signs of UMN motor signs, neuropathic pain, paraesthesia at a sensory level, autonomic features such as autonomic dysreflexia, urinary retention, constipation. Prognosis - rule of 1/3 1/3 full recovery, 1/3 moderate disability, 1/3 severe and permanent disability

Answer 62

1. ALS - most common. Mixed UMN/LMN. Limb and bulbar involvements 2. Primary lateral sclerosis - rare. Pure UMN syndrome, slower rate of progression 3. Progressive muscular atrophy - rare. Only develops LMN signs, often in older males. Associated with improved survival. 4. Progressive bulbar palsy - most commonly seen in menopausal women with worst prognosis. 5. Flail arm syndrome - affects arms only. Symmetric proximal and distal bibrachial wasting with positive babinskins sign. Male predominance 9:1. Trend towards improved survival.

Answer 63

1. UMN signs - spasticity, hyperreflexia 2. LMN signs - weakness, muscle atrophy, fasciculations 3. Bulbar involvement - due to CN motor nuclei degeneration in medulla. Usually mixed flaccid and spastic pseudobulbar palsy. 4. Frontotemporal dementia - cognitive dysfunction are present in 30-50% of patients. Important negatives - sensory symptoms, bowel/bladder involvement, ocular palsy.

Answer 64

Miller-Fisher syndrome (MFS), which is observed in about 5% of all cases of GBS, classically presents as a triad of ataxia, areflexia, and ophthalmoplegia. [19] Acute onset of external ophthalmoplegia is a cardinal feature. [12] Ataxia tends to be out of proportion to the degree of sensory loss. Patients may also have mild limb weakness, ptosis, facial palsy, or bulbar palsy. Patients have reduced or absent sensory nerve action potentials and absent tibial H reflex. [20] Anti-GQ1b antibodies are prominent in MFS, and have a relatively high specificity and sensitivity for the disease. [21] Dense concentrations of GQ1b ganglioside are found in the oculomotor, trochlear, and abducens nerves, which may explain the relationship between anti-GQ1b antibodies and ophthalmoplegia

Answer 65

purely motor disorder that is more prevalent in pediatric age groups. [14] AMAN is generally characterized by rapidly progressive symmetrical weakness and ensuing respiratory failure. ## Footnote Nearly 70-75% of patients with AMAN are seropositive for Campylobacter, with the majority of cases of AMAN being associated with preceding C jejuni diarrhea. Patients typically have high titers of antibodies to gangliosides (ie, GM1, GD1a, GD1b). Inflammation of the spinal anterior roots may lead to disruption of the blood-CNS barrier. [12] Biopsies show wallerianlike degeneration without significant lymphocytic inflammation. Many patients can be hyperreflexic - unclear mechanism. Hyperreflexia is significantly associated with the presence of anti-GM1 antibodies

Answer 66

Acute motor-sensory axonal neuropathy (AMSAN) is a severe acute illness differing from AMAN in that it also affects sensory nerves and roots. [17] Patients are typically adults. AMSAN often presents as rapid and severe motor and sensory dysfunction. Marked muscle wasting is characteristic, and recovery is poorer than it is from electrophysiologically similar cases of AMAN. As with AMAN, AMSAN is often associated with preceding C jejuni diarrhea. Pathologic findings show severe axonal degeneration of motor and sensory nerve fibers with little demyelination.

Answer 67

Motor: Innervates the muscles of the posterior thigh and the hamstring portion of the adductor magnus. The sciatic nerve also indirectly innervates several other muscles, via its two terminal branches: 1. Tibial nerve – the muscles of the posterior leg (calf muscles), and some of the intrinsic muscles of the foot. 2. Common fibular nerve – the muscles of the anterior leg, lateral leg, and the remaining intrinsic foot muscles. Sensory: No direct sensory functions. Indirectly innervates (via its terminal branches) the skin of the lateral leg, heel, and both the dorsal and plantar surfaces of the foot. 1. Tibial nerve – Innervates the posterolateral and anterolateral sides of the leg, and the plantar surface of the foot (the sole). 2. Common fibular nerve – Innervates the lateral leg and the dorsal surface of the foot.

Answer 68

1. Dysphasia 2. Inattention/neglect 3. Alexia - disturbance of reading in dominant posterior cerebral artery infarct 4. Agraphia, agraphthesia (unable to recognize number drawn with finger on the palm despite intact sensation), astereognosia (unable to recognize object with touch) 5. Acalculia

Answer 69

1. TACI - large infarct with poor prognosis. Have hemiparesis, hemianopia and cortical signs (dysphasia, inattention) 2. PACI - smaller infarct with better prognosis. 2/3 of TACI symptoms 3. LACI - no cortical signs. Types include pure motor, pure sensory, sensorimotor, ataxis hemiparesis, dysarthria-clumsy hand syndrome 4. POCI - storke with brainstem/cerebellar features. Variable prognosis. Signs include ataxia, ophthalmoplegia, quadriparesis

Answer 70

ACA supplies medial 2/3 of the brain Affects: 1. Contralateral leg weakness / sensory impairment 2. Akinetic mutism (abulia) – a state of severely limited responsiveness to the environment in the absence of gross alteration of sensorimotor mechanisms. 3. Disturbance of judgment and/or emotion 4. Transcortical motor aphasia (with dominant lesions) - non fluent aphasia with intact repetition, poverty of speech due to problem of speech initiation. 5. Non-dominant limb apraxia (with dominant lesions) 6. Urinary dysfunction

Answer 71

The MCA is the largest of the intracranial cerebral vessels arising from then internal carotid artery. The MCA first supplies deep penetrators to the basal ganglia and internal capsule. In the Sylvian Fissure, the MCA typically bifurcates in a Superior and Inferior Division. The Superior Division supplies the lateral Frontal and Parietal lobes Inferior Division supplies the Temporal and Posterior Parietal Lobes.

Answer 72

The Superior Division supplies the lateral Frontal and Parietal lobes... therefore: Contralateral hemiplegia, usually face and arm \> leg Contralateral sensory loss (esp. cortical sensory - two point discrimination, graphesthesia, stererognosia, etc.) Contralateral homonymous hemianopia (predominantly lower quadrant) Gaze preference to the ipsilateral side of stroke Aphasia, expressive (dominant hemisphere) Neglect syndrome (non-dominant hemisphere)

Answer 73

Inferior branch of MCA supplies the temporal and parietal lobe, therefore... Contralateral homonymous superior quadrantanopsia Aphasia, receptive (dominant hemisphere) Constructional apraxia (non-dominant hemisphere) - inability or difficulty to build, assemble, or draw objects. Behavioral disturbance (non-dominant hemisphere)

Answer 74

The only way to differentiate clinically if a stroke is secondary to ICA stroke versus MCA stroke would be a history of amaurosis fugax (transient visual loss in one eye). This occurs due to disruption of blood flow in the ophthalmic artery, a branch of the ICA.

Answer 75

Due to basilar artery stroke. Should suspect this in patients with decreased GCS at presentation w ithout cardiovascular collapse. Should have CT angio if NCCT excludes brainstem/large hemispheric ICH. Pons affected, tegmentum unaffected. 1. Tetraplegia (all four limbs, face and bulbar muscles) 2. Intact level of consciousness and sleep-wake cycles 3. Impairment of horizontal eye movements 4. Vertical eye movements and blinking spared 5. Bilateral babinski signs Thus, the patient has relatively intact perception of the environment, but is unable to communicate except with blinking or vertical eye movements. These deficits occur due to massive infarction of the brainstem including basis pontis (ventral pons) which results in disruption of the corticobulbar and corticospinal tract fibers. The wakefulness of the patient are intact due to sparing of the reticular activating system in the tegmentum. The vertical eye movement and blinking are intact due to sparing of the dorsal midbrain supranuclear ocular pathways.

Answer 76

Usually indicates good collaterals rather than reperfusion - high chance of later worsening.

Answer 77

L5 nerve root affects both evresion and inversion, while as common peroneal nerve affects eversion only.

Answer 78

Painful numbness involving the lateral cutaneous nerve of the thigh, due to wearing tight garments and obesity

Answer 79

Both will have wrist drop however in radial nerve palsy flexion on the wrist will be preserved (C7 affects both)

Answer 80

1. CIDP - often proximal symmetrical weakness with absent reflexes, can have both MOTOR and SENSORY involvement. NCS will show demyelination pattern including block and neurogenic EMG pattern (large polyphasic motor units) 2. Multiple motor neuropathy - multiple LMN pure motor weakness, relfexes sometimes preserved, PAINLESS (as opposed to mononeuritis multiplex). Usually discrete nerves involved. NCS will show conduction block at 'non-compressed sites. Anti-GM1 positve. 3. MND - pure motor, mix of UMN/LMN usually with bulbar/respiratory signs 4. MG - pure motor defect with fatiguability, bulbar/respiratory signs, diplopia.

Answer 81

1. Spontaneous activity - fibrillation, positive sharp waves. Indicate denervation or inflammatory myopathy. 2. Neurogenic (due to re-innervation, high amplitude and duration, polyphasic) 3. Myopathic - low amplitude and duration 4. Myotonia - dive-bomber sound

Answer 82

1. GBS - AIDP/AMAN 2. Myasthenia gravis 3. Acute cord lesions eg transverse myelitis 4. Botulism 5. Porphyria 6. Heavy metal poisoning

Answer 83

Very sensitive for presence of myasthenia gravis especially if tested in the weak muscle (99% sensitivity). Due to huge variation in muscle fibre firing.

Answer 84

Botulism toxin which acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetylcholine's release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. This causes paralysis. Differentiated from other causes of diffuse weakness due to significant autonomic manifestations such as dilated pupils, ptosis, diplopia, bradycardia, hypotension.

Answer 85

1. Thyroid diseases 2. Pernicious anaemia

Answer 86

1. Diabetes 2. Alcohol abuse 3. Medications - chemotherapy, amiodarone, thalidomide, colchicine... 4. Vitamin deficiency (b12/folate, thiamine, B6) 5. Thyroid diseases 6. Paraproteinaemia 7. Vasculitides

Answer 87

1. Previous intracranial bleeding 2. Surgery/trauma last 2 weeks 3. Gi/GU bleeding last 3 weeks 4. BP \>185/105 5. Hypoglycaemia - fix first 6. INR \>1.7 7. Aortic dissection (but cervical/vertebral/carotid artery dissections are OK)

Answer 88

Used to distinguish between vestibular neuritis vs stroke. Stands for Head impulse, nystagmus, test of vertical skew. HINTS should be performed if hours to days of ongoing vertigo with spontaneous nystagmus. Following are worrying signs of central lesion: 1. Bidirectional nystagmus 2. Vertical skew on testing 3. Normal head impulse test.

Answer 89

1. Inherited thrombophilias 2. Any causes of acquired thrombophilias - malignancy, APLS, IBD, OCP, polycythaemia, Behcet's disease 3. Local sepsis - local sepsis/mastoiditis

Answer 90

Loss of taste.

Answer 91

Hu (ANNA-1) - limbic encephalitis, peripheral neuropathy. Associated with SCLC Yo(also known as purkinje cell antibody type 1 PCA-1) - associated with cerebellar degeneration. Seen in breast/ovarian cancers Ma - seen in males with testicular cancers. Associated with brainstem, cerebellar, limbic signs.

Answer 92

Stands for: cerebral Autosomal Dominant arteriopathy subcortical infarcts and leucoencephalopathy. Characterized by triad of: 1. Migraine with aura (5x incidence of normal population) 2. Stroke with mean age of 50 3. Dementia MRIs show hypointensities on T1-weighted images and hyperintensities on T2-weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic. These lesions are concentrated around the basal ganglia, peri-ventricular white matter, and the pons. Associated with NOTCH-3 mutation.

Answer 93

AChR Ab: Respiratory involvement uncommon. Both PLEX and IVIg works. Thymectomy is helpful if thymoma is present. Ocular \> bulbar \> limb. MuSK +: More frequent ICU involvemnt. PLEX works best. No clear benefit of thymectomy. Bulbar \> ocular \>\> limb.

Answer 94

* Device permanently implanted into Left Atrial Appendage via catheter * Non-inferior to Warfarin for CV death, stroke and systemic embolisation * Significantly less haemorrhage in WATCHMAN group Patients need to tolerate warfarin and aspirin for 45 days post implantation, followed by clopidogrel and warfarin for 6 months, then aspirin indefinitely.

Answer 95

Among patients with nonvalvular atrial fibrillation (AF), the vast majority of thrombus material is located within or involves the left atrial appendage (LAA). The intense fibrosis and inflammation seen in the left atrium of patients with AF, which are likely predisposing factors to thrombus formation, are particularly intense in the LAA. In addition, the fibrillating LAA is the only area within the left atrium that is comprised of pectinate muscle and can create an appropriate milieu for blood stasis and thrombus formation. It is estimated that 90 percent of left atrial thrombi are located in the LAA

Answer 96

* Dabigatran, Apixaban, Rivaroxaban * All 3 non-inferior to warfarin for stroke and systemic embolism prevention * All significantly reduced haemorrhagic stroke risk compared to warfarin * All non-inferior to Warfarin for major bleeding – Dabigatran 110mg significantly reduced major bleeding * Rivaroxaban and Dabigatran 150mg increased GI bleeding – but not in Apixaban or Dabigatran 110mg BD * No differences in mortality

Answer 97

* Pooled analysis shows reduced mortality, but increases the number of moderate to moderately severe functionally impaired survivors * Evidence good for \<60 - reduce death and dependence * Reduces mortality for \>60, but no change in dependence

Answer 98

1. Time from onset of symptoms • Traditionally thought that risk highest in the first few weeks • Newer study shows that TIA risk increases up to 3 months (10% at 1 week; 18% at 3 months; 5%/year) 2. Aetiology of Stroke symptoms • Large artery stenosis – OR 4.97 for 90-day recurrence event (OR 7.73 for 7 days!) if severe symptomatic extra/intra-cranial disease • AF; high risk cardiac source of embolism 3. Imaging • Showing multiple strokes or vessel occlusion 4. MRI • DWI +ve: higher risk of recurrence (technically these are Strokes not TIAs) 5. Clinical Risk Score – ABCD2 • Misclassifies 50% of those with high risk mechanism s as low risk • Other predictors described above increasingly observed as more important than ABCD2 score

Answer 99

• Older age • Acute Coronary Syndrome o Unstable Angina o STEMI and NSTEMI

Answer 100

* Hypertension highest risk factor (for both ischaemic and ICH) – OR 2.64 * Cardiac Disease – OR 2.38 * Current Smoking – OR 2.09

Answer 101

* Age \>70 * Past history of stroke * History of carotid artery stenosis * Peripheral vascular disease * Unstable angina * Prolonged cardiopulmonary bypass time

Answer 102

· Symptomatic Stenosis 70-99% - strong evidence of benefit NB not if already severely disabled · Symptomatic Stenosis 50-69% - benefit if low surgical morbidity and good life expectancy o Males benefit o Females do not benefit with 50-69% stenosis - more benefit from medical therapy, more operative risk · Carotid occlusion/trickle flow - low risk of recurrent stroke, generally not suitable for surgery

Answer 103

· Clinically significant cardiac disease · Severe pulmonary hypertension · Contralateral carotid occlusion · Previous radical neck surgery / neck irradiation · Recurrent stenosis after carotid surgery · \>80 years old

Answer 104

· GCS 3-4 is worst prognosis · Other prognostic indicators include o GCS 5-12 o ICH volume \>30mL o Intraventricular extension o Infra-tentorial extension o Age \>80

Answer 105

Large, myelinated axons include motor axons and the sensory axons responsible for vibration sense, proprioception and light touch. Small myelinated axons are composed of autonomic fibers and sensory axons and are responsible for light touch, pain and temperature. Small, unmyelinated axons are also sensory and subserve pain and temperature. Neuropathies involving primarily the latter two fiber types are called small-fiber neuropathies. Clinically, large-fiber neuropathies can be distinguished from small-fiber neuropathies during neurologic testing: large fibers carry sensation for vibration and proprioception, while small fibers carry sensation for pain and temperature. Sensation for light touch is carried by both large and small nerve fibers.

Answer 106

1. Is it actually a peripheral neuropathy? (think other mimics such as myopathy, NMJ disorders, spinal cord lesions) 2. Distribution of symptoms? a. Focal - think compression, entrapment, malignancy, trauma b. Multifocal - vasculitides, sarcoid, HIV, diabetes c. Symmetric 3. If symmetric, is it proximal or distal? a. Proximal - GBS, CIDP, paraprotein associated neuropathies, HIV/AIDS, diabetes b. Distal - Think toxic and metabolic causes (metal/toxic poisoning), Nutritional (alcohol, B12/folate deficiency), Diabetes 4. Small/large fibre neuropathy? 5. Temporal course? - Trauma/infarction will be acute - Hereditary/metabolic causes will be chronic - GBS will be relapsing and remitting

Answer 107

1. Generalized epilepsies - sodium valproate, howevever lamotrigine is a good alternative agent esp in young women 2. Myoconic seizures - clonazepam 3. Absence seizures - ethosuximide 4. Focal epilepsies - carbamazepine

Answer 108

1. Vigabatrin - elevates brain GABA by preventing breakdown 2. Lamotrigine - blocks voltage depnedent sodium channels 3. Topiramate - multiple actions (blocks sodium channels, enhances GABAergic transmission, blocks kainate/AMPA glutamate receptors) 4. Levetiracetam - Binds to synaptic vesicular protein (SV2A) 5. Lacosamide - selectively enhances sodium channel slow inactivation 6. Perampanel - Blocks post-synaptic AMPA (glutamate) receptors

Answer 109

1. Acute/subaute unilateral eye pain 2. Variable visual loss especially central scotoma 3. Colour desaturation especially red 4. RAPD or Marcus Gunn pupil

Answer 110

40% - optic neuritis 30% - transverse myelitis 20% - brainstem/cerebellum involvement 10% - others including paroxysmal stiffness, limb pasm, bladder/cognitive issues, episodic fatigue, L'hermitte's sign... MS is predicted by number of T2 lesions on baseline MRI. If MRI is abnormal, risk is 60-90% over next 3-5 years. If normal, this risk is 10-30% at 3-5 years.

Answer 111

Also called post-infectious encephalomyelitis Seen usually after any infectious prodrome. Presents with encephalopathy with behavioural changes such as irritability, confusion, lethargy, drowsiness Multifocal polysymptomatic neurological deficits (predominantly MOTOR over sensory) Treat with IVMP - most recover completely.

Answer 112

1. Restoration of functional BBB 2. Reduction of inflammatory oedema 3. T cell apoptosis and endothelial adhesion molecule thereby suppressing inflammation

Answer 113

Active metabolite of leflunomide, used in MS Interferes with lymphocyte proliferation by inhibiting pyrimidine synthesis and reducing TK activity. May prevent interaction of lymphocytes and APCs. Not safe in pregnancy.

Answer 114

Lysing Anti-CD52 antibody. CD52 is a B and T cell antigen, however treatment with alemtuzumab depletes B cells more than T cells. Given as a daily infusion for 5 days once a year for treatment of MS. Very effective when compared with interferon beta - 75% relapse reduction, 65% reduction in disability progression. SE: ITP, Graves disease, Goodpastures syndrome

Answer 115

Dose related increase in PR duration which can lead to dizziness and falls especially if used with concurrent sodium channel blockers

Answer 116

The median nerve passes through the cubital fossa and passes between the two heads of pronator teres muscle into the forearm. It then runs between flexor digitorum superficialis and flexor digitorum profundus muscles and enters the hand through the carpal tunnel. The most common cause is entrapment of the median nerve between the two heads of the pronator teres muscle. The characteristic physical finding is tenderness over the proximal median nerve, which is aggravated by resisted pronation of the forearm.

Answer 117

1. Family history 2. NF2 (Chromosome 22 mutation) 3. Previous ionizing radiation 4. Female (meningiomas have oestrogen receptor) 5. Obesity

Answer 118

1. Diabetes 2. Alcohol 3. Uraemia 4. Toxin/drugs 5. Paraneoplastic syndrome 6. Nutritional

Answer 119

5% of peripheral neuropathy. Can affect sensory (DRG) or motor (AHC or anterior horn cells) Often largely involve one modality (motor, sensory, autonomic) Distribution - proximal AND distal, arms are involved early, and face/bulbar involvement are common. ASYMMETRIC. Develops over weeks/months. Sensory deficits are often severe and poorly responsive to therapy.

Answer 120

1. Idiopathic 2. Immune (sjogrens, paraneoplastic syndrome eg anti-Hu) 3. Drugs (pyridoxine deficiency, doxorubicin, cisplatinum) 4. Hereditary - Fabry's disease

Answer 121

Can be distinguished clinically: Sensory ataxias - absent reflexes, impaired joint position sense, no nystagmus or dysarthria. Rhombergs positive. Cerebellar ataxia - dysarthria (in form of stacatto or scanning speech) is present, and also nystagmus Joint position sense and reflexes are intact. Rhomberg test is classically negative

Answer 122

Part of the immune mediated neuropathies. Clinical features involve: 1. Symmetric motor and sensory deficits involving both proximal and distal, weakness out of keeping with wasting. 2. Absent or decreased reflexes. 3. Sensory loss over LL more than UL 4. Gradual onset over months to years. Natural history can be variable - chronic progressive course in 60%, relapsing and remitting pattern in 30%, monophasic in 10%. Males are more affected than females, with mean age of onset at 50 years. INVESTIGATIONS 1. NCS typically shows demyelination picture - motor slowing, conduction block, dispersion, long distal/F wave latencies 2. CSF protein elevated, WBC typically \<10 cells/mm TREATMENT 1. Prednisone 2. IVIG 3. PLX

Answer 123

1) MMN affects predominantly (but not exclusively) the upper limbs 2) MMN usually lacks bulbar or respiratory involvement 3) muscle weakness in MMN is associated with less atrophy, unless it becomes severe or longstanding 4) cramps and fasciculations can occur in motor neuron disease but are less prominent than in MMN, occurring in up to 50% of patients with MMN 5) MMN has no upper motor neuron signs 6) MMN has a characteristic electrophysiological pattern of motor conduction block which is pathognomic 7) MMN can be associated with normal (20%) or even brisk (8%) deep tendon reflexes. Imortant to distinguish between MND and MMN as MMN is autoimmune (Anti-GM1 antibody associated) and treatable with IVIG, IV CYC or rituximab! No resonse to steroids/PLX which distinguishes it from other demyelinating diseases.

Answer 124

1. Dementia - rapidly progressive 2. Ataxia - cerebellar dysfunction 3. Psychiatric manifestations - behavioural dysfunction witha gitation, depression, confusion 4. Myoclonus - most constant physical sign in 90% 5. Pyramidal and extrapyramidal dysfunction with abnormal reflexes, spasticity, tremors and rigidity.

Answer 125

It is a normal neuronal protein which is released into the CSF in response to a variety of neuronal insult.s Generally a non-specific finding but can be used to support a diagnosis of CJD. Other diseases such as HSV encephalitis, recent CVA, haemorrhage etc can give rise to high CSF- 14-3-3

Answer 126

Domperidone - peripherally acting D2 antagonist. Safe as it does not cross the BBB\>

Answer 127

One of parkinsonian plus syndromes Most common symptomat disease onset is related to mobility. Diplopia occurs in 2/3 - horizontal disconjugacy suggesting INO, eventually all ey emovements may be lost. Eyelid apraxia in 50% - delay in lid openig, markedly reduced blink rate, repetitive blinking in response to flashlight stimulus (failure to habituate) Applause sign - inability to clap just 3 times. Also frontal dysexecutive features - apathy, impulsivity, repetitive behaviours. Development of falls, speech problems or diplopia within 1 year, and swallowing problems within 2 years.

Answer 128

CGG repeat expansion \>200 in the promotor region of FMR-1 gene, leading to gene's silencing through methylation of the promotor, and resulting deficit in Fragile X mental retardation protein (FMRP gene) leading to severe neurodevelopmental changes. Most widespread single gene cause of autism and inherited cause of mental retardation among boys. Spectrum involves IHC, large/protruding ears, social anxiety, macroorchidism, behavioural characteristics such as stereotypic movements (hand flapping)

Answer 129

Does not manifest as fragile x syndrome, howevre they have been linked to the late onset severe movemnet disorder termed Fragile X associated tremor/ataxia syndrome (FXTAS) OCcurs in nearly 40% of the premutation carriers affected after age of 65.

Answer 130

Binds to alpha2delta subunit of the voltage dependent calcium channel in the CNS, thereby decreasing the release of neurotransmitters including glutamate, norepinephrine, substance P, and calcitonin gene related peptides.

Answer 131

After initiating treatment with dopamine replacement or DA, the symptoms of RLS starts to happen earlier in the day, spreads to other parts of the body (most commonly the arms) and becomes more intense and occurs more quickly during periods of rest. Most commonly occurs within 6 months of starting treatment or as medications are uptitrated. 20% of RLS patients develop augmentation. Predictors of augmentation: 1. Higher agonist dose 2. Low ferritin levels at baseline

Answer 132

1. CMAP - potential elicited by stimulation 2. Dispersion - increase in duration of CMAPp compared with CMAPd 3. Conduction block - decay in amplitude with normal dispersion due to demyelination induced conduction failure

Answer 133

1. Motor unit potential - the sum of all muscle fibre action potentials in a motor unit 2. MUP amplitude - Reflects density of muscle fibres in one unit 3. Polyphasia - complex shape arising from decreased temporal synchrony of firing of individual muscle fibres in a single motor unit 4. Recruitment - assesses number of functional motor units in relation to generated force. Early in myopathy, reduced in neuropathy 5. Interference pattern - extent of muscle activity at full force.

Answer 134

Day 3-7 - motor nerve conduction fails Day 6-10 - sensory nerve conductionf ails Therefore NCS will not distinguish between demyelinating and axonal lesions prior to day 7, as motor conduction distal to an axonal lesion may still be preserved.

Answer 135

1. Riluzole slows disease progression and improves survival (inhibits glutamate release from presynaptic terminals, stabilizes the inactive state of voltage dependent sodium channels, inhibits high affinty uptake of GABA) 2. PEG feeding if worsening dysphagia or significant weight loss 3. NIV for respiratory insufficiency

Answer 136

Riluzole is used early in disease. 1. Duration \<5 years 2. FVC \>60% 3. Not undergone tracheostomy or respiratory failure 4. Ambulatory 5. Able to use upper limbs 6. Able to swallow

Answer 137

Demyelinating disease. AD/X linked 80% due to DUPLICATION of PMP-22 gene. NCS will show slow conduction velocities without block (myelin never formed properly therefore nerves are generally working slowly) Histology shows demyelination with 'onion bulb' - palpably enlarged Distal involvement, impaired sensation, CN/autonomic systems usually preserved. Key features include pes cavus, striking calf atrophy.

Answer 138

F wave latency.

Answer 139

Duration of disease - CIDP has a more protracted course with maximal deficit \>8weeks from onset and it rarely follows preceeding infection. Also CIDP responds to steroids while AIDP does not.

Answer 140

Lateral temporal lobe. Often involved in alzheimers as disease progresses from medial temporal lobe to lateral temporal lobe. Loses ability to differentiate different ideas such as characteristics of animals etc.

Answer 141

Patients who presents with gait disturbance are best to respond to VP shunting. Those who have developed dementia symptoms responds poorly.

Answer 142

Bulbar palsy - LMN lesion of CN 9, 10, 12 Pseudobulbar palsy - UMN lesion of 9, 10, 12