Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation

Abstract

General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 09 May 2018Early 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''. Patients and 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.Post-traumatic seizures are classified as early when they occur within a week after head injury.1 Early seizures may increase the probability of epilepsy later in life.2 3 The risk of early post-traumatic seizures increases with greater severity of the injury, the presence of intracranial haemorrhage and a younger age.1 4 5 Early seizures may occur, although rarely, after trivial head trauma, then usually in combination with sometimes very severe cerebral oedema. 4 6-8 In children, this is often called ''...

17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations

“…Genes encoding the alpha, beta and alpha2-delta subunit of voltage-gated calcium channels have already been associated with epilepsy. 44,45 For both patients, it is possible that the deletion of the CACNG cluster is also a susceptibility factor for their seizures.…”

RNA expression profiling in brains of familial hemiplegic migraine type 1 knock-in mice

“…These neurobiological consequences are more pronounced in S218L mice. In line with the more complex phenotype seen in S218L patients, only S218L KI mice exhibit cerebellar ataxia and an increased susceptibility to seizures and mild head trauma-induced edema (5,6,8). For the present study we wanted to know whether neurobiological differences and cerebellar ataxia can be explained by changes at the RNA level.…”

“…The clinical phenotype with FHM1 mutations can range from pure hemiplegic migraine (e.g. with can result in fatal coma in the case of mutation S218L (5,6).…”

Peculiarities of Hemiplegic Migraine in Children

“…У всех в анамнезе отмечалась четкая связь между началом атаки и предшествующей ей легкой травмой головы. Травма как возможная причина заболевания описана у пациентов с CCNA1A-мутацией [8]. Стресс относится также к группе известных экзо-генных факторов, прово-цирующих развитие ата-ки [9].…”