Haematology

Question 1

Renal biopsy in nephrotic syndrome of amyloidosis

Answer 1

Renal biopsy:
- Amorphous acellular mesangial deposit —> Congo red stain: salmon pink deposition —> apple green birefringence under polarised light
- immunoreative to amyloid P

Question 2

AL amyloidosis

Answer 2

Primary AL amyloidosis

• Deposition of protein derived from immunoglobulin light chain fragments
• Usually due to plasma cell dyspraxia that produce monoclonal light chains

Common presentation:
- proteinuria, nephrotic range
- restrictive cardiomyopathy
- peripheral and autonomic neuropathy
- hepatomegaly, deranged LFT

Question 3

Amyloidosis

Answer 3

Definition:
fibrillation protein that is deposited in extracellular interstitial tissue, resulting organ dysfunction by pressure atrophy of adjacent cells (but not evoking inflammation)

Types:
Systemic:
- Primary AL amyloidosis: multiple myeloma
- Reactive AA amyloidosis (usually due to infection, e.g. TB, osteomyelitis), chronic inflammation e.g. RA, AS, IBD —> changing epidemiology across time
- beta2-microglobulin accumulation: Dialysis-associated amyloidosis: long-term haemodialysis
- Transthyretin accumulation
1) ATTR-wt Senile systemic amyloidosis (cardiomyopathy and carpel tunnel syndrome but rarely ESRD
2) ATTR variant (usually present with peripheral neuropathy), related to mutations, treated by tafamidis, Parisiran
- Hereditary amyloidosis —> all autosomal dominant with variant penetrance —> most common type is fibrinogen A alpha chain (reach ESRD early), Apolipoprotein A1 (rarely reach ESRD), lysozyme amyloidosis
- AH/ AHL amyloidosis (less cardiac involvement and better prognosis than AL), related to lymphoproliferative diseases)

Localised: Alzheimer’s disease [amyloid beta], MTC [calcitonin]

Clinical features
- Kidney: nephrotic syndrome
- CVS: restrictive cardiomyopathy
- Organomegaly: hepatomegaly, splenomegaly, macroglossia, pseudohypertrophy of muscles

Diagnosis:
- Congo red stain under polarised light - aple-green briefringence
- false +ve and -ve are common in immunofluorescence stain in renal biopsy , extremely expensive but gold standard for mass spectrometry for amyloid typing

Mx:
- as usual CKD —> ACEI, control HT

Question 4

PCA Stroke

Answer 4

Occipital
Inferior temporal
Thalamus
Midbrain

Visual disturbance (occipital lobe)
• Unilateral: contralateral homonymous hemianopia with macular sparing (Dual supply from MCA + PCA)
• Bilateral: cortical blindness with preserved pupillary light reaction

Hemisensory loss (thalamus) without hemiplegia
+/- contralateral hemiballismus (subthalamic nu.)
+/- prosopagnosia (fusiform gyrus)

Question 5

Weber syndrome

Answer 5

Medial midbrain

CN3 palsy (eyes down and out, ptosis, dilated pupils)
Contralateral hemiplegia (cerebral peduncle)
+/- contralateral Parkinsonism (substantia nigra)

Question 6

Claude stroke

Answer 6

tegmentum of midbrain

CN 3 palsy (eyes down and out, ptosis, dilated pupil)
Contralateral ataxia (red nu. & rubro- tracts)

Question 7

Benedikt stroke

Answer 7

Rostral midbrain

Similar to Claude’s, but more tremor and choreoathetotic movements

Question 8

Parinaud stroke

Answer 8

Dorsal midbrain

Upward conjugate gaze palzy —> sunsetting eyes (vertical gaze centre in riMLF in superior colliculus)
Light-near dissociation^: pupils can accommodate but unresponsive to
light (pretectal nu. in superior colliculus)
Convergence-retraction nystagmus
Eyelid retraction

Question 9

Locked in syndrome

Answer 9

Bilateral median pons + midbrain (paramedian branches of basilar a.))

Quadriplegia
Bulbar plegia sparing eye movements (oculomotor pathways are more dorsal in midbrain and thus spared)

Question 10

Top of basilar syndrome

Answer 10

Bilateral midbrain, thal, temp. & occp. Lobes

Cognitive: COMA, hypersomnolence, agitation
Oculomotor: vertical gaze palsy, slow pupil reaction
Motor: usually no significant deficit

Question 11

Foville stroke

Answer 11

Medial inferior pons
(paramedian branches
of basilar a.)

One-and-a-half syndrome (= INO + horizontal gaze palsy)
Example: left MLF + left PPRF lesion:
- Left eye cannot adduct (MLF) + cannot abduct (CN 6)
- Right eye cannot adduct (PPRF)
Known as “8.5 syndrome” if 1.5 syndrome + CN 7 palsy

Nystagmus, ataxia (MCP, vestibular nu.)
Contralateral UMNL of face & limbs (pyramidal tract)
Impaired tactile & proprioception (medial lemniscus)

Question 12

Marie Foix stroke

Answer 12

Lateral inferior pons (AICA)

Vertigo, nystagmus, n/v (vestibular nu.), hearing loss +/- tinnitus (cochlear nu)
Cerebellar ataxia (MCP)
Decrease pain & temp sensation on ipsilateral face (spinal V nu) & contralat. limbs (STT)
Ipsilateral LMNL of face (CN 7 / facial nu)
Ipsilateral Horner’s syndrome (sympathetic)

Question 13

Wallenberg syndrome

Answer 13

Lateral medulla (PICA)

Vertigo, nystagmus, n/v (vestibular nu.)
Cerebellar ataxia (ICP)
Decreased pain & temp sensation on ipsilateral face (spinal V nu) & contralat. limbs (STT)
Bulbar signs: Dysphagia, dysphonia, dysarthria, Decreased gag reflex, deviated uvula (nu. ambiguus)
Ipsilateral Horner’s syndrome (hypothalamospinal tract)

Question 14

Dejerine

Answer 14

Medial medulla (ant. Spinal a.)

LMN CN12 palsy: flaccid paralysis, atrophy and fasciculations of tongue
Contralateral hemiplegia & loss of proprioception

Question 15

Malignant MCA syndrome

Answer 15

• Massive MCA territory infarct
—> Rapid neurological deterioration due to cerebral oedema or haemorrhagic transformation
• S/S: eye deviation, dense hemiplegia, progressive drowsiness, unequal pupil sizes
• CT: significant infarct with midline shift
• Mx: decompressive hemicraniectomy with durotomy within 48h, medical Mx for ICP*

Question 16

Stroke mimics

Answer 16

Structural:
CNS tumours: primary / metastatic
CNS infection e.g. brain abscess

Functional
Todd’s paresis (after epileptic seizure)
Hypoglycemia
Hemiplegic migraine
Focal seizures
Wernicke’s encephalopathy

Question 17

Acute Ms of stroke

Answer 17

• Admit acute stroke unit (ASU)
• Resuscitation: airway, breathing, circulation, GCS
• NPO until swallowing test, NG tube if fail
• Monitoring: vitals Q4h, neuro-obs Q30min x 2 then Q1h (risk of cerebral edema in 2-3d: malignant MCA Sx / cerebellar infarct)
• Baseline investigations*
o Urgent non-contrast CT brain: differentiate between haemorrhagic and ischaemic stroke
- Door-to-CT time: within 25 minutes
- Arrange CT angiogram (CTA) +/- perfusion scan for EVT triage (do not withhold tPA)
o Bloods: CBC, LRFT, clotting (for tPA), blood glucose (hypoglycaemia mimics stroke, hyperglycaemia worsens prognosis), HbA1c, lipids, ESR/CRP (vasculitis)
o CXR (r/o aortic dissection), ECG (AF, old MI, LVH)
• Ensure good hydration & oxygenation: IV NS Q6h (dextrose toxic to brain), supplemental O2
• Control blood sugar (aim normoglycemia) and pyrexia
• Antihypertensive: IV labetalol / nitroprusside / nicardipine for cautious and gradual lowering of BP
o Ischaemic stroke: aim BP < 220/120 (non-tPA) or 185/110 (pre-tPA) or 180/105 (maintain first 24h post-tPA)
o Haemorrhagic stroke: aim SBP < 140 unless clinical evidence of increased ICP
o Avoid hydralazine / nifedipine: direct-acting cerebral vasodilator à fall in cerebral blood flow

Question 18

Ischemic stroke classification

Answer 18

1) Cardioembolic (20%)
- Atrial fibrillation (AF) / flutter
Septic emboli (SBE)
Valvular disease e.g. MS, prosthetic valve
Recent MI / CHF / DCM
- Cortical / Cerebellar dysfunction
- Lesion > 1.5cm
Wedge-shaped / cortical infarcts +/- dense artery sign
Large infarcts (∵acute onset, no collaterals)

2) Large vessel atherosclerosis (25%)
- Atherosclerosis —> thrombosis
Artery-to-artery embolism
- Cortical/cerebellar dysfunction
- Lesion > 1.5cm
Watershed infarcts / border zone
Small infarcts (∵ collaterals)

3) Small vessel disease (25%)
- Hypertensive lipohyalinosis: (ageing of
astrocytes and gliovascular unit)
- Lacunar syndrome
- Lesion < 1.5cm

4) Stroke of other determined etiologies (5%)
- Cardiac: venous Patent foramen ovale
Vascular:
—> Dissection (carotid / vertebral /
basilar a.)
—> Vasculitis (SLE, Takayasu arteritis,
Moyamoya disease*)
—> Post-NPC radiation vasculopathy
—> Central venous thrombosis
Haematological: APLS, thrombophilia
Genetics: CADASIL (AD mutation of NOTCH3 gene)

5) Cryptogenic e.g. ESUS (embolic stroke of undetermined source) (25%)
- Emboli in aortic arch (not revealed by echo)
Paradoxical embolism e.g. PFO
Paroxysmal AF
- Non-lacunar infarcts with normal
cardiac (24h Holter + echo) & vascular workup (<50% stenosis)

Question 19

Mx of ischemic stroke

Answer 19

• PO Aspirin 300mg stat —> 80mg daily (delay 24h if tPA given)
o If allergic: clopidogrel 300mg stat —> 75mg daily
o Consider DAPT x 3 weeks for high-risk TIA / minor stroke

• Thrombolytic therapy (tPA)
o Mechanism: tPA converts plasminogen to plasmin —> breaks up thrombus into FDP
o Pre-requisite: onset < 4.5h (or last time seen well) + good premorbid function
o Absolute C/I:
- History: prior ICH, intracranial neoplasm,
ischaemic stroke/ intracranial surgery / severe
HI / MI within 3mo
- Clinical: S/S suggestive of SAH, uncontrolled
HT > 185/110, active internal bleeding, aortic
dissection
- Radiological: intracranial haemorrhage,
extensive infarct (ASPECTS ≤7 but no absolute cutoff)
- Haematological: INR > 1.7, Plt < 100, use of LMWH within 24h / DOAC within 48h
o Administration: IV alteplase 0.9mg/kg, max 90mg (10% as bolus, 90% as slow infusion over 1h) / IV Tenecteplase 0.25mg/kg bolus —> repeat CT brain 24h later
- If on dabigatran for 48h, can consider idarucizumab 5g IV stat
o Benefits: prevent complications, improve function, does not decrease mortality
o Risks:
- Haemorrhagic transformation / ICH (6%): suspect if deterioration 2-3 days after stroke
—> Ix: Urgent CT brain, urgent bloods (CBC, clotting, fibrinogen, X-match)
—> Mx: discontinue tPA, give IV 1000mg tranexamic acid + 10U cryoprecipitate
- Systemic bleeding: generally do not require stop tPA unless major GI bleed
- Orolingual angioedema: rapidly cause airway obstruction
—> Mx: discontinue tPA, IV methylprednisolone / antihistamines, +/- SC adrenaline
- Failed recanalization (success rate only 15-20%)

• Endovascular thrombectomy (EVT)
o Pre-requisites:
- CT angiogram (CTA) confirming large vessel occlusion
—> Large vessel: CCA, ICA, MCA M1, basilar artery
- Time of onset: up to 24h
—> Onset <6h (HERMES study: meta-analysis)
—> Onset 6-24h + CT perfusion scan for clinical-core mismatch (core-penumbra mismatch)
o Relative contraindication: ASPECTS < 7
o Technique: aspiration thrombectomy, stent retriever (e.g. Merci retriever), NO tPA given
o Recanalization rate: up to 80%
o Risks: vascular injury (e.g. dissection, perforation), puncture site complications (e.g. retroperitoneal haematoma), cholesterol embolization syndrome (S/S: liverdo reticularis, blue toe syndrome, renal impairment, hypereosinophilia, increased EDR/CRP), contrast allergy / nephropathy
- maintain post-EVT BP to 140/80-90

• Anticoagulation with warfarin/DOAC:
o Indicated in
- Documented cardio-embolism (echocardiogram): immediate if TIA / minor stroke, withhold 2 weeks if
large infarct / symptoms of haemorrhagic transformation / poorly controlled HT
- Extracranial carotid/vertebral artery dissection (CTA +/- DSA) (Intracranial is C/I due to risk of SAH)
- Cerebral venous thrombosis (MRI venogram)
o Contraindications: BP > 180/110, large infarct

• ICP management in malignant MCA syndrome / massive cerebellar infarct
o Elevate head of bed > 30° , IV mannitol / hypertonic saline, hyperventilation
o Refer NS for decompressive hemicraniectomy +/- duroplasty
- Can consider cranioplasty (replace skull bone) if within 6 months to protect brain tissue
o Consider external ventricular drainage

Question 20

Complications of acute ischaemic stroke

Answer 20

• Cerebral oedema with mass effect: mostly occur 2-3 days after stroke
• Haemorrhagic transformation:
o Mechanism: reperfusion injury (∴­risk in tPA) + collateral flow
o Suspect if power keeps on deteriorating after stroke, mostly occur 2-3 days after stroke
• Hydrocephalus: cerebellar infarct à edema compresses onto 4th ventricle —> obstructive hydrocephalus
• Seizure: prophylactic anticonvulsants are not recommended
• Vascular dementia
• Dysphagia & aspiration pneumonia

Question 21

Transient ischaemic attack (TIA)

Answer 21

Clinical features
• Fully reversible lasting <24 hours without evidence of infarction on imaging
• Symptoms maximal at the onset
• Gradual progression of symptoms suggests other DDx, e.g. MS, tumour

ABCD2 score: age, BP, clinical, duration of Sx, DM (max 7)
• ABCD2 score < 4: 2-day risk of stroke minimal —> MRI in 7 days + aspirin daily for life
• ABCD2 score ≥4: 2-day risk of stroke high (~8%) —> MRI within 24h + DAPT for 3 weeks (initiated within 24h of index ischemic event) then lifelong aspirin

Investigations
• Exclude stroke mimics by brain imaging: MRI with DWI
• Etiology
o Vascular: MRA/CTA, carotid Doppler
o Cardiac: Holter, echocardiogram
o Haemat: CBC, clotting
o Metabolic: fasting glucose, HbA1c, lipid profile

Question 22

Primary prevention of ischemic stroke

Answer 22

• Lifestyle modification
• Treat atherosclerotic risk factors (HT, DM, HL)
• Oral anticoagulation: if CHADS2-VASc score ≥ 2
• Aspirin: net benefit is marginal
• Asymptomatic carotid stenosis: intensive medical therapy ± consider carotid enderterectomy (CEA)/carotid angioplasty and stenting (CAS) if severe (>70%)

Question 23

Secondary prevention of ischemic stroke due to atherosclerosis

Answer 23

1) Atherosclerotic:
CVS risk reduction: ACEI, statins, smoking cessation, drinking, exercise
Single anti-platelet agent: HA use aspirin 80mg daily / aspirin + tds dipyridamole (s/e: headache)
• Studies prefer: Aggrenox (aspirin + ER dipyridamole – PDE3 inhibitor), Plavix only
Short-term DAPT (aspirin + clopidogrel) only in following settings:
• C/I in major ischemic stroke (too high bleeding risk)
• 3 weeks if high risk TIA (ABCD2 ≥4) or minor stroke (NIHSS ≤3) – [CHANCE]
• ICAD > 50% stenosis: 3 months
• ECAD: bridging to revascularization / post-CAS

Carotid stenosis: intensive medical therapy + revascularisation within 2 weeks of stroke (for ECAD)
• ECAD ≥70% (>50% can consider) carotid endarterectomy (CEA) vs carotid angioplasty &
stenting (CAS)
1. CEA (preferred)
- More effective
- GA risk —> MI
- Preferred in Elderly: tortuous vessels / difficult for stenting
- DAPT Not required

2. CAS (more common in PWH)
   - Less effective
   - Ischemic stroke (clot embolization)
   - Radiation-induced arteriopathy
   Re-stenosis after CEA
   Unfit for surgery
   Difficult surgical access
   - DAPT required for Pre-op 5-7 days, post-op 3 months

• ICAD: high peri-procedural stroke risk à only if recurrent stroke despite best medical therapy

Question 24

Secondary prevention for ischemic stroke due to carotid/vertebral dissection

Answer 24

Aetiology: idiopathic, trauma
S/S: neck pain/ headache à stroke symptoms
Mx:
• tPA if within 4.5h
• Antiplatelet / anticoagulation for 6 months
• Carotid stenting: if failed medica

Question 25

Secondary prevention for ischemic stroke due to cardioembolic /APLS

Answer 25

Anticoagulation: if CHADS2-VASc score ≥ 2 (aspirin has risk but no benefit!)
DOAC (e.g. dabigatran):
• Pros: fixed dose, ↓risk of ICH (lowest in dabigatran), few DDI and food interaction
• Cons: short half-life (risk of stroke after missing 1-2 doses), no monitoring method,
expensive antidotes, not suitable for renal/ liver impairment
• Antidotes: idarucizumab (dabigatran), recombinant FXa (apixaban/ rivaroxaban)

-Start immediately if TIA / minor stroke, but withhold 2 weeks if large infarcts to lower risk of haemorrhagic transformation

Question 26

Definitions of haemorrhagic stroke

Answer 26

Intracranial haemorrhage/ haemorrhagic stroke: collective term characterised by extravascular accumulation of blood
within different intracranial spaces, including
• Intra-axial haemorrhage: intracerebral haemorrhage ICH, intraventricular haemorrhage IVH
• Extra-axial haemorrhage: extradural (EDH), subdural (SDH), subarachnoid (SAH)

Question 27

intracerebral haemorrhage

Answer 27

Aetiology (in order of prevalence)
• Hypertensive arteriopathy (rupture of capillary microaneurysms): deep ICH – more central
o Common sites: pons, cerebellum, putamen, thalamus
• Cerebral amyloid angiopathy (CAA): lobar ICH – more peripheral
• Others: coagulopathy, structural vascular lesions (e.g. Berry aneurysms, AVM), drugs (e.g. cocaine)

Clinical features: Gradual increase of S/S (over min-hours)
• FND, e.g. hemiplegia (putamen), quadriplegia, coma, pinpoint pupils (pons), ataxia (cerebellum) – deep ICH
• Seizures – more common in lobar ICH

Investigations
• Urgent NCCT brain: size and location of haematoma, any IVH / hydrocephalus, any mass effect
• MRI brain
• Investigations for underlying causes: CBC/ clotting (coagulopathy), CTA (aneurysm/ AVM), blood culture/ ECHO (mycotic aneurysm), tumour markers (brain met)

Management
• Antihypertensive: IV labetalol
o Treat if SBP > 150 (unless evidence of increased ICP)
o Target SBP <140, but avoid rapid BP reduction (renal complications)
• Urgent reversal of anticoagulation if INR↑ (see [Clin Pharm])
o E.g. Warfarin: vit K1 5mg IV + Prothrombinex 50 units/kg + FFP (recheck INR after 15 mins)
• Anticonvulsant: if seizure (not prophylaxis)
• Consult neurosurgery: open craniotomy for clot evacuation +/- external ventricular drainage in
o Supratentorial haematoma (>30mL) with life-threatening mass effect (e.g. midline shift)
o Cerebellar haematoma >3cm / large cerebellar infarct (risk of brainstem compression & hydrocephalus)
o Intraventricular haemorrhage (risk of hydrocephalus)

Question 28

Subarachnoid haemorrhage

Answer 28

Aetiology
• Aneurysm: ACOM (35%) = PCOM (35%) > MCA (20%)
o Berry/ saccular: familial (e.g. CT disease, ADPKD, Moyamoya), HT, smoking, alcohol
o Fusiform: atherosclerosis
o Mycotic: SBE
• Non-aneurysmal: trauma, AVM, coagulopathy, cocaine abuse

Clinical features
• Headache: sudden onset, severe “thunderclap” / worst headache ever had
• Brief LOC
• Meningism: neck stiffness, photophobia, n/v

Complications (9H)
• Early: haematoma, intracranial HT, systemic HT (compensate ↑ICP), HF / arrhythmia / APO
• Late: haemorrhage (re-bleed), hypoperfusion (vasospasm), hydrocephalus, hypovolaemia (CSW), hypoNa (SIADH)

Grading: World Federation of Neurosurgical Societies (WFNS) system - based on GCS and motor deficits

Investigations
• Urgent NCCT brain: hyperdensity in basal cisterns around circle of Willis (65%) or Sylvian fissure (30%)
• LP (2nd line if CTB normal): bloody CSF, xanthochromia (12h to 12d), persistent ­RBC > 100000, ­protein
• Non-invasive vascular imaging for cerebral aneurysms: CTA/MRA —> DSA

Management – consult neurosurgeons
• Resuscitation (ABC)
• Watch out for cervical spine injury and other associated injury: neck collar, CXR, C-spine X ray ± CT C spine
• Bed rest, NPOEM, IV fluids, monitor vitals + neuro-obs
• Correct hypoglycemia, temperature / fluid / electrolyte abnormalities
• Symptomatic: analgesics, anticonvulsant, stool softener prn
o Antihypertensive: Nimodipine 60mg Q4h PO / IV (prevent vasospasm, decreased risk of delayed cerebral infarction)
o Closely monitor BP: target SBP < 160 (note risk of rebleeding vs maintenance of CPP)
o Tranexamic acid: for < 72h or until surgical treatment (risk of thrombosis)
• Early aneurysm occlusion to reduce risk of rebleeding
o Endovascular (1st line): DSA + coil embolization of aneurysm; Cx contrast allergy, embolism
- New modality: flow diverter (~ EVAR)
o Surgical: craniotomy + microsurgical clipping

Question 29

Cerebral venous thrombosis

Answer 29

Clinical features (require high index of suspicion)
• 1% of stroke
• S/S depends on site:
o Cerebral venous sinus thrombosis (90%): ↑↑ICP (headache, papilledema,↓GCS), seizure
o Cavernous sinus thrombosis: proptosis, painful ophthalmoplegia, CN 3, 4,
6, V1 involvement
o Deep cerebral venous thrombosis (10%)

• Investigations:
o Plain CT / MRI: dense delta sign, infarct not following arterial territory
o CT/MRI venogram for filling defect
- Empty delta sign: superior sagittal sinus involvement (fig.)

• Management:
o Anticoagulation: LMWH —> warfarin (the ONLY indication of anticoagulants in ICH)
o Endovascular thrombolysis in selected patients
o ICP management

Question 30

Primary and secondary prevention for haemorrhagic stroke

Answer 30

• Control of modifiable risk factors: Hypertension
• Avoid unnecessary antithrombotic drugs: Choose DOAC (dabigatran) if strongly indicated (lower ICH risk than warfarin)

Question 31

Hyperkinesia - action tremor

Answer 31

Def:
Tremor that occurs during voluntary muscle contraction, 4-11Hz

Ddx:
• Exacerbated physiological tremor (MC): fine postural tremor 10-12Hz, e.g. hyperT4, drug-induced (e.g. SABA, valproate), anxiety, fever
Parkinsonism)
• Essential tremor: 8-10Hz, involve bilateral arms, head nodding, voice; FHx in 50% (genes: ETM1, ETM2)
• Cerebellar tremor: coarse, 4-6Hz, past-pointing, a/w other cbll signs
• Psychogenic (functional)

Mx:

Ix: TFT, Ix for cerebellar syndromes

Essential tremor: propranolol(1st line), gabapentin, topiramate, clonazepam (anxiety predominant), Botox injection, DBS at thalamus (rarely done)

Question 32

Dystonia

Answer 32

Def:
Sustained muscle contractions, causing twisting /repetitive movements or abnormal posture

ddx:
- Primary, e.g. sporadic blepharospasm, cervical dystonia, task-specific (writer’s cram, musician dystonia)
- Secondary, e.g. CO, drug-induced (antipsychotic levodopa), infection (JBE), Wilson’s s disease

Mx:
R/o Wilson’s disease if young
Botulinum toxin injection
Artane, tetrabenazine (DA deleting agent), clonazepam
DBS at GPi

Question 33

Choreiform movements (Ballism-chorea-athetosis)

Answer 33

Def:
A spectrum of involuntar, continuous, irregular movements
Ballism: wild flinging with large amplitude, most severe
Chore: dance-like movement
Athetosis: slow writhing movement of distal limbs

Ddx:
- Hereditary: Huntington’s chorea (CAG repeats)
-Drug induced: antipsychotics (tar dive dyskinesia), levodopa (“on” dyskinesia)
- Endocrine: thyrotoxicosis
- Vascular: lacunar infarct at basal ganglia (subthalamic nucleus) —> hemiballism
- immunological: Sydenham’s chorea (rheumatic fever), SLE

Mx:
Tetrabenazine, valbenazine, deutetrabenazine

DBS at GPi

Question 34

Myoclonus

Answer 34

Def:
Positive myoclonus: sudden brief jerks due to active muscle contractions
Negative clonus: asterixis (flapping tremor)

ddx:
- physiological: sleep jerks, hiccups
- metabolic: hepatic/renal failure (flapping tremor)
- epilepsy
- essential myoclonus

Mx:
Clonazepam
Anti-epileptic: valproate, levetiracetam

Question 35

Tics

Answer 35

Stereotyped brief repetitive actions due to inner urge
- simple motor (e.g. eye blinking, neck jerking, facial grimacing)
- simple vocal (e.g. running, barking)
- complex motor (e.g. jumping, copropraxia)
- complex vocal (e.g. repeat words, coprolalia)

Ddx:
- Tourette syndrome diagnosed with multiple motor + vocal tics for > 1 year, a/w OCD and ADHD
- transient tic disorder < 1 year
- drug induced

Mx:
DA antagonist
Clonidine
Tetrabenazine
Psychotherapy