Longer contraindicated medication use in the first 5 years of disease affects adversely cognitive outcome in Dravet syndrome

de Lange IM, Gunning B, Sonsma ACM, van Gemert L, van Kempen M, Verbeek NE, Nicolai J, Knoers NVAM, Koeleman BPC, Brilstra EH. Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A-related seizure phenotypes. Epilepsia.2018 May 11. doi: 10.1111/epi.14191. [Epub ahead of print]

Abstract

OBJECTIVE:

Pathogenic variants in SCN1A can give rise to extremely variable disease severities that may be indistinguishable at their first presentation. We aim to find clinical features that can help predict the evolution of seizures into Dravet syndrome and clinical features that predict cognitive outcome in Dravet syndrome. We specifically investigate the role of contraindicated medication (CIM) as a possible modifier of cognitive decline.

METHODS:

A cohort of 164 Dutch participants with SCN1A-related seizures was evaluated. Clinical data were collected from medical records and semistructured telephone interviews. Cognitive function was classified by a child neurologist, neuropsychologist, and clinical geneticist. Several clinical variables, including duration of CIM use in the first 5 years of disease, were evaluated in univariate and multivariate analyses.

RESULTS:

A longer duration of CIM use in the first 5 years after seizure onset was significantly associated with a worse cognitive outcome at time of inclusion, and with lower interpolated intelligence quotient/developmental quotient scores after the first 5 years of disease in Dravet syndrome patients. CIM use remained a significant predictor for cognitive outcome in a multivariate regression model, as did age at the first observation of developmental delay and age at first afebrile seizure. Age at first afebrile seizure was the most accurate predictor for evolution of seizures into Dravet syndrome for the complete cohort.

SIGNIFICANCE:

Our data suggest that a longer CIM use in the first 5 years of disease can have negative effects on cognitive outcome in Dravet syndrome. An early diagnosis is essential to avoid these drugs. Furthermore, we identified age at first afebrile seizure as an important predictor for evolution of seizures into Dravet syndrome and for the severity of Dravet syndrome, which can be used to counsel parents of young patients with SCN1A-related seizures.

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Experts aspired to explore clinical features that can help predict the evolution of seizures into Dravet syndrome and clinical features that predict cognitive outcome in Dravet syndrome as well as investigating the role of contraindicated medication (CIM) as a possible modifier of cognitive decline. For this investigation, a cohort of one hundred sixty-four Dutch members with SCN1A-related seizures was evaluated. In Dravet syndrome, a longer CIM use in the first 5 years of a disease could have negative effects on cognitive outcome. Therefore, an early diagnosis was essential to avoid these drugs. Age at first afebrile seizure was identified as an important predictor for the evolution of seizures into Dravet syndrome and for the severity of Dravet syndrome, which could be used to counsel parents of young patients with SCN1A-related seizures.

https://www.mdlinx.com/journal-summaries/cognition-dravet-syndrome-em-scn1a-em/2018/05/24/7521936?spec=neurology