Treating seizures in SYN1-related epilepsy: a systematic review.

Introduction: Synapsin1-related epilepsy is a rare entity, in which patients typically present reflex seizures, provoked by contact with water. Moreover, patients carrying a pathogenic variant of the synapsin 1 gene (SYN1) can present developmental delay, behavior disorders, and other types of seizures. While SYN1-related epilepsy becomes better characterized, there is still no consensus on the appropriate antiseizure medication (ASM) to use.

Materials And Methods: To compare ASMs efficacies in this particular syndrome, we performed a systematic literature review according to the PRISMA guidelines by using PubMed and Embase databases. All the studies reflecting the seizure outcome associated with the treatment of SYN1-related epilepsy were included in the present review, except those that were not written in English or were in the forms of poster, commentary, or conference abstract.

Results: Eight studies and a total of 52 patients with well-documented treatment were retrieved from the literature. The most frequently used ASMs were valproic acid (VPA) (58 %), lamotrigine (LTG) (35 %) and carbamazepine (CBZ) (35 %). Regarding seizure-free patients, the most effective ASMs were lacosamide (LCM) (50 %), oxcarbazepine (OXC) (44 %) and CBZ (38 %). When considering seizure-freedom or significant (≥ 50 %) seizure reduction, the best treatment is LTG (63 %), followed by LCM (50 %) and CBZ (50 %). LTG, CBZ, OXC and LCM seem to be associated with a more favorable seizure outcome compared to levetiracetam (LEV) or VPA, with a statistically significant difference in terms of seizure reduction (p = 0.028) and seizure freedom for patients carrying a non-truncating variant (p = 0.047).

Conclusion: Based on our systematic literature review, patients with SYN1-related epilepsy show better seizure frequency reduction when treated with LCM, LTG, CBZ, or OXC, compared to VPA and LEV, despite VPA being the most prescribed anti-seizure medication for this syndrome. Hence, sodium channel blockers appear to represent the best therapeutic option for these patients.