Objective: To study the clinical spectrum of CACNA1A S218L mutation carriers with special attention for ″early seizures and cerebral edema after trivial head trauma″ (ESCEATHT), a combination of symptoms which resembles ″the juvenile head trauma syndrome″.
Patients and Methods: We sequenced all exons of CACNA1A in two patients with ESCEATHT. Both patients also had hemiplegic migraine and ataxia. Subsequently, we screened the literature for S218L mutation carriers.
Results: In both patients we found a de novo S218L mutation in the CACNA1A gene. In addition, we identified 11 CACNA1A S218L carriers from literature. From these 13 S218L mutation carriers, twelve (92%) patients had ataxia or cerebellar symptoms. 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 edema as detected by MRI/CT.
Conclusions: The CACNA1A S218L mutation is associated with FHM, 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 edema 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.