Delayed cerebral edema and fatal coma after minor head trauma: Role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine
Article first published online: 2 APR 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 49, Issue 6, pages 753–760, June 2001
How to Cite
Kors, E. E., Terwindt, G. M., Vermeulen, F. L.M.G., Fitzsimons, R. B., Jardine, P. E., Heywood, P., Love, S., Van Den Maagdenberg, A. M.J.M., Haan, J., Frants, R. R. and Ferrari, M. D. (2001), Delayed cerebral edema and fatal coma after minor head trauma: Role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol., 49: 753–760. doi: 10.1002/ana.1031
- Issue published online: 5 JUN 2001
- Article first published online: 2 APR 2001
- Manuscript Accepted: 2 JAN 2001
- Manuscript Revised: 29 DEC 2000
- Manuscript Received: 17 AUG 2000
- Netherlands Organisation for Scientific Research. Grant Number: 903–52-291
- Migraine Trust
- Asclepiacie Association
Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval (“delayed cerebral edema”). Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium channel subunit gene on chromosome 19 are associated with a wide spectrum of mutation-specific episodic and chronic neurological disorders, including FHM with or without coma. We investigated the role of the CACNA1A gene in three subjects with delayed cerebral edema. Two subjects originated from a family with extreme FHM, and one subject was the previously asymptomatic daughter of a sporadic patient with hemiplegic migraine attacks. In all three subjects with delayed severe edema, we found a C-to-T substitution resulting in the substitution of serine for lysine at codon 218 (S218L) in the CACNA1A gene. The mutation was absent in nonaffected family members and 152 control individuals. Haplotype analysis excluded a common founder for both families. Neuropathological examination in one subject showed Purkinje cell loss with relative preservation of granule cells and sparing of the dentate and inferior olivary nuclei. We conclude that the novel S218L mutation in the CACNA1A calcium channel subunit gene is involved in FHM and delayed fatal cerebral edema and coma after minor head trauma. This finding may have important implications for the understanding and treatment of this dramatic syndrome.