title: Recurrent stroke due to a novel voltage sensor mutation in Cav2.1 responds to verapamil.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  CACNA1A mutations should be considered in the diagnostic workup of childhood stroke, especially if associated with ataxia and migraine.
authors.affiliation: Department of Neuropediatrics, Charité Universitätsmedizin Berlin, D-13353 Berlin, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Knierim
authors.forename: Lilia
authors.initials: L
authors.lastname: Leisle
authors.forename: Christiane
authors.initials: C
authors.lastname: Wagner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Weschke
authors.forename: Barbara
authors.initials: B
authors.lastname: Lucke
authors.forename: Georg
authors.initials: G
authors.lastname: Bohner
authors.forename: Jens P
authors.initials: JP
authors.lastname: Dreier
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D020864:Calcium Channels, N-Type / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D014700:Verapamil; C105656:CACNA1A protein, human