Neurology Flashcards
Clinical features of Parkisonism
Motor:
- Bradykinesia
- Tremor
- Rigidity
- Postural instability
- Masked face & monotone
- Striatal hand phenomenon
- Gait (shuffling gait, stooped posture, reduced arm swing)
- Micographia
Non-motor:
- sensory (pain)
- Autonomic - constipation
- Psychiatric: REM sleep behaviour disorder, excessive daytime sleepiness
Special test of PD
- Bradykinesia
- Gait
Parki-plus
- Vertical gaze (PSP)
- Cerebellar signs (MSA)
- BP
-MoCA
-Writing
-Drug history
Causes of Parkisonism
- Idiopathic Parkinson’s disease (80%)
- Parkinson-plus syndromes: MSA, PSP, CBD, DLB
- Vascular parkinsonism: lacunar infarcts at basal ganglia (characterized by lower body involvement)
- Drug-induced: dopamine antagonists (antipsychotics, antiemetics), valproate, methyldopa
- Metabolic disorders: Wilson’s disease, Huntington’s disease, anoxic brain damage post-cardiac arrest
- Toxins: CO, Mn, MPTP
- Infections: post-encephalitis, neurosyphilis, etc.
- Structural brain lesions: tumors of basal ganglia, normal pressure hydrocephalus, head trauma (Pugilist
Parkinson-plus syndromes differentiate from typical Parkinson’s disease
Red flags of atypical Parkinsonism:
o Early falls / postural instability
o Early dementia
o Bilateral symmetrical onset
o Early ANS dysfunction
o Poor response to L-DOPA
shorter survival, rapid progression, more frequent complications
What is Multiple system atrophy?
Clinical features, Subtypes, Radiological
Clinical features:
- Dysautonomia
- Cerebellar signs
- Pyramidal signs
Subtypes:
- MSA-P
- MSA-C
- Shy-Drager syndrome
Radiological:
- hot cross bun sign
What is Progressive supranuclear palsy?
Clinical features, Radiological sign
Clinical features:
- Axial rigidity —> hyperextended neck
- Vertical gaze palsy —> downward gaze
- Pseudobulbar palsy e.g. dysarthria, dysphagia
- Frontal signs: cognitive impairment, apathy, depression
Radiological sign:
- Hummingbird sign on sagittal MRI
- Mickey Mouse sign on transverse MRI
What is Corticobasal degeneration (CBD)?
Clinical features
Clinical features:
o Marked asymmetry (unlike other Parki-plus): clumsiness of one hand
o Cortical signs: limb apraxia, agnosia, alien limb phenomenon
o Dementia (late)
What is Dementia with Lewy bodies?
Clinical features
Diagnosis
Treatment
Clinical features:
- Dementia onset within 1 year
- Day-to-day cognitive fluctuations
- Visual hallucinations
- REM sleep behaviour disorder
Diagnosis:
- CT brain
Treatment:
- AChE inhibitors (Dementia)
- clozapine (Psychosis)
- levodopa-carbidopa (Parki)
- melatonin (RBD)
How to diagnose IPD?
Clinical diagnosis: Movement Disorder Society criteria
- Presence of Parkisonism
- more than 2 supportive criteria
- No red flag of atypical Parkinsonism
- Absence of absolute exclusion
if < 50 years old / other neurological signs (e.g. UMN) / suspect atypical Parki
• Imaging:
o MRI brain
o Dopamine transporter single-photon emission CT (SPECT): demonstrate loss of DA neurons, but cannot tell
PD from Parki-plus
• Others: TFT, B12/folate, VDRL, Wilson’s disease (ceruloplasmin, serum Cu, 24h urine Cu)
Management of IPD
Multidisciplinary team approach:
- exercise, speech therapy, screen depression, caregiver stress, fall prevention
Pharmacological therapy:
Start ALL patients on dopaminergic therapy
o MAO-B inhibitors: selegiline, rasagiline - neuroprotective effect
o If functional impairment (ADL, falls), add medications
—> Young (< 70) + good QoL: dopa-sparing drugs, e.g. dopamine agonist, anticholinergic
—> Old (>70) or poor QoL: levodopa combination (e.g. Sinemet, Madopar)
o Amantadine for dyskinesia
o SC Apomorphine for rescue
Surgical therapy:
- Deep brain stimulation: subthalamic nucleus (STN) or globus pallidus (GPi)
What is MAO-B inhibitor?
Can be used as monotherapy / combined with L-DOPA
• Potential neuroprotective effect
Example:
selegiline (available as patch),
rasagiline (more potent, less risk of cognitive S/E)
Side effects: insomnia, stomatitis, headache, serotonin syndrome (if +SSRI)
Levodopa use in IPD
Mechanism of action
Counselling for administration
Side effects
levodopa-carbidopa (Sinemet)
levodopa-benserazide (Madopar)
Mechanism of action:
- dopamine precursor
- combined with peripheral DOPA decarboxylase inhibitor to increase CNS bioavailability and reduce nausea
Counselling for administration:
- start at low dose with meals
- then take on empty stomach
- do not stop abruptly (Parkinsonism-hyperpyrexia syndrome)
- require multiple dosing (short half life)
Side effects:
- n/v —> increase dose of carbidopa and add domperidone
- Postural hypotension —> decrease anti-HT, give compression stockings, increase fludrocortisone, midodrine
- VH, delusion
- Motor fluctuation
o Types: wearing-off, delayed-on, no-on, random on-off
o Duration of benefit becomes shorter after long-term use
o Off phenomenon (end-of-dose akinesia):
—> Frequency / Switch to CR form
—> Add DA agonist/ COMT inhibitor/ MAOB inhibitor
—> SC apomorphine (short-acting DA agonist): rescue agent
o Peak-dose dyskinesia: choreiform in nature —> increase frequency, decrease dose, CR form —> Add amantadine (NMDA receptor antagonist) —> Offer DBS to young patients
What is DA agonist in IPD?
Type
S/E
Used to delay the use of L-DOPA
• Ergots (risk of restrictive valvular disease, retroperitoneal fibrosis): e.g. cabergoline
• Non-ergots (preferred): e.g. ropinirole / pramipexole PO, rotigotine daily patch
Side effects: similar to L-DOPA, but more non-motor side effects
• Impulse control disorders (activation of reward system)
o Risk factors: male, young, Hx/FHx of ICD / mood disorders
• Excessive daytime sleepiness
• Hallucinations
How is anti-cholinergics used in IPD?
Example: benzhexol/trihexyphenidyl (Artane)
Helpful for resting tremor-predominant PD
Side effects: dry mouth, constipation, AROU, glaucoma, cognitive decline —> caution in elderly
How is COMT inhibitor used in IPD?
Can only be used as adjunct to L-DOPA e.g. levodopa-carbidopa-entacapone (Stalevo)
Decrease GI metabolism of levodopa
might dyskinesia
Examples: entacapone, tolcapone
Side effects: brownish-orange urine discolouration, deranged LFT (tolcapone only)
Treatment for non-motor symptoms in IPD
• Depression: pramipexole / traditional antidepressants
• REM sleep behaviour disorder: clonazepam, melatonin
• Excessive daytime sleepiness: modafinil, methylphenidate
• Constipation: stool softeners, laxatives
Deep brain stimulation in IPD
Selection of patients:
o Idiopathic PD
o Advanced: > 5 years since diagnosis
o Excellent response to L-dopa (predict response to DBS)
o Motor fluctuations from L-dopa therapy (e.g. peak-dose dyskinesia) despite optimal treatment
o Age ≤ 75
o Severity: UPDRS motor score >30/108 at off state, Hoehn-and-Yahr grade ≥ 3
C/I:
o General: coagulopathy, medically unfit
o Specific: Parkinson-plus syndrome, mentally unfit (e.g MMSE < 24 / 30, comorbid psychiatric problem /
dementia)
Site of implantation:
- subthalamic nucleus
- globus pallidus interna
Procedure:
o Pre-operative: Madopar challenge test, MMSE, assessment by psychiatrist
Causes of syncope
- vasovagal - neurally related
—> associated with standing, emotion, situational (micturition), post exercise - orthostatic - postural related
—> related to plasma volume and drug (vasodilators), can be related to autonomic dysfunction or neurodegeneration - cardiac
—> arrhythmia related, tachycardia/ bradycardia, e.g. severe AS, HOCM, PE
Vasovagal syncope
Tiring (prodromal signs) —> syncope —> slow regain of consciousness (no neurological deficit but very tired)
Pathogenesis:
Trigger (emotional…) —> increase sympathetic system —> increase BP —> carotid body sense this —> activate parasympathetic system -> vasodilation + decrease HR —> but para > sym -> vasovagal syncope
VS cardiac cause, —> cardiac cause does not have prodromal signs
Syncope ddx
Neurogenic
- seizure, GTC
- ICH
-TIA
Vascular
-subcalvian steal syndrome
Metabolic
- hypoxia
-hypoglycaemia
Intoxication
Psychogenic
Definition and DDx of Spastic paraparesis
Definition: spasticity (velocity-dependent) + paraparesis (paralysis of both lower limbs)
DDx
1. Spinal cord
-Extrinsic cause
• Trauma
• Space occupying lesion
• Prolapsed disc / spondylosis
-Intrinsic causes
• Space occupying lesions
• Inflammation (transverse myelitis): MS, NMOSD,
ADEM, SLE
• Vascular: infarct (anterior spinal artery occlusion)
• Infection: TB, HSV, syphilis
• Iatrogenic: post-RT myelopathy
• Metabolic: B12 deficiency (subacute combined
degeneration of cord)
• Paraneoplastic
• Neurodegenerative: MND, Friedreich’s ataxia
• Hereditary: hereditary spastic paraparesis (usually AD)
- Brain stem
-Tumor - Cerebral
-cerebral palsy
-parasgaittal meningioma
Clinical feature of spastic paraparesis
Clinical features
• Initial phase may present as spinal shock (LMN: flaccid paralysis, areflexia, loss of sensation) for 1-2 weeks
• Recovery: hyperreflexia, return of anal tone & bulbocavernosus reflex
• Bilateral pyramidal signs
• Gait: scissoring gait, high steppage gait (UMN weakness of dorsiflexors), sensory ataxia
• Look for features of underlying causes
-Cord compression —> Sensory level (may be falsely localizing)
-Trauma —> scars/deformity
-MS —> Dorsal column sign, Cerebellar signs, eye signs
-B12 deficiency —> Peripheral neuropathy, upgoing plantar but absent ankle jerk, Anemia, jaundice, glossitis, splenomegaly
-Taboparesis(syphilis) —> Upgoing plantar but absent ankle jerk, Argyll-Robertson pupils
-Friedreich’s ataxia —> Cerebellar signs, pes cavus, kyphoscoliosis
-cervical myelopathy —> Lhermitte’ sign, myelopathy hand signs (e.g. inverted supinator jerk)
-Anterior spinal artery occlusion —> AF
What is Transverse myelitis?
Definition
Etiology
S/S
Ix
Mx
Definition: inflammation of spinal cord (without structural abnormalities, i.e. trauma / cord compression)
Aetiology
• Idiopathic
• Demyelinating disease (MC), e.g. MS, NMOSD, ADEM - i.e. TM as a precursor in MS spectrum
• Infection: HSV, enterovirus, syphilis
• Autoimmune: RA, SLE, AS, etc
• Paraneoplastic syndrome
S/S: severe neck/ back pain, subacute paraparesis with a sensory level
Investigations
• Demonstrate cord inflammation without compression:
o MRI spine with gadolinium contrast
o CSF: pleocytosis with elevated IgG
• Workup for underlying causes (e.g. B12, AQP-4, viral serology, malignancy screening, autoimmune panel)
Management
• IV methylprednisolone 1g daily for 7 days then taper dose —> if failed —> plasma exchange
• Treat underlying cause
• Consider prophylaxis if recurrent TM e.g. azathioprine
• Supportive care for complications, e.g. respiratory support, NG tube, analgesics, antispasmodic
What is cervical myelopathy?
Causes
Clinical features
Causes
• Cervical spondylosis (MC): degenerative disc, OPLL
• Trauma (whiplash injury)
• Tumor
• Inflammation: MS, NMOSD
• Infection: TB
Clinical features
• Motor: LMN at lesion level (fasciculations, wasting), UMN below lesion level
• Sensory: dermatomal pattern
• Pseudoathetosis: unconscious writhing movement of fingers with eyes closed (dorsal column damage)
• Lhermitte’s sign: shock-like sensation upon forced flexion of neck
• Myelopathic hand signs:
o Mid-cervical reflex pattern if C5-C7 affected: inverted biceps (biceps extends) & inverted supinator reflexes
(finger flexes), brisk triceps
o Finger escape test
o 10-second test / Grip and release test: should be able to open and close fist for ≥20 times
o Hoffman sign: flick DIP of middle finger à index and thumb will flex
Types of CNS demyelinations diseases
CNS inflammatory demyelinating diseases (IDD)
• MS
• NMOSD
• Myelin oligodendrocyte glycoprotein (MOG)-IgG+
disease: ADEM, ON, myelitis, etc
Definition, pathlogy and clinical patterns of multiple sclerosis
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)
Clinical features of multiple sclerosis
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)
How to investigate and diagnose multiple sclerosis?
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
Management of multiple sclerosis
• 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
MS in pregnancy
• 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
Progressive multifocal leukoencephalopathy (PML)
• 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
Neuromyelitis optica spectrum disorder (NMOSD)
• 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
Acute disseminated encephalomyelitis (ADEM)
• 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
Anti-NMDA receptor encephalitis
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
Etiology Cerebellar syndromes
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
Clinical features of Cerebellar syndromes
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
Hereditary ataxias
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
Etiology, Clinical features, Diagnosis and management of Amyotrophc lateral sclerosis
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)
Kennedy’s disease (X-linked spinobulbar muscular atrophy)
• 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
Spinal muscular atrophy
• 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
Poliomyelitis
• 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)
Clinical features, Ix and DDx of peripheral neuropathy
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
Guillain-Barré syndrome
Pathophysiology and clinical features
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)
Variant of GBS
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
Ix and Mx of GBS
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
Chronic inflammatory demyelinating polyradiculopathy (CIDP)
• 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
B12 deficiency neuropathy
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)
Charcot-Marie-Tooth disease (CMT)
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
Causes of myopathy
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
Clinical features, Ix and Mx of myopathy
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
Type of myopathy
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
Classification and Pathophysiology of Myasthenia gravis
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,
Clinical features of MG
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
Grading, Ix and Mx of MG
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
Myasthenic crisis
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
Cholinergic crisis
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
Lambert-Eaton Myasthenic syndrome (LEMS)
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
Botulism
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
Diplopia
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
Increased ICP Etiology
• SOL: tumour, abscess, haematoma
• Cerebral oedema: trauma, infection, post-stroke
• Hydrocephalus: obstructive (IVH, tumour), communicating (post-meningitis, post-SAH)
• Idiopathic intracranial hypertension (IIH)
Clinical features of increased ICP
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)
Differential diagnosis of hydeocephalus
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
How to diagnose stroke?
Clinical diagnosis
- Sudden onset of focal neurological deficit
- majority have background of risk factors (age, smoking, HT, HL…)
- symptoms maximum at few minutes
CT brain in stroke
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
Large-vessel atherosclerosis in stroke
- 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
Cardioembolic in stroke
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
Small vessel disease of stroke
Cannot show blockage of vessel in MRA/CTA
Small vessel disease of stroke
Cannot show blockage of vessel in MRA/CTA
Secondary stroke prevention
- Extracranial and intracranial steno-occlusive diseases
- Atherosclerotic and radiation-induced lesions
- Limitation of stenting
Young on-set stroke
Subclavian steal syndrome
Cortical signs
- Global aphasia
- Eye deviation (frontal lobe control conjugate gaze)
- hemineglect
Indications of endovascular thrombectomy
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
ASPECTS score
- 10 zone
- if early ischemic change in 1 zone, minus 1 mark
- max. 10 marks
Mx of increased ICP
• 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
Idiopathic intracranial hypertension
• 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
Normal pressure hydrocephalus (NPH)
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
Cerebral oedema
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
DDx of headache
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
Migraine
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)
Tension headache
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
Cluster headache
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
Trigeminal neuralgia (Tic douloreux)
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)
Horner’s syndrome
Miosis (constrictive pupil)
Ptosis
Anhidrosis
Enophalmosis (inset eyeball)
Deifinition of seizure, convulsion, epilepsy and resolved epilepsy
• 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
Clinical features of seizure
Ix of seizure
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)
Generalized seizure
• 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
Focal seizure
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
Mx of seizure
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
Broad spectrum AED
Broad-spectrum AED: all seizure type
- 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
Narrow-spectrum AED
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
Pregnancy in seizure
• 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
Driving in seizure
• 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
COVID vaccine in seizure
• 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
Mx of refractory epilepsy
• Ketogenic diet
• Vagal nerve stimulation
• Deep brain stimulation
• Epileptic surgery
o Example: temporal lobectomy (MC) for temporal lobe epileps
Status epilepticus
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
ACA stroke
Median frontoparietal
- Contralateral hemiplegia* (leg > arm) & hemisensory loss
- Cognitive deficits: confusion, poor judgement, disinhibition
MCA stroke
- 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
Type of dysarthria
Donald-duck speech (spastic speech)
Reason for recurrent stroke
- Any large atherosclerosis
- Any autoimmune disorder (anti-phospholipid syndrome)
- Any malignancy
- Any family history (CADASIL)
Triad of Wernicke encephalopathy
Triad: Ophthalmoplegia, ataxia, confusion
Carotid carvernous fistula
Auscultation of the eyeball
S/S: red eye, tortuous vessel on sclera, proptosis, periorbital swelling, orbital bruit
Type: direct, indirect
Ix: CTA, DSA
