Ischemic Stroke
Acute neurological deficit caused by interruption of blood supply to a region of the brain, typically due to thrombotic or embolic arterial occlusion, resulting in cerebral infarction.
Ischemic stroke is defined as the rapid onset of clinical symptoms and signs of focal (or global) disturbances of cerebral functions due to non-traumatic vascular causes, lasting > 24 hours, with structural brain damage on neuroimaging [1][2]. The word itself breaks down: "ischemic" (Greek: ischein = to hold back + haima = blood) → literally "holding back blood" from the brain.
The key mechanistic concept: brain tissue is exquisitely sensitive to oxygen deprivation — approximately 2 million neurons die per minute during complete ischemia [3]. The brain constitutes only ~2% of body weight but receives ~15-20% of cardiac output and consumes ~20% of total body oxygen. It has virtually no energy reserves (minimal glycogen stores), so any interruption of blood flow rapidly leads to neuronal injury and death.
Stroke vs TIA — the critical distinction
Transient ischemic attack (TIA): transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction — fully reversible, lasting < 24 hours, and NO evidence of infarction on neuroimaging [1][2]. The modern tissue-based definition emphasises that if there is diffusion restriction on MRI (i.e., actual infarction), it is a stroke regardless of symptom duration.
The distinction matters because ischemic stroke implies irreversible structural damage (infarction), while TIA is a warning event — up to 10-15% of TIA patients will have a stroke within 90 days, with the highest risk in the first 48 hours.
Epidemiology
- Most common adult neurological disease [3]
- 2nd and 3rd leading cause of death in China and Hong Kong respectively [3]
- Ischemic stroke accounts for 75–80% of all strokes; intracerebral hemorrhage (ICH) ~20%; subarachnoid hemorrhage (SAH) < 5% [1][2][3]
- Higher risk in men at most ages compared with women, except ages 35–44 years and > 85 years [1][2]
- Leading cause of long-term adult disability worldwide
- In HK, stroke is the 4th leading cause of death (Hospital Authority data, 2023–2024)
- Intracranial atherosclerotic disease (ICAD) is disproportionately common in Chinese/East Asian populations compared with Caucasians, where extracranial carotid disease predominates — this has major implications for treatment (medical optimisation vs. carotid endarterectomy)
- High prevalence of hypertension, diabetes, and atrial fibrillation in the aging HK population drives ischemic stroke burden
- Small vessel disease (lacunar infarcts) accounts for ~25% of ischemic strokes in Chinese populations — driven by the high prevalence of hypertension [1][4]
| Outcome | Ranking (worst → best) |
|---|---|
| Mortality | SAH (50% death at 1 month) > ICH (40% at 1 month, 50% at 1 year) > Cortical infarct (20% at 1 month, 35% at 1 year) > Lacunar infarct |
| Disability | SAH (50% with severe deficits) > Cortical infarct > ICH > Lacunar infarct |
Why is lacunar infarct the 'best' prognosis?
Because lacunar infarcts are small (< 1.5 cm) and confined to deep structures. They do not cause mass effect, rarely cause raised ICP, and typically present with pure motor, pure sensory, or mixed syndromes without cortical features. The clinical deficit is limited.
Risk Factors
Understanding risk factors is crucial because they directly inform secondary prevention strategy.
- Old age — single strongest risk factor; risk roughly doubles every decade after age 55
- Male sex — higher risk at most ages (oestrogen may be protective pre-menopausally)
- Previous vascular event (prior stroke/TIA, MI, peripheral vascular disease) — prior events indicate established atherosclerotic burden
- Family history of stroke or cardiovascular disease
- Ethnicity — Chinese/East Asian populations have higher intracranial atherosclerosis
| Risk Factor | Mechanism / Why it causes stroke |
|---|---|
| Hypertension | Single most important modifiable risk factor. Accelerates atherosclerosis in large vessels + causes lipohyalinosis in small penetrating arteries → lacunar infarcts. DM + HT together double the risk of stroke [5] |
| Diabetes mellitus | Accelerates atherosclerosis (glycation of vessel walls, endothelial dysfunction), promotes prothrombotic state |
| Hyperlipidaemia | Drives atherosclerotic plaque formation (LDL oxidation → foam cells → plaque) |
| Atrial fibrillation (AF) | Most important cardiac source of emboli. Stagnant blood in a non-contracting left atrial appendage → thrombus formation → embolism to brain |
| Cigarette smoking | Endothelial injury, pro-thrombotic state, accelerates atherosclerosis; strongest RF for peripheral arterial disease |
| Obesity and sedentary lifestyle | Promotes metabolic syndrome (HTN + DM + dyslipidaemia as a "bundle deal") [5] |
| Alcohol excess | Increases BP, promotes AF, direct toxic effects on vasculature |
| Carotid artery stenosis | Artery-to-artery embolism or haemodynamic compromise |
| Cardiac disease — CHF, recent MI, IE, valvular disease | Sources of cardioembolism |
| Blood abnormalities | High fibrinogen, polycythaemia, hyperhomocysteinaemia, OCP/HRT use, antiphospholipid syndrome |
High Yield — Risk Factors for Arterial vs Venous Thrombosis
Inherited thrombophilias (Protein C/S deficiency, Factor V Leiden, Antithrombin deficiency, Prothrombin G20210A mutation) are risk factors for venous thromboembolism (VTE) only, NOT arterial thrombosis (including stroke). If a patient has recurrent stroke or MI, no point checking for inherited thrombophilia causes [6].
Exceptions that cause both arterial and venous thrombosis:
- Antiphospholipid syndrome (APS) — the classic example
- Hyperhomocysteinaemia — the only inherited thrombophilia that may increase both (controversial)
Risk factors only for arterial thrombosis (not VTE): hypercholesterolaemia, DM, HT, CKD, male gender [6].
Anatomy and Cerebrovascular Supply
Understanding the vascular anatomy is essential because the clinical syndrome tells you which vessel territory is affected, which in turn tells you the mechanism and guides treatment.
The brain receives blood from two paired arterial systems:
-
Anterior (Carotid) circulation (~80% of cerebral blood flow)
-
Posterior (Vertebrobasilar) circulation (~20%)
- Vertebral arteries → join to form basilar artery → terminates as posterior cerebral arteries (PCA)
An arterial anastomotic ring at the base of the brain connecting anterior and posterior circulations:
- ACA → AComA → contralateral ACA
- ICA → PComA → PCA
The Circle of Willis provides collateral flow — if one vessel is occluded slowly (e.g., chronic atherosclerosis), the collaterals can compensate. However, if occlusion is sudden (e.g., embolism), there is no time for collateral recruitment → large infarct.
| Artery | Territory Supplied | Key Structures |
|---|---|---|
| ACA | Medial frontal and parietal lobes | Lower limb motor/sensory cortex (homunculus: leg is medial) |
| MCA | Lateral frontal, parietal, temporal lobes; deep structures via lenticulostriate arteries | Face and arm motor/sensory cortex, Broca's area (dominant frontal), Wernicke's area (dominant temporal), basal ganglia, internal capsule |
| PCA | Occipital lobe, medial temporal lobe, thalamus | Visual cortex, hippocampus |
| Basilar/Vertebral | Brainstem, cerebellum | Cranial nerve nuclei, long tracts, cerebellar peduncles |
| Lenticulostriate arteries (branches of MCA) | Internal capsule, basal ganglia | Motor fibres densely packed → small infarct → large deficit |
- Small penetrating arteries arise from the Circle of Willis (ACA, AComA, PCA, PComA), MCA stem, basilar artery, and distal vertebral artery [1][2]
- These supply deep structures: pons, thalamus, internal capsule/corona radiata, basal ganglia [1][2]
- These are the vessels affected in small vessel disease → lacunar infarcts
- They lack anastomoses (end-arteries) → occlusion causes discrete small infarcts
- Infarct core: irreversibly damaged tissue (CBF < 10 mL/100g/min). Neurons die within minutes.
- Ischemic penumbra: functionally impaired but still viable tissue surrounding the core (CBF 10–22 mL/100g/min). This tissue is kept alive by collateral blood flow.
- The entire rationale for acute reperfusion therapy (tPA, thrombectomy) is to salvage the penumbra before it progresses to infarction.
Why does "time is brain" matter? Because the penumbra is progressively recruited into the infarct core with each passing minute. The longer you wait, the less tissue there is to save.
Etiology (with Pathophysiology)
The TOAST Classification
The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is the standard framework for categorising ischemic stroke etiology [4]. Understanding this is essential because the cause determines the treatment strategy — e.g., cardioembolic → anticoagulation; large vessel atherosclerosis → antiplatelets ± surgery; small vessel → BP control.
Pathophysiology:
- Atherosclerotic plaques form at arterial bifurcations and curves (turbulent flow → endothelial injury → LDL infiltration → foam cell formation → fibrous cap with lipid core)
- Plaque rupture → exposure of thrombogenic subendothelial matrix → platelet adhesion and aggregation → thrombus formation → arterial occlusion (this is essentially the same process as in ACS — atherothrombosis [8])
- Can cause stroke by:
- In-situ thrombosis: thrombus forms at the plaque site and occludes the vessel
- Artery-to-artery embolism: thrombus or plaque material dislodges and travels distally to occlude a smaller cerebral artery (e.g., carotid bifurcation plaque → MCA embolism)
- Haemodynamic compromise: tight stenosis reduces distal perfusion pressure → watershed (boundary zone) infarcts between two arterial territories
Sites:
- Intracranial: Circle of Willis and its branches — atherosclerosis is the commonest cause [1][3]
- Also: arterial dissection, vasospasm (migraine), Moyamoya disease (chronic progressive cerebrovascular disease with stenosis/occlusion of arteries around Circle of Willis with prominent collaterals appearing as "puff of smoke" on angiography) [1]
- Extracranial: CCA, ICA (especially bifurcation), vertebral arteries — atherosclerosis commonest [1][3]
- Also: arterial dissection, vasculitis (Takayasu arteritis, giant cell/temporal arteritis), fibromuscular dysplasia (non-inflammatory non-atherosclerotic disorder leading to arterial stenosis, occlusion, aneurysm, dissection, and tortuosity) [1]
CT findings: Lesion > 1.5 cm, watershed infarcts / border zone infarcts, small infarcts (because collaterals have time to develop) [4]
HK-Relevant Point
In Chinese/East Asian populations, intracranial atherosclerotic disease (ICAD) is more prevalent than extracranial disease. This is the opposite of Western populations where carotid bifurcation disease predominates. This means carotid endarterectomy is less commonly indicated in Asian stroke patients — medical optimisation with antiplatelets, statins, and risk factor control is the mainstay.
Pathophysiology:
- Thrombus forms in the left heart → dislodges → travels through arterial system → lodges in a cerebral artery (usually at branch points)
- No time for collateral development because occlusion is sudden → large infarcts [4]
CT findings: Lesion > 1.5 cm, wedge-shaped / cortical infarcts ± dense artery sign, large infarcts (because of acute onset with no collaterals) [4]
| Source | Mechanism |
|---|---|
| Atrial fibrillation (AF) | Stagnant blood in non-contracting atrium → thrombus in left atrial appendage. Most common cardiac source. |
| Atrial flutter | Similar mechanism to AF |
| Sick sinus syndrome (SSS) | Bradycardia-tachycardia → stasis during bradycardia |
| Recent MI (within 1 month) | Akinetic/dyskinetic ventricular wall → mural thrombus |
| Chronic MI with LVEF < 28% | Dilated, poorly contracting ventricle → stasis → thrombus |
| CHF / DCM | Same as above |
| Valvular heart disease — Rheumatic mitral/aortic disease, prosthetic valves | Abnormal valve surface → thrombus formation |
| Infective endocarditis (IE) | Septic emboli from vegetations; large vegetations > 1 cm are prone to breaking off and causing ischemic stroke [9] |
| Non-bacterial thrombotic endocarditis (NBTE) — Malignancy (Marantic), SLE (Libman-Sacks), APS | Sterile vegetations on valves → embolism |
| Patent foramen ovale (PFO) | Paradoxical embolism — venous thrombus crosses from RA → LA through PFO → arterial embolism to brain |
| Cardiac tumours (atrial myxoma) | Tumour or thrombus on tumour surface embolises |
| Aortic arch atheroma | Artery-to-artery embolism from diseased aortic arch |
Why does AF cause such devastating strokes?
AF causes sudden, large emboli that occlude major cerebral arteries (often MCA). Because the occlusion is sudden, there is no time for collateral development → the entire downstream territory infarcts. This is why AF-related strokes tend to be larger and more disabling than atherothrombotic strokes.
Pathophysiology — Lipohyalinosis with fibrinoid degeneration:
- Lipid deposition and accumulation of foamy macrophages in the walls of small penetrating arteries [1]
- Hyalinisation and thickening of vessel wall [1]
- Fibrinoid degeneration (necrosis) of vessel wall [1]
- Blockage of artery by medial hypertrophy and lipid admixed with fibrinoid material in the hypertrophied arterial wall [1]
- Secondary to hypertension mainly and aging process [1]
- Also: microatheroma — atheroma formation at origin of small arteries or in parent large artery [1]
Clinical result: Lacunar infarcts — small (< 1.5 cm) deep infarcts in characteristic locations
Common sites of lacunar infarcts [1][2]:
- Pons
- Thalamus
- Internal capsule / Corona radiata
- Basal ganglia (caudate, putamen, globus pallidus, subthalamic nuclei, substantia nigra)
CT findings: Lesion < 1.5 cm, small hypodense area, usually in basal ganglia and periventricular white matter [10]
The TOAST classification identifies the aetiology — hypertensive lipohyalinosis (ageing of astrocytes and gliovascular unit) is the key pathology in small vessel stroke [4].
- Arterial dissection (especially in young patients — carotid or vertebral)
- Vasculitis — CNS vasculitis, Takayasu, GCA, SLE
- Haematological — polycythaemia vera, essential thrombocytosis, sickle cell disease (hemolysis and vasculopathy → ischemic stroke [11]), antiphospholipid syndrome, thrombotic thrombocytopenic purpura (TTP — microthrombi → CNS involvement: headache, confusion, seizure, stroke, coma [12])
- Moyamoya disease
- Hypercoagulable states — Protein C/S deficiency (note: these are more classically venous but can cause arterial events in certain settings, especially in neonates/children)
- Drug-related — cocaine (vasospasm), amphetamines
- No cause identified despite complete workup
- Many of these are now suspected to be due to embolic stroke of undetermined source (ESUS) — likely subclinical/paroxysmal AF or occult PFO
- Extended cardiac monitoring often reveals paroxysmal AF in these patients
- Reduced perfusion due to cardiac pump failure or decreased CO [1][2]
- Hypoxaemia further reduces the amount of O₂ carried to the brain [1]
- Boundary zone (border/watershed) regions between major cerebral artery supply are most vulnerable [1][2]
- Symptoms of brain dysfunction typically are diffuse and non-focal in contrast to other categories of ischemia [1][2]
Why watershed zones? These are at the "end of the pipe" — the most distal territories of each major artery. When perfusion pressure drops globally, these areas lose flow first.
Classification
| Category | % | Clinical Course | CT Pattern |
|---|---|---|---|
| Large vessel atherosclerosis | 25% | Stuttering progression with periods of improvement | > 1.5 cm, watershed/border zone |
| Cardioembolism | 20% | Sudden onset with deficit maximal at onset | > 1.5 cm, wedge-shaped, cortical ± dense artery sign |
| Small vessel disease | 25% | Subacute, stuttering | < 1.5 cm, deep (BG, IC, pons, thalamus) |
| Other determined | 5% | Variable | Variable |
| Cryptogenic | 25% | Variable | Variable |
| Territory | Artery | Key Clinical Syndrome |
|---|---|---|
| Anterior circulation | ACA | Contralateral leg weakness > arm/face |
| MCA (most common) | Contralateral face + arm weakness > leg, ± aphasia (dominant), ± neglect (non-dominant) | |
| Posterior circulation | PCA | Contralateral homonymous hemianopia, memory impairment |
| Basilar/vertebral | Cranial nerve palsies, crossed signs (ipsilateral CN + contralateral limb), ataxia, vertigo, diplopia, dysphagia |
| Syndrome | Site | Features |
|---|---|---|
| Pure motor hemiparesis | Posterior limb of internal capsule or pons | Contralateral face, arm, leg weakness (NO sensory loss, NO cortical signs) |
| Pure sensory stroke | Thalamus (VPL/VPM nuclei) | Contralateral numbness/paraesthesia (NO weakness) |
| Ataxic hemiparesis | Pons or internal capsule | Ipsilateral cerebellar ataxia + contralateral hemiparesis |
| Sensorimotor stroke | Thalamus + internal capsule | Combined motor + sensory deficit |
| Dysarthria-clumsy hand | Pons or genu of internal capsule | Dysarthria + ipsilateral hand clumsiness |
Key point: lacunar infarcts do not produce cortical signs (aphasia, neglect, visual field defects, seizures) because they affect deep structures supplied by penetrating arteries, not the cortex.
| Type | Abbreviation | Criteria |
|---|---|---|
| Total anterior circulation infarct | TACI | All 3: (1) contralateral hemiparesis/hemisensory loss, (2) homonymous hemianopia, (3) higher cortical dysfunction (aphasia or neglect) |
| Partial anterior circulation infarct | PACI | 2 of the above 3 criteria, OR isolated higher cortical dysfunction |
| Lacunar infarct | LACI | Pure motor, pure sensory, sensorimotor, ataxic hemiparesis, or dysarthria-clumsy hand; NO cortical signs |
| Posterior circulation infarct | POCI | Brainstem/cerebellar signs, isolated homonymous hemianopia, or combination |
Clinical Features
The hallmark of stroke is sudden onset of focal neurological deficit. The specific deficit depends on which vascular territory is affected.
Clinical course differs by mechanism [1][2]:
- Thrombotic stroke: stuttering progression with periods of improvement — evolves over hours as thrombus extends and collaterals fail
- Embolic stroke: sudden onset with deficit maximal at onset — the embolus arrives abruptly, no time for adaptation
- ICH: gradual progression over minutes to hours (expanding haematoma)
Symptoms (with Pathophysiological Basis)
| Symptom | Pathophysiological Basis |
|---|---|
| Contralateral hemiparesis/hemiplegia (most common presentation) | Upper motor neuron lesion: ischemia of motor cortex (precentral gyrus) or its descending fibres (corona radiata → internal capsule → cerebral peduncle). The corticospinal tract decussates at the medullary pyramids, so a lesion above this level causes contralateral weakness |
| Face and arm > leg weakness (MCA territory) | The motor homunculus on the lateral convexity of the precentral gyrus represents face and upper limb (MCA territory), while the lower limb is represented on the medial surface (ACA territory) |
| Leg > arm and face weakness (ACA territory) | Medial cortex (leg area of homunculus) supplied by ACA |
| Dysarthria | Weakness/incoordination of muscles of speech articulation — can occur with lesions of motor cortex, internal capsule, brainstem (CN nuclei for VII, IX, X, XII), or cerebellum |
| Dysphagia | Weakness of pharyngeal muscles — bilateral cortical/subcortical lesions or brainstem (nucleus ambiguus — CN IX, X). The title of GC087 is "Sudden hemiplegia dysphagia" — dysphagia is a key presenting complaint of stroke [13] |
| Symptom | Pathophysiological Basis |
|---|---|
| Contralateral hemisensory loss / paraesthesia | Ischemia of sensory cortex (postcentral gyrus) or thalamus (VPL for body, VPM for face). Sensory pathways (dorsal column-medial lemniscus and spinothalamic tract) decussate below the cortex → contralateral loss |
| Thalamic pain syndrome (Déjerine-Roussy) | Late complication of thalamic infarcts (PCA territory) → dysaesthetic, burning, often severe contralateral pain |
| Symptom | Pathophysiological Basis |
|---|---|
| Aphasia (dominant hemisphere, usually left in right-handed) | Broca's aphasia (expressive/non-fluent): ischemia of inferior frontal gyrus (Broca's area, frontal operculum) — patient understands but cannot produce fluent speech. Wernicke's aphasia (receptive/fluent): ischemia of posterior superior temporal gyrus — patient produces fluent but nonsensical speech, cannot comprehend. Global aphasia: both areas (large MCA territory infarct) |
| Neglect / inattention (non-dominant hemisphere, usually right) | Ischemia of right parietal lobe → patient ignores left hemispace. They do not acknowledge or attend to stimuli on the contralateral side. This is more than just a visual field defect — it is a failure of spatial attention |
| Confusion / reduced consciousness | Large territory infarcts with significant oedema → raised ICP → altered consciousness. Also basilar artery occlusion → reticular activating system ischemia → coma |
| Symptom | Pathophysiological Basis |
|---|---|
| Contralateral homonymous hemianopia | Ischemia of visual cortex (occipital lobe, PCA territory) or optic radiation (MCA territory in temporal/parietal lobe). Visual fibres from each eye representing the contralateral visual field travel to the ipsilateral occipital cortex → lesion causes contralateral visual field loss |
| Amaurosis fugax (transient monocular blindness) | Emboli from ipsilateral ICA → transient occlusion of ophthalmic artery / central retinal artery → monocular vision loss. This is a form of TIA and a warning sign of impending stroke. The pathology is usually carotid bifurcation atherosclerosis [14] |
| Diplopia (double vision) | Brainstem ischemia → CN III, IV, or VI palsy → extraocular muscle dysfunction |
| Central retinal artery occlusion (CRAO) | Embolic occlusion (usually from carotid atherosclerosis) → sudden profound monocular vision loss, cherry-red spot on fundoscopy, RAPD. Important to identify due to stroke risk [14] |
| Symptom | Pathophysiological Basis |
|---|---|
| Vertigo | Ischemia of vestibular nuclei in brainstem (NOT typically from carotid stenosis — vertigo and syncope are NOT generally caused by carotid stenosis [7]) |
| Ataxia (limb or gait) | Cerebellar infarction → ipsilateral incoordination (cerebellum controls ipsilateral limbs) |
| Nausea/vomiting | Involvement of area postrema or vestibular nuclei |
| Crossed signs | Ipsilateral cranial nerve palsy + contralateral hemiparesis — hallmark of brainstem lesions. Why? CN nuclei are in the brainstem (ipsilateral control before exit), while corticospinal tract is passing through and has already or will decussate at medullary pyramids |
| Dysphagia, dysarthria, hoarseness | Lateral medullary (Wallenberg) syndrome: CN IX, X involvement |
| Horner syndrome (miosis, ptosis, anhidrosis) | Disruption of descending sympathetic fibres in lateral brainstem |
| Symptom | Pathophysiological Basis |
|---|---|
| Headache | Can occur in ischemic stroke (especially large vessel occlusion or posterior circulation) — due to meningeal irritation, vascular distension, or raised ICP. More typical of hemorrhagic stroke but does not exclude ischemic |
| Seizures | Occur in ~5% of ischemic strokes, more common in cortical infarcts. Ischemic tissue becomes electrically irritable |
| Nausea/vomiting | Raised ICP (large territory infarct with oedema) or posterior fossa involvement |
Signs (with Pathophysiological Basis)
| Sign | Significance / Mechanism |
|---|---|
| Hypertension | Present in majority; may be reactive (Cushing response to raised ICP) or pre-existing |
| Atrial fibrillation (irregularly irregular pulse) | Source of cardioembolism — feel the pulse in every stroke patient! |
| Heart murmur | Valvular disease → potential embolic source |
| Carotid bruit | Turbulent flow through stenotic carotid artery → potential source of artery-to-artery embolism. However, absence of bruit does not exclude stenosis, and a bruit does not always indicate haemodynamically significant stenosis |
| Fundoscopy — Hollenhorst plaques | Cholesterol crystal emboli from carotid atherosclerosis lodging at retinal arteriolar bifurcations → evidence of proximal embolic source |
| Xanthelasma, xanthoma | Signs of hyperlipidaemia → atherosclerotic risk |
Understanding why UMN signs occur: The lesion is above the anterior horn cell (lower motor neuron). The upper motor neuron normally exerts inhibitory control over spinal reflexes. When this inhibition is lost, reflexes become exaggerated.
Acutely (first hours to days):
- Flaccid paralysis with decreased reflexes — this is spinal shock (transient loss of reflex activity below the level of the lesion due to sudden loss of descending facilitatory input)
After days to weeks (UMN signs evolve):
| Sign | Mechanism |
|---|---|
| Spasticity (increased tone, "clasp-knife") | Loss of inhibitory descending input → hyperexcitability of spinal stretch reflexes |
| Hyperreflexia | Same mechanism — uninhibited reflex arcs |
| Upgoing plantar (Babinski sign) | Loss of corticospinal inhibition → primitive extensor plantar response re-emerges |
| Clonus | Sustained rhythmic involuntary contractions from hyperexcitable stretch reflex loop |
| No muscle wasting (initially) | LMN and muscle are intact — the problem is upstream |
| Pronator drift | Subtle UMN sign — when arms are held outstretched supinated with eyes closed, the weak arm pronates and drifts downward due to weakness of supinators (which are relatively weaker in UMN lesions) |
MCA Territory (most common):
- Contralateral hemiparesis (face + arm > leg) + hemisensory loss
- Homonymous hemianopia (optic radiation involvement)
- Dominant hemisphere: Broca's/Wernicke's/Global aphasia
- Non-dominant hemisphere: Hemispatial neglect, anosognosia (denial of deficit)
- Gaze deviation: eyes deviate toward the lesion (frontal eye field pushes gaze contralaterally; when damaged, the intact side pushes gaze ipsilaterally — "eyes look toward the lesion")
ACA Territory:
- Contralateral leg weakness > arm/face
- Personality change, abulia (lack of will/motivation) — frontal lobe involvement
- Urinary incontinence (medial frontal involvement of micturition centres)
- Contralateral grasp reflex (frontal release sign)
PCA Territory:
- Contralateral homonymous hemianopia with macular sparing (dual blood supply to macular cortex from MCA and PCA)
- Memory impairment (hippocampal involvement — medial temporal lobe supplied by PCA)
- Alexia without agraphia (dominant hemisphere — patient can write but cannot read)
- Thalamic syndrome (sensory loss, pain)
Basilar Artery Occlusion:
- "Locked-in syndrome" — bilateral ventral pontine infarct → quadriplegia + anarthria but consciousness preserved (reticular activating system in dorsal pons is spared). Patient can only communicate via vertical eye movements and blinking
- Bilateral CN palsies, bilateral motor/sensory deficits
- Coma if reticular formation involved
Lateral Medullary Syndrome (Wallenberg — PICA/vertebral artery):
- Ipsilateral: facial pain/temperature loss (CN V nucleus), Horner syndrome, ataxia, dysphagia/hoarseness (CN IX, X)
- Contralateral: body pain/temperature loss (spinothalamic tract)
- Vertigo, nystagmus, nausea/vomiting
Dense MCA Sign on CT
Dense MCA sign on non-contrast CT indicates atheroma, thrombus, or embolism in the MCA. Hyperdense vessel segments can occur in ALL vessels but are most often observed in MCA [10]. This is a hyperacute sign — it may be the only finding on the initial CT before the infarct becomes visible.
- Symptoms are identical to stroke but resolve completely within 24 hours (most within < 1 hour)
- Embolic TIA: discrete, usually single, more prolonged (hours) [3]
- Lacunar (small vessel) TIA: brief stereotyped clinical S/S that may be followed by lacunar stroke [3]
- Low-flow TIA: usually short-lived (minutes), stereotyped clinical S/S with frequent recurrence (e.g., once per week) — due to tightly stenotic atherosclerotic lesion at large vessels (e.g., ICA) [3]
ABCD2 Score — estimates risk of ischemic stroke in the first 2 days after TIA [1][2]:
| Component | Points |
|---|---|
| Age ≥ 60 | 1 |
| BP elevation: SBP ≥ 140 OR DBP ≥ 90 | 1 |
| Clinical: Unilateral weakness | 2 |
| Clinical: Isolated speech disturbance | 1 |
| Duration ≥ 60 min | 2 |
| Duration 10–59 min | 1 |
| Diabetes present | 1 |
| Score | 2-day stroke risk |
|---|---|
| 0–3 | Low (1%) |
| 4–5 | Moderate (4%) |
| 6–7 | High (8%) |
Hospitalise if ABCD2 ≥ 3 (or lower score with uncertainty about outpatient workup completion or other evidence of focal ischemia) [1][2].
From GC lecture slides: Stroke is a neurological emergency. "Time is brain" — the goal is rapid recognition, rapid imaging, and rapid treatment [13][15].
Key Principles in the Acute Setting
- Urgent non-contrast CT brain: differentiate ischemic from hemorrhagic stroke — Door-to-CT time: within 25 minutes [4]
- Arrange CT angiogram (CTA) ± perfusion scan for EVT (endovascular thrombectomy) triage — do not withhold tPA while awaiting CTA [4]
- Bedside blood glucose — hypoglycaemia mimics stroke; hyperglycaemia worsens prognosis [4]
- ECG — identify AF, acute MI (can be concurrent or the cause)
- NPO until swallowing assessment — dysphagia screening before any oral intake to prevent aspiration pneumonia [4]
Critical Teaching Point — From GC087 Lecture
Never give thrombolysis without first ruling out hemorrhagic stroke on CT. Thrombolysing a patient with ICH is catastrophic. Also, never assume it's "just a TIA" if the deficit is ongoing — treat as stroke until proven otherwise.
CT Appearance of Ischemic Stroke (Radiology — High Yield)
The appearance evolves with the age of the infarct [10][16]:
| Phase | Time | CT Findings |
|---|---|---|
| Hyperacute | 0–6 hours | Loss of grey-white matter differentiation (due to cytotoxic oedema); ± hyperdense MCA and basilar tip sign |
| Acute | 6–72 hours | Hypoattenuation (infarcted tissue becomes dark); swelling |
| Subacute | 3 days – 3 weeks | Improving swelling; ± increased cortical density due to petechial haemorrhages (NOT haemorrhagic transformation) |
| Chronic | > 3 weeks | Swelling subsides; encephalomalacia (focal volume loss) due to liquefactive necrosis |
- Dense MCA sign — indicating atheroma, thrombus, or embolism in MCA
- Loss of insular ribbon cortex — insular cortex supplied by most distal branch of lenticulostriate artery → first part affected by ischemia → grey matter becomes hypodense → loss of grey-white junction [10]
- Rather inconspicuous (mild hypodensity with subtle loss of grey-white junction) → rely on clinical or MRI findings [10]
- CT: < 1 day = 48% sensitive → 10-11 days = 74% — sensitivity increases with time after infarct
- MRI: 86–100% sensitive — MRI with diffusion-weighted imaging (DWI) is far superior for early detection
- Hyperdensity in original hypodense infarct (fresh blood is hyperdense on CT)
- Risk factors: older age, larger stroke size, cardioembolic stroke, anticoagulation, elevated systolic BP in acute setting, thrombolytic therapy, delayed recanalisation therapy [16]
High Yield Radiology Pearl
On a hyperacute CT, the scan may look near-normal — you must actively look for subtle early signs (dense MCA, loss of insular ribbon, loss of grey-white differentiation). If clinical suspicion is high and CT is negative, MRI with DWI is the gold standard for confirming acute infarction.
Epidemiology: F > M — pregnancy, use of COC; 1% of stroke [17]
Clinical features — require high index of suspicion [17]:
- Cerebral venous sinus thrombosis (90%): raised ICP (headache, papilloedema, ↓GCS), seizure, focal neurological deficit
- Cavernous sinus thrombosis: proptosis, painful ophthalmoplegia, CN 3, 4, 6, V1 involvement
- Deep cerebral venous thrombosis (10%)
Investigations [17]:
- CT brain: can be normal
- MRI brain + MR venogram for filling defect
High Yield Summary
-
Definition: Rapid onset focal neurological deficit from non-traumatic vascular cause > 24h with structural damage. TIA = same but < 24h with NO infarction on imaging.
-
Epidemiology: 75–80% of strokes are ischemic; HK: 2nd–4th leading cause of death; intracranial atherosclerosis more common in Chinese than Caucasians.
-
Risk Factors: HTN is the single most important modifiable RF. AF is the most important cardiac source. Inherited thrombophilias → VTE only, NOT arterial stroke (except APS and hyperhomocysteinaemia).
-
TOAST Classification: Large vessel atherosclerosis (25%), cardioembolism (20%), small vessel disease (25%), other (5%), cryptogenic (25%).
-
Clinical Course: Thrombotic = stuttering; embolic = maximal at onset.
-
Lacunar Infarcts: < 1.5 cm, deep structures (pons, thalamus, internal capsule, BG), NO cortical signs. Pure motor/pure sensory/ataxic hemiparesis/sensorimotor/dysarthria-clumsy hand.
-
MCA territory (most common): contralateral face + arm weakness > leg, ± aphasia (dominant) / neglect (non-dominant), homonymous hemianopia, gaze deviation toward lesion.
-
CT: Hyperacute — loss of grey-white differentiation, dense MCA sign, loss of insular ribbon. CT < 48% sensitive in first day; MRI DWI 86–100%.
-
Time is brain: 2 million neurons/min die. Door-to-CT < 25 min. Penumbra is salvageable.
-
ABCD2 Score: Age, BP, Clinical features, Duration, Diabetes — stratifies TIA patients for 2-day stroke risk.
Active Recall - Ischemic Stroke (Definition, Epidemiology, Risk Factors, Etiology, Pathophysiology, Classification, Clinical Features)
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1210–1215) [2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1135–1140) [3] Senior notes: Ryan Ho Neurology.pdf (Section 3.2: Cerebrovascular Diseases, pp. 74–75) [4] Senior notes: Maksim Medicine Notes.pdf (Neurology — Acute management of stroke, p. 241) [5] Senior notes: Block A - High blood pressure_ hypertension.pdf (pp. 7, 32) [6] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p. 6) [7] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Vascular Diseases — Carotid artery stenosis, p. 894) [8] Senior notes: Block A - Accelerating chest pain_ Acute Coronary Syndromes.pdf (p. 5) [9] Senior notes: Block A - Cardiology Interactive Tutorial.pdf (p. 3); Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (p. 30) [10] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p. 40) [11] Senior notes: Block A - Many members of the family have anaemia.pdf (p. 7) [12] Senior notes: Ryan Ho Haemtology.pdf (p. 139) [13] Lecture slides: GC 087. Sudden hemiplegia dysphagia.pdf [14] Senior notes: Ryan Ho Opthalmology.pdf (p. 65) [15] Lecture slides: GCBA_Fundamentals_Neuro_Introduction to Neurological Investigations and Emergencies_Prof KC Teo.pdf [16] AOS material: AOS - Radiology.pdf (p. 11); Senior notes: Ryan Ho Radiology.pdf (p. 22) [17] Senior notes: Maksim Surgery Notes.pdf (p. 358)
Differential Diagnosis of Ischemic Stroke
When a patient presents with sudden focal neurological deficit, the immediate reflex is to think "stroke." But here's the critical clinical reality: not all sudden neurological deficits are strokes. Misdiagnosing a stroke mimic as stroke can lead to unnecessary and dangerous thrombolysis (e.g., giving tPA to someone with hypoglycaemia is both futile and risky). Conversely, missing a true stroke delays life-saving reperfusion therapy. The differential diagnosis therefore serves two purposes:
- Rule out stroke mimics — conditions that look like stroke but are not vascular in origin
- Differentiate between stroke subtypes — ischemic vs. hemorrhagic (because management is diametrically opposite: thrombolysis for ischemic, haemostasis for hemorrhagic)
From GC lecture slides: The clinical approach requires you to derive a set of differential diagnoses from the presenting history and identify key clinical features that help distinguish specific causes [18]. General examination with careful observation can give you a lot of clues to the anatomical and pathological diagnosis [19].
Think of the DDx in two tiers:
Tier 1: Is this really a stroke, or a stroke mimic? Tier 2: If it is a stroke, is it ischemic or hemorrhagic? And what is the ischemic subtype?
Stroke mimics account for approximately 20–30% of initial "code stroke" activations. The key distinguishing principle is:
Stroke/TIA invariably produces negative symptoms (i.e., loss of function — weakness, numbness, visual loss, speech loss). Consider an alternative diagnosis if positive symptoms dominate (e.g., seizure activity, visual scintillations, tingling that "marches" across a limb) [3].
Also: stroke is usually focal instead of global, and rarely changes in modality (i.e., a patient with pure motor deficit does not suddenly develop purely sensory symptoms in the same distribution — that evolution suggests something else) [3].
The differential diagnosis can be organised by the VINDICATE + E framework (Vascular, Infection, Neoplasm, Degenerative/Demyelinating, Inflammatory, Congenital, Autoimmune, Trauma/Toxins, Endocrine) [19]:
| Category | Condition | Key Differentiating Features | Why It Mimics Stroke |
|---|---|---|---|
| Endocrine / Metabolic | Hypoglycaemia | Check bedside blood glucose immediately in every "code stroke." Rapidly reversible with glucose. Drug Hx: insulin, oral hypoglycaemic agents [1][2]. Hypoglycaemia can cause focal deficits (hemiparesis, aphasia) because vulnerable neurons become dysfunctional without glucose — it does not kill them immediately, so it is reversible | Hypoglycaemia mimics stroke because neurons need glucose as their primary energy substrate; focal regions with higher metabolic demand fail first [4] |
| Vascular | Intracerebral haemorrhage (ICH) | Gradual progression during minutes or hours (vs. embolic stroke which is maximal at onset) [1][2]. Headache and vomiting favour hemorrhagic stroke [1][2]. CT: hyperdense lesion (acute blood is white on CT). Common sites: basal ganglia, cerebellum, pons, thalamus (hypertensive) or lobar (amyloid angiopathy) [20] | Both cause sudden focal deficit; only CT can reliably distinguish them |
| Vascular | Subarachnoid haemorrhage (SAH) | Abrupt onset of sudden, severe thunderclap headache ("worst headache in life") [1][2]. Meningism, ↓GCS. CT: hyperdense blood in subarachnoid cisterns | SAH can cause focal deficits (from vasospasm or aneurysmal compression of CN III), but the dominant feature is the catastrophic headache and raised ICP, not a focal cortical syndrome |
| Vascular | Subdural haematoma (SDH) | History of trauma (may be trivial, especially in elderly on anticoagulants). Fluctuating consciousness. More insidious onset. CT: crescent-shaped extra-axial collection | Chronic SDH can present with progressive hemiparesis mimicking stroke, but the tempo is wrong — gradual onset over days to weeks |
| Vascular | Cerebral venous sinus thrombosis (CVST) | F > M, pregnancy, COC use [17]. Headache (raised ICP), seizures, focal deficits. CT brain may be normal; MRI + MR venogram for filling defect [17]. Can present with both venous infarcts and haemorrhagic infarcts | Often presents with headache + seizures rather than pure focal deficit; the combination of headache + seizure + focal deficit in a young woman on OCP should trigger suspicion |
| Seizure | Seizure with Todd's paralysis | Postictal paresis — a period of worsened neurologic function related to the location of the seizure in the brain [1][2]. Look for: witnessed convulsive activity, tongue bite, urinary incontinence, post-ictal confusion. History of epilepsy [1][2]. Resolves within 24–48 hours. Key difference: seizure produces positive then negative symptoms (jerking THEN weakness), while stroke produces negative symptoms from the start | After a focal motor seizure, the postictal "exhaustion" of the motor cortex can cause flaccid paralysis of the previously convulsing limbs — this resolves as neurons recover |
| Migraine | Migraine aura / Hemiplegic migraine | Migraine aura [1][2]. Gradual onset (typically builds over 5–20 minutes) with positive symptoms (visual scintillations, tingling) followed by negative symptoms (scotoma, numbness), plus severe headache, nausea, photophobia. Hemiplegic migraine causes transient hemiparesis. Gradual progression of symptoms suggests other DDx [4]. Family history often present | The gradual "march" of symptoms across a cortical territory (reflecting cortical spreading depression) is the key distinction from the sudden, maximal-at-onset deficit of embolic stroke |
| Infection | Brain abscess | Fever, subacute onset over days–weeks, raised inflammatory markers. CT: ring-enhancing lesion with surrounding oedema. History of sinusitis, otitis, dental infection, endocarditis, or immunosuppression | Mass effect from the abscess can cause progressive focal deficit, but the tempo is subacute and there is usually fever/systemic upset |
| Infection | Encephalitis | Fever, altered mental status, seizures, behavioural change. Often a viral prodrome. HSV encephalitis has a predilection for temporal lobes (aphasia, behavioural change). MRI: hyperintense temporal lobes | The diffuse encephalopathic picture with fever and seizures distinguishes it, though temporal lobe encephalitis can mimic MCA stroke with aphasia |
| Neoplastic | Brain tumour | Gradual progression over weeks to months. Headache worse in morning / with Valsalva (raised ICP). Weight loss, constitutional symptoms. CT/MRI: mass lesion ± ring enhancement ± surrounding oedema. Focal neurological symptoms, constitutional symptoms → mass lesion [21] | A tumour can occasionally present acutely (haemorrhage into tumour, seizure, sudden oedema), but the history of progressive symptoms is the key distinguishing feature |
| Degenerative / Demyelinating | Multiple sclerosis (MS) | Young patient (20–40y), relapsing-remitting course, optic neuritis, internuclear ophthalmoplegia. MRI: periventricular white matter lesions disseminated in time and space. Symptoms evolve over days (not seconds/minutes) | A new MS relapse can cause sudden-onset focal deficit (e.g., hemiparesis, hemisensory loss), but the age group, history of prior episodes, and MRI pattern differ |
| Degenerative | Compressive myelopathy (e.g., cervical spondylotic myelopathy) | Insidious bilateral UMN signs in legs, LMN signs in arms at level of compression, bladder dysfunction. MRI spine diagnostic | The gradual onset and bilateral/spinal pattern distinguish this from a cerebral stroke |
| Trauma | Head trauma / Epidural haematoma | Clear history of trauma. Epidural haematoma: "lucid interval" then rapid deterioration. CT: lentiform (biconvex) hyperdense collection [20] | Trauma is usually evident from history; however, elderly patients may have trivial or forgotten trauma |
| Autoimmune / Inflammatory | CNS vasculitis | Headache, encephalopathy, multifocal neurological deficits (not confined to a single vascular territory), raised inflammatory markers, abnormal CSF. Angiography: beading of vessels | Vasculitis causes ischemic strokes, but the pattern is multifocal and there are systemic inflammatory features |
| Metabolic | Metabolic encephalopathy (hepatic, uraemic, hyponatraemia) | Usually global, non-focal dysfunction (confusion, drowsiness, coma) rather than focal. Check metabolic panel | Severe metabolic derangement can occasionally produce focal signs, but the dominant picture is diffuse encephalopathy |
| Functional | Functional neurological disorder (conversion disorder) | Inconsistent examination findings (e.g., give-way weakness, Hoover's sign positive, non-anatomical sensory loss). Often young patient with psychological stressors. A diagnosis of exclusion — must still image to rule out stroke | Can perfectly mimic stroke clinically; neuroimaging is essential |
| Other | Syncope | Transient loss of consciousness, usually with prodrome (lightheadedness, pallor, diaphoresis). Rapid recovery. No focal deficit on recovery. Vertigo and syncope are NOT generally caused by carotid stenosis [7] | Syncope causes transient global cerebral hypoperfusion → loss of consciousness, not focal deficit |
The Top 3 Stroke Mimics to Always Exclude
- Hypoglycaemia — check bedside glucose STAT in every "code stroke." Reversible and potentially fatal if missed.
- Seizure with Todd's paralysis — ask about witnessed convulsive activity, tongue bite, incontinence, prior epilepsy history.
- Intracranial haemorrhage — urgent NCCT brain is mandatory before any reperfusion therapy.
These three are the most common and most dangerous mimics to miss or mismanage.
Key clues from the history [3]:
| Feature | Stroke | Mimic |
|---|---|---|
| Nature of symptoms | Negative symptoms (loss of function) | Positive symptoms suggest seizure or migraine (jerking, scintillations, marching paraesthesia) |
| Extent | Usually focal | Global suggests metabolic/toxic cause |
| Progression | Rarely changes in modality | Changing modalities (motor → sensory → visual) suggest migraine aura or seizure |
| Onset | Sudden (embolic) or stuttering (thrombotic) | Gradual progression suggests other DDx: MS, tumour [4] |
| Associating symptoms | Risk factor history (AF, HTN, DM, prior stroke) | Headache + aura → migraine; Fever → infection; Convulsion → seizure; Drug history: insulin, OHAs, anticoagulants, drug abuse [1][2] |
Once you have confirmed this is a stroke (and not a mimic), the next critical step is to determine: is it ischemic or hemorrhagic? This distinction is impossible to make reliably on clinical grounds alone — you must have neuroimaging (CT or MRI).
However, certain clinical features favour one over the other [1][2]:
| Feature | Ischemic Stroke | Hemorrhagic Stroke |
|---|---|---|
| Onset | Sudden (embolic) or stuttering (thrombotic) | Gradual progression over minutes to hours |
| Headache and vomiting | Less common | Favours hemorrhagic stroke [1][2] |
| Level of consciousness | Usually preserved unless large territory | More commonly reduced (mass effect, raised ICP) |
| Seizures at onset | Less common | More common (blood irritates cortex) |
| Neck stiffness | Absent | Present in SAH (blood in CSF irritates meninges) |
| Risk factors | AF, recent MI, carotid stenosis, atherosclerotic RFs | Hypertension (deep ICH), anticoagulation, amyloid angiopathy (lobar ICH) |
| CT appearance | Hypodense (after hours) or normal (hyperacute) | Hyperdense (acute blood is white) [20] |
Once ischemic stroke is confirmed, determine the mechanism (TOAST classification) because this determines secondary prevention:
| Feature | Large Vessel Atherosclerosis | Cardioembolism | Small Vessel Disease |
|---|---|---|---|
| Clinical course | Stuttering, with periods of improvement [1] | Sudden, maximal at onset [1] | Subacute |
| Cortical signs | Present or absent | Present (aphasia, neglect, hemianopia) | Absent (no cortical involvement) |
| Infarct size on CT | > 1.5 cm | > 1.5 cm | < 1.5 cm |
| CT pattern | Watershed / border zone or territorial | Wedge-shaped, cortical ± dense artery sign [4] | Small deep lacune |
| Associated findings | Carotid bruit, peripheral vascular disease, prior TIA in same territory | AF, valvular disease, recent MI, IE vegetation | HTN, DM |
| Workup priority | Carotid Doppler, CTA/MRA | ECG, Holter/telemetry, echocardiography | BP control, r/o secondary HTN |
Young Stroke (Age < 45 years)
A young patient with stroke demands a wider differential because atherosclerosis is less common and unusual causes predominate. The GC interactive tutorial case demonstrates this: a 30-year-old housewife from China presenting with clumsiness and unsteady gait [18].
| Cause | Key Features |
|---|---|
| Arterial dissection (carotid or vertebral) | Neck pain/headache after trauma or manipulation, Horner syndrome (carotid), lateral medullary syndrome (vertebral) |
| Cardioembolism from rheumatic heart disease | Still relevant in HK/China; mitral stenosis → AF → embolism |
| Patent foramen ovale (PFO) | Paradoxical embolism; consider if young stroke with no other cause + DVT/PE history |
| Antiphospholipid syndrome (APS) | Recurrent arterial/venous thrombosis, pregnancy morbidity, livedo reticularis; check anticardiolipin Ab, lupus anticoagulant, anti-β2GP1 |
| Moyamoya disease | More common in East Asian populations; progressive stenosis at Circle of Willis with "puff of smoke" collaterals on angiography [2] |
| Illicit drugs — cocaine, amphetamines | Vasospasm (cocaine blocks noradrenaline reuptake → vasoconstriction), direct endothelial toxicity |
| Oral contraceptive pill (OCP) | Prothrombotic state; risk multiplied by smoking and migraine with aura |
| CVST | F > M, pregnancy, COC [17]; headache, seizure, focal deficit |
| Sickle cell disease | Hemolysis and vasculopathy → ischemic stroke [11] (mainly in Black ancestry; rare in Chinese) |
| Vasculitis — primary CNS or systemic (SLE, Takayasu, Behçet) | Multifocal deficits, systemic inflammation |
| Inherited cardiac conditions | e.g., atrial myxoma, hereditary cardiomyopathies with mural thrombus |
GC Lecture Case — Young Woman with Stroke
The GC interactive tutorial case [18] presents a 30-year-old woman from China with clumsiness and unsteady gait — this is a posterior circulation stroke in a young patient. The learning objectives explicitly ask you to identify from presenting history and key clinical features which help identify specific causes [18]. In a young woman, always consider: rheumatic heart disease with AF, arterial dissection, CVST (OCP), APS, Moyamoya, and PFO.
Case 9 from the surgery cerebrovascular disease lecture: F/27, sudden onset right hemiplegia and dysphasia — the slides ask "? Diagnosis, ? Management" [22]. This is a young woman with an anterior circulation stroke; the differential must include all the young stroke causes listed above.
From senior notes, the history taking for stroke DDx should include [1][2]:
- Time of onset: Time of stroke onset = time that is LAST SEEN WELL, rather than last seen unwell — essential for reperfusion eligibility
- Headache and vomiting: Favours hemorrhagic stroke [1][2]
- Medical history: epilepsy (Todd's paralysis), prior stroke/TIA, migraine, malignancy
- Drug history: anticoagulants (increased haemorrhage risk), insulin / oral hypoglycaemic agents (hypoglycaemia mimic), drug overdose or abuse (cocaine → vasospasm) [1][2]
Even among the "mimics," some are life-threatening and require urgent treatment:
| Condition | Why It's Urgent |
|---|---|
| Hypoglycaemia | Prolonged hypoglycaemia causes irreversible neuronal death — treat immediately with IV dextrose |
| Bacterial meningitis / encephalitis | Delay in antibiotics/antivirals dramatically increases mortality |
| Epidural haematoma | Rapid expansion → uncal herniation → death within hours without surgical evacuation |
| CVST | Requires anticoagulation even if there is haemorrhagic infarction (counterintuitive!) |
| Aortic dissection with stroke | Type A dissection can extend into carotid arteries causing ischemic stroke; thrombolysis is absolutely contraindicated in aortic dissection [23]. CXR to rule out aortic dissection is part of baseline stroke workup [4] |
Aortic Dissection Presenting as Stroke — A Deadly Trap
Stanford Type A aortic dissection can propagate into the carotid arteries and present as acute ischemic stroke. If you give tPA to such a patient, the dissection worsens catastrophically. This is why suspected aortic dissection is an absolute contraindication to thrombolysis [23], and why a CXR (looking for widened mediastinum) is part of the baseline stroke workup [4]. Always ask about severe tearing/ripping chest pain radiating to the back [24] in any acute stroke patient.
After the acute phase, a critical long-term DDx consideration is whether cognitive decline post-stroke represents vascular cognitive impairment and dementia (VCID) vs. other dementias:
From GC 241 reference on vascular neurocognitive disorder criteria [25]:
- Onset of cognitive deficits is temporally related to ≥ 1 clinical strokes
- Multiple strokes may be associated with a stepwise or fluctuating course
- Physical signs consistent with stroke: hemiparesis, lower facial weakness, Babinski sign, pronator drift, sensory deficit, visual field defect, pseudobulbar syndrome, cerebellar signs
- Subcortical ischemic pathology: gradual onset, slowly progressive, predominantly affecting attention, processing speed, and executive functioning
- Memory impairment typically involves inefficient encoding and/or retrieval (vs. consolidation and storage in Alzheimer disease)
The Hachinski ischaemic score helps differentiate vascular dementia from Alzheimer's disease: ≥ 7 = multi-infarct dementia, 5–6 = mixed, ≤ 4 = AD [26].
High Yield Summary — Differential Diagnosis of Ischemic Stroke
-
Always rule out the "Big 3" mimics first: Hypoglycaemia (bedside glucose), ICH/SAH (urgent NCCT), and seizure with Todd's paralysis (history of witnessed convulsion).
-
Stroke produces negative, focal symptoms — positive symptoms (seizure, migraine aura) or global symptoms (metabolic encephalopathy) suggest a mimic.
-
Clinical features cannot reliably distinguish ischemic from hemorrhagic stroke — NCCT is mandatory.
-
Headache and vomiting favour hemorrhagic stroke.
-
Gradual progression suggests non-stroke pathology (tumour, MS, abscess) unless it follows the "stuttering" pattern of thrombotic stroke.
-
Young stroke (< 45 years) demands a wider workup: dissection, PFO, APS, Moyamoya, CVST, drugs, rheumatic heart disease.
-
Aortic dissection can mimic stroke — thrombolysis is absolutely contraindicated. Always consider in stroke + chest/back pain.
-
Time of onset = last seen well — this determines reperfusion eligibility.
Active Recall - Differential Diagnosis of Ischemic Stroke
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1210, 1221–1223) [2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1137, 1146–1148) [3] Senior notes: Ryan Ho Neurology.pdf (Section 3.2: Cerebrovascular Diseases, pp. 76, 78) [4] Senior notes: Maksim Medicine Notes.pdf (Neurology — Stroke, TIA, pp. 241, 243, 247) [7] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Vascular Diseases — Carotid artery stenosis, p. 894) [9] Senior notes: Block A - Cardiology Interactive Tutorial.pdf (p. 3) [11] Senior notes: Block A - Many members of the family have anaemia.pdf (p. 7) [17] Senior notes: Maksim Surgery Notes.pdf (Cerebral venous thrombosis, p. 358) [18] Lecture slides: GC_Interactive tutorial (Neuro-CVA case) student copy.pdf (p. 1) [19] Lecture slides: CFB_Neuro clinical skills demonstration_01.08.22_file to students.pdf (p. 8) [20] Senior notes: Ryan Ho Diagnostic Radiology.pdf (pp. 40–41) [21] Senior notes: Ryan Ho Fundamentals.pdf (p. 313) [22] Lecture slides: Cererbrovascular disease.pdf (pp. 46, 51) [23] Senior notes: Ryan Ho Cardiology.pdf (Thrombolysis contraindications, p. 138) [24] Senior notes: Block A - Sudden severe chest pain_ acute myocardial infarction; aortic dissection.pdf (p. 6) [25] Lecture slides: GC 241. Reference (2) - New vascular neurocognitive disorder criteria JAMA.pdf (pp. 5–6) [26] Senior notes: Ryan Ho Psychiatry.pdf (pp. 88, 93)
Diagnostic Criteria and Clinical Diagnosis
Ischemic stroke does not have a single set of "diagnostic criteria" in the same way that, say, rheumatic fever has the Jones criteria. Instead, the diagnosis is made through the integration of:
- Clinical presentation — sudden onset focal neurological deficit consistent with a vascular territory
- Neuroimaging — confirming infarction AND excluding haemorrhage
- Etiological workup — determining the underlying mechanism (TOAST classification) to guide management
From the GC Fundamentals Neurology lecture (Prof KC Teo): Neuroimaging is essential — you cannot diagnose stroke on clinical grounds alone because you must exclude haemorrhage before initiating reperfusion therapy [15].
The operational clinical definition of ischemic stroke is:
- Rapid onset of focal (or global) disturbances of cerebral function
- Due to non-traumatic vascular causes
- Lasting > 24 hours (or leading to death)
- With evidence of structural brain damage on neuroimaging (infarction on CT or MRI)
Clinical Assessment Tools
The neurological deficit should be documented by the National Institute of Health Stroke Scale (NIHSS) [3]. This is a standardised, validated 42-point scale that quantifies stroke severity and guides treatment decisions.
Why the NIHSS matters:
- It provides a common language for communicating stroke severity between clinicians
- It is used for tPA eligibility assessment (generally NIHSS 4–25 for IV tPA consideration)
- It provides prognostic information and tracks response to treatment
- It is required documentation in acute stroke units
| NIHSS Score | Severity | Interpretation |
|---|---|---|
| 0 | No deficit | Normal exam |
| 1–4 | Minor stroke | Consider whether reperfusion is needed |
| 5–15 | Moderate stroke | Strong indication for reperfusion |
| 16–20 | Moderate-severe stroke | Consider EVT if LVO |
| 21–42 | Severe stroke | High mortality/disability risk |
NIHSS components (11 items):
| Item | What It Tests | Max Points |
|---|---|---|
| 1a. Level of consciousness | Alertness | 3 |
| 1b. LOC questions | Orientation (month, age) | 2 |
| 1c. LOC commands | Following commands (close eyes, grip) | 2 |
| 2. Best gaze | Horizontal eye movements (CN III, VI) | 2 |
| 3. Visual fields | Confrontation visual fields | 3 |
| 4. Facial palsy | Facial symmetry (CN VII, UMN) | 3 |
| 5. Motor arm | Arm drift (L and R separately) | 4 each |
| 6. Motor leg | Leg drift (L and R separately) | 4 each |
| 7. Limb ataxia | Finger-nose-finger, heel-shin | 2 |
| 8. Sensory | Pin-prick sensation | 2 |
| 9. Best language | Aphasia (naming, reading, describing) | 3 |
| 10. Dysarthria | Clarity of speech | 2 |
| 11. Extinction/Inattention | Neglect (visual, tactile, anosognosia) | 2 |
NIHSS Limitations — Exam Trap
The NIHSS is biased toward anterior circulation (MCA) strokes — it heavily weights language and motor function. Posterior circulation strokes (brainstem, cerebellar) can present with devastating deficits (locked-in syndrome, coma) yet score low on NIHSS because items like ataxia, vertigo, and cranial nerve palsies are under-represented. A "low NIHSS" does NOT mean "not a serious stroke."
Already detailed in Part 1. Key point: ABCD2 ≥ 3 → hospitalise for urgent workup. ABCD2 ≥ 4 → 2-day stroke risk ~8% → MRI within 24h + DAPT [4].
Diagnostic Algorithm
The diagnostic algorithm for ischemic stroke is driven by a single imperative: identify candidates for reperfusion therapy as rapidly as possible. Every minute of delay means more penumbra lost.
The key time windows:
- IV tPA (alteplase): within 4.5 hours of symptom onset [1][2]
- Endovascular thrombectomy (EVT): within 6 hours (up to 24 hours in selected patients with favourable penumbral imaging) [4]
- Door-to-CT time: within 25 minutes [4]
- Door-to-needle time (tPA): within 60 minutes (target)
Time of stroke onset = time that is LAST SEEN WELL, rather than last seen unwell — if the patient wakes with symptoms or cannot provide a reliable onset time, the last known well time is used [1][2].
High Yield — GC Lecture Point: Do NOT Delay tPA for CTA
Arrange CTA ± perfusion scan for EVT triage but do NOT withhold tPA [4]. The CTA can be done after tPA bolus is given. The two treatments are complementary, not sequential.
Investigation Modalities — Comprehensive Breakdown
The investigations for ischemic stroke serve three purposes:
- Confirm the diagnosis (imaging — is there infarction? Is there haemorrhage?)
- Guide acute treatment (is the patient eligible for tPA/EVT? What is the vascular anatomy?)
- Determine the etiology (TOAST classification — what caused this stroke and how do we prevent the next one?)
A. Emergent Neuroimaging
Mainstay of imaging in acute stroke [10][16].
Why CT first?
- Available 24/7 in virtually every emergency department
- Fast (< 1 minute scan time) [27]
- Excellent at detecting acute haemorrhage (acute blood is hyperdense/white)
- Allows differentiation of ischaemic and haemorrhagic stroke [10]
- Rules out haemorrhage before thrombolytic/antiplatelet therapy [28]
What CT tells you in the hyperacute setting:
| Finding | Interpretation | Significance |
|---|---|---|
| Hyperdense MCA sign (at M1) | Atheroma, thrombus, or embolism in MCA [10] | Confirms large vessel occlusion; hyperdense vessel segments can occur in ALL vessels but most often observed in MCA [10] |
| MCA dot sign (at M2, Sylvian fissure) | Thrombus in M2 segment | Same significance as above [4] |
| Loss of insular ribbon cortex | Insular cortex supplied by most distal branch of lenticulostriate artery → first part affected by ischaemia → grey matter becomes hypodense → loss of grey-white junction [10] | Early ischaemic change |
| Loss of grey-white matter differentiation | Cytotoxic oedema (intracellular water accumulation as Na⁺/K⁺ ATPase fails) [4][16] | Early ischaemic change |
| Frank hypodensity > 1/3 MCA territory | Consistent with irreversible injury [1][2] | CONTRAINDICATION to tPA — thrombolysis of a massive established infarct → high risk of haemorrhagic transformation |
| Normal CT | Does NOT exclude ischaemic stroke | CT sensitivity < 1 day = only 48% [10]; early ischaemic changes are rather inconspicuous → rely on clinical or MRI findings [10] |
Evolution of CT findings in ischemic stroke [4]:
| Phase | Timing | Density | Margin | Mass Effect | Other Signs |
|---|---|---|---|---|---|
| Acute | 0–6h | Isodense | Ill-defined | None/subtle | Hyperdense MCA sign, MCA dot sign, loss of grey-white differentiation, loss of insular ribbon |
| Subacute | 1–5 days | Hypodense | Fairly defined | Increased (peak day 2–3) | Haemorrhagic transformation: petechial haemorrhage (small foci, does NOT affect prognosis) vs. secondary haematoma (DOES affect prognosis) |
| Chronic | > 5 days | Hypodense | Well defined | Decreased | Encephalomalacia (brain volume loss). CT fogging at 2–3 weeks: infarcted brain appears normal due to decreased oedema → use CT with contrast |
Mass effect includes effacement of sulci and ventricles, midline shift, and herniation [4].
Early ischaemic changes are only seen in MCA territory (large vessel occlusion) [4] — small vessel/lacunar infarcts are typically invisible on acute NCCT.
CT Fogging Phenomenon — Exam Favourite
At 2–3 weeks post-stroke, the infarcted brain can appear normal on CT because the oedema has resolved but the tissue has not yet undergone complete liquefactive necrosis. This is the CT fogging phenomenon [4]. If you scan a patient at this time and see a "normal" CT, you may falsely conclude there was no infarct. Solution: use CT with contrast (enhancing damaged blood-brain barrier highlights the infarct) or MRI.
Role: to assess eligibility for intra-arterial thrombolysis or clot retrieval, and to look for underlying vascular cause by evaluating carotid and vertebral arteries [4].
CTA:
- Performed immediately after NCCT (same scanner, same session, just add contrast bolus)
- Shows the entire arterial tree from aortic arch to Circle of Willis
- Identifies large vessel occlusion (LVO) — the target for EVT
- Identifies extracranial carotid/vertebral stenosis — important for secondary prevention
- Do NOT withhold tPA while waiting for CTA [4]
CT Perfusion (CTP):
- Advanced imaging that maps cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-maximum (Tmax)
- Distinguishes infarct core (irreversibly damaged — low CBV) from ischemic penumbra (at risk but salvageable — low CBF but preserved CBV, prolonged Tmax)
- Critical for late-window EVT decisions (6–24 hours) — based on the DAWN and DEFUSE-3 trials, patients with a large penumbra relative to core ("mismatch") may benefit from thrombectomy even up to 24 hours
More specific and sensitive than NCCT; sensitivity 86–100% [4][10][27].
| Sequence | Timing | Finding | Interpretation |
|---|---|---|---|
| Diffusion-Weighted Imaging (DWI) | Minutes | Hyperintense lesion (restricted diffusion) | Best for ischaemic stroke [4] — cytotoxic oedema causes water molecules to be trapped intracellularly, restricting their Brownian motion → bright on DWI |
| ADC map | Minutes | Hypointense lesion | Distinguishes ischaemic lesion from other DDx [4] — true restricted diffusion is dark on ADC (confirms genuine cytotoxic oedema, not T2 shine-through) |
| T2/FLAIR | 6+ hours | Hyperintense | Vasogenic oedema, later changes |
| T1 | 16+ hours | Hypointense | Later parenchymal changes |
| MR Angiography (MRA) | — | Vessel occlusion/stenosis | May be able to locate site of occlusion [27] |
| SWI/GRE | — | Hypointense "blooming" | Detects haemorrhage (even chronic microbleeds) — important for identifying cerebral amyloid angiopathy and haemorrhagic transformation risk |
DWI-FLAIR mismatch: If DWI is positive (bright) but FLAIR is negative (normal), this suggests the infarct is < 4.5 hours old (because FLAIR takes ~4.5 hours to become positive). This is used to guide thrombolysis in "wake-up strokes" where the onset time is unknown — if DWI+/FLAIR−, the stroke is likely within the treatment window.
CT vs MRI comparison [27]:
| Feature | CT | MRI |
|---|---|---|
| Radiation | Yes | No |
| Examination time | 1 min | 20 min |
| Availability | Good | Fair |
| Sensitivity for infarct | Poor (early) | Good |
| Sensitivity for haemorrhage | Good | Good |
When to Use MRI Over CT
MRI is reserved for those with doubtful diagnosis or together with MRA [3]. Specific indications:
- Suspected posterior fossa stroke (CT is poor at brainstem/cerebellar imaging due to bone artefact)
- Wake-up stroke or unknown onset time (DWI-FLAIR mismatch)
- Small lacunar infarct not seen on CT
- Need to distinguish acute from chronic infarcts
- Suspected CVST (MR venogram)
From GC Fundamentals Neurology lecture (Prof KC Teo): Vascular imaging includes non-invasive (ultrasound carotid/vertebral arteries, CTA, MRA) and invasive (digital subtraction angiography — DSA). DSA is the gold standard for assessment of vascular lesion and allows interventional procedures (stenting/coiling) but carries inherent risk: stroke, dissection, infection, bleeding [15].
| Modality | What It Shows | When to Use | Key Points |
|---|---|---|---|
| Carotid Doppler ultrasound | Look for extracranial large vessel disease (carotid/vertebral artery stenosis) [4] | All ischemic stroke patients with anterior circulation symptoms | Non-invasive, no radiation, widely available. Operator-dependent. Measures stenosis severity (NASCET criteria) and flow velocities |
| Transcranial Doppler (TCD) ultrasound | Look for intracranial large vessel disease (around Circle of Willis) [4] | Suspected intracranial atherosclerosis (especially relevant in Chinese populations) | Emerging tool to differentiate ischaemic vs haemorrhagic stroke; monitor complications including haemorrhagic transformation [4]. Also used for microembolic signal detection (identifying embolic sources) |
| CTA | Full arterial tree aortic arch → Circle of Willis | Acute setting for EVT triage; vascular anatomy assessment | Already discussed above |
| MRA | Similar to CTA without radiation | When MRI brain is performed | No iodinated contrast needed (TOF-MRA uses flow itself). Slightly lower spatial resolution than CTA |
| Digital Subtraction Angiography (DSA) | Gold standard for vascular lesion assessment [15] | When non-invasive imaging is equivocal, or for intervention (EVT, stenting, coiling) | Diagnostic + therapeutic (performed during EVT) [4]. Cons: inherent risk → stroke, dissection, infection, bleeding [15] |
Since cardioembolism accounts for ~20% of ischemic strokes, every stroke patient needs a cardiac workup:
| Investigation | What It Finds | Key Points |
|---|---|---|
| 12-lead ECG | AF, old MI, LVH [4] | Must be done immediately. AF is the most important treatable cardiac source. Also look for ST changes suggesting concurrent ACS |
| Continuous cardiac monitoring / Telemetry | Paroxysmal AF | Many AF episodes are silent and short-lived. Telemetry during ASU admission catches events missed by a single ECG |
| Holter monitor (24–72h) | Paroxysmal AF | Extended outpatient monitoring; detect intermittent arrhythmias |
| Implantable loop recorder (ILR) | Paroxysmal AF in cryptogenic stroke | Up to 3 years of monitoring. The CRYSTAL-AF trial showed ILR detected AF in ~30% of cryptogenic strokes at 3 years |
| Transthoracic echocardiogram (TTE) | Valvular disease, LV dysfunction, mural thrombus, vegetations | Standard cardiac assessment. Limited sensitivity for left atrial appendage thrombus |
| Transoesophageal echocardiogram (TOE) | Left atrial appendage thrombus, PFO, aortic arch atheroma, small vegetations | Superior to TTE for visualising the left atrium, interatrial septum, and aortic arch. Use when cardioembolism is suspected but TTE is non-diagnostic |
| Bubble contrast echocardiography | Patent foramen ovale (PFO) | Inject agitated saline; bubbles appearing in left atrium within 3 cardiac cycles after Valsalva confirms right-to-left shunt |
Bloods: CBC, LRFT, clotting (for tPA), blood glucose (hypoglycaemia mimics stroke, hyperglycaemia worsens prognosis), HbA1c, lipids, ESR/CRP (vasculitis) [4].
| Investigation | Purpose | Key Findings / Interpretation |
|---|---|---|
| Bedside blood glucose | Hypoglycaemia mimics stroke [4]; hyperglycaemia worsens infarct volume (increased anaerobic glycolysis → lactic acidosis in penumbra) | Must be checked before CT |
| CBC with differential | Anaemia (↓O₂ delivery), thrombocytopenia (PLT < 100 × 10⁹/L = tPA contraindication [1][2]), polycythaemia (hyperviscosity), leukocytosis (infection, leukostasis) | |
| Clotting profile (PT/INR, APTT) | Assess for coagulopathy; PT > 15s / APTT > 40s / INR > 1.7 = tPA contraindication [1][2] | Essential before thrombolysis. Also identifies patients on anticoagulants |
| Renal function (U&E, Cr) | Baseline for contrast administration (CTA requires eGFR assessment); electrolyte derangement can mimic neurological symptoms | |
| Liver function | Coagulation factor synthesis; hepatic dysfunction may cause coagulopathy | |
| Fasting lipids | Assess atherosclerotic risk; guides statin therapy | |
| HbA1c | Assess glycaemic control; diagnose/monitor DM | |
| ESR / CRP | Vasculitis screen [4]; also elevated in IE, GCA, other inflammatory causes | |
| Troponin | Concurrent MI (stroke can be caused by MI, and acute stroke itself can cause takotsubo/myocardial injury from catecholamine surge) | |
| Blood glucose (repeated) | Monitor for hyperglycaemia which worsens prognosis [4] |
| Investigation | When to Order | What It Finds |
|---|---|---|
| Thrombophilia screen (APS, lupus anticoagulant, anticardiolipin Ab, anti-β2GP1) | Young stroke (< 45), recurrent stroke, no conventional risk factors, history of venous thrombosis or pregnancy morbidity | Antiphospholipid syndrome — causes both arterial AND venous thrombosis |
| Haemoglobin electrophoresis | Patients of Black African descent; anaemia with haemolysis | Sickle cell disease |
| Serum homocysteine | Young stroke, cryptogenic stroke | Hyperhomocysteinaemia |
| Lumbar puncture | Suspected CNS vasculitis, infection, or SAH with negative CT | CSF analysis: xanthochromia (SAH), pleocytosis (infection/vasculitis), protein/glucose |
| Autoimmune panel (ANA, anti-dsDNA, ANCA, complement) | Suspected vasculitis or autoimmune disease | SLE, primary CNS vasculitis |
| HIV test | Young stroke, risk factors for HIV | HIV-associated vasculopathy, opportunistic infections |
| Blood cultures | Fever + murmur + stroke → suspected IE | Large vegetations > 1 cm prone to embolisation causing ischemic stroke [9] |
| Toxicology screen | Young stroke, suspected drug use | Cocaine → vasospasm; amphetamines |
| Pregnancy test | Women of childbearing age | CVST, eclampsia, peripartum cardiomyopathy |
CXR is part of baseline investigations: rule out aortic dissection [4].
| Finding | Significance |
|---|---|
| Widened mediastinum | Suggests aortic dissection — absolute contraindication to tPA |
| Cardiomegaly | CHF, DCM → potential embolic source |
| Pulmonary oedema | Concurrent heart failure |
| Rib notching | Coarctation of the aorta (rare cause of hypertension → stroke) |
NPO until swallowing test; NG tube if fail [4]. This is technically a diagnostic assessment (does the patient have dysphagia?) with direct therapeutic implications (preventing aspiration pneumonia, which is the leading cause of post-stroke death).
Key Contraindications to IV tPA — From the Diagnostic Workup
The reason for rapid blood tests and imaging is largely to screen for tPA contraindications. These must be memorised:
- Ischemic stroke > 4.5 hours of symptom onset
- History of intracranial hemorrhage
- History of ischemic stroke, severe head trauma, or intracranial/intraspinal surgery within 3 months
- History of intracranial neoplasm
- History of GI malignancy or bleeding within 3 weeks
- Use of LMWH within 24 hours
- Use of direct thrombin inhibitor / direct Factor Xa inhibitor with evidence of anticoagulant effect
- Active internal bleeding
- Symptoms suggestive of SAH
- Infective endocarditis
- Aortic arch dissection
- BP > 185/110 mmHg (must be lowered first)
- Blood glucose < 2.8 mmol/L
- Thrombocytopenia < 100 × 10⁹/L
- PT > 15s / APTT > 40s / INR > 1.7
- Evidence of intracerebral hemorrhage on NCCT
- Frank hypodensity on CT > 1/3 MCA territory consistent with irreversible injury
Why is Extensive Early Hypodensity a Contraindication?
If > 1/3 of the MCA territory already shows frank hypodensity on CT, this indicates a large completed infarct with irreversible tissue death. Thrombolysing this tissue will not save any neurons (there is no penumbra left to rescue) but WILL dramatically increase the risk of haemorrhagic transformation — because reperfusion into already necrotic tissue with damaged blood-brain barrier causes massive bleeding into the infarct. The risks far outweigh the benefits.
| Timing | Investigations |
|---|---|
| Immediate (ED) | Bedside glucose, NCCT brain, ECG, CBC, clotting, renal function |
| Within 1 hour | CTA ± CTP (if EVT candidate), IV tPA if eligible |
| Within 24 hours | MRI DWI (if CT non-diagnostic or wake-up stroke), carotid Doppler, TTE, Holter initiation, fasting lipids, HbA1c, ESR/CRP |
| During admission | TEE (if cardioembolism suspected), bubble study (if PFO suspected), extended cardiac monitoring |
| Outpatient / Selected | ILR (cryptogenic), thrombophilia screen (young), DSA (if non-invasive imaging equivocal), genetic testing (Moyamoya, CADASIL) |
High Yield Summary — Diagnosis of Ischemic Stroke
-
No single diagnostic criterion set — diagnosis integrates clinical presentation + neuroimaging + etiological workup.
-
NCCT brain is first-line: rules out haemorrhage (the primary purpose), identifies early ischaemic signs. Sensitivity only ~48% in first 24h.
-
MRI DWI is most sensitive (86–100%): restricted diffusion = cytotoxic oedema = acute infarction. DWI-FLAIR mismatch guides wake-up stroke thrombolysis.
-
CTA identifies large vessel occlusion for EVT triage — do NOT delay tPA for CTA.
-
Baseline bloods: glucose (mimic), CBC + clotting (tPA eligibility), HbA1c + lipids (risk factors), ESR/CRP (vasculitis).
-
ECG + cardiac monitoring: AF is the most important treatable embolic source.
-
Carotid Doppler: all anterior circulation strokes need extracranial vessel assessment.
-
tPA contraindications are determined by the diagnostic workup — history, clinical, biochemical, and radiological screens.
-
Frank hypodensity > 1/3 MCA territory on CT = irreversible injury = tPA contraindicated.
-
Time of onset = LAST SEEN WELL — critical for reperfusion eligibility.
Active Recall - Diagnostic Criteria, Algorithm and Investigations for Ischemic Stroke
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1213, 1228–1230) [2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1138–1140, 1153–1155) [3] Senior notes: Ryan Ho Neurology.pdf (Section 3.2: Cerebrovascular Diseases, p. 76) [4] Senior notes: Maksim Medicine Notes.pdf (Neurology — Stroke imaging, acute management, pp. 241, 243, 245, 247) [9] Senior notes: Block A - Cardiology Interactive Tutorial.pdf (p. 3) [10] Senior notes: Ryan Ho Diagnostic Radiology.pdf (pp. 40, 50) [15] Lecture slides: GCBA_Fundamentals_Neuro_Introduction to Neurological Investigations and Emergencies_Prof KC Teo.pdf (p. 42) [16] Senior notes: Ryan Ho Radiology.pdf (p. 22) [27] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p. 50) [28] Senior notes: Ryan Ho Radiology.pdf (p. 17)
Management of Ischemic Stroke
The management of ischemic stroke follows a logical sequence rooted in pathophysiology:
- Keep the patient alive (ABC, supportive care)
- Save the penumbra (reperfusion therapy — tPA, EVT)
- Prevent early complications (cerebral oedema, haemorrhagic transformation, aspiration)
- Find the cause (etiological workup — TOAST)
- Prevent the next stroke (secondary prevention — antiplatelets, anticoagulation, risk factor control, surgery)
- Restore function (rehabilitation)
From GC 087 lecture slides: The key acute treatments are recombinant tissue plasminogen activator within 3 (4.5) hours of onset of stroke and mechanical thrombectomy within 6 hours of onset of stroke due to large artery occlusion — these are the two pillars of acute reperfusion. The concept underlying late-window treatment is penumbra-based reperfusion therapy [13].
Phase 1: General Acute Management ("Must Know" — SAQ Level)
It is essential to identify site, subtype, cause and risk factors of stroke [4].
- Admit acute stroke unit (ASU) [4] — evidence shows organised stroke unit care reduces death and disability by ~20% compared with general ward care
- Resuscitation: airway, breathing, circulation, GCS [4]
- NPO until swallowing test; NG tube if fail [4] — why? Because stroke commonly causes dysphagia (CN IX, X, bilateral cortical input to swallowing centre); aspiration pneumonia is the leading cause of post-stroke death
- Monitoring: vitals Q4h, neuro-obs Q30min × 2 then Q1h [4]
- Why such frequent neuro-obs? Risk of cerebral oedema peaks at 2–3 days: watch for malignant MCA syndrome / cerebellar infarct [4]. Deterioration in GCS or new pupil asymmetry signals imminent herniation
- Airway support and ventilatory assistance are recommended for patients with decreased consciousness or bulbar dysfunction causing airway compromise [2]
- Supplemental oxygen should be provided to maintain SaO₂ > 94% [2]
- Supplemental oxygen is NOT recommended in non-hypoxic patients [2] — why? Hyperoxia may paradoxically cause vasoconstriction and generate free radicals, worsening ischaemic injury
This is one of the most commonly examined and most nuanced aspects of acute stroke management. The underlying principle is permissive hypertension:
Why do we tolerate high BP in acute ischemic stroke? The ischaemic penumbra has lost its ability to autoregulate blood flow. It depends entirely on systemic blood pressure to maintain perfusion. If you drop the BP aggressively, the penumbra loses its blood supply and infarcts. This is why acute stroke is a contraindication for emergency reduction of BP [5] — the rapid reduction causes loss of cerebral autoregulation, less perfusion, and consequent risk of cerebral infarction [5].
BP targets by scenario:
| Clinical Scenario | BP Target | Rationale |
|---|---|---|
| Not eligible for tPA | Do NOT treat unless > 220/120 mmHg [2][4] | Permissive hypertension to maintain penumbral perfusion |
| Pre-tPA | Lower to ≤ 185/110 mmHg before starting tPA [2][4] | High BP during tPA increases haemorrhagic transformation risk |
| Post-tPA (first 24h) | Maintain < 180/105 mmHg [2][4] | Same reasoning — fragile reperfused tissue bleeds if BP too high |
| After first 24h | Restart home antihypertensives if neurologically stable [2] | Long-term BP control for secondary prevention |
Preferred antihypertensives:
- IV labetalol / nicardipine / nitroprusside for cautious and gradual lowering [4]
- Avoid hydralazine / nifedipine — these are direct-acting cerebral vasodilators → cause a fall in cerebral blood flow [4]. Why? They dilate cerebral vessels preferentially, causing a "steal" phenomenon where blood is diverted away from the ischaemic territory
High Yield Exam Point — BP Management in Stroke
Students commonly make the mistake of treating every hypertensive stroke patient aggressively. Remember: BP should be CAREFULLY LOWERED since some degree of BP elevation may be necessary to maintain cerebral blood flow to ischaemic brain regions [2]. The only indication for acute lowering below 220/120 is if the patient is a tPA candidate (target ≤ 185/110 pre-tPA).
- Hyperglycaemia worsens prognosis [4] — why? High glucose promotes anaerobic glycolysis in ischaemic tissue → lactic acidosis → accelerated neuronal death. Also promotes cerebral oedema and impairs reperfusion
- Hypoglycaemia mimics stroke [4] — and if left untreated causes its own neuronal injury
- Treatment of hyperglycaemia with insulin is required; closely monitor to prevent hypoglycaemia [2]
- Aim normoglycaemia [4]
- Ensure good hydration and oxygenation: IV normal saline Q6h [4]
- Dextrose is toxic to the brain in the ischaemic setting [4] — why? Dextrose provides substrate for anaerobic glycolysis → more lactic acid production in the penumbra → worsens injury. Always use normal saline, never dextrose-containing fluids
- Source of hyperthermia should be identified and treated [2]
- Antipyretic medications should be administered to lower temperature in hyperthermic patients [2] — fever increases metabolic demand in already-ischaemic tissue, worsening infarct size
- Routine prophylactic antibiotics have NOT been shown to be beneficial [2]
Phase 2: Acute Reperfusion Therapy
This is the most critical time-sensitive intervention in ischemic stroke. There are two modalities:
Mechanism: Alteplase is a recombinant tissue plasminogen activator (rtPA) — "alteplase" → "alt" (altered) + "plase" (plasminogen activator). It converts plasminogen → plasmin, which lyses fibrin within the thrombus, dissolving the clot and restoring blood flow. It is fibrin-specific (preferentially activates plasminogen bound to fibrin in the clot, rather than circulating plasminogen), which theoretically reduces systemic bleeding [30].
Why limit alteplase to 4.5 hours? ECASS study: capillaries in infarcted areas are damaged → recanalisation increases haemodynamic stress → risk of haemorrhagic transformation increases as ischaemia time prolongs [4].
Key details:
| Parameter | Detail |
|---|---|
| Aim | Reverse neurological deficit by dissolution of thrombus occluding vessels [3] |
| Indication | Ischaemic stroke onset within 3–4.5 hours of onset (or last seen well time) with good premorbid function [3][4][13][31] |
| Dose | rtPA 0.9 mg/kg (10% as IV bolus, rest as 1-hour infusion), max dose 90 mg [3] |
| Timing | Should be given ASAP — better prognosis with decreased door-to-needle time [3] |
| Effectiveness | Very effective for small vessel occlusion but ineffective for large arteries with high mortality despite IV rtPA at 19% [3] — this is why EVT was developed |
| Major risk | Haemorrhagic stroke (~1%) [30] |
GC 087 High Yield — Thrombolysis Key Points
Recombinant Tissue Plasminogen Activator within 3 (4.5) hours of the onset of stroke being effective; more hemorrhagic complications. Numerous contraindications. Intravenous streptokinase with unacceptable risk of hemorrhagic complications [13].
Note: streptokinase is used in STEMI but is NOT used for ischaemic stroke because the bleeding risk is unacceptably high in the cerebral circulation.
Contraindications to IV tPA (Must Memorise):
Organised by the source of information [1][2]:
History-based:
- Ischaemic stroke > 4.5 hours of symptom onset
- History of intracranial hemorrhage (ICH)
- History of ischaemic stroke, severe head trauma, or intracranial/intraspinal surgery within 3 months
- History of intracranial neoplasm
- History of GI malignancy or bleeding within 3 weeks
- Use of LMWH within 24 hours
- Use of direct thrombin inhibitor or direct Factor Xa inhibitor with evidence of anticoagulant effect
Clinical:
- Active internal bleeding
- Symptoms suggestive of SAH
- Infective endocarditis
- Aortic arch dissection
Biochemical:
- BP > 185/110 mmHg
- Blood glucose < 2.8 mmol/L
- Thrombocytopenia < 100 × 10⁹/L
- PT > 15s / APTT > 40s / INR > 1.7
Radiological:
- Evidence of ICH on NCCT
- Frank hypodensity on CT > 1/3 MCA territory consistent with irreversible injury
From the HK Handbook of Internal Medicine 2024 [31]:
- Usual contraindication for IV thrombolysis: presence of extensive early infarct changes or intracranial bleed on CT; active internal bleeding; use of warfarin with INR > 1.7; use of therapeutic dose of LMWH within 24 hours
- Use of anti-Factor Xa inhibitor DOACs within 24 hours (high risk within 24–48h)
- For patients on Dabigatran who are NOT candidates for mechanical thrombectomy but ARE candidates for thrombolysis: Idarucizumab 5 g IV bolus STAT can be given for reversal of Dabigatran's effect, followed by thrombolysis [31]
This is the game-changer in acute stroke management over the past decade. Five landmark RCTs in 2015 (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) established EVT as the new standard of care for large vessel occlusion [22].
Mechanism: A catheter is advanced (usually via femoral artery → aorta → carotid → intracranial) to the site of the occluding thrombus. The clot is then physically removed using either:
- Stent retriever (e.g., Solitaire, Trevo) — a self-expanding stent deployed across the clot, which engages the thrombus, then the entire device + clot is withdrawn
- Aspiration thrombectomy — a large-bore catheter applies suction directly to the clot face
Why is IV tPA insufficient for large vessel occlusion? Because large thrombi in the ICA, M1 MCA, or basilar artery have too much fibrin mass for systemic tPA to dissolve within the narrow time window. The recanalization rate with tPA alone for large vessel occlusion is only ~15-30%, while EVT achieves recanalization rates up to 80% [4].
Key details:
| Parameter | Detail |
|---|---|
| Indication | Ischaemic stroke due to large vessel occlusion (CCA, ICA, MCA M1, basilar artery) [4][31] |
| Time window | Standard: within 6 hours (HERMES meta-analysis) [4]; Extended: 6–24 hours if CT perfusion shows clinical-core mismatch (large salvageable penumbra) — DAWN, DEFUSE-3 trials [4] |
| Good premorbid function required [31] | |
| CTA confirmation of LVO required [31] | |
| Relative contraindication: ASPECTS < 7 [4] (ASPECTS = Alberta Stroke Program Early CT Score — a 10-point score of early ischaemic changes on CT; score < 7 suggests too much irreversible damage) | |
| Technique | Aspiration thrombectomy, stent retriever (e.g., Merci retriever); NO tPA given intrarterially [4] |
| DSA | Diagnostic + therapeutic — performed during EVT [4] |
Risks of EVT [4]:
- Vascular injury (e.g., dissection, perforation)
- Puncture site complications (e.g., retroperitoneal haematoma)
- Cholesterol embolization syndrome — S/S: livedo reticularis, blue toe syndrome, renal impairment, hypereosinophilia, ↑ ESR/CRP [4]
- Contrast allergy / nephropathy
GC 087 High Yield — Mechanical Thrombectomy
Mechanical thrombectomy within 6 hours of onset of stroke due to large artery occlusion [13]. Penumbra-based reperfusion therapy extends the window up to 24 hours in selected patients with imaging evidence of salvageable tissue [13].
Key point from the HK Handbook of Internal Medicine 2024: Patients with bleeding diathesis may still be candidates for mechanical thrombectomy despite being contraindicated for intravenous thrombolysis [31]. This is because EVT is a mechanical procedure — you are physically removing the clot, not dissolving it chemically, so coagulopathy is less of an issue.
Relationship between IV tPA and EVT:
- They are complementary, not mutually exclusive
- If a patient is eligible for tPA AND has a large vessel occlusion, give IV tPA first (start the clock, begin dissolving the clot) then proceed to EVT ("drip and ship" or "drip and drive" model)
- Do NOT withhold tPA while waiting for CTA or EVT [4]
Aspirin 80 mg to 300 mg PO STAT dose [31]. This is the cornerstone of acute ischemic stroke management when thrombolysis is not given.
- Withhold aspirin for the first 24 hours if thrombolytic therapy was given [31] — why? Combining aspirin with tPA in the first 24h significantly increases haemorrhagic transformation risk
- If allergic to aspirin: clopidogrel — loading dose 300 mg STAT if clopidogrel-naïve, followed by 75 mg daily [31]
- Dual antiplatelet therapy (DAPT) with aspirin + clopidogrel may be considered in high-risk TIA or minor stroke, preferably for a short course of 3 weeks [31] — based on the CHANCE study [4]
The rationale for DAPT in minor stroke/TIA: The CHANCE trial (Chinese population-dominant study, highly relevant to HK) showed that 21 days of aspirin + clopidogrel started within 24 hours of a minor ischaemic stroke or high-risk TIA reduced the 90-day stroke risk by ~32% compared with aspirin alone, without significantly increasing haemorrhagic risk. After 3 weeks, continue aspirin monotherapy lifelong [4].
Anticoagulation is NOT for all ischemic strokes — it is indicated only for specific etiologies:
Immediate anticoagulation may be considered for acute ischaemic stroke in [4][31]:
- Documented cardiac source of embolism (e.g., LV thrombus) — immediate if TIA / minor stroke; withhold 2 weeks if large infarct / symptoms of haemorrhagic transformation / poorly controlled HT [4]
- Cerebral venous thrombosis (MRI venogram) [4]
- Extracranial carotid or vertebral artery dissection (CTA ± DSA) [4] — (intracranial dissection is C/I due to risk of SAH [4])
Contraindications to anticoagulation in acute stroke: BP > 180/110, large infarct [4][31].
The use of anticoagulation in acute stroke due to large artery thrombosis is controversial [31].
Choice of anticoagulant for AF-related stroke:
- DOAC (Direct Oral Anticoagulant) preferred over warfarin for non-valvular AF — dabigatran, apixaban, rivaroxaban, edoxaban [32]
- Warfarin still indicated for valvular AF (mechanical prosthetic valves, moderate-to-severe mitral stenosis)
- Timing of initiation: The "1-3-6-12 day rule" (practical guideline):
- TIA → start anticoagulation at day 1
- Minor stroke (NIHSS < 8) → day 3
- Moderate stroke → day 6
- Large stroke → day 12 (or later, after repeat imaging excludes haemorrhagic transformation)
Phase 5: Management of Acute Complications
When a large MCA territory infarcts, cytotoxic and vasogenic oedema cause massive brain swelling peaking at day 2–3 [4]. This can cause:
- Midline shift → uncal herniation → death
- "Malignant MCA syndrome": massive MCA territory infarct with eye deviation, dense hemiplegia, and progressive drowsiness ± unequal pupil size. Serial CT shows significant infarct with swelling and midline shift [31]
Management [4]:
- Elevate head of bed > 30° (promotes venous drainage from the head)
- IV mannitol / hypertonic saline (osmotic therapy — draws water out of brain tissue into the intravascular space)
- Hyperventilation (↓PaCO₂ → cerebral vasoconstriction → ↓intracranial blood volume → ↓ICP — only a temporary bridge measure)
- Refer neurosurgery for decompressive hemicraniectomy ± duroplasty [4][31] — the HAMLET trial showed this reduces mortality in malignant MCA syndrome. Can consider cranioplasty (replace skull bone) within 6 months to protect brain tissue [4]
- Consider external ventricular drainage [4]
- Risk factors: older age, larger stroke size, cardioembolic stroke, anticoagulation, elevated systolic BP in acute setting, thrombolytic therapy, delayed recanalisation therapy [16]
- Suspect if power keeps deteriorating after stroke, mostly occurs 2–3 days after stroke [4]
- Management: Stop anticoagulation/antiplatelets, urgent repeat CT, supportive care, consider reversal agents if on anticoagulation
| Complication | Management | Rationale |
|---|---|---|
| Infection | Treat aggressively + ↓ core temperature if fever [3] | Fever worsens ischaemic injury |
| Pulmonary complications | Careful feeding practice, early mobilisation, chest physiotherapy [3] | Aspiration pneumonia prevention |
| VTE prophylaxis | SC UFH / LMWH in immobilised patients; aspirin if anticoagulants contraindicated; intermittent pneumatic compression devices [1][2][3] | Immobility post-stroke → high DVT/PE risk |
| Pressure sores | Reposition weak limbs, frequent turning, cushions, egg-crate/air mattress [3] | Immobility → skin breakdown |
| Genitourinary | Indwelling catheter or condom catheter; intermittent catheterisation; measure post-void residual [3] | Avoid bladder overdistension and UTI |
| Bowel | High-fibre diet + stool softener (NOT laxative) [3] | Prevent constipation and faecal impaction |
| Depression | Structured depression inventory screening recommended routinely; treat with antidepressants [1][2] | Post-stroke depression affects ~30% of patients and worsens functional recovery |
Phase 7: Secondary Prevention
This is arguably the most important phase — the goal is to prevent the next stroke. The approach depends on the TOAST etiology:
| Risk Factor | Target | Agent / Intervention |
|---|---|---|
| Hypertension | < 130/80 mmHg (post-acute phase) | ACEI/ARB preferred (cerebrovascular protective effects) |
| Diabetes | HbA1c < 7% | Metformin, SGLT2 inhibitors, insulin as needed |
| Hyperlipidaemia | LDL < 1.8 mmol/L (or ≥ 50% reduction) | High-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) — statins have pleiotropic effects beyond lipid lowering: anti-inflammatory, plaque stabilisation, endothelial function improvement |
| Smoking | Complete cessation | Counselling, NRT, varenicline |
| Obesity | BMI < 25 | Diet, exercise |
| Alcohol | Moderation (≤ 2 drinks/day men, ≤ 1 women) | Counselling |
| Exercise | ≥ 150 min/week moderate intensity | Structured rehabilitation programme |
- Aspirin 75–100 mg daily — lifelong
- Clopidogrel 75 mg daily — alternative if aspirin intolerant
- DAPT (aspirin + clopidogrel) for 3 weeks after minor stroke/high-risk TIA, then aspirin monotherapy [31]
- PDE inhibitor (dipyridamole) + aspirin — can be used as combination therapy for secondary prevention of stroke [32]
- DOACs (dabigatran, apixaban, rivaroxaban, edoxaban) preferred over warfarin for non-valvular AF — stroke prevention in AF patients: 4 main pillars [32]
- Warfarin for valvular AF (mechanical valves, moderate-severe MS)
- Target INR 2.0–3.0 for warfarin
- Carotid endarterectomy (CEA) — indicated for symptomatic carotid stenosis ≥ 70% (NASCET criteria); benefit also shown for 50–69% stenosis in selected patients
- Should be performed within 2 weeks of the index event (TIA or non-disabling stroke) for maximum benefit
- Carotid artery stenting (CAS) — alternative when CEA is high risk (e.g., surgically inaccessible lesion, radiation-induced stenosis, restenosis after prior CEA)
- For asymptomatic carotid stenosis, benefit of CEA is marginal — best medical therapy (BMT) with aggressive risk factor control is often preferred
Early rehabilitation is a cornerstone of stroke recovery [3]:
| Service | Indication | Goal |
|---|---|---|
| Physiotherapy (PT) | All stroke patients with motor deficit | Restore mobility, strength, balance; prevent contractures |
| Occupational therapy (OT) | All patients with functional impairment | Restore activities of daily living, adaptive equipment |
| Speech and language therapy (SLT) | Dysphagia or speech/language problems [1][2][3] | Swallowing rehabilitation, aphasia therapy, communication aids |
| Clinical psychology | Depression, anxiety, cognitive impairment | Structured depression screening + treatment |
| Social work | Discharge planning, carer support | Community reintegration |
Special Situations
From the HK Handbook of Internal Medicine 2024 [31]:
For patients on dabigatran who are candidates for thrombolysis: Idarucizumab 5 g IV bolus STAT for reversal, followed by thrombolysis [31]. Idarucizumab ("ida" + "ru" + "cizumab") is a monoclonal antibody fragment that binds dabigatran with 350× higher affinity than thrombin, neutralising it within minutes.
Patients on dabigatran who are candidates for mechanical thrombectomy: can proceed directly to EVT without giving idarucizumab or thrombolysis [31] — because EVT is mechanical, not pharmacological.
High Yield Summary — Management of Ischemic Stroke
General Measures:
- Admit ASU. ABC + GCS. NPO until swallowing test. IV NS (never dextrose). Neuro-obs Q30min then Q1h.
- BP: permissive hypertension unless > 220/120 (non-tPA) or > 185/110 (pre-tPA). Avoid hydralazine/nifedipine.
- Glucose: aim normoglycaemia. Treat fever.
Reperfusion Therapy:
- IV alteplase: within 4.5h, 0.9 mg/kg (10% bolus + 1h infusion), max 90 mg. Know all contraindications.
- EVT: within 6h (up to 24h with penumbral mismatch) for large vessel occlusion. Recanalization rate ~80%.
- tPA + EVT are complementary. Never delay tPA for CTA. Streptokinase is NOT used for stroke.
Antiplatelets:
- Aspirin 80-300 mg STAT (withhold 24h if tPA given). DAPT × 3 weeks for minor stroke/high-risk TIA.
Anticoagulation:
- Only for cardioembolic source, CVST, or extracranial dissection. Delay if large infarct.
- DOACs preferred over warfarin for non-valvular AF.
Complications:
- Cerebral oedema (day 2-3) → mannitol, hemicraniectomy. Haemorrhagic transformation → stop anticoagulants.
- Seizures: treat but do NOT prophylax. VTE prophylaxis in immobilised patients.
Secondary Prevention:
- Antiplatelets (non-embolic), anticoagulation (AF), CEA (symptomatic carotid stenosis ≥ 70%).
- Statin, BP control, DM control, smoking cessation.
Rehabilitation:
- PT, OT, SLT, depression screening — early referral.
Active Recall - Management of Ischemic Stroke
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1228, 1231, 1233) [2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1153, 1155, 1158) [3] Senior notes: Ryan Ho Neurology.pdf (Section 3.2: Cerebrovascular Diseases, pp. 79, 82) [4] Senior notes: Maksim Medicine Notes.pdf (Neurology — Stroke management, pp. 241–243, 247) [5] Senior notes: Block A - High blood pressure_ hypertension.pdf (p. 55) [13] Lecture slides: GC 087. Sudden hemiplegia dysphagia.pdf (p. 22) [16] AOS material: AOS - Radiology.pdf (p. 11) [22] Lecture slides: Cererbrovascular disease.pdf (p. 20) [29] Senior notes: Ryan Ho Fluids and Nutrition.pdf (p. 9) [30] Senior notes: Block A - Sudden severe chest pain_ acute myocardial infarction; aortic dissection.pdf (p. 18) [31] Lecture slides: Handbook of Internal Medicine 2024.pdf (pp. 329–330) [32] Senior notes: Block A - Clinical pharmacology of antiplatelets and anticoagulation.pdf (p. 3)
Complications of Ischemic Stroke
Understanding complications is essential because they are the main drivers of morbidity and mortality after the initial ischaemic insult. A patient may survive the stroke itself but die from aspiration pneumonia, pulmonary embolism, or brain herniation. Complications can be divided into CNS (neurological) and systemic categories, and further subdivided by timing (acute vs. chronic) [1][2][3].
A. CNS (Neurological) Complications
Mostly occurs 2–3 days after stroke [4].
Pathophysiology:
- In the first hours, cytotoxic oedema develops: ischaemic neurons lose ATP → Na⁺/K⁺ ATPase fails → Na⁺ and water enter cells → cells swell. This is intracellular swelling that does not initially cross the blood-brain barrier (BBB).
- Over 24–72 hours, the damaged BBB breaks down → vasogenic oedema develops: plasma proteins and water leak into the extracellular space → massive brain swelling.
- The rigid skull cannot accommodate this swelling → raised ICP → midline shift → herniation (uncal, transtentorial, or tonsillar) → brainstem compression → death.
Malignant MCA Syndrome: This is the most feared manifestation. It occurs when a large MCA territory infarct causes so much swelling that the brain herniates. Massive MCA territory infarct with eye deviation, dense hemiplegia, and progressive drowsiness ± unequal pupil size. Serial CT will show significant infarct with swelling and midline shift [31].
Clinical features to monitor:
- Decreasing GCS (the earliest and most important sign)
- Unequal pupils (CN III compression = uncal herniation)
- Eye deviation becoming fixed
- Cushing's triad (hypertension, bradycardia, irregular respirations — a late and ominous sign of brainstem compression)
- Elevate head of bed > 30° — promotes cerebral venous drainage
- IV mannitol / hypertonic saline — osmotic agents draw water out of brain tissue
- Hyperventilation — ↓PaCO₂ → cerebral vasoconstriction → ↓intracranial blood volume (only a temporary bridge)
- Refer neurosurgery for decompressive hemicraniectomy ± duroplasty [4][31] — HAMLET / DECIMAL / DESTINY trials demonstrated reduced mortality (but survivors may have significant disability — discuss with family)
- Consider external ventricular drainage [4]
From GC 109 Key Messages: Haemorrhagic stroke — deep vs. superficial — surgery in selected patients [33]. This principle also applies to massive ischaemic infarcts requiring surgical decompression.
Mechanism: reperfusion injury (hence increased risk in tPA) + collateral flow [4].
Pathophysiology explained from first principles: When brain tissue is ischaemic, the capillary endothelium becomes damaged (BBB disruption). If blood flow is then restored (either spontaneously, via collaterals, or through thrombolysis/thrombectomy), the reperfused blood leaks through the damaged capillaries into the infarcted tissue. The longer the ischaemia, the worse the capillary damage, and the higher the risk of haemorrhagic transformation — this is why alteplase is limited to 4.5 hours: ECASS study showed capillaries in infarcted areas are damaged → recanalisation increases haemodynamic stress → risk of haemorrhagic transformation increases as ischaemia time prolongs [4].
Risk factors [16]:
- Older age
- Larger stroke size
- Cardioembolic stroke (embolic infarcts are at higher risk because they involve cortical tissue with rich collateral supply)
- Anticoagulation
- Elevated systolic blood pressure in acute setting
- Thrombolytic therapy
- Delayed recanalisation therapy
Clinical suspicion: if power keeps on deteriorating after stroke, mostly occurring 2–3 days after stroke [4].
Two types [4]:
- Petechial haemorrhage: small foci within the infarct — does NOT affect prognosis [4]. This is actually a normal part of infarct evolution (petechial blood leaks through damaged capillaries as collateral flow improves)
- Secondary haematoma: significant parenchymal bleeding — DOES affect prognosis [4]. This is the feared complication — essentially a new ICH within the infarcted territory
CT appearance: Hyperdensity within the original hypodense infarct [16].
Management of tPA-related ICH (5–7% symptomatic ICH rate) [1][2]:
- Discontinue IV alteplase
- Blood for CBC, PT (INR), APTT, fibrinogen level, type and cross-match
- Emergent NCCT
- Administer 10U cryoprecipitate (includes Factor VIII) over 10–30 minutes; additional dose if fibrinogen < 200 mg/dL
- Administer IV 1000 mg tranexamic acid over 10 min (OR) IV 4–5 g aminocaproic acid (antifibrinolytic agents that inhibit plasmin — the very enzyme activated by tPA)
Why Cryoprecipitate for tPA-Related Bleeding?
tPA activates plasminogen → plasmin, which lyses fibrin. Excess plasmin also degrades fibrinogen (a key clotting factor). The resulting hypofibrinogenaemia impairs the patient's ability to form new clots. Cryoprecipitate replenishes fibrinogen (along with Factor VIII, vWF, and Factor XIII), restoring clot-forming capacity. Tranexamic acid directly inhibits plasmin, blocking the fibrinolytic cascade that tPA has initiated.
Other tPA complications [1][2]:
- Systemic bleeding: usually oozing from IV catheter sites, ecchymoses, gum bleeding — does not usually require cessation of treatment. Serious bleeding (GI, GU) may require discontinuation
- Orolingual angioedema (1–8%): mechanism involves complement activation and bradykinin generation by plasmin. Management:
- ET tube if oedema involves larynx, palate, floor of mouth, or oropharynx with rapid progression within 30 min
- Discontinue tPA and withhold ACEI (ACEI inhibits bradykinin degradation, worsening angioedema)
- IV methylprednisolone 125 mg
- IV diphenhydramine 50 mg (H1 antagonist)
- IV ranitidine 50 mg or famotidine 20 mg (H2 antagonist)
- SC 0.3 mL or nebulised 0.5 mL of 0.1% epinephrine if further progression
Cerebellar infarct → oedema compresses onto 4th ventricle → obstructive hydrocephalus [4].
Pathophysiology: The 4th ventricle sits just anterior to the cerebellum. When a cerebellar infarct swells, it compresses the 4th ventricle, blocking CSF drainage from the lateral and 3rd ventricles (which drain through the aqueduct of Sylvius into the 4th ventricle, then out through the foramina of Luschka and Magendie). This creates non-communicating (obstructive) hydrocephalus → rapidly rising ICP → coma → death.
Post-stroke seizure complicates 11% of stroke patients without previous history of seizure [13].
Pathophysiology: Ischaemic brain tissue undergoes a cascade of excitotoxic changes — glutamate release, calcium influx, free radical generation — that make the surrounding cortex hyperexcitable. The infarcted tissue forms a cortical scar that can act as an epileptogenic focus. Seizures are more common with cortical (vs. subcortical) strokes because the cortex contains the seizure-generating neuronal networks.
Timing:
- Early seizures (within 7 days): due to acute metabolic derangement and excitotoxicity in perilesional tissue; do not necessarily predict long-term epilepsy
- Late seizures (after 7 days): due to gliotic scarring and reorganisation; higher risk of developing post-stroke epilepsy
- Recurrent seizures should be treated — usually with IV phenytoin acutely, transitioning to oral anticonvulsants
- Prophylactic use of anticonvulsants is NOT recommended [1][2][31]
- Seizures should be treated promptly but prophylactic anticonvulsant is not indicated [31]
- Early anticonvulsant if any seizures → wean off (except in delayed seizures) [3]
Exam Trap — Seizure Prophylaxis
A consequence of severe cerebral oedema or haemorrhagic transformation.
Types relevant to stroke:
- Uncal herniation (most common in large MCA infarct): medial temporal lobe herniates through the tentorial notch → compresses CN III (ipsilateral fixed dilated pupil) → compresses cerebral peduncle (contralateral hemiparesis, or paradoxically ipsilateral hemiparesis if the contralateral peduncle is pushed against the tentorium — Kernohan's notch phenomenon)
- Central (transtentorial) herniation: symmetrical downward displacement → bilateral pupil dilation → bilateral motor dysfunction → coma
- Tonsillar herniation (relevant in cerebellar infarct): cerebellar tonsils herniate through foramen magnum → compress brainstem → respiratory arrest
B. Systemic Complications
These are the complications arising from immobility, dysphagia, and the systemic effects of acute brain injury. They are the leading causes of death in the subacute and chronic phases.
Dysphagia and aspiration pneumonia are listed as key complications [4].
Pathophysiology: Stroke disrupts the neural control of swallowing. The swallowing centre in the brainstem (nucleus tractus solitarius, nucleus ambiguus — CN IX, X) requires bilateral cortical input. A unilateral cortical stroke can impair swallowing because the "backup" from the contralateral cortex is insufficient. Brainstem strokes directly damage the swallowing nuclei. The result is:
- Impaired pharyngeal reflexes → food/liquid enters the airway
- Impaired cough reflex → cannot clear aspirated material
- Aspiration pneumonia — often the proximate cause of death after stroke
Prevention:
- NPO until swallowing test [4] — this cannot be overemphasised
- Careful feeding practice, early mobilisation, chest physiotherapy [3]
- Speech therapist referral for dysphagia assessment [1][2]
- NG tube feeding if swallowing assessment fails; PEG tube if prolonged dysphagia expected
From GC 087 lecture slides: Stroke-related nursing care and complication prevention are explicitly tested, including preventing pressure sores by repositioning of weak limbs, frequent turning, the use of cushions, egg-crater mattress and air mattress and early physiotherapy, use of occupational therapy devices [13].
Pathophysiology: Post-stroke patients are at very high VTE risk due to Virchow's triad — stasis (immobility of the hemiplegic limb), endothelial injury (systemic inflammatory response), and hypercoagulability (acute-phase prothrombotic response). PE is the second commonest cause of death in the first 2–4 weeks after stroke.
- SC unfractionated / LMWH in immobilised patients
- Aspirin reasonable for VTE prophylaxis in patients who cannot receive anticoagulants
- Intermittent external (pneumatic) compression devices for patients who cannot receive anticoagulants
- Elastic stockings [3]
Pathophysiology: Stroke can disrupt the pontine micturition centre or its cortical connections, causing urinary retention (overflow incontinence) or detrusor overactivity (urge incontinence). Urinary retention → bladder overdistension → stasis of urine → bacterial colonisation → UTI. Indwelling catheters (often placed for monitoring) are a major risk factor for catheter-associated UTI (CAUTI).
Prevention [3]:
- Indwelling catheter or condom catheter (if incontinent male) → avoid bladder overdistension and genitourinary infection
- Intermittent catheterisation → measure post-void residual volume
- Remove indwelling catheters as soon as possible
- Avoid routine use of prophylactic antibiotics
Pathophysiology: Prolonged pressure on bony prominences (sacrum, heels, trochanters) in an immobile hemiplegic patient → ischaemia of skin and subcutaneous tissue → tissue necrosis → ulceration → secondary infection (can lead to osteomyelitis, sepsis).
Myocardial infarction (MI) and heart failure are listed as systemic complications [1][2].
Pathophysiology: The brain-heart connection in acute stroke involves:
- Sympathetic surge: acute brain injury → massive catecholamine release → myocardial injury (takotsubo/stress cardiomyopathy), arrhythmias (AF, VT/VF), or demand-related ischaemia
- Patients with stroke share the same atherosclerotic risk factors as those with IHD → they often have concurrent coronary artery disease
- ECG abnormalities are common in acute stroke (ST changes, T-wave inversion, QT prolongation) even without underlying coronary disease — these are "neurogenic" changes from autonomic dysregulation
Pathophysiology: Dysphagia prevents adequate oral intake. Cognitive impairment and reduced consciousness further limit nutritional intake. Combined with insensible losses and sometimes inappropriate fluid restriction → dehydration and malnutrition → impaired wound healing, immune dysfunction, worse functional recovery.
Management:
- Ensure good hydration: IV NS Q6h [4]
- NG tube feeding if swallowing assessment fails
- Dietician referral for nutritional assessment
Pathophysiology: A hemiplegic limb, if left immobile, undergoes shortening of muscles and tendons → contractures (fixed joint deformity). Additionally:
- Shoulder subluxation: the weight of the paralysed arm pulls the humeral head inferiorly out of the glenoid fossa (lost rotator cuff tone)
- Frozen shoulder (adhesive capsulitis): develops from prolonged immobility of the shoulder joint
- Falls → fractures (especially in osteoporotic elderly)
Prevention [3]:
- Early physiotherapy and occupational therapy [3]
- Correct positioning of the hemiplegic arm (support in sling or trough)
- Passive range-of-motion exercises from day 1
C. Long-Term / Chronic Complications
Prevalence of depression observed at any time after stroke = 29% [1][2].
Pathophysiology: Post-stroke depression is multifactorial:
- Biological: disruption of monoaminergic pathways (serotonin, noradrenaline) by the infarct, particularly in left frontal and basal ganglia lesions; inflammatory cytokines; HPA axis dysregulation
- Psychological: grief reaction to lost function, independence, and social role
- Social: isolation, dependency, loss of employment
Depression at 3 months after stroke is correlated with a poor outcome at 1 year [1][2]. Depression impairs rehabilitation participation, medication compliance, and social reintegration.
Predictors of post-stroke depression [1][2]:
- Disability
- Anxiety
- Pre-stroke depression
- Cognitive impairment
- Increased severity of stroke
- Administration of a structured depression inventory is recommended routinely to screen for post-stroke depression [1][2]
- Patients diagnosed with post-stroke depression should be treated with antidepressants in the absence of contraindications and monitored closely to verify effectiveness [1][2]
- Watch out for depression [13]
- SSRIs (e.g., sertraline, citalopram) are generally first-line
GC 087 — Complications to Watch For
The GC 087 lecture slide explicitly lists the following complications to actively monitor for:
- Prevent pressure sores by repositioning of weak limbs, frequent turning, the use of cushions, egg-crater mattress and air mattress
- Early physiotherapy, use of occupational therapy devices
- Control seizures with anticonvulsant therapy (post-stroke seizure complicates 11% of stroke patients without previous history of seizure)
- Watch out for depression
- Avoid iatrogenic complications [13]
Vascular dementia is listed as a complication of ischaemic stroke [4].
Pathophysiology: Repeated strokes (or strategic single infarcts in critical locations like the thalamus, angular gyrus, or hippocampus) cause cumulative neuronal loss → cognitive decline. Small vessel disease causes diffuse white matter ischaemia → disconnection of cortical-subcortical circuits.
Clinical features [26]:
- Stepwise deterioration with usually preserved insight
- Cortical syndrome: executive dysfunction, abulia, apathy (medial frontal); aphasia, apraxia, agnosia (left parietal); hemineglect, visuospatial and constructional apraxia (right parietal); anterograde amnesia (medial temporal)
- Subcortical syndrome: focal motor signs, early apraxic or Parkinsonian gait, pseudobulbar palsy; personality and mood changes, apathy, depression, emotional incontinence, relatively mild memory deficits; early urinary frequency or urgency
- Cognitive deficits most prominent in frontal executive function, attention, and processing speed (less in memory — distinguishing feature from Alzheimer's disease) [26]
- Pseudobulbar affect = pathological laughing or crying [26]
Evaluation [26]:
- MoCA more appropriate than MMSE (better at detecting executive dysfunction)
- Hachinski score: ≥ 7 = multi-infarct, 5–6 = mixed, ≤ 4 = AD [26]
- Neuroimaging: MRI more sensitive for small vessel diseases
Management [26]:
- Risk factor management: healthy lifestyle, HTN, DM, statins, aspirin
- Cholinesterase inhibitors: small benefit of uncertain clinical significance
- Memantine: benefit uncertain
Prognosis [26]:
- Disease course: stepwise progression with periods of deterioration and improvements
- Life expectancy: variable but usually shorter than AD (~5 years), with ~50% dying from IHD
Without secondary prevention, the annual recurrence rate of ischaemic stroke is approximately 5–15%. The risk is highest in the first 90 days after the index event. This is why secondary prevention (antiplatelets, anticoagulation for AF, statins, BP control, carotid revascularisation) is so critical.
Pathophysiology: Loss of upper motor neuron inhibition → exaggerated stretch reflexes → velocity-dependent increase in muscle tone. Develops over weeks to months. Affects antigravity muscles preferentially:
- Upper limb: flexor pattern (shoulder adduction, elbow flexion, forearm pronation, wrist/finger flexion)
- Lower limb: extensor pattern (hip adduction/extension, knee extension, ankle plantarflexion/inversion)
Management: Physiotherapy (stretching, splinting), botulinum toxin injection (for focal spasticity), oral baclofen or tizanidine (for generalised spasticity), intrathecal baclofen pump (severe cases).
Pathophysiology: Thalamic infarct (PCA territory) → disruption of thalamic sensory relay nuclei → aberrant central pain signalling → severe, burning, dysaesthetic contralateral pain. Onset typically weeks to months after stroke. Notoriously difficult to treat.
Management: Amitriptyline, gabapentin/pregabalin, lamotrigine. NSAIDs and opioids are generally ineffective because the pain is centrally generated, not peripherally mediated.
| Timing | CNS Complications | Systemic Complications |
|---|---|---|
| Acute (days 1–7) | Cerebral oedema / herniation (peak day 2–3), haemorrhagic transformation (day 2–3), seizures, hydrocephalus (cerebellar infarct) | Aspiration pneumonia, cardiac arrhythmia/MI, acute urinary retention |
| Subacute (weeks 1–4) | Ongoing oedema resolution, late seizures | DVT/PE, UTI, pressure sores, dehydration/malnutrition |
| Chronic (months+) | Vascular dementia, post-stroke epilepsy, central post-stroke pain | Post-stroke depression, spasticity/contractures, recurrent stroke, shoulder subluxation/frozen shoulder |
High Yield Summary — Complications of Ischemic Stroke
CNS Complications:
- Cerebral oedema — peaks day 2–3; malignant MCA syndrome (eye deviation + dense hemiplegia + drowsiness ± unequal pupils). Mx: elevate HOB, mannitol, hemicraniectomy.
- Haemorrhagic transformation — reperfusion injury; suspect if power deteriorating after stroke. RFs: older age, large stroke, cardioembolic, anticoagulation, tPA, high BP. Petechial (benign) vs. secondary haematoma (affects prognosis).
- Hydrocephalus — cerebellar infarct compresses 4th ventricle → obstructive hydrocephalus → EVD.
- Seizures — 11% incidence; treat when they occur but do NOT prophylax (except SAH).
- Herniation — uncal (CN III palsy), transtentorial, tonsillar (cerebellar).
Systemic Complications: 6. Aspiration pneumonia — leading cause of post-stroke death. NPO until swallowing test. SLT referral. 7. DVT/PE — immobility + hypercoagulability. SC heparin + IPC devices. 8. UTI — retention → stasis → infection. Minimise catheter use. 9. Pressure sores — 2-hourly turning, cushions, air mattress. 10. Post-stroke depression — 29% prevalence; screen routinely; treat with SSRIs.
Chronic Complications: 11. Vascular dementia — stepwise decline, executive dysfunction > memory. Hachinski score ≥ 7 = multi-infarct. 12. Spasticity/contractures — early PT prevents these. 13. Central post-stroke pain — thalamic syndrome; treat with amitriptyline/gabapentin. 14. Recurrent stroke — secondary prevention is paramount.
Active Recall - Complications of Ischemic Stroke
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1229, 1231, 1233, 1238–1240) [2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Neurological Diseases — Stroke, pp. 1156, 1158, 1163, 1165) [3] Senior notes: Ryan Ho Neurology.pdf (Section 3.2: Cerebrovascular Diseases, pp. 80, 82) [4] Senior notes: Maksim Medicine Notes.pdf (Neurology — Complications, pp. 241, 243, 247–248) [13] Lecture slides: GC 087. Sudden hemiplegia dysphagia.pdf (p. 20) [16] AOS material: AOS - Radiology.pdf (p. 11) [26] Senior notes: Ryan Ho Psychiatry.pdf (pp. 88, 93) [31] Lecture slides: Handbook of Internal Medicine 2024.pdf (pp. 329–330, 332) [33] Lecture slides: GC 109. Headache and loss of consciousness Acute stroke, subarachnoid haemorrhage and vascular malformation.pdf (p. 25)
High Yield Summary
-
Definition: Rapid onset focal neurological deficit from non-traumatic vascular cause > 24h with structural damage. TIA = same but < 24h with NO infarction on imaging.
-
Epidemiology: 75–80% of strokes are ischemic; HK: 2nd–4th leading cause of death; intracranial atherosclerosis more common in Chinese than Caucasians.
-
Risk Factors: HTN is the single most important modifiable RF. AF is the most important cardiac source. Inherited thrombophilias → VTE only, NOT arterial stroke (except APS and hyperhomocysteinaemia).
-
TOAST Classification: Large vessel atherosclerosis (25%), cardioembolism (20%), small vessel disease (25%), other (5%), cryptogenic (25%).
-
Clinical Course: Thrombotic = stuttering; embolic = maximal at onset.
-
Lacunar Infarcts: < 1.5 cm, deep structures (pons, thalamus, internal capsule, BG), NO cortical signs. Pure motor/pure sensory/ataxic hemiparesis/sensorimotor/dysarthria-clumsy hand.
-
MCA territory (most common): contralateral face + arm weakness > leg, ± aphasia (dominant) / neglect (non-dominant), homonymous hemianopia, gaze deviation toward lesion.
-
CT: Hyperacute — loss of grey-white differentiation, dense MCA sign, loss of insular ribbon. CT < 48% sensitive in first day; MRI DWI 86–100%.
-
Time is brain: 2 million neurons/min die. Door-to-CT < 25 min. Penumbra is salvageable.
-
ABCD2 Score: Age, BP, Clinical features, Duration, Diabetes — stratifies TIA patients for 2-day stroke risk.
High Yield Summary — Differential Diagnosis of Ischemic Stroke
-
Always rule out the "Big 3" mimics first: Hypoglycaemia (bedside glucose), ICH/SAH (urgent NCCT), and seizure with Todd's paralysis (history of witnessed convulsion).
-
Stroke produces negative, focal symptoms — positive symptoms (seizure, migraine aura) or global symptoms (metabolic encephalopathy) suggest a mimic.
-
Clinical features cannot reliably distinguish ischemic from hemorrhagic stroke — NCCT is mandatory.
-
Headache and vomiting favour hemorrhagic stroke.
-
Gradual progression suggests non-stroke pathology (tumour, MS, abscess) unless it follows the "stuttering" pattern of thrombotic stroke.
-
Young stroke (< 45 years) demands a wider workup: dissection, PFO, APS, Moyamoya, CVST, drugs, rheumatic heart disease.
-
Aortic dissection can mimic stroke — thrombolysis is absolutely contraindicated. Always consider in stroke + chest/back pain.
-
Time of onset = last seen well — this determines reperfusion eligibility.
High Yield Summary — Diagnosis of Ischemic Stroke
-
No single diagnostic criterion set — diagnosis integrates clinical presentation + neuroimaging + etiological workup.
-
NCCT brain is first-line: rules out haemorrhage (the primary purpose), identifies early ischaemic signs. Sensitivity only ~48% in first 24h.
-
MRI DWI is most sensitive (86–100%): restricted diffusion = cytotoxic oedema = acute infarction. DWI-FLAIR mismatch guides wake-up stroke thrombolysis.
-
CTA identifies large vessel occlusion for EVT triage — do NOT delay tPA for CTA.
-
Baseline bloods: glucose (mimic), CBC + clotting (tPA eligibility), HbA1c + lipids (risk factors), ESR/CRP (vasculitis).
-
ECG + cardiac monitoring: AF is the most important treatable embolic source.
-
Carotid Doppler: all anterior circulation strokes need extracranial vessel assessment.
-
tPA contraindications are determined by the diagnostic workup — history, clinical, biochemical, and radiological screens.
-
Frank hypodensity > 1/3 MCA territory on CT = irreversible injury = tPA contraindicated.
-
Time of onset = LAST SEEN WELL — critical for reperfusion eligibility.
High Yield Summary — Management of Ischemic Stroke
General Measures:
- Admit ASU. ABC + GCS. NPO until swallowing test. IV NS (never dextrose). Neuro-obs Q30min then Q1h.
- BP: permissive hypertension unless > 220/120 (non-tPA) or > 185/110 (pre-tPA). Avoid hydralazine/nifedipine.
- Glucose: aim normoglycaemia. Treat fever.
Reperfusion Therapy:
- IV alteplase: within 4.5h, 0.9 mg/kg (10% bolus + 1h infusion), max 90 mg. Know all contraindications.
- EVT: within 6h (up to 24h with penumbral mismatch) for large vessel occlusion. Recanalization rate ~80%.
- tPA + EVT are complementary. Never delay tPA for CTA. Streptokinase is NOT used for stroke.
Antiplatelets:
- Aspirin 80-300 mg STAT (withhold 24h if tPA given). DAPT × 3 weeks for minor stroke/high-risk TIA.
Anticoagulation:
- Only for cardioembolic source, CVST, or extracranial dissection. Delay if large infarct.
- DOACs preferred over warfarin for non-valvular AF.
Complications:
- Cerebral oedema (day 2-3) → mannitol, hemicraniectomy. Haemorrhagic transformation → stop anticoagulants.
- Seizures: treat but do NOT prophylax. VTE prophylaxis in immobilised patients.
Secondary Prevention:
- Antiplatelets (non-embolic), anticoagulation (AF), CEA (symptomatic carotid stenosis ≥ 70%).
- Statin, BP control, DM control, smoking cessation.
Rehabilitation:
- PT, OT, SLT, depression screening — early referral.
High Yield Summary — Complications of Ischemic Stroke
CNS Complications:
- Cerebral oedema — peaks day 2–3; malignant MCA syndrome (eye deviation + dense hemiplegia + drowsiness ± unequal pupils). Mx: elevate HOB, mannitol, hemicraniectomy.
- Haemorrhagic transformation — reperfusion injury; suspect if power deteriorating after stroke. RFs: older age, large stroke, cardioembolic, anticoagulation, tPA, high BP. Petechial (benign) vs. secondary haematoma (affects prognosis).
- Hydrocephalus — cerebellar infarct compresses 4th ventricle → obstructive hydrocephalus → EVD.
- Seizures — 11% incidence; treat when they occur but do NOT prophylax (except SAH).
- Herniation — uncal (CN III palsy), transtentorial, tonsillar (cerebellar).
Systemic Complications: 6. Aspiration pneumonia — leading cause of post-stroke death. NPO until swallowing test. SLT referral. 7. DVT/PE — immobility + hypercoagulability. SC heparin + IPC devices. 8. UTI — retention → stasis → infection. Minimise catheter use. 9. Pressure sores — 2-hourly turning, cushions, air mattress. 10. Post-stroke depression — 29% prevalence; screen routinely; treat with SSRIs.
Chronic Complications: 11. Vascular dementia — stepwise decline, executive dysfunction > memory. Hachinski score ≥ 7 = multi-infarct. 12. Spasticity/contractures — early PT prevents these. 13. Central post-stroke pain — thalamic syndrome; treat with amitriptyline/gabapentin. 14. Recurrent stroke — secondary prevention is paramount.