title: Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation.
abstract: OBJECTIVE
  To study the clinical spectrum of CACNA1A S218L mutation carriers with special attention to "early seizures and cerebral oedema after trivial head trauma (ESCEATHT)", a combination of symptoms which resembles the "juvenile head trauma syndrome".
  
  
  METHODS
  In two patients with ESCEATHT all exons of CACNA1A were sequenced. Both patients also had hemiplegic migraine and ataxia. Subsequently, we screened the literature for S218L mutation carriers.
  
  
  RESULTS
  In both patients, a de novo S218L mutation in the CACNA1A gene was found. In addition, we identified 11 CACNA1A S218L carriers from the literature. Of these 13 S218L mutation carriers, 12 (92%) had ataxia or cerebellar symptoms and nine (69%) had hemiplegic migraine that could be triggered by trivial head trauma. Three mutation carriers had the complete ESCEATHT phenotype. Seven (54%) had seizures (four had early post-traumatic seizures) and five (38%) had oedema as detected by MRI/CT.
  
  
  CONCLUSIONS
  The CACNA1A S218L mutation is associated with familial hemiplegic migraine, ataxia and/or ESCEATHT. A minority of S218L mutation carriers have the complete ESCEATHT phenotype but a high percentage of patients had one or more ESCEATHT symptoms. As the S218L mutation enhances the propensity for cortical spreading depression (CSD), we postulate a role for CSD not only in hemiplegic migraine but also in early seizures and cerebral oedema after trivial head trauma. As this combination of symptoms is part of the unexplained "juvenile head trauma syndrome", a similar molecular mechanism may underlie this disorder.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Stam
authors.forename: G-J
authors.initials: GJ
authors.lastname: Luijckx
authors.forename: B T
authors.initials: BT
authors.lastname: Poll-Thé
authors.forename: I B
authors.initials: IB
authors.lastname: Ginjaar
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
authors.forename: J
authors.initials: J
authors.lastname: Haan
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: A M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
mesh_terms: D001259:Ataxia / Q000209:etiology; D001929:Brain Edema / Q000235:genetics*; D001930:Brain Injuries / Q000150:complications*; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type