Reversible Cerebral Vasoconstriction Syndrome

Reversible cerebral vasoconstriction syndrome is recurrent thunderclap headache, with or without focal deficits or seizures, associated with multifocal segmental vasoconstriction of cerebral arteries that resolves spontaneously within 3 months.

Epidemiology. It most often affects women aged 20 to 50 years, and occurs in the postpartum period. It may be underdiagnosed. Complications occur in 20 to 40% (convexity subarachnoid haemorrhage, intracerebral haemorrhage, ischaemic stroke, posterior reversible encephalopathy syndrome). Death and permanent disability are uncommon.

Triggers. Postpartum state and pre-eclampsia, serotonergic drugs (selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors), triptans and ergots, cannabis, cocaine and amphetamines, nasal decongestants (pseudoephedrine), blood products, immunosuppressants (tacrolimus, ciclosporin), phaeochromocytoma, sexual activity, exertion, straining, cold exposure and emotional stress. About half have no trigger.

Pathophysiology. Transient dysregulation of cerebral vascular tone with sympathetic overactivity, endothelial dysfunction and oxidative stress is proposed. Segmental narrowing and dilation appear in a "string of beads" pattern and peak at 2 to 3 weeks, with a lag after headache onset.

Presentation is abrupt severe headache reaching peak within a minute (thunderclap), recurring over 1 to 3 weeks, often triggered by exertion, Valsalva, sex, bathing or emotion. Others are nausea, photophobia, visual disturbance, seizures, focal neurological deficits, confusion and hypertension. Neurological deficits may appear after the headaches, in the second week.

Red flags.

• First thunderclap headache (must exclude subarachnoid haemorrhage).
• Focal deficit, seizures or visual loss.
• Postpartum period with hypertension.

CT head and CT angiography at presentation, then MRI and MR angiography. Imaging may be normal in the first week, so repeat vascular imaging after 1 to 2 weeks if suspicion remains. Lumbar puncture is normal or shows mildly raised protein and under 15 cells/mm3, and excludes subarachnoid haemorrhage if CT is negative and presentation within 6 hours (otherwise CSF analysis and CT angiography).

Catheter angiography is reserved for uncertain cases (risk of complications). Screen for triggers, urine drug screen, pregnancy test and phaeochromocytoma tests if hypertension and sweating. Diagnosis criteria: acute severe headache, multifocal segmental vasoconstriction on imaging, no aneurysmal haemorrhage, normal or near normal CSF, and reversibility within 12 weeks.

Differential diagnosis. Aneurysmal subarachnoid haemorrhage, primary angiitis of the central nervous system, cervical artery dissection, cerebral venous thrombosis, pituitary apoplexy, posterior reversible encephalopathy syndrome, vasculitis and hypertensive emergency.

Remove triggers. Stop serotonergic drugs, triptans, ergots, decongestants, cannabis and cocaine. Avoid straining, exertion and Valsalva for several weeks.

Calcium channel blockers. Nimodipine 30 to 60 mg orally every 4 to 6 hours (maximum 360 mg daily), or verapamil 120 to 240 mg orally daily in divided doses, for 4 to 12 weeks. Monitor blood pressure (avoid hypotension and cerebral hypoperfusion) and heart rate. Evidence is limited, but they are widely used for headache control.

Analgesia. Paracetamol 1 g every 6 hours (maximum 4 g daily, 3 g if weight is under 50 kg or liver disease) with opioid for severe pain (for example codeine 30 to 60 mg every 4 to 6 hours), and anti-emetics. Avoid vasoconstrictors (triptans, ergots) and non-steroidal drugs in postpartum hypertension.

Blood pressure. Treat severe hypertension (systolic over 180 mmHg) with caution: labetalol 20 mg IV then 20 to 80 mg every 10 minutes, or nicardipine 5 mg/h IV, aiming to reduce by no more than 15 to 25% in the first hours, because lowering too far risks watershed infarction.

Seizures. Levetiracetam 60 mg/kg IV (maximum 4500 mg) for seizures. Prophylaxis is not usually needed.

Corticosteroid. Avoid, since steroids are associated with worse outcomes.

Refractory or severe vasoconstriction with deficits. Intra-arterial vasodilator (nimodipine, milrinone or verapamil) and angioplasty in specialist centres, with intensive care monitoring.

Complications. Treat intracerebral or subarachnoid haemorrhage (blood pressure control, neurosurgical input), and ischaemic stroke (supportive care).

Follow up. Repeat vascular imaging at 4 to 12 weeks to confirm resolution. Counsel on avoiding triggers and recurrence (uncommon).

Monitoring. Neurological examination, blood pressure, imaging for complications and daily headache assessment.

Referral and escalation. Neurology and neuroradiology. Neurocritical care for deficits, haemorrhage or refractory vasoconstriction.

Special groups. In postpartum patients, exclude pre-eclampsia, treat hypertension (labetalol, nifedipine) and avoid ergot based lactation suppressants. In breastfeeding, nimodipine is used with specialist advice.