Nicotine as target-therapy in Sleep-Related Hypermotor Epilepsy due to nAChR genes mutation: case report and systematic review of literature

Objective Ten to fifteen per cent of Sleep-Related-Hypermotor-Epilepsy (SHE) has genetic origin, mainly related to pathogenic variants of genes coding for nicotinic cholinergic receptor (nAChR) system. We reported a subject with SHE due to CHRNA4 mutation, successfully treated with Nicotine. We also provided a systematic review on the use of Nicotine as an anti-seizure-medication and sleep regulator in SHE due to nAChR genes mutation. Methods We conducted a comprehensive search on PubMed/MEDLINE, SCOPUS and EMBASE in accordance with PRISMA guidelines, using the keywords: “epilepsy” and “Nicotine”. We included studies with at least one subject with SHE due to nAChR genes mutation treated with Nicotine (tobacco, snuff or patch). The aim was to evaluate the effectiveness and safety of Nicotine medication. Results Our patient benefited from treatment with nicotine patches, reporting reduction in seizure frequency and improved sleep quality as confirmed by polysomnographic and actigraphic monitoring. In our systematic review we identified 31 patients with nAChR-related-SHE treated with Nicotine. Seventy-nine percent of subjects had drug-resistant epilepsy when Nicotine trial was started. Ninety-four percent of subjects achieved a significant decrease in seizure frequency and 47 % of patients reached a seizure freedom condition. In no patient the seizure frequency increased. Side effects occurred in 23 % of patch-treated subjects; in 14 %, they were not controlled by dose reduction. The most frequently used patch dosage and the one with the lowest incidence of side effects was 7mg/24 h. Conclusion Nicotine patch seems effective and relatively safe in patients with SHE due to nAChR gene mutation. Randomized case-control studies are needed to better assess its therapeutic role.