Abstracts

Rationale: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first idiopathic epilepsy for which a genetic basis has been identified. Mutations in genes (CHRNA4 and CHRNB2) coding for neuronal nicotinic acetylcholine receptor (NACHR) subunits (alpha 4 and beta2, respectively) have been identified in relation to ADNFLE. How NACHR mutations linked to ADNFLE cause seizures during sleep remains elusive. Seizures typically involve clusters of brief motor seizures during sleep. The course of ADNFLE is variable, but majority of patients respond to anti-seizure drugs, specifically carbamazepine. Use of nicotine has been explored as a treatment option. Studies showed increased seizure freedom in regular smokers with ADNFLE and with use of a nicotine transdermal system in an adult patient. In addition, an animal study showed nicotine treatment to mutated NACHR in mouse cell led to recovery of receptor subunit stoichiometry to normal state explaining the possible pathophysioloy of ADNFLE mutation and the action mechanism of nicotine. Methods: We present a 5-1/2 year old female with sporadic ADNFLE gene mutation (CHRNA4 Ser284Leu), confirmed by genetic testing. Results showed she is heterozygous for a mutation in the CHRNA4 gene. Her Ser284Leu missense change was initially found to segregate with ADNFLE in four affected individuals in a Japanese family. Family history was negative for epilepsy or neurological concerns. Results: This child had a heavy burden of nocturnal seizures during NREM sleep since the age of two years. Frequency of seizures ranged from 10 to more than 20 seizures in one night, based on parental report and vEEG studies affecting her quality of life as well as the parents'. Her seizure did not respond to oxcarbazepine, lamotrigine, levetiraceta, zonisamide, clobazam, acetazolamide, and ketogenic diet. Based on the previous case report in adult ADNFLE patient, we recommended nicotine 7 mg transdermal patch which stopped seizures immediately, but caused recurrent vomiting and hyperactivity. After titrating down to 1/16^th slice of 7 mg nicotine patch, patient was able to tolerate and stayed seizure free. Her overnight video-EEG confirmed the disappearance of nocturnal seizures and restoration of normal sleep architecture. Conclusions: The nicotine transdermal system should be considered a treatment option for children affected by autosomal dominant nocturnal frontal lobe epilepsy when anti-seizure drugs fail to provide seizure freedom. Long-term side effect of nicotine in developing brain may need to be discussed with patients and parents.