Stroke and TIA

Ischaemic Stroke

Pathophysiology and aetiological classification

Ischaemic stroke is focal neurological dysfunction caused by cerebral, retinal, or spinal infarction. The central concept is the ischaemic core, where cerebral blood flow is typically <10–12 ml/100 g/min and irreversible energy failure occurs, surrounded by the penumbra, where flow is reduced but tissue remains potentially salvageable if reperfusion is timely. Excitotoxic glutamate release, calcium influx, mitochondrial failure, free-radical injury, blood–brain barrier disruption, and inflammatory thrombosis drive progression from penumbra to infarct.

Classification	Key features	Exam relevance
Large-artery atherosclerosis	Extracranial or intracranial stenosis/occlusion; artery-to-artery embolism or haemodynamic failure	Carotid stenosis, cortical signs, recurrent stereotyped events
Cardioembolism	AF, recent MI, LV thrombus, valvular disease, endocarditis, PFO in selected patients	Sudden maximal deficit; multiple vascular territories; anticoagulation timing
Small-vessel disease	Lipohyalinosis or microatheroma affecting perforators; infarcts usually <15–20 mm	Pure motor, pure sensory, ataxic hemiparesis; no cortical signs
Other determined cause	Dissection, vasculitis, thrombophilia, moyamoya, drug-related vasospasm	Young stroke, neck pain, systemic inflammatory clues
Undetermined	Cryptogenic, incomplete evaluation, or competing mechanisms	Prolonged rhythm monitoring for paroxysmal AF

Immediate assessment, scoring, and imaging

Management is time-critical: “time is brain”, with an estimated loss of approximately 1.9 million neurons per minute during untreated large-vessel occlusion. Initial priorities are airway, oxygenation if hypoxic, capillary glucose, temperature, blood pressure, anticoagulant history, and exact time last known well. Hypoglycaemia, seizure with Todd’s paresis, migraine aura, functional neurological disorder, and intracranial haemorrhage are key mimics.

The NIH Stroke Scale quantifies deficit severity: 0 normal, 1–4 minor, 5–15 moderate, 16–20 moderate–severe, >20 severe. It is weighted towards anterior circulation cortical deficits and may underestimate posterior circulation stroke. Pre-stroke and post-stroke disability are assessed by the modified Rankin Scale: 0 no symptoms, 1 no significant disability, 2 slight, 3 moderate requiring some help, 4 moderately severe, 5 severe, 6 death.

Non-contrast CT is first-line to exclude haemorrhage and major established infarction; early ischaemic changes may be subtle, including loss of grey–white differentiation, insular ribbon sign, sulcal effacement, and hyperdense MCA sign. ASPECTS scores early MCA infarction from 10 normal to 0 diffuse involvement; many thrombectomy trials used ASPECTS ≥6, although selected lower scores may now be considered in specialist centres. CT angiography identifies large-vessel occlusion; CT perfusion or MRI DWI–FLAIR/perfusion mismatch can select patients with unknown or late onset. MRI DWI is highly sensitive for acute infarction, but early posterior circulation infarcts can still be DWI-negative.

Reperfusion therapy

Therapy	Eligibility and dose	Key evidence / cautions
IV alteplase	Within 4.5 h of onset if disabling deficit and haemorrhage excluded. Dose 0.9 mg/kg IV, maximum 90 mg; give 10% as bolus then remainder over 60 min. BP must be <185/110 mmHg before treatment and maintained <180/105 mmHg for 24 h.	NINDS showed improved 3-month functional outcome within 3 h but symptomatic ICH about 6.4% versus 0.6%. ECASS III supported 3–4.5 h treatment with increased symptomatic ICH. Avoid if active bleeding, recent intracranial surgery/haemorrhage, severe uncontrolled hypertension, or significant coagulopathy.
IV tenecteplase	Single IV bolus 0.25 mg/kg, maximum 25 mg, increasingly used especially when thrombectomy is planned.	Greater fibrin specificity and longer half-life than alteplase; trials suggest non-inferiority and possible higher early recanalisation in LVO. Do not use 0.4 mg/kg routinely.
Mechanical thrombectomy	Anterior circulation intracranial ICA or proximal MCA occlusion, usually within 6 h; selected patients up to 24 h using perfusion/core mismatch criteria. Give IV thrombolysis if eligible; do not delay thrombectomy.	MR CLEAN and subsequent trials established benefit; HERMES meta-analysis showed markedly improved disability outcomes, with number needed to treat around 2–3 for reduced disability. DAWN and DEFUSE 3 support late-window selection.

Antithrombotic and supportive management

If not thrombolysed, give aspirin 300 mg as soon as intracranial haemorrhage is excluded, usually continued for 2 weeks before switching to long-term secondary prevention. If thrombolysis is given, withhold antiplatelet and anticoagulant therapy for 24 h and repeat imaging before starting. Therapeutic heparin is not routine in acute ischaemic stroke because early recurrent ischaemia reduction is offset by haemorrhagic transformation.

Physiological optimisation is examinable: treat hypoxia, fever, hypoglycaemia and severe hyperglycaemia; avoid aggressive BP reduction unless thrombolysis/thrombectomy thresholds require it, hypertensive emergency exists, or BP is extreme. Swallow screening must precede oral intake. Intermittent pneumatic compression reduces DVT risk in immobile stroke patients; routine graduated compression stockings are ineffective. Malignant MCA infarction causes oedema peaking at 2–5 days; consider decompressive hemicraniectomy within 48 h in selected patients, classically aged ≤60 years with large MCA infarction and reduced consciousness, as it substantially reduces mortality at the cost of survival with disability.

TIA

Transient ischaemic attack (TIA) is a transient episode of focal neurological, retinal, or spinal cord dysfunction caused by ischaemia, without acute infarction on appropriate imaging. This tissue-based definition supersedes the older arbitrary “symptoms <24 hours” definition: most TIAs last <60 minutes, and diffusion-weighted MRI (DWI) demonstrates acute infarction in approximately 30–50% of clinically defined TIAs, reclassifying them as minor ischaemic stroke. The clinical importance is prognostic: early stroke risk is front-loaded, approximately 5% at 48 hours and 10–20% at 90 days, with highest risk in large-artery atherosclerosis and cardioembolism.

Mechanisms and clinical patterns

TIA mechanisms mirror ischaemic stroke mechanisms but with spontaneous reperfusion or collateral compensation. The key mechanisms are: artery-to-artery embolism from extracranial carotid or vertebral plaque; cardioembolism, particularly atrial fibrillation; small vessel lipohyalinosis causing lacunar symptoms; and haemodynamic hypoperfusion across severe carotid stenosis, often posture- or blood-pressure-dependent. TIAs usually produce negative neurological symptoms of abrupt onset: loss of power, sensation, vision, or language. Gradual “marching” positive symptoms favour migraine aura; stereotyped positive motor/sensory phenomena followed by deficit suggest focal seizure with Todd paresis.

Presentation	Likely vascular territory/mechanism	Exam-relevant notes
Monocular visual loss, “curtain descending”	Retinal ischaemia; ipsilateral carotid plaque	Amaurosis fugax; urgent carotid imaging
Aphasia, contralateral face/arm weakness	Dominant MCA territory	Aphasia localises to dominant hemisphere, not confusion
Pure motor or pure sensory symptoms	Lacunar syndrome	Usually internal capsule/thalamic small-vessel disease
Diplopia, dysarthria, ataxia, bilateral weakness	Vertebrobasilar circulation	Isolated dizziness is rarely TIA unless focal brainstem signs coexist

Risk stratification and assessment

Current UK guidance emphasises specialist assessment within 24 hours of suspected TIA and advises against using ABCD2 to determine referral urgency. Nevertheless, ABCD2 remains examinable as a prognostic tool: Age ≥60 years 1 point; Blood pressure ≥140/90 mmHg 1; Clinical features unilateral weakness 2 or speech disturbance without weakness 1; Duration ≥60 minutes 2 or 10–59 minutes 1; Diabetes 1. Scores 0–3, 4–5, and 6–7 correspond broadly to low, moderate, and high early stroke risk, but performance is limited because it omits carotid stenosis, recurrent events, AF, and DWI positivity. ABCD3-I adds dual TIA, carotid stenosis, and imaging infarction, improving discrimination.

Assessment seeks confirmation, localisation, mechanism, and exclusion of mimics. Brain imaging is not required for every classic resolved TIA before treatment, but MRI with DWI is preferred when diagnostic uncertainty exists or posterior circulation/minor stroke is suspected. CT is less sensitive for small acute infarcts but is useful when haemorrhage, tumour, or subdural haematoma is plausible. All patients require ECG; prolonged rhythm monitoring detects paroxysmal AF. Carotid imaging by duplex, CT angiography, or MR angiography is indicated urgently for anterior circulation symptoms if intervention is possible. Baseline tests include FBC, U&E, glucose/HbA1c, lipids, coagulation if anticoagulation is contemplated, and ESR/CRP when giant cell arteritis is a retinal-ischaemia differential.

Immediate and secondary prevention

For suspected TIA without contraindication, give aspirin 300 mg orally immediately and continue until specialist review. Aspirin irreversibly acetylates platelet COX-1, suppressing thromboxane A2 for the platelet lifespan of 7–10 days; its plasma half-life is only approximately 20 minutes, but antiplatelet effect persists. After confirmation of non-cardioembolic TIA, long-term first-line therapy is usually clopidogrel 75 mg once daily; alternatives include aspirin 75 mg daily plus modified-release dipyridamole 200 mg twice daily if clopidogrel is unsuitable.

Strategy	Evidence/guideline relevance	Practical point
Aspirin 300 mg immediately	Recommended by NICE for suspected TIA	Do not delay for outpatient imaging unless haemorrhage strongly suspected
Short-course dual antiplatelet therapy	CHANCE and POINT: aspirin plus clopidogrel reduced early recurrent stroke in high-risk TIA/minor stroke; POINT showed increased major bleeding	Common specialist regimen: clopidogrel loading 300–600 mg plus aspirin, then DAPT for 21 days, followed by monotherapy; avoid prolonged routine DAPT
Ticagrelor plus aspirin	THALES: modest reduction in stroke/death at 30 days but increased severe bleeding	Selected patients; not routine MRCP default
Anticoagulation for AF	DOACs reduce intracranial haemorrhage versus warfarin in non-valvular AF	After TIA, anticoagulation can usually start once intracranial haemorrhage is excluded; warfarin target INR 2.0–3.0 if mechanical valve/moderate-severe mitral stenosis

High-intensity lipid lowering is standard: atorvastatin 80 mg nightly unless contraindicated, with lower doses considered in frailty, interactions, or hepatic disease. Treat hypertension after the hyperacute diagnostic phase; long-term targets are typically <140/90 mmHg, or <130/80 mmHg in diabetes/CKD if tolerated. Smoking cessation, exercise, weight reduction, diabetes optimisation, and alcohol moderation materially reduce recurrence.

Carotid intervention

Symptomatic carotid stenosis is time-critical. For non-disabling anterior circulation TIA with ipsilateral internal carotid stenosis 50–99% by NASCET criteria, carotid endarterectomy should be performed urgently, ideally within 48 hours and generally within 14 days, provided perioperative stroke/death risk is acceptable. Benefit is greatest for 70–99% stenosis; 50–69% has more selective benefit, especially in men and hemispheric rather than retinal events. Carotid stenting is considered when surgical risk or anatomy is unfavourable, but peri-procedural stroke risk is higher in older patients.

Stroke Syndromes

Stroke syndromes are clinical localisation patterns reflecting arterial territory, collateral supply, lesion size and whether cortical, subcortical, brainstem or cerebellar structures are involved. In MRCP Part 1, accurate recognition allows inference of vascular territory and mechanism: cortical syndromes usually imply embolic or large-artery disease, whereas lacunar syndromes suggest small penetrating artery occlusion, classically due to lipohyalinosis or microatheroma.

Clinical classification: Oxfordshire Community Stroke Project

The Oxford/Bamford classification is bedside-based and remains exam-relevant. It predicts prognosis and recurrent stroke risk, but CT/MRI frequently refines the anatomical diagnosis.

Syndrome	Required clinical features	Usual territory	Key implications
TACS Total anterior circulation syndrome	All 3: contralateral motor/sensory deficit involving ≥2 of face/arm/leg; homonymous hemianopia; higher cortical dysfunction such as dysphasia, neglect, apraxia or visuospatial impairment	Large MCA stem or ICA occlusion	Severe stroke; high early mortality; often NIHSS >15; consider large vessel occlusion
PACS Partial anterior circulation syndrome	Any 2 TACS components, or isolated cortical dysfunction, or restricted motor/sensory deficit	MCA branch, ACA branch, or embolic cortical infarct	Often embolic; cortical signs distinguish from lacunar stroke
LACS Lacunar syndrome	No cortical signs or visual field defect; one of classical lacunar patterns	Penetrating arteries: lenticulostriate, thalamoperforator, paramedian pontine	Small vessel disease; lesions typically <15–20 mm on MRI
POCS Posterior circulation syndrome	Brainstem/cerebellar signs, isolated homonymous hemianopia, or bilateral motor/sensory deficits	Vertebrobasilar, PCA, cerebellar arteries	May have low NIHSS despite high risk; dysphagia, coma or basilar occlusion can be catastrophic

Anterior circulation syndromes

Middle cerebral artery (MCA) infarction is the commonest territorial syndrome. Dominant hemisphere MCA stroke produces contralateral face-arm predominant weakness and sensory loss with aphasia: Broca aphasia from inferior frontal involvement, Wernicke aphasia from posterior superior temporal involvement, and global aphasia with proximal MCA occlusion. Non-dominant MCA stroke produces hemispatial neglect, anosognosia, constructional apraxia and extinction. Gaze deviation is usually toward the lesion acutely due to frontal eye field involvement. Superior division MCA infarcts cause expressive aphasia and face-arm weakness; inferior division infarcts cause receptive aphasia or neglect with relatively less weakness.

Anterior cerebral artery (ACA) infarction causes contralateral leg-predominant weakness and sensory loss, abulia, akinetic mutism, urinary incontinence and primitive reflexes. Bilateral ACA infarction, often from anterior communicating artery pathology or embolus to an azygos ACA, may mimic frontal lobe dementia or catatonia.

Internal carotid artery (ICA) occlusion may cause MCA, ACA or watershed syndromes. Transient monocular blindness suggests ipsilateral retinal ischaemia via the ophthalmic artery. Border-zone infarction classically affects cortical watershed areas between ACA-MCA or MCA-PCA territories, producing proximal arm/leg weakness (“man-in-the-barrel”) in severe hypoperfusion.

Lacunar syndromes

Lacunar infarcts arise from occlusion of deep perforators supplying the internal capsule, basal ganglia, thalamus, corona radiata and pons. They lack cortical features: no dysphasia, neglect, apraxia, agnosia, gaze preference or homonymous hemianopia. Classical syndromes include:

• Pure motor stroke: contralateral face, arm and leg weakness; posterior limb internal capsule or basis pontis.
• Pure sensory stroke: contralateral hemisensory deficit; ventroposterolateral thalamus.
• Sensorimotor stroke: combined motor and sensory deficit without cortical signs.
• Ataxic hemiparesis: ipsilateral limb ataxia with pyramidal weakness; pons, internal capsule or corona radiata.
• Dysarthria–clumsy hand syndrome: dysarthria, facial weakness, dysphagia and clumsy hand; often basis pontis or genu of internal capsule.

Although lacunar syndromes suggest small vessel disease, embolic small deep infarcts occur; conversely cortical strokes may initially appear “lacunar” if cortical signs are subtle. Diffusion-weighted MRI has sensitivity around 88–100% for acute infarction but can be falsely negative early, particularly in posterior circulation and small brainstem strokes.

Posterior circulation syndromes

Posterior circulation strokes account for approximately 20–25% of ischaemic strokes. They are commonly missed because symptoms are non-specific: vertigo, vomiting, diplopia, dysarthria, ataxia, dysphagia, drop attacks or reduced consciousness. A normal early CT does not exclude posterior fossa infarction.

Territory/syndrome	Characteristic clinical pattern
Posterior cerebral artery (PCA)	Contralateral homonymous hemianopia with macular sparing; visual agnosia; alexia without agraphia if dominant splenium/occipital involvement; thalamic pain if thalamogeniculate branches affected
Lateral medullary syndrome (Wallenberg; PICA/vertebral)	Ipsilateral facial pain-temperature loss, contralateral body pain-temperature loss, dysphagia/hoarseness from nucleus ambiguus, vertigo, nystagmus, ipsilateral ataxia, Horner syndrome
Medial medullary syndrome (anterior spinal artery)	Contralateral hemiparesis, contralateral loss of proprioception/vibration, ipsilateral hypoglossal palsy
Lateral pontine syndrome (AICA)	Facial weakness, reduced lacrimation/salivation, vertigo, deafness from labyrinthine artery involvement, ipsilateral ataxia
Basilar artery occlusion	Quadriparesis, coma, gaze palsies, pupillary abnormalities; may cause locked-in syndrome with preserved consciousness and vertical eye movements
Cerebellar infarction	Severe vertigo, vomiting, gait ataxia, nystagmus; risk of obstructive hydrocephalus or brainstem compression requiring urgent neurosurgical decompression

Scoring and localisation pitfalls

The NIH Stroke Scale ranges from 0 to 42 and weights anterior circulation deficits, especially language and motor signs; posterior circulation strokes may score deceptively low despite life-threatening basilar disease. Scores ≥6 often correlate with large vessel occlusion, while ≥10 has higher specificity, but absence of a high NIHSS must not reassure when there is diplopia, dysphagia, truncal ataxia or fluctuating consciousness.

Exam questions often contrast cortical signs with lacunar disease. Aphasia localises to the dominant hemisphere cortex, neglect to the non-dominant parietal cortex, and visual field loss to optic radiation/occipital cortex. Crossed findings—ipsilateral cranial nerve deficit with contralateral long-tract signs—localise to the brainstem. Monocular visual loss is retinal/optic nerve ischaemia, not occipital stroke. Acute vestibular syndrome with direction-changing nystagmus, skew deviation or normal head impulse suggests posterior circulation stroke rather than vestibular neuritis.