Abstracts

Rationale: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an inherited seizure disorder characterized by mutations in the gene encoding the neuronal nicotinic acetylcholine receptor (nAChR). Based on our review, there is only one case report on the use of nicotine to treat ADNFLE. Willoughby et al (2003) observed that smoking and nicotine exposure correlated with a decrease in seizures in one patient with ADNFLE and a longstanding smoking history. Brodtkorb & Picard (2006) found that tobacco use was associated with improved seizure control in 22 subjects with ADNFLE. To our knowledge there have been no studies investigating the use of nicotine to treat ADNFLE in non-smoking pediatric patients. Methods: We report a non-smoking 15 year-old African American female, with ADNFLE who responded to treatment with a nicotine patch. Seizures were refractory to numerous antiepileptic drugs, and refractory to right-frontal resection. Despite the use of medication and surgery, she continued to have at least 15 to 20 seizures per day, occurring during wakefulness and sleep. We initiated treatment using one-half of a 7 mg nicotine patch (Nicoderm CQ 7 mg; GlaxoSmithKline, USA) for a two-week period, which resulted in no change in seizures. The patient remained on Keppra 2000mg BID, in combination with Prozac 20mg daily due to anxiety. We increased to one 7 mg nicotine patch daily, for two weeks, which again resulted in no change in seizures. We discontinued the nicotine patch for a few months, and the patient continued to have at least 15 to 20 seizures per day. Vimpat 200mg BID was then added, and seizures decreased to 10 to 15 events per day. We then pursued a trial with a 14 mg nicotine patch, in combination with her other medications, which resulted in an immediate response. Seizure frequency and duration decreased to one to two seizures per day, with seizures lasting one to four seconds. The patient and her family reported a profound improvement in seizure control and in overall quality of life. Results: Seizures remained refractory to the use of half of a 7 mg nicotine patch and to one 7 mg patch. There was no response until the dose was increased to 14 mg, resulting in a distinct and profound improvement in seizure control. This significant response was noted immediately after starting the 14 mg patch. Conclusions: This is the second case report using nicotine to treatment ADNFLE. However, this is the first case report on the use of nicotine in the treatment of intractable ADNFLE in a non-smoking, pediatric patient. In this N-of-one study, nicotine was clearly therapeutic for treatment of seizures, which has never been reported in an individual without a previous tobacco addiction. These novel findings suggest that nicotine may be beneficial for other pediatric and adult patients with ADNFLE, without a prior smoking history. This promising case report will ideally lead to future studies and ongoing research evaluating the use of nicotine in ADNFLE for patients of all ages. Additional studies are needed to further clarify effective dosing recommendations for transdermal nicotine.