Intracranial Atherosclerotic Disease

Intracranial atherosclerotic disease is atherosclerotic narrowing of the large intracranial arteries (intracranial internal carotid, middle cerebral, vertebral and basilar arteries). Symptomatic stenosis of 70 to 99% carries a high risk of recurrent stroke.

It causes about 10% of ischaemic strokes in white patients and 30 to 50% in East Asian, Black and Hispanic populations. It is increasingly recognised with wider vascular imaging.

Risk factors. Hypertension, diabetes, dyslipidaemia, metabolic syndrome, smoking, older age and chronic kidney disease.

Risk of recurrence. With antithrombotic treatment alone, stroke recurrence in the territory of a 70 to 99% stenosis is about 15 to 20% in the first year, highest in the first weeks.

Mechanisms of stroke. Artery to artery embolism, in situ thrombosis, perforator occlusion and haemodynamic failure.

Pathophysiology.

Intimal plaque with lipid, inflammation and calcification narrows the lumen and can rupture, causing thrombus. The vessel may also remodel positively, so lumen stenosis understates the plaque burden.

Distal hypoperfusion with poor collaterals produces border zone infarction.

• TIA or ischaemic stroke in the territory of the stenotic vessel; stuttering or fluctuating course, especially with severe stenosis.
• Recurrent short stereotyped events with posture changes or hypotension suggest haemodynamic failure.
• Cognitive impairment from chronic hypoperfusion.
• Basilar and vertebrobasilar disease causes vertigo, diplopia, ataxia and drop attacks.

Red flags.

• Fluctuating deficit with hypotension or dehydration.
• Recurrent TIAs in one territory.
• Posterior circulation symptoms with a severe basilar stenosis.

• CT angiography or MR angiography of the head and neck; transcranial Doppler is useful for screening and monitoring.
• Digital subtraction angiography is the reference test, and high resolution vessel wall MRI distinguishes atherosclerosis from dissection, vasculitis and moyamoya disease.
• Degree of stenosis measured by the percentage reduction in diameter; symptomatic stenosis of 50% or more is relevant, and 70 to 99% is high risk.
• Perfusion imaging for haemodynamic significance; ECG and rhythm monitoring to exclude cardioembolism.
• Blood tests: lipids, glucose, HbA1c, creatinine, full blood count.

Differential diagnosis. Cervical or intracranial dissection, vasculitis, moyamoya disease, reversible cerebral vasoconstriction syndrome, fibromuscular dysplasia, radiation vasculopathy, embolism and thrombosis from cardiac sources.

• Intensive medical management is the first line.
• Aspirin 300 mg orally once as a loading dose, then 75 to 100 mg orally once daily with food, long term after dual therapy. Maximum 300 mg daily. Monitor bleeding and dyspepsia and check full blood count. Avoid in active peptic ulcer, bleeding disorders, aspirin sensitive asthma and in children under 16 years; use caution when eGFR is under 10; low dose use is acceptable in pregnancy.
• Clopidogrel 75 mg orally once daily (300 mg once as a loading dose), combined with aspirin for 90 days after a recent symptomatic 70 to 99% stenosis, then a single agent long term. Maximum 75 mg daily after loading. Monitor bleeding and full blood count. Avoid in active bleeding; use caution in severe hepatic impairment; reduced effect in CYP2C19 poor metabolisers; avoid omeprazole and esomeprazole; avoid in pregnancy unless clearly needed.
• Cilostazol 100 mg orally twice daily, taken 30 minutes before or 2 hours after food, long term, as an alternative to a second antiplatelet in East Asian practice. Maximum 200 mg daily. Monitor heart rate, bleeding and full blood count. Contraindicated in heart failure of any grade and when creatinine clearance is under 25 mL/min; reduce to 50 mg twice daily with strong CYP3A4 or CYP2C19 inhibitors; avoid in moderate or severe hepatic impairment and in pregnancy. Evidence outside East Asia is limited.
• Atorvastatin 80 mg orally once daily, long term. Maximum 80 mg daily. Monitor lipids at 4 to 12 weeks and ALT at baseline and if symptoms occur. No dose change in renal impairment; avoid in active liver disease; limit to 20 mg daily with clarithromycin; contraindicated in pregnancy and breastfeeding. Aim for LDL cholesterol under 1.8 mmol/L.
• Blood pressure under 130/80 mmHg in the long term (avoid sharp falls in the first days, especially with haemodynamic stenosis); treat diabetes and stop smoking; exercise and weight loss.
• Endovascular angioplasty or stenting is reserved for recurrent events despite intensive medical treatment, because early stroke and death risk with stenting is higher than with medical care.
• Anticoagulation with warfarin gave no benefit over aspirin and increased bleeding.

Monitoring. Review at 1 week, 1 month, 3 months and 6 months, then yearly; repeat vascular imaging at 6 to 12 months.

Referral and escalation. Stroke or neurovascular centre for recurrent events; interventional assessment for failure of medical care.

Special groups. Older adults: avoid excessive blood pressure lowering. Diabetes: aim for an HbA1c of about 53 mmol/mol (7%).