Authors :
Presenting Author: Shashwat Pokharel, MBBS – The Johns Hopkins
Babitha Haridas, MBBS – Johns Hopkins Hospital
Sarah Kelley, MD – Johns Hopkins Hospital
Christopher Carosella, MD – Johns Hopkins Hospital/Kennedy Krieger Institute
Rationale:
Effectiveness of transdermal nicotine patch for seizures in Sleep related Hypermotor Epilepsy (SHE) due to CHRNA4 (Cholinergic receptor nicotinic alpha 4 subunit) gene mutation has been well documented in literature but is unknown for CHRNB2 (Cholinergic receptor nicotinic beta 2 subunit) gene mutation related SHE.
Methods: This is a case report. Detailed history, diagnostic workup and treatment responses are mentioned below in the results section.
Results:
This is a 9-year-old female with a history of in-utero drug exposure, congenital syphilis, and unknown family history of epilepsy. Seizures started at 7 years of age. The patient has had a single semiology consisting of asymmetric tonic contraction of the face (right > left) with truncal flexion and tonic flexion or extension of the right arm, then hypermotor movements of the body out of sleep. Seizures lasted 30-70 seconds without a post-ictal state. An MRI Brain epilepsy protocol was normal. A routine EEG showed a normal awake and drowsy EEG. Incremental increases in levetiracetam to 60mg/kg/day failed to control the child’s seizures. Lacosamide at a dose of 4mg/kg/day showed an initial excellent response. In the interim, an epilepsy gene panel identified a pathogenic variant in CHRNB2 [c.923T >C (p. Val308Ala)] that is associated with autosomal dominant nocturnal frontal lobe epilepsy. After 4 months of seizure freedom on lacosamide monotherapy, there was an explosive re-emergence of sleep related focal hyper-motor seizures with seizures (5-6 times a night). Seizures did not respond to 10mg/kg/day lacosamide nor to clonazepam. The patient was urgently admitted to the pediatric Epilepsy Monitoring Unit (EMU) at our center for characterization and medication titration. Seizures occurred 2-4 times every 20-30 minutes out of stage II NREM sleep, typically lasting 30-70 seconds, followed by a rapid return to baseline. The above-mentioned semiology had an EEG onset of bilateral left maximal asymmetrical frontocentral sharp waves embedded in a K complex or rhythmic delta-theta activity with left frontocentral prominence and this pattern usually propagated as rhythmic 6-7 Hz activity to the bilateral fronto-central regions, with gradual offset (Figure 1). Owing to previous efficacy, the patient received a lacosamide load of 200mg in the EMU without significant improvement. Considering her CHRNB2 mutation, a nicotine patch was placed at a dose of 7mg/24hr. The seizures reduced in intensity, duration and frequency after 24 hours (Figure 2). She was discharged from the EMU on a nicotine patch 7mg/24 hour and lacosamide 10mg/kg/day. At the time of this writing, the patient has been seizure free for 7.5 months without any treatment regimen changes.Conclusions:
There have been no other cases in the literature with a pathogenic variant of CHRNB2 heterozygous mutation with SHE, who achieved complete seizure freedom after initiating treatment with transdermal nicotine patch. Our patient's case is a rare example of such a response with supporting video EEG and quantitative EEG evidence.
Funding: None