Recurrent stroke due to a novel voltage sensor mutation in Cav2.1 responds to verapamil

• Published in: Stroke (1970) Vol. 42; no. 2; pp. e14 - e17
• Main Authors: Knierim, Ellen, Leisle, Lilia, Wagner, Christiane, Weschke, Bernhard, Lucke, Barbara, Bohner, Georg, Dreier, Jens P, Schuelke, Markus
• Format: Journal Article
• Language: English
• Published: United States 01.02.2011
• Subjects: Ataxia; Calcium channels; Calcium channels (voltage-gated); Calcium Channels - genetics; Calcium Channels, N-Type - genetics; Calcium influx; Channel opening; Child; Children; Consciousness; Female; Fever; Genetic analysis; Head; Headache; Humans; Ischemia; Migraine; Mutation; Mutation - genetics; Paresis; Secondary Prevention; Sodium channels; Stroke; Stroke - drug therapy; Stroke - genetics; Stroke - prevention & control; Trauma; Verapamil; Verapamil - therapeutic use
• DOI: 10.1161/STROKEAHA.110.600023
• ISSN: 1524-4628

Familial hemiplegic migraine is characterized by recurrent migraine, hemiparesis, and ataxia. Causes may be mutations in calcium and sodium channels or in a subunit of the Na/K-ATPse. Migraine treatment with calcium channel blockers was only successful in some patients. Summary of Case- We describe a 6-year-old girl with recurrent ischemic strokes after minor head trauma associated with seizures, hemiparesis, fever, and altered consciousness. Genetic analysis revealed a spontaneous, novel dominant CACNA1A mutation (c.4046G→A, p.R1349Q) that removed a highly conserved arginine of the voltage sensing region of the P/Q-type Ca(v)2.1 channel. Because a homologous mutation in the tottering-5J mouse increased open probability of the channel as well as calcium influx, we treated the patient with the calcium channel blocker verapamil during characteristic prodromi after head trauma. Treatment was instantly effective and prevented a new stroke. CACNA1A mutations should be considered in the diagnostic workup of childhood stroke, especially if associated with ataxia and migraine.