Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients

Eylert Brodtkorb; Sverre Myren-Svelstad; Kristin Marie Knudsen-Baas; Karl Otto Nakken; Olav Spigset

doi:10.1016/j.eplepsyres.2021.106792

Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients

Epilepsy Res. 2021 Dec:178:106792. doi: 10.1016/j.eplepsyres.2021.106792. Epub 2021 Oct 25.

Authors

Eylert Brodtkorb¹, Sverre Myren-Svelstad², Kristin Marie Knudsen-Baas³, Karl Otto Nakken⁴, Olav Spigset⁵

Affiliations

¹ Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: eylert.brodtkorb@ntnu.no.
² Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: sverre.myren-svelstad@ntnu.no.
³ The National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway. Electronic address: kristinmkb@gmail.com.
⁴ The National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway. Electronic address: karln@ous-hf.no.
⁵ Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: Olav.Spigset@stolav.no.

PMID: 34763266
DOI: 10.1016/j.eplepsyres.2021.106792

Abstract

Purpose: To report the clinical outcome of nicotine exposure in patients with autosomal dominant sleep-related hypermotor epilepsy (ADSHE), along with serum concentrations of the major nicotine metabolite cotinine.

Methods: We recruited 17 ADSHE patients with CHRNA4 mutations (12 with p.S280F and 5 with p.L291 dup). Clinical characteristics were collected from hospital records. A telephone interview was performed on the use and seizure-reducing effect of nicotine applying a six-point rating scale from "none" to very good". Serum concentrations of cotinine were measured in 14 nicotine users.

Results: All patients but one had ever used nicotine. Nine had used snuff; seven were current users. Eleven had used transdermal nicotine; nine were current users. Seven reported long-lasting seizure control, all used nicotine, four transdermal nicotine and three snuff. In 78% of patients using continuous transdermal nicotine, the effect was rated as good or very good. Cotinine concentrations were 453 ± 196 (mean ± SD) nmol/l in seven patients using transdermal nicotine only vs. 1241 ± 494 nmol/l in seven using other forms of nicotine. No correlation with seizure control was found. Three patients experienced improvement with transdermal delivery compared to snuff.

Conclusion: This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.

Keywords: Autosomal dominant sleep-related hypermotor epilepsy; Cotinine; Nicotine; Precision treatment; Seizures; Transdermal.

Publication types

Observational Study

MeSH terms

Cotinine
Epilepsy, Reflex* / drug therapy
Humans
Nicotine / therapeutic use
Receptors, Nicotinic* / genetics
Receptors, Nicotinic* / metabolism
Sleep

Substances

Receptors, Nicotinic
Nicotine
Cotinine