Hemiplegic Migraine

Hemiplegic migraine is migraine with aura including fully reversible motor weakness, along with visual, sensory or speech aura. It can be familial (autosomal dominant) or sporadic, and attacks can be severe and prolonged, mimicking stroke.

The prevalence is about 0.01% of the population. Onset is usually in childhood or adolescence, and it is slightly more common in girls.

Genetics. Familial hemiplegic migraine type 1 (CACNA1A), type 2 (ATP1A2) and type 3 (SCN1A); other genes are also reported. About two thirds of sporadic cases have no known variant.

Clinical course. Aura lasts from minutes up to 72 hours for motor weakness (typically under 24 hours). CACNA1A variants can cause permanent cerebellar signs, epilepsy, intellectual disability and, rarely, coma or cerebral oedema after minor head trauma.

Pathophysiology.

Gain-of-function variants in ion channels or pumps increase neuronal and glial release of glutamate and potassium, making cortical spreading depolarisation easier to trigger.

Spreading depolarisation causes the aura, and trigeminovascular activation produces headache.

• Motor weakness of one side of the body, often with visual, sensory or aphasic aura, evolving over 5 minutes or more and lasting up to 72 hours.
• Headache with migraine features after or with the aura, with nausea and photophobia.
• Possible confusion, fever, drowsiness and seizures in severe attacks.
• Between attacks, normal examination, or cerebellar signs in CACNA1A disease.

Red flags.

• First attack of hemiplegia, or a deficit lasting over 72 hours.
• Fever with altered consciousness (encephalopathy).
• Acute onset in later life or progressive deficit, which suggests stroke or another cause.

• Clinical diagnosis by ICHD-3: aura with fully reversible motor weakness and at least one other aura symptom, with a first degree relative for the familial form.
• First attack or atypical attack: urgent MRI with diffusion weighted imaging, vascular imaging and EEG to exclude stroke, dissection, seizure and encephalitis.
• Genetic testing for CACNA1A, ATP1A2 and SCN1A in familial or severe cases, with counselling.
• Cerebrospinal fluid analysis when infection or inflammation is possible.

Differential diagnosis. Stroke and TIA, focal seizure with Todd paresis, MELAS, CADASIL, arteriovenous malformation, reversible cerebral vasoconstriction syndrome, multiple sclerosis and venous thrombosis.

• Acute attacks: avoid triptans and ergots (vasoconstrictors) as a precaution, because evidence of safety is limited; rest, hydration and symptomatic treatment.
• Paracetamol 1 g orally every 6 hours as needed, maximum 4 g in 24 hours (3 g if under 50 kg, chronic alcohol excess or liver disease), for the shortest period that controls pain. Monitor liver function with prolonged use. Reduce dose in hepatic impairment; extend dosing interval when eGFR is under 30.
• Metoclopramide 10 mg orally or intravenously every 8 hours as needed for nausea. Maximum 30 mg daily and 5 days of use. Monitor for extrapyramidal effects, drowsiness and QT interval. Halve the dose when creatinine clearance is under 60 mL/min or in severe hepatic impairment; avoid in phaeochromocytoma, gastrointestinal obstruction and Parkinson disease; acceptable in pregnancy when needed.
• Prolonged or severe attacks: admission, EEG and treatment of seizures and cerebral oedema.
• Prevention is needed for frequent or disabling attacks. Verapamil 40 mg orally three times daily, increased by 40 mg weekly to 120 mg three times daily as tolerated. Maximum 480 mg daily. Monitor ECG (PR interval), blood pressure, heart rate and constipation. Avoid in heart block, severe left ventricular dysfunction, sinus node disease and with intravenous beta blockers; reduce dose in hepatic impairment; use caution with statins and other CYP3A4 drugs.
• Lamotrigine 25 mg orally once daily for 2 weeks, then 50 mg daily for 2 weeks, then increases of 50 mg every 1 to 2 weeks to a usual 100 to 200 mg daily. Maximum 400 mg daily. Monitor for rash and Stevens-Johnson syndrome. Reduce dose in hepatic impairment; levels fall with oestrogen containing contraception and in pregnancy.
• Acetazolamide 250 mg orally twice daily, increased to a maximum of 1000 mg daily in divided doses if needed. Monitor electrolytes, bicarbonate, renal function and kidney stones. Avoid in severe renal or hepatic impairment, hyponatraemia and sulphonamide allergy; avoid in pregnancy unless benefit outweighs risk. Evidence is weak.
• Avoid oestrogen containing contraception and smoking; avoid head trauma with CACNA1A variants.

Monitoring. Review every 3 months at first, then yearly; keep an attack diary and review neurological signs.

Referral and escalation. Neurology for diagnosis and prevention; genetic counselling for familial disease; emergency care for prolonged deficit.

Special groups. Pregnancy: avoid prevention drugs where possible and choose with specialist advice. Children: specialist paediatric neurology care.