Neurology Flashcards

Question

Types of CNS demyelinations diseases

Answer 1

CNS inflammatory demyelinating diseases (IDD) • MS • NMOSD • Myelin oligodendrocyte glycoprotein (MOG)-IgG+ disease: ADEM, ON, myelitis, etc

Answer 2

Definition: chronic inflammatory demyelinating neurodegenerative disease in young adults, characterised by multiple plaques of demyelination in CNS with dissemination in space & time Pathology • Epidemiology: 1/1000 in HK, female predominant • Heterogenous and multifactorial: o Genetics: HLA-DRB1 gene o Environment: reduced vitamin D/ sun exposure, virus (EBV, HHV-6) • Disrupted blood brain barrier à autoreactive T cell + B cell infiltration à microglia and astrocyte activation à white + grey matter demyelination (cortical lesions, brain atrophy) Clinical patterns • Relapsing remitting (RRMS): MC (85%); 75% go into SPMS • Primary progressive (PPMS) • Secondary progressive (SPMS): often pyramidal weakness + cerebellar signs • Progressive relapsing (PRMS)

Answer 3

Clinical features 4 areas: sensory + cerebellar + UMN + optic • Patchy neurological deficits in any part of CNS, with predilection at o Optic nerve (1/3): § Optic neuritis: ¯VA, ¯colour vision, unilateral eye pain, optic atrophy on fundoscopy, RAPD +ve o Brainstem (1/3): § Gaze palsies: Bilateral INO, conjugate horizontal gaze palsy, one-and-a-half syndrome § Bulbar S/S: dysarthria, dysphagia § Facial weakness (UMN type) o Spinal cord (1/3): § Spastic paraparesis esp. LL, pyramidal signs (corticospinal tract) § Loss of proprioception & vibration, sensory ataxia with Romberg’s test +ve (DCML) § Paresthesia / hypesthesia (STT) § Lhermitte’s sign, myelopathic hand signs (e.g. pseudoathetosis) o Cerebellar signs: ataxia, dysmetria, dysdiadochokinesia o Autonomic neuropathy: § Bladder dysfunction (>90%): urgency (MC), frequency, retention of urine § Bowel dysfunction (e.g. constipation), sexual dysfunction • Uhthoff's phenomenon: symptoms worse in heat (heat-induced conduction blockade)

Answer 4

Diagnosis: revised McDonald criteria (2017) Three components: DIT + DIS + exclude alternate DDx • Dissemination in time (DIT) can be demonstrated by any one of: o ≥ 2 clinical attacks o New T2-hyperintense / gadolinium-enhancing lesions on follow-up MRI (irrespective of timing of baseline MRI) o Simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time o *CSF oligoclonal bands (intrathecal IgG production) • Dissemination in space (DIS) can be demonstrated by: o T2-hypertense lesions in ≥2 of the 4 CNS regions (periventricular, cortical*/juxtacortical, infratentorial, spinal cord) • Exclude alternative diagnosis *New additions in 2017 criteria Investigations • MRI brain + whole spine with gadolinium contrast o Old plaques: T2/FLAIR-hyperintense, T1-iso/hypointense (“T1 black holes”) o New plaques: T2/FLAIR-hyperintense, gadolinium-enhancing (marker of active disease: BBB breakdown —> leakage of Gd) **Dawson fingers** o Neurodegeneration: brain atrophy of both gray matter and white matter with volume loss > 0.4%/year • CSF (not routine): oligoclonal bands with intrathecal IgG • Antibodies: anti-AQP4, anti-MOG

Answer 5

• Treatment goal: achieve NEDA (No Evidence of Disease Activity) – 4 parameters! o Clinical: no confirmed relapses, no sustained disability progression (EDSS: Expanded Disability Standard Scale) o Imaging (MRI = best biomarker): no new/enlarging T2 lesions, no annual brain volume loss (BVL) >0.4% • Management of acute MS flare o IV high-dose methylprednisolone (1g daily x 3-7 days) § Then short term (2 weeks) tapering oral prednisolone (e.g. 40mg à 30mg à 20mg à 10mg) o Severe: may require plasma exchange or IVIG 0.4mg/kg/day x 5 days • Disease modifying therapy (DMT) o Approaches: escalation (most patients) vs induction (for multiple/disabling relapses or extensive MRI) o First line: - IFNb 1a/1b: IM injection, S/E: flu-like illness (myalgia, fatigue, fever), injection site reaction - Teriflunomide (Aubagio): PO QD, C/I in pregnancy, S/E: headache, n/v/d, alopecia - Dimethyl fumarate (Tecfidera): PO BD, S/E: flushing, abdo pain, n/v/d o Second line (more potent, but more S/E): SFI - Fingolimod (PO): first-line for induction approach in highly active patients, S/E: n/v/d, headache - Natalizumab: IV monthly, risk of PML (note) - Alemtuzumab o Rituximab: for refractory MS / overlap with NMOSD o Potential role: autologous HSCT, cladribine, siponimod, ocrelizumab, ofatumumab • Offer annual MRI monitoring for new/enlarging and enhancing lesions • Symptomatic treatment o Spasticity: baclofen, benzodiazepines, Botox, splinting o Urinary retention: anticholinergic, self-catheterisation o Sexual dysfunction: PDE5 inhibitors o Fatigue: methylphenidate o Weakness, ataxia, gait disturbance: PT, OT, walking aids o Dysarthria, dysphagia: ST

Answer 6

• Pre-conception counselling: avoid pregnancy until MS activity is quiescent for 1 year • Teratogenicity of certain DMT (e.g. teriflunomide, fingolimod): consider drug holiday if stable condition o Teriflunomide: prescribe oral cholestyramine / activated charcoal for active elimination • Interferons and natalizumab are safe • Relapse rate reduces during pregnancy • Risk of post-partum flare up: DMT can be resumed immediately postpartum

Answer 7

• Severe CNS demyelinating disease due to reactivation of JC virus (John Cunningham virus) • Risk factors: immunocompromised (HIV, use of natalizumab / rituximab) • S/S: altered MS, motor deficit, sensory deficit, etc

Answer 8

• Pathology: demyelination + axonal degeneration (c.f. MS) • Predilection of plaques at optic nerve + spinal cord ≥ 3 consecutive spinal segments IPND diagnostic criteria for NMOSD (2015) Stratified according to AQP4 status • AQP4-IgG +ve: at least 1 core clinical characteristics • AQP4-IgG -ve: at least 2 different core clinical characteristics (i.e. recurrent ON / recurrent TM alone insufficient), with at least 1 of bolded ones, plus supporting features on MRI Core clinical characteristics: optic neuritis (ON), acute myelitis with LETM, area postrema syndrome (APS), acute brainstem syndrome, symptomatic narcolepsy + typical diencephalic lesions, symptomatic cerebral signs + typical brain lesions NMO - Age of onset: Late 30s - 50 - M:F 1:9 - Race: Asians S/S Less recovery, more relapses (>90%) • Optic nerve: usually bilateral optic neuritis • Lower brainstem: area postrema syndrome (intractable hiccups, n/v), no INO • Spinal cord: Longitudinal extensive transverse myelitis (LETM) (e.g. symmetrical paraparesis, sensory level, autonomic failure) - Serology: Anti-aquaporin-4 (anti-AQP4 / NMO-IgG) (60%) (AQP-4: water channel at foot of astrocytes) - Pleocytosis (↑WBC) No oligoclonal bands - MRI Brain: Brain: atypical changes (50%), brainstem lesions (15%) Spinal cord: affect ≥3 consecutive spinal segments (LETM) - Acute treatment: Steroid, plasma exchange, IVIG (for NMOSD) - Long-term immunosuppressant: Treat for at least 5 years if seropositive (AQP4 +ve) - Prednisolone, azathioprine, MMF, rituximab Others: eculizumab (C5 inhibitor), satralizumab (anti-IL6), inebilizumab (anti-CD19) Avoid MS-specific DMT: e.g. IFN/ fingolimod/ natalizumab

Answer 9

• Multifocal monophasic demyelinating disease seen after viral infection (esp. measles, VZV) or vaccination • S/S: meningism, encephalopathy (confusion, memory impairment), seizures • CT/MRI: small homogenous lesions (i.e. no dissemination in time & space) • CSF: rule out meningitis/encephalitis, +/- increased protein and lymphocytosis • Mx: IV high-dose methylprednisolone +/- IVIG / plasmapheresis

Answer 10

Clinical features: Young female, associated with ovarian teratoma (paraneoplastic syndrome) • Neuropsychiatric symptoms • Memory deficits & Movement disorders • Decreased GC and catatonia & Language dysfunction • Autonomic dysfunction • Seizure + Sleep disturbances Investigations: • Serum & CSF Ab panel: CSF anti-NMDAR titre correlates with clinical outcome and is more sensitive o CSF may also show lymphocytic pleocytosis / oligoclonal bands +ve • Brain MRI (50% sensitivity): transient FLAIR / contrast-enhancing abnormalities in cortical / subcortical regions Management: • Treat underlying malignancy if any • IVIG + IV methylprednisolone • Alternatives: plasma exchange, cyclophosphamide, rituximab Prognosis Poor prognostic factors include: not associated with malignancy, did not receive immunosuppression during 1st attack

Answer 11

Unilateral: • vascular: Cerebellar stroke (ischemic/haemorrhage) • Neoplastic: cerebellopontine angle tumour Bilateral: • Drugs and toxins: anti-epileptics (e.g. phenytoin), lithium, chemotherapy (e.g. 5- FU), alcohol intoxication • Metabolic: chronic alcoholism, Wernicke’s encephalopathy, hypothyroidism • Autoimmune: multiple sclerosis, Miller-Fisher syndrome, SLE • Paraneoplastic: anti-Yo (gynae / breast), anti-Hu (SCLC, prostate) • Neurodegenerative: MSA, PSP • Hereditary: Wilson’s disease (AR), spinocerebellar ataxia (AD), Friedreich’s ataxia (AR), ataxia-telangiectasia (AR) • Infection: viral/TB meningitis

Answer 12

Ipsilateral lesion Midline lesion: ocular and balance abnormalities • eye signs: gaze-evoked nystagmus, broken pursuit, hypermetric saccades • Truncal ataxia: wide-based gait. Worsened on tandem walking, Romberg’s test -ve Hemispheric lesion: limb abnormalities - Dysmetria: past-pointing - Dysdiadochokinesia - Intension tremor - Scanning dysarthria - Pronation drift and rebound test +ve - Pendular knee jerk

Answer 13

Spinocerebellar ataxia • Genetics: trinucleotide repeat expansion (CAG) • Most common subtype in Asia: Type 3 (AD) o Characterized by ataxia, pyramidal signs (UMN), extra-pyramidal signs (Parkinsonism), ophthalmoplegia • Investigations: genetic testing, electrophysiology, neuroimaging Friedreich’s ataxia • Genetics: trinucleotide repeat expansion (GAA) à loss-of-function mutation in frataxin gene (Chr 9q13) o Inheritance: AR o Severity depends on number of expansions: earlier onset & loss of ambulation, more cardiomyopathy • Clinical features: o Pes cavus, inverted foot, hammer toes (long-standing peripheral neuropathy ~CMT) o Limb ataxia: cerebellar & sensory ataxia o Cerebellar eye signs: gaze-evoked nystagmus, broken pursuit, hypermetric saccades o Kyphoscoliosis o Associations: diabetes, hypertrophic cardiomyopathy (MC cause of death: heart failure), optic atrophy, sensorineural hearing loss, high-arched palate Ataxia-telangiectasia • Genetics: ATM gene (Chr 11), AR inheritance • Clinical features: o Immunodeficiency: bronchiectasis o Telangiectasias o Increased risk of lymphoma/leukemia

Answer 14

Most common form of progressive MND Amyotrophic (LMN denervation of anterior horn cells) + lateral sclerosis (UMN lesion of corticospinal tracts) Etiology • 90% sporadic • 10% familial: AD mutations in c9orf72 / SOD1 • Pathophysiology: excitotoxicity hypothesis, free radical hypothesis Clinical features • Mixed UMN and LMN signs (both corticospinal and bulbar) • NO sensory signs / autonomic dysfunction / cognitive impairments Bulbar: - UMN: Spastic dysarthria Exaggeration of motor expression of emotions (“pseudobulbar affect”) Laryngospasm - LMN: Difficulty in chewing Dysphagia Difficulty in movement of face and tongue Tongue fasciculations Limbs: - UMN: Stiffness out of proportion to weakness Hyperreflexia, spasticity, myoclonic jerk - LMN: Hyporeflexia, fasciculation Foot drop Diagnosis World Federation of Neurology criteria / El Escorial criteria • Simultaneous UMN and LMN involvement in 4 areas (bulbar, cervical, thoracic, lumbosacral) o Definite ALS: 3 out of 4 involved • Exclude all alternate diagnoses Management Multidisciplinary team approach • Symptomatic treatment o Drooling: anticholinergics (e.g. hyoscine patch) o Dysphagia: ST / dietician, food thickeners, tube feeding o Fasciculations: vit E supplement o Spasticity / weakness: PT, OT (splint, neck support), baclofen o Respiratory: NIV • Disease-modifying treatment: riluzole (glutamate release inhibitor: reduce excitatory neurotoxicity) o S/E: n/v/d, dLFT Other forms of MND • Progressive muscular atrophy (LMN) • Primary lateral sclerosis (UMN) • Progressive bulbar palsy (bulbar) • ALS-plus syndromes (e.g. ALS+FTD)

Answer 15

• Genetics: X-linked recessive, trinucleotide repeat expansion (CAG) in androgen receptor gene on X Chr • Pathology: degeneration of both motor and sensory neurons affecting both limbs and bulbar • Clinical features: o LMN signs: fasciculation and wasting of face, tongue and hand muscles o Sensory involvement similar to peripheral neuropathy o Endocrine S/S: gynaecomastia, testicular atrophy • Investigations: EMG, enzyme study (hexaminidase deficiency), blood CK & testosterone, genetic testing • Management: supportive

Answer 16

• AR mutation of survival motor neuron (SMN1) gene on 5q13.2 à degeneration of anterior horn cells o Partially compensated by SMN2 gene (severity inversely correlates with SMN2 copy numbers) • Classified into types 0-4 SMA-0 • Prenatal onset • S/S: In utero presentation e.g. IUGR At birth: severe weakness, hypotonia, areflexia arthrogryposis • Prognosis: Death due to respiratory failure (6-12m) SMA-I (Werdnig-Hoffmann) • Infantile onset < 3m • S/S: Floppy, cannot sit unsupported “Frog leg” posture, slip-through sign Tongue atrophy & fasciculations (upper CN spared) • Prognosis: Respiratory failure (die before 2yo) SMA-II (Dubowitz) • Onset before 18m • S/S: Able to sit unassisted (but delayed), but cannot stand/walk independently Proximal weakness, LL > UL, tongue atrophy & fasciculation • Prognosis: Progressive scoliosis + respiratory insufficiency Expectancy ~25 yo SMA-III (juvenile) (Kugelberg-Welander) • Juvenile onset (after 2yo) • S/S: Independent ambulation / wheelchair-bound onset No tongue fasciculation • Prognosis: No debilitating respiratory muscle weakness —> normal lifespan SMA-IV • Adult-onset Mild symptoms, ambulation maintained throughout life • Normal lifespan • Diagnosis: genetic testing with targeted mutation analysis (homozygous deletions of exons 7 of SMN1 gene) • Treatment: mainly supportive o Supportive treatments: chest PT, NIV, PT with spinal bracing, aspiration prevention o Disease-modifying therapy: - Nusinersen: antisense oligonucleotide that modifies splicing of SMN2 gene - Onasemnogene abeparvorec: replace mutated SMN1 with normal SMN1

Answer 17

• Poliovirus infection transmitted faecal-orally —> Viral replication in spinal motor neurons • Clinical features o Acute infection: acute flaccid weakness, S/S of viral meningitis (e.g. neck stiffness, headache) o Old polio: - Hypoplastic limb with leg length discrepancy (look for heel-lift shoes) - Pes cavus, hammer toes, (DDx: CMT) ± contractures or surgical scars - Proximal and distal wasting and weakness (DDx: GBS) - No sensory involvement (DDx: MND) - LMN pattern: hypotonia, hyporeflexia, downgoing plantar reflexes • Complications o Asymmetrical weight bearing: osteoarthritis, scoliosis o Post-polio syndrome: progressive weakness years after acute infection due to ongoing viral proliferation • Diagnosis: o Stool / CSF x poliovirus RNA PCR o MRI spine: rule out myelopathy • Management: supportive o Fall precautions o Refer physiotherapy: muscle strengthening, footwear o Refer orthopaedics: surgery for contractures o Assess respiratory function • Vaccination: both contain all 3 strains o Inactivated polio virus (IPV) – as DTaP-IPV in HK (2,4,6 months; booster in 18m, P1, P6) o Oral live attenuated polio virus (OPV)

Answer 18

Clinical features • Motor (LMN signs) – distal (e.g. foot drop) vs proximal (e.g. difficulty standing up, combing hair) • Sensory – large fibers (proprioception) vs small fibers (pain and temperature) • Autonomic dysfunction • Skeletal deformities: claw hand, pes cavus, kyphoscoliosis • Trophic changes: disuse atrophy, ulcers, Charcot joints • Nerve thickening (e.g. CMT, CIDP) Diagnostic approach • Baseline bloods: CBC, LRFT, glucose, B12/folate, TFT, ESR/CRP, autoimmune (ANA, RF, ANCA), SPE Ig • CSF if suspect GBS / CIDP • Electrodiagnostics: nerve conduction study (NCS), needle EMG o Confirm distribution of neuropathy, involvement of sensory / motor / autonomic fibers o Pattern: axonal (normal velocity, ↓amplitude) vs demyelinating: ↓velocity, normal amplitude) • Nerve biopsy: last resort for inflammatory / infective / infiltrative disorders Differential diagnosis of peripheral neuropathy (polyneuropathy) – need to know! • Metabolic: DM, alcohol, B12 (sensory), hypothyroidism, uremia, chronic liver disease • Inflammatory: GBS(AIDP)/CIDP, vasculitides • Malignancy: paraneoplastic, paraproteinemia# • Hereditary: CMT (HSMN) • Drugs: isoniazid, vincristine, cisplatin, metronidazole (sensory), colchicine (sensory) • Infective: HIV, Lyme’s disease • Infiltrative: amyloidosis, sarcoidosis #POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy & skin changes

Answer 19

Definition: acute inflammatory demyelinating polyneuropathy (AIDP) affecting nerve roots (c.f. CNS in MS) Pathophysiology • Trigger: infection (e.g. Campylobacter jejuni, Mycoplasma pneumoniae, CMV, EBV), vaccination within 4 weeks, lymphoma, etc. • Molecular mimicry: the organisms share epitopes with an antigen on peripheral nerve (GQ1b, GM1) —> autoantibody-mediated damage to peripheral nerve Clinical features • Subacute: peak in 3-4 weeks, resolve by 8 weeks • Motor: symmetrical ascending flaccid paralysis (weakness starting distally in legs, but proximal muscles more affected), areflexia, myalgia o +/- bulbar / respiratory involvement (—> respiratory failure) • Sensory: distal and symmetric paresthesia • Autonomic dysfunction (common): labile BP, arrhythmia, bladder dysfunction, paralytic ileus, but NO fever • NO new-onset UMN signs / sensory level (DDx: spinal cord problems) **lack of muscle wasting due to subacute onset** 5A of GBS: - Acute inflammatory demyelinating polyneuropathy (AIDP) - Ascending paralysis - Ataxia - Autonomic dysfunction -Areflexia - Arrhythmia DDx: - Poliomyelitis - Other causes of polyneuropathy (e.g. toxins, vasculitis, lymphomatous infiltration, critical illness polyneuropathy) - NMJ disorders (e.g. MG, botulism)

Answer 20

AIDP – most common - NCS shows demyelinating pattern - No specific Ab Acute motor axonal neuropathy (AMAN) / Acute motor sensory axonal neuropathy (AMSAN) - NCS shows axonal pattern - GM1, GD1a Miller-Fisher syndrome (MFS) - Triad: bilateral ophthalmoplegia + areflexia + ataxia, Descending weakness (i.e. eye first), only 25% have limb weakness - GQ1b (specific) Bickerstaff brainstem encephalitis -↓GCS, ophthalmoplegia, hyperreflexia, ataxia

Answer 21

Investigations (SAQ!) GBS is a clinical diagnosis! LP / NCS may be normal in 1st week, but it does not rule out the diagnosis. • ECG (arrhythmia), FVC (respiratory failure) • Anti-ganglioside Ab panel: GQ1b [MFS], GM1 & GD1a [AMAN, AMSAN] • LP: cytoalbuminologic dissociation (high protein, normal WBC) – ↑WBC points to DDx (e.g. poliomyelitis) • NCS: decreased velocity (demyelination – 95%) vs GBS variants (axonal degeneration) • MRI spine: r/o cord compression, transverse myelitis • Underlying cause: Stool culture for C. jejuni, serology for CMV / mycoplasma Management (SAQ!) Similar to management of myasthenic crisis (ABCD) • Airway: swallowing test +/- Ryles tube feeding • Breathing: monitor FVC (mechanical ventilation if FVC < 15ml/kg / hypercarbia / hypoxemia) • Circulation: cardiac monitoring (ECG for arrhythmia, BP/P for hypotension/bradycardia) • Drugs: immunotherapy in severe cases (For MFS, only give if respiratory/bulbar involvement) o IVIG 0.4g/kg daily for 5 days (S/E: anaphylaxis, dermatitis, hyperviscosity) o OR: Plasma exchange 50ml/kg/session for 5 sessions over 2 weeks - similar efficacy as IVIG o Steroid has NO benefit • Other supportive measures: Foley to monitor I/O (risk of AROU), DVT prophylaxis with early mobilization

Answer 22

• Definition: chronic relapsing counterpart of GBS, of autoimmune origin • Clinical features: similar to GBS, but o Fluctuating course ≥ 8 weeks (c.f. acute onset, shorter duration in GBS) o Mostly relapsing-remitting (c.f. most completely recover in GBS) o Lack of association with preceding infection o More prominent sensory symptoms o Good response to steroids • Investigations: NCS for demyelination, LP for cytoalbuminologic dissociation • Management: o High-dose PO prednisolone 1mg/kg/day or pulse IV methylprednisolone (c.f. no use in GBS) o Alternatives: IVIG, plasmapheresis - more rapid improvement, but not change mortality **more muscle wasting**

Answer 23

Clinical features • Subacute combined degeneration of cord o Dorsal column: loss of proprioception and vibration, Romberg’s sign +ve o Corticospinal tract: brisk knee jerks, upgoing plantar reflexes o Peripheral neuropathy: absent ankle jerks • Other signs of B12 deficiency: pallor (megaloblastic anemia), glossitis, MMSE for dementia • Search for etiology: surgical scars (gastrectomy / terminal ileum resection), vitiligo (pernicious anemia), AR pupils (r/o tabes dorsalis) Management • Immediate B12 replacement: loading (1mg IM 3x/week for 2 weeks) à maintenance (long IM Q3months) • Folate replacement: delay until later (risk of exacerbating cord degeneration if given early)

Answer 24

Pathology • Prevalence: 1/2500 • Hereditary motor and sensory neuropathy (HMSN) • Subtypes of CMT (Type 1: Type 2 = 2:1) Type 1 (MC) - Type 1A: AD mutation of PMP22 gene on Chr 17 - Type 1B: AD mutation of MPZ gene on Chr 1 - NCS: Demyelinating - Palpable nerve: Yes (biopsy: “onion bulb”*) Type 2: present later - AD mutation in MFN2 gene - NCS:Axonal - palpable nerve: No Type 3: more severe - AR mutation (a.k.a. Dejerine-Sottas disease) - - - NCS: Demyelinating - Palpable nerve: Yes Clinical features Usually motor predominant (c.f. CIDP) Lower limb • Bilateral symmetrical distal muscle wasting & weakness, with relative preservation of thigh musculature —> “Inverted champagne bottle” appearance / “stork legs” • Bilateral pes cavus (DDx: Friedreich’s ataxia) • Hammer toes, claw toes • Areflexia / hyporeflexia, downgoing plantar • Palpable common peroneal nerve around neck of fibula • Foot drop with high steppage gait (weakened dorsiflexion) • +/- “glove-and-stocking” pattern of sensory loss • +/- positive Romberg’s test • +/- surgical scars at Achilles tendon / popliteal fossa for contractures Upper limb • Small hand muscle wasting: dorsal guttering, hypothenar/thenar wasting • Claw hands, Froment’s sign • Palpable ulnar nerve To complete: check for cerebellar signs (r/o Friedreich’s ataxia), examine spine for scoliosis, ask for FHx (e.g. pes cavus) Investigations • Nerve conduction study +/- nerve biopsy • Genetic testing • Exclude other causes: CBC, LRFT, TFT, glucose, B12/folate Management • Multidisciplinary team approach: o PT: exercise maintain function of limbs o OT: assess need of foot-drop splint / walking aids o Ortho: surgery to correct deformities

Answer 25

Causes: - Hereditary: • Muscular dystrophy e.g. DMD/BMD • Congenital myopathy e.g. Prader- Willi syndrome • Metabolic myopathy e.g. glycogen storage disorders, channelopathies • Mitochondrial myopathy e.g. CPEO, KSS -Aquired: • Inflammatory myopathy (see [Rheumat]) • Endocrine: hyper/hypothyroidism, Cushing's, Addison's disease • Infection: viral (e.g. influenza, Coxsackie), toxoplasmosis, trichinosis, cysticercosis • Drug-induced (e.g. statin, steroid) • Electrolyte imbalance: hypoK, hyperCa • Rhabdomyolysis

Answer 26

Clinical features • Symmetrical proximal muscle weakness (except myotonic dystrophy) o Waddling gait: hip abductor weakness à inability to fix pelvis while walking (Trendelenburg sign +ve) o Lordotic posture: trunk and hip weakness • Normal reflex, no fatigability (DDx: MG) • No sensory loss Investigations • Muscle enzymes: CK, ALT, LDH o CK: 200-1000 for most myopathies; >1000 for inflammatory myopathies, rhabdomyolysis, DMD/BMD • NCS: to rule out neuropathy (can also cause reduced motor response) • EMG: polyphasic, low-amplitude motor unit potential • Muscle biopsy • Ix for underlying causes: see below Management • No specific treatment • Supportive care with multidisciplinary approach: PT, OT, genetic counselling • Management of complications: heart failure, arrhythmia, respiratory failure

Answer 27

Muscular dystrophy - Duchenne/ Becker (XR), Facioscapulohumeral (AD), Limb-girdle (AD/ AR), Oculopharyngeal (AD), Emery-Dreifuss (XR/AD) - Calf pseudohypertrophy, Gower’s sign, Tip-toe gait (tight Achilles) - Genetic testing (dystrophin - Xp21.2), ECG / echo: dilated cardiomyopathy —> Myotonic dystrophy (AD) - Type 1: CTG trinucleotide repeat in DMPK gene Type 2: CCTG tetranucleotide repeat in CNBP gene - Distal muscle weakness, Myotonia*: hand grip, close eyes, percussion myotonia Myopathic facies (tented open mouth, elongated face, expressionless) Frontal baldness, temporalis wasting, bilateral ptosis, cataract, cardiomyopathy - Genetic testing (DMPK) ECG / echo: dilated cardiomyopathy Examine mother Metabolic myopathy - Periodic paralysis (HypoK: Ca channelopathy; hyperK: Na channel, rare) - Episodic weakness, normal between attacks - Serum K, TFT Mitochondrial myopathy - Chronic progressive external ophthalmoplegia (CPEO) - progressive bilateral ptosis and ophthalmoplegia, proximal myopathy - Muscle biopsy: ragged-red fibre —> Kearns-Sayre syndrome - Triad of CPEO, pigmentary retinopathy & heart block - Muscle biopsy: ragged-red fibre Endocrine: - Hypo/Hyper thyroidism, Cushing’s, Addison’s disease - TFT, 8AM cortisol, ACTH Infection: - Viral - Myalgia - Myoglobulin, viral PCR, Tissue biopsy Drug: - Statin-induced myopathy - Simvastatin highest risk

Answer 28

Classifications • Generalised (85%): all three groups are involved • Ocular (15%): only involved eyelids & EOM; only certain after 2 years of ocular alone presentations (50% risk of converting to generalised MG in first 2 years) Pathophysiology • T-cell dependent immunological attack at Ach receptor or associated proteins (seropositive = anti-AChR / MuSK) o Anti-AChR (post-synaptic membranes of NMJ): found in 90% of generalized MG & 50% of ocular MG, titre correlate with disease severity o Anti-MuSK (required for formation of NMJ): more bulbar and respiratory involvement, higher risk of MG crisis, poorer response to anticholinesterase o Anti-LRP4 (LDL receptor-related protein 4): more eye involvement • Disease associations: o Thymic disorders: thymic hyperplasia (85%), thymoma (15%) o Autoimmune disease (1/3), e.g. Graves’, Hashimoto’s, T1DM, RA, SLE o Malignancy: SCLC, Hodgkin’s lymphoma • Triggers: o Intercurrent illness, surgery o Thyroid dysfunction o Drugs (recite!): antibiotics (aminoglycosides, quinolones, macrolides, metronidazole), antihypertensives (BB, CCB), antimalarials (HCQ, quinine), penicillamine, procainamide, lithium, phenytoin, lidocaine,

Answer 29

Clinical features - Variable presentation, disease course, prognosis and response to treatment - Early stage usually shows diurnal variation (worse at night), but late stage would be more persistent • Ptosis (can be unilateral / bilateral but asymmetrical): test • Multidirectional strabismus and diplopia (weakness of EOM) • Pupils spared • Cogan’s lid twitch: downward gaze (rest) then look up —> upper eyelid overshoot • Curtain sign: manually elevate ptotic lid —> contralateral side will increase ptosis • Peek sign: ask patient to close eyelid forcefully —> gradual opening of eyelids • Pseudo-INO (fatigue of MR) à does not correct after cover test unlike true INO • NO nystagmus - Facial “Myasthenic facies”: • Failed eyelid closure • Expressionless: mouth hang open with drooling of saliva • Myasthenic snarl: corner of lips cannot contract while smiling • Jaw supporting sign -Bulbar : Dysarthria, dysphonia (weakened nasal voice) Dysphagia, jaw weakness (cannot finish whole meal -Respiratory: SOBOE, orthopnea, tachypnea, respiratory failure -Limb: Proximal muscle weakness (UL > LL) -Axial: Head drop (failed neck flexion/extension) Specific tests for MG: • Sustained upward gaze • Count out loud from 1 to 20: demonstrate voice fatigability • Fatigability of shoulder abduction: test baseline power à press on elbow of one side à test again To complete the examination: • Look for thymectomy scar, assess speech and swallowing • Bedside spirometry: assess FVC and exercise tolerance • Look for Cushingoid features due to long-term steroid use • Assess for features of associated diseases e.g. hyper/hypothyroidism, SLE/RA, DM

Answer 30

Osserman’s grading of MG Type 1: Focal —> Ocular MG only Type 2A: Mild generalized —> Generalized MG with limb involvement Type 2B: Moderate generalized —> Generalized MG with bulbar involvement Type 3: Acute fulminating —> Severe symptoms (MG crisis) with respiratory muscle involvement, rapid onset (<6mo) Type 4: Late severe —> Severe symptoms, >2 years after onset, high mortality rate Investigations • Bedside test to demonstrate reversibility: o Ice pack test: ice pack applied to ptotic eyelid for 2-5min o Tensilon test (IV edrophonium): 2mg test dose then Q1min until total 10mg § S/E: bradycardia (arrhythmia or even asystole), weakness (depolarising NMB), SLUDGE (salivation, lacrimation, urination, diarrhoea, GI discomfort, emesis) § Caution: cardiac monitor, resuscitation trolley with atropine stand-by, double-blinded test • Serology: anti-AChR; +/- anti-MuSK / anti-LRP4 if negative • Repetitive nerve stimulation (RNS): fatigability defined by ≥10% decremental response in CMAP (compound muscle action potential) amplitude upon 3Hz stimulation • +/- Single fiber EMG: most sensitive diagnostic test • Associations: CXR + CT thorax with contrast (thymoma), TFT (thyroid diseases), autoimmune panel • Pre-steroid workup: HBsAg, TB (IGRA) Management • NPO until pass swallowing test • Close monitoring with spirometry (FVC): inform if <1L / <15mL/kg • Pharmacotherapy o Anticholinesterase for symptomatic relief e.g. pyridostigmine (Mestinon ⼤⼒丸), neostigmine § S/E: cholinergic crisis (bradycardia, SLUDGE esp. diarrhea) o Long-term immunosuppressants: indicated if remain symptomatic on pyridostigmine § Low dose prednisolone 10-15mg/day (1st line): —> Risk of paradoxical worsening if high dose: prevented by bridging with IVIG / plasmapheresis —> Add-on azathioprine (2nd line) —> Refractory: MMF / rituximab (anti-CD20) Ø [RITUMAX] (2022): early use of RTX may reduce flare, improve disease control, and reduce steroid use • Thymectomy (usually VATS): immunomodulatory treatment, indicated in o All thymomas (potential for malignancy) o Without thymoma: young (18-65) + generalised MG + early disease (<5y) + AChR +ve • Avoid offending drugs e.g. beta-blockers, aminoglycosides • Issues in pregnancy: o Risk of flare-up during 1st trimester and post-partum period o Medication use: MMF / MTX are tetratogenic, others (e.g. prednisolone, azathioprine) are safe o Avoid pregnancy for 1 year after finishing rituximab o Risk of transient neonatal myasthenia (15%) **MUSK MG: use roxanolixizumab, not pyridostigmine, no need thymectomy**

Answer 31

Definition: MG with respiratory failure or bulbar weakness and requiring ventilator assistance Triggers: infection (URTI), drugs (aminoglycosides, b-blockers), tapering of immunosuppressant, surgery, childbirth Main differential diagnosis: cholinergic crisis (overtreat vs undertreat) Clinical features • Bulbar involvement, e.g. dysphagia, drooling of saliva, dysphonia • Respiratory involvement, e.g. orthopnoea, SOB, accessory muscle use, paradoxical abdominal movement Diagnosis: • FVC, ABG, ECG, CXR • Tensilon test NOT recommended: risky + not reliable in distinguish MG crisis vs cholinergic crisis Management: similar to GBS (ABCD) • Airway: NPO before swallowing test • Breathing: closely monitor FVC, SaO2 and ABG (mechanical ventilation if < 15ml/kg or respiratory failure) • Circulation: not required • Drugs: o IVIG 0.4g/kg/day x 5 days o Alternative: Plasma exchange 50mL/kg/session x 5 sessions on alternate days ± Rituximab o PO prednisolone 1mg/kg/day for inducing remission § Risk of paradoxical worsening, but generally safe with IVIG cover & intubation o Withhold pyridostigmine if § Intubated: avoid excessive respiratory secretions § Suspected cholinergic crisis • Identify and treat precipitating conditions (e.g. infection) • Supportive care: urinary retention, constipation, clear secretion, early mobilisation, DVT prophylaxis

Answer 32

Clinical features • Similar to MG crisis in terms of flaccid paralysis & respiratory failure • Differentiated by S/S or Tensilon test (not reliable) o Excessive salivation & sweating o Bradycardia (tachycardia in MG) o Miosis (pupils spared in MG) o Muscle fasciculations (absent in MG) o Abdominal cramp, diarrhoea Management: withhold pyridostigmine, start atropine, supportive management

Answer 33

Pathophysiology • Autoantibodies against presynaptic voltage-gated Ca2+ channels —> continued muscle use causes build-up of neurotransmitters and thus symptom relief • Association: SCLC (60%) Clinical features: • Predominantly affect LL (UL & eyes spared), with warm-up phenomenon (improve with exercise) • Reduced tendon reflex: improved with exercise • Autonomic dysfunction: anticholinergic symptoms, e.g. dry mouth, constipation Investigations: • Anti-VGCC • EMG: incremental response upon high frequency RNS (~20Hz) • Screening for SCLC: CT thorax Management: • Treat underlying SCLC • 3,4-diaminopyridine: K channel blocker à prolong depolarization of motor nerve terminals à Ach release • +/- Immunotherapy: steroids, IVIG, plasmapheresis

Answer 34

Pathogen: Clostridium botulinum Pathophysiology: botulinum toxin blocks Ach release Risk factors: ingestion (expired canned food), wound infection Clinical features • Occur 6-48h after ingestion • Prodromal GI symptoms (absent in wound infection): n/v, diarrhoea, abdominal pain • Descending paralysis: pupil à bulbar à limbs • Autonomic involvement: dilated pupils, dry mouth, postural hypotension Investigations • Presumptive clinical diagnosis • Detection of toxin in stool/ blood takes time Management • Monitoring: cardiac monitor, pulse oximetry, etc • Antitoxin

Answer 35

Always consider: MG, Graves’ disease, Miller-Fisher syndrome CN 3 Surgical: pupil fixed and dilated • Posterior communicating artery aneurysm • Uncal herniation • Cavernous sinus syndrome: NPC, meningioma at wing of sphenoid • Superior orbital fissure syndrome Medical: pupil spared • Ischemic mononeuropathy / Mononeuritis multiplex: DM, vasculitis • Inflammation: MS, GCA • Vascular: infarct / haemorrhage (Weber’s syndrome) • Infection: TB meningitis, Lyme disease, syphilis • Trauma CN 4 • Trauma (MC) • Mononeuritis multiplex • Tumor CN 6 • Ischemic mononeuropathy / Mononeuritis multiplex (MC): DM, vasculitis • Raised ICP (false localizing sign) • Inflammation: MS, GCA • Neoplasm: pontine tumor, NPC, lymphoma • Vascular: infarct / haemorrhage • Infection: TB meningitis, Lyme disease, syphilis • Trauma Not fit into any • Graves’ ophthalmopathy • Myasthenia gravis • Miller-Fisher syndrome • Chronic progressive external ophthalmoplegia (CPEO) • Muscular dystrophie

Answer 36

• SOL: tumour, abscess, haematoma • Cerebral oedema: trauma, infection, post-stroke • Hydrocephalus: obstructive (IVH, tumour), communicating (post-meningitis, post-SAH) • Idiopathic intracranial hypertension (IIH)

Answer 37

Symptoms • Headache: worse with lying down or straining • N/V: early morning (hypoventilation during sleep —> pCO2 increased —> cerebral vasodilation —> increased —> ICP) • Blurred vision (papilloedema) Signs • CN: papilloedema, CN6 palsy, sunsetting eyes (Parinaud syndrome) • Cushing's ulcer: epigastric pain • Uncal herniation: "blown pupil" (fixed dilated pupil due to CN3 palsy), contralateral hemiplegia (cerebral peduncle), reduced consciousness (RF) • Tonsillar herniation: Cushing's triad (systemic HT, bradycardia, respiratory depression)

Answer 38

Obstructive: at ventricular system/ aqueduct-ventricular enlargement proximal to block (4th ventricle normal) 1. Aquired - Tumours: CPA tumour (vestibular schwannoma/ meningioma), brain metastasis, gliomas, craniopharyngioma/ pituitary macroadenoma) - Vascular: cerebellar infarct, ICH, IVH - Infections: ventriculitis, post-infective aqueductal stenosis, brain abscess, neurocysticercosis 2. Congenital - Dandy-Walker malformation, Type II Chiari malformation, congenital aqueductal stenosis Communicating: at arachnoid villi - all ventricles dilated (4th ventricle enlarged) 1. Acquired - Tumours: leptomeningeal carcinomatosis - Vascular: SAH, IVH - Infections: basal meningitis (e.g. TB, Cryptococcal) - Normal pressure hydrocephalus

Answer 39

Clinical diagnosis - Sudden onset of focal neurological deficit - majority have background of risk factors (age, smoking, HT, HL…) - symptoms maximum at few minutes

Answer 40

CT brain no change suggest ischemic stroke —> ASPECTS score —> evasement of sulci, loss in grey-white differentiation (early ischemic changes) CT brain with hyper enhancement may suggest haemorrhagic stroke, but if bilateral dentate (star-shaped) hyper enhancement at cerebellum or bilateral basal ganglia may suggest calcificationj

Answer 41

- 5-10mm above bifurcation of aorta —> most turbulant flow (carotid bruit) —> vessel wall wound —> platelet want to form thrombosis —> stroke - artery-artery embolism —> anti-platelets

Answer 42

Stasis of blood since heart cannot contract properly, stasis of blood at arterial appendages… —>forming clot —> embolism of clot —> stroke at proximal artery Give anti-coagulation

Answer 43

Cannot show blockage of vessel in MRA/CTA

Answer 44

Cannot show blockage of vessel in MRA/CTA

Answer 45

- Extracranial and intracranial steno-occlusive diseases - Atherosclerotic and radiation-induced lesions - Limitation of stenting

Answer 46

Subclavian steal syndrome

Answer 47

- Global aphasia - Eye deviation (frontal lobe control conjugate gaze) - hemineglect

Answer 48

1) pre-stroke mRS score of 0 to 1 2) causative occlusion of the ICA or MCA M1 segment 3) ASPECTS of > or equal to 6 Within 24 hours

Answer 49

- 10 zone - if early ischemic change in 1 zone, minus 1 mark - max. 10 marks

Answer 50

• ICP monitoring: intraventricular catheter/ external ventricular drainage (EVD) by burr hole • Resuscitation: O2, fluid to keep MAP > 90 (to keep CPP≥70 & ICP ≤ 20mmHg) • Intracranial contents & corresponding management Blood (1st if urgent): - Elevate head of bed to 30o: improve venous drainage - Hyperventilation (keep PaCO2 < 4-4.5 kPa): reduce CBF Brain tissue (1st if urgent): - 20% mannitol 0.5g/kg: osmotic diuretic, stop if OsM > 320, C/I hypovolemia - Hypertonic saline 3%: if hypovolemia CSF: - External ventricular drainage SOL, e.g. haematoma: - Evacuation • Decompressive hemicraniectom

Answer 51

• Typical presentation: obese young women presenting with headache and visual disturbances Investigations • CT brain: to rule out intracranial lesion • LP for opening pressure o Opening pressure: CSF pressure in the spine, measured via LP using a manometer; normal <20cmH2O o ICP: pressure measured by pressure sensor directly into skull; normal <15mmHg (<20cmH2O) Management Weight reduction Medical therapy • Diuretics: acetazolamide (1st line) +/- frusemide (2nd line) • Steroid: in severe case (acute vision loss) • Serial LP ineffective (CSF reforms quickly) Surgical therapy: optic nerve sheath fenestration (ONSF), CSF shunting

Answer 52

Definitions: pathologically enlarged ventricle with normal opening pressures on lumbar puncture Pathophysiology: impaired CSF absorption (e.g. IVH, SAH) causing local pressure effect but overall normal pressure Clinical features: Adam’s triad • Urinary incontinence (wet) • Gait disturbance (wobbly / magnetic gait; may mimic Parkinsonism) • Dementia (wacky; may mimic AD) Investigations • CT brain: ventriculomegaly out of proportion to sulcal enlargement (cerebral atrophy) • LP (high volume 30-50ml): note clinical improvement Management: surgical shunting, e.g. VP shunt

Answer 53

1) Vasogenic oedema Aetiology: - Tumours - Abscess Pathophysiology: - Extracellular: fluid leakage from capillaries to white matter - Disrupted BBB CT brain: - Pronounced grey-white matter differentiation 2) Cytotoxic oedema Aetiology: - Ischaemia Pathophysiology: - Intracellular: defective Na/K ATPase pump Intact BBB CT brain: - Loss of grey-white matter differentiation

Answer 54

Differential diagnosis • Primary headache: migraine, tension, cluster • Secondary: o Deadly (VIVID): - Vascular: SAH, cerebral venous sinus thrombosis - Infection: meningitis, encephalitis - Vision-threatening: e.g. GCA, glaucoma, cavernous sinus thrombosis - Increased ICP: SOL, malignant hypertension, idiopathic intracranial hypertension - Dissection o Common: trigeminal neuralgia, post-herpetic neuralgia, sinus headache, zoster, drugs (e.g. nitrates, cilostazol, CCB), OSA o Others: post-LP, referred pain (e.g. cervical spondylosis) Investigations • Bloods: CBC, ESR/ CRP • Imaging: NCCT brain, MRI brain Red flags for severe causes: • Systemic upset: constitutional symptoms • Neurological signs • Onset: new and sudden • Other associated symptoms: early morning headache with n/v, visual S/S, meningococcal rash, photophobia • Progression from previous • Persistent

Answer 55

Site: Unilateral (70%) Bifrontal or global (30%) Onset: Gradual Duration: Over 4-72h Frequency: - monthly Characteristics: - pulsatile, crescendo Activity: Rest in dark quiet room Risk factors: Food: cheese, chocolate, coffee Sleep deprivation, stress, OCP Associated symptoms: Aura: most commonly visual (zigzag lines à scintillating scotoma), sensory (numbness), motor (hemiplegia) During attacks: n/v, photophobia, phonophobia Acute Mx: Dark quiet room, avoid ppt. Analgesics (paracetamol/ NSAID) *Triptans, e.g. sumatriptan Ergots, e.g. ergotamine Prophylaxis: Beta blocker, e.g. propranolol Topiramate, candesartan TCA (S/E: dry mouth, sedation) Botox, CGRP inhibitors (“gepants”, erenumab) ** *Triptans • MOA: 5-HT1 receptor agonist —> vasoconstriction, ↓CN V neurotransmission • Examples: sumatriptan (oral / SC / nasal), naratriptan (PO) • Administration: take early after onset of attack (within 30min) • C/I: coronary artery disease, stroke, severe hypertension, concomitant MAOI (serotonin syndrome) ^Ergots: last resort due to S/E (e.g. retroperitoneal fibrosis, valvular fibrosis)

Answer 56

Site: Bilateral Onset: Gradual Duration: Variable Frequency: Weekly Characteristics: Band-like Activity: Remain active/rest Risk factors: Stressful events Associated symptoms: Psychiatric: depression, insomnia Acute Mx: Analgesics (paracetamol/NSAID) Prophylaxis: Antidepressant, e.g. TCA, SSRI Behavioural therapy: relax, stress management

Answer 57

Site: Always unilateral, orbital/supraorbital/temporal Onset: Rapid over 5-10 mins Duration: 30min - 3h Frequency: Daily (multiple episodes) Characteristics: Crescendo within minutes to become explosive deep pain Activity: Remain active Risk factors: Alcohol Associated symptoms: Ipsilateral • Lacrimation • Conjunctival injection • Nasal congestion / rhinorrhea • Horner’s syndrome Acute Mx: High-flow O2 Nasal/ SC triptans Intranasal lidocaine Prophylaxis: CCB, e.g. verapamil Lithium (if severe) Avoid trigger, e.g. alcohol, shift work

Answer 58

Pathophysiology: compression of trigeminal nerve —> focal demyelination —> ephaptic transmission Causes • Idiopathic: compression of trigeminal nerve at root exit zone (REZ) by a vascular loop (usually superior cerebellar a. or superior petrosal sinus) • Secondary: compression (e.g. tumor), inflammation (e.g. post-herpetic, MS), Chiari malformation Clinical presentation • Paroxysmal attacks of unilateral severe sharp shooting/stabbing pain along CN V distribution (usually V2/V3) • Usually pain-free between atacks • Usually lasts seconds to 2 minutes • Triggers: certain daily activities (e.g. shaving, washing face, brushing teeth, combing), dental procedures, TM joint movement, cold Diagnosis: Trigeminal neuralgia is a clinical diagnosis • Contrast brain MRI: rule out secondary causes Management • Medical therapy (first-line): Carbamazepine 100-300mg BD for classical TN o Other medications: pregabalin, gabapentin, valproate • Ablative treatments: percutaneous fluoroscopic-guided (via foramen ovale) o Radiofrequency ablation of Gasserian ganglion o Chemical ablation • Surgical treatment if refractory: o Microvascular decompression (MVD) – MC retrosigmoid approach o Rhizotomy (partially transect the nerve)

Answer 59

Miosis (constrictive pupil) Ptosis Anhidrosis Enophalmosis (inset eyeball)

Answer 60

• Epileptic seizure: sudden change in behavior due to abnormally excessive neuronal activity in cerebral cortex o Provoked seizures/ acute symptomatic seizures: seizures in the setting of an acute medical condition - Structural: brain tumour, ICH, acute ischemic stroke, trauma - Systemic: drug intoxication & withdrawal, electrolyte disturbances (e.g. hypoNa, hypoCa) o "Unprovoked": absence of temporary or reversible factors that lower the seizure threshold • Non-epileptic seizure: sudden change in behaviour not caused by any neuronal activity change in cerebral cortex o E.g. Hyperventilation, migraine, panic attack, syncope, psychogenic seizures, TIA, transient global amnesia • Convulsion: seizure with motor components • Epilepsy: defined by any of o ≥ 2 unprovoked seizures occurring >24h apart o 1 unprovoked seizure + probability of future seizures similar to general recurrence risk after 2 unprovoked seizures (i.e. ≥60%) over next 10 years o Diagnosis of an epilepsy syndrome • Epilepsy is considered “resolved” if: o Seizure-free for last 10 years with no seizure medicines for last 5 years

Answer 61

Risk factors: Fever, head injury, sleep deprivation Substance/ alcohol use/withdrawal PMHx / FHx of seizure Onset: Sudden Prodrome: Aura: hallucinations, rising sensation in epigastrium, fear/anger, n/v Event: More convulsive element: limb twitching, up- rolling eyeballs, tongue biting, incontinence, fixed dilated pupils Injury common Post-event: Post-ictal convulsion Todd’s paralysis Investigations: Bloods: glucose, LRFT, electrolytes (+Ca, Mg) CBC D/C, septic workup CT / MRI brain Toxicology & AED levels Inter-ictal EEG Prolactin ( 2-3x if true seizures)

Answer 62

• Focal (originate from one hemisphere) vs Generalised (originate from both hemispheres) o Focal seizures can progress into generalized seizure 1)Generalized (discharge from both hemispheres) • General Features: - No warning - Symmetrical seizures - Bilateral synchronous discharge on EEG - Always LOC Absence seizure : • Transient LOC, abrupt onset & termination • Without motor phenomena (except mild flickering of eyelids) • Can be typical (petit mal) or atypical • Precipitated by hyperventilation Myoclonic seizure • Brief, repetitive, jerking movements of limbs/neck/trunk • (myoclonus also seen in normal conditions e.g. hiccups, sleep myoclonus in Stage II sleep) Tonic seizure: Generalised increased tone Tonic-clonic seizure • Last seconds to minutes • Tonic phase: all muscles contract, may fall to ground and cyanose • Clonic phase: follows jerking of limbs, irregular breathing, biting of tongue, incontinence of urine • Post-ictal unconsciousness/deep sleep for a few hours Atonic seizure • Often combined with myoclonic jerk • Transient loss of muscle tone

Answer 63

2) Focal (discharge from one / part of one hemisphere General features: - May have an aura - May or may not LOC - May evolve to generalized Frontal lobe seizure • Involve motor/pre-motor cortex: clonic movements that may travel part of one hemisphere) proximally (Jacksonian march) • May have asymmetrical tonic seizures: bizarre, hyperkinetic Temporal lobe seizure (MC) • Olfactory / gustatory hallucinations, epigastric ‘rising’ sensation • Lip-smacking, automatism (e.g. walking in non-purposeful manner) • Deja-vu / Jamais vu feelings, stare blankly Occipital lobe seizure - Stereotyped visual hallucinations Parietal lobe seizure - Contralateral dysaesthesias / distorted body image

Answer 64

General: first aid, rescue meds (e.g. rectal diazepam / intranasal midazolam), admit if post-ictal confusion / suspected HI / no carer for next 24h Lifestyle modification • Avoid triggers, e.g. sleep deprivation, alcohol, recreational drug use • Avoid potentially dangerous activities, e.g. driving, operating high-risk power equipment, working at heights, hiking alone, swimming alone, cooking over fire alone Antiepileptic drugs (AED) - Indications: • ≥2 unprovoked seizures • 1 unprovoked seizure with high-risk features: epileptiform EEG, CNS structural disease (e.g. brain tumour, CNS infection), status epilepticus (> 5min), high-risk occupations (e.g. pilot) • Post-neurosurgery / post-head injury: usually at least 1 year Drug choice: Initial: sodium valproate, ethosuximide (absence seizure) • Efficacy: 60-70% seizure-free after 1st or 2nd AED o No improvement after 1st drug: substitution o Modest improvement (but not complete) after 1st drug: add-on therapy S/E: General side effects: (3D 2A) drowsiness, dizziness, diplopia, ataxia, amnesia Specific side effects: refer to table DDI: • CYP inducers: phenytoin, phenobarbitone, carbamazepine —> OC pills, warfarin • CYP inhibitor: valproate Stopping: Consider if seizure free for 2 years: gradually taper off dose

Answer 65

Broad-spectrum AED: all seizure type 1. Valproate (Epilim) - All types (GTC, myoclonic, absence) - Na channel blocker, GABA transaminase inhibitor - Weight gain, PCOS, tremor, teratogenicity, reversible alopecia, hepatotoxicity, pancreatitis, thrombocytopenia - Metabolized in liver, C/I inpregnancy - Monitoring: CBC, LFT, trough level (50-150 ug/mL) 2) Lamotrigine (Lamictal) - All types (esp. GTC) - Na channel blocker, T-type CCB - Mild cytopenias, rash, SJS/TEN (Least teratogenic) - Metabolized in liver, decreased dose if use with valproate 3) Topiramate (Topamax) - All types (esp. myoclonic) - Multiple: Na, Ca, GABA - Renal stone, glaucoma, numbness 4) Levetiracetam (Keppra) - All types Unclear (SV2A) - Mood problems, fatigue - Metabolism NOT by CYP, well tolerated with few DDI

Answer 66

For focal ± secondary generalized epilepsy Carbamazepine (Tegretol) - Focal / GTC (X absence) - Na channel blocker - HypoNa (SIADH), rash (5-10%), SJS/TEN (0.1%), teratogenicity, agranulocytosis (rare) - Metabolized in liver, Check HLA-B*1502 - Monitoring: CBC, LRFT, trough level Phenytoin (Dilantin) - Focal / GTC - Na channel blocker - Gum hypertrophy, hirsutism, rash, SJS/TEN, peripheral neuropathy - Metabolized in liver - monitoring trough level Phenobarbitone - Focal / GTC - GABA-A receptor agonist - Cognitive side effects, Dupuytren’s contracture - Metabolized in liver Ethosuximide - Absence only - T-type CCB Vigabatrin - infantile spasm - GABA transaminase inhibitor - visual field defects **anti-epileptic drug hypersensitivity syndrome occur in aromatic AEDs such as phenytoin, carbamazepine, phenobarbital and primidone**

Answer 67

• Contraception: AED affects efficacy of all hormonal contraception (e.g. COCP, prog. Implants) o Advise barrier contraception: condom, copper IUCD o Increase dosage if must use hormonal methods • AED —> Risk of foetal malformation (cleft palate, spina bifida, congenital heart malformation, hypospadias) o Highest risk in valproate and if polytherapy o Changing to lamotrigine or levetiracetam, use monotherapy at lowest effective dose o Folic acid 5mg daily 3 months before conception, until 3 months of gestation • Haemorrhagic disease of newborn: o Higher risk in enzyme-inducing AED (carbamazepine, phenytoin, phenobarbitone) o Mx: 1mg IM Vit K in the last month of gestation • Acute seizure during pregnancy o Differentiate epileptic seizures from other pregnancy-related causes (e.g. eclampsia) • Postnatal management o Breast-feeding: older AED preferred (water insoluble) o Anticipate breakthrough in postpartum due to stress and sleep deprivation

Answer 68

• Prohibited from driving if diagnosed: must be seizure-free for ≥5 years to drive ordinary motor vehicle, ≥10 years without meds for buses and large goods vehicles • No mandatory reporting by doctors in HK, but need clear documentation • Counselling: encourage patient to disclose their condition to Transport Department

Answer 69

• Pros and cons similar to general public: risk of allergy, Bell’s palsy, GBS, myocarditis, etc. • Sinovac has cautionary note on epilepsy, but BioNtech has no remarks. Both ok

Answer 70

• Ketogenic diet • Vagal nerve stimulation • Deep brain stimulation • Epileptic surgery o Example: temporal lobectomy (MC) for temporal lobe epileps

Answer 71

Operational definition • Continuous seizures lasting ≥ 5 min (formal definition: 30 min) • ≥ 2 epileptic seizures without full recovery of consciousness between attacks • Note: non-convulsive status epilepticus (NCSE) - impaired consciousness without convulsion o High index of suspicion is needed and consider EEG Management (SAQ!) • ABC: remove obstructing FB • Check H’stix: if Hstix < 4, give IV thiamine 100mg then IV D50 50ml • Resume usual AED if known epilepsy – change to IV formulation • Consult ICU • Stage 1: Early (0-10min) - benzodiazepines o IV lorazepam 4mg over 2 min, repeat once in 5-10min (up to 8mg) – include dose given pre-hospital o IV diazepam 10mg over 2 min (if lorazepam N/A) o IM midazolam 10mg: if no IV access • Stage 2: Established (10-30min) - antiepileptic o IV phenytoin 15mg/kg over 30min - Undiluted (precipitation with dextrose) slow infusion (cardiotoxicity), use large vein - S/E: —> Bradycardia, hypotension (Na channel blocker – cardiac monitoring) —> Purple glove syndrome (worsening distal limb oedema & discolouration causing skin necrosis and limb ischaemia) —> Allergy / SJS (cross-reactivity if HLA-B*1502 +ve) o Alternatives: - IV valproate 20mg/kg (check NH3, C/I if liver failure, S/E: thrombocytopenia) - IV levetiracetam 20mg/kg (for renal impairment) • Stage 3: Refractory (seizure despite BZD and 1 AED) o General anaesthesia: maintain for ≥24h before gradual withdrawal - Drug of choice: midazolam / propofol / thiopental - EEG to monitor treatment response and look for NCSE - Maintain high level of AED • Stage 4: Super-refractory (seizure despite GA 24h): consider o Ketamine o MgSO4 o Immunotherapy (methylprednisolone, IVIG, plasma exchange): check CSF and blood for autoimmune panel o Non-drug therapy: ketogenic diet, therapeutic hypothermia (32-35°C), epilepsy surgery • Investigations: o Random glucose, electrolytes, RFT, LFT, TFT o Toxicology screen, drug level (AED) o ECG, CXR, CT brain o ± Autoantibody, e.g. anti-NMDA receptor Ab

Answer 72

Median frontoparietal - Contralateral hemiplegia* (leg > arm) & hemisensory loss - Cognitive deficits: confusion, poor judgement, disinhibition

Answer 73

- Contralateral hemiplegia (face/ arm > leg) & hemisensory loss - Contralateral homonymous hemianopia (optic radiation - +/- Gaze deviation to lesion side - Dominant sphere (left): aphasia, Gerstmann syndrome • Broca’s aphasia: superior division of MCA • Wernicke’s aphasia: inferior division of MCA • Gerstmann syndrome: agraphia, acalculia, finger agnosia, left-right dissociation - Non-dominant sphere (right): contralateral hemineglect, apraxia

Answer 74

Donald-duck speech (spastic speech)

Answer 75

- Any large atherosclerosis - Any autoimmune disorder (anti-phospholipid syndrome) - Any malignancy - Any family history (CADASIL)

Answer 76

Triad: Ophthalmoplegia, ataxia, confusion

Answer 77

Auscultation of the eyeball S/S: red eye, tortuous vessel on sclera, proptosis, periorbital swelling, orbital bruit Type: direct, indirect Ix: CTA, DSA

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