Murat Mert Atmaca, Candan Gürses
Turkish Journal of Neurology - 2025;31(4):472-474
Herein, we reported a patient with genetic generalized epilepsy (GGE) who exhibited focal electroencephalogram (EEG) and clinical findings and responded well to perampanel. The diagnosis was supported with whole-exome sequencing (WES), which showed a missense variant in the chloride channel protein 2 (CLCN2) gene. A 29-year-old male patient who had been seizure-free for many years after the age of five but continued to receive antiseizure medication (ASM) due to EEG findings was admitted to our neurology outpatient clinic. The patient did not have a family history of epilepsy. In the patient's EEGs, 3.5 to 4 Hz generalized spike- and slow-wave discharges, occasionally asymmetric in the left hemisphere, were observed (Figure 1). After 2019, the patient started to have seizures once a year, characterized by elevation of the right arm and index finger, speech arrest, and preserved consciousness. The patient was using levetiracetam 3000 mg/day and carbamazepine 800 mg/day. The neurological examination was normal. Brain magnetic resonance imaging and brain positron emission tomography/computed tomography were normal. Neuropsychological testing revealed only mild impairment in the ability to maintain attention. Considering that carbamazepine could worsen generalized epileptiform discharges in EEGs, it was replaced with lamotrigine. Although EEG abnormalities improved, the frequency of the patient's usual seizures increased to five to eight per month. Lacosamide, topiramate, clonazepam, and valproic acid were added successively, but the seizures continued. Seizures characterized by unresponsiveness, such as his phone slipping from his hand, and seizures that started with contraction in the right arm and became bilateral tonic-clonic were recorded in video EEG. Ictal EEG findings were evaluated as generalized epileptiform discharges, predominant in the left frontocentral region in most of the seizures (Figure 2). However, in one of the seizures, a rhythmic sharp wave activity in F7 and T3 electrodes was observed at the beginning of the seizure. Perampanel was added, and WES was planned. The number of seizures decreased significantly after the dose of perampanel was increased to 10 mg/day. The patient has been using perampanel for two years, and after the dose was increased to 10 mg/day, he had three seizures in the last 12 months. The patient suffered from excessive sleepiness six months after the dose was increased to 10 mg/day. This adverse event improved when the patient changed the time he took the medication from 22:00 to 24:00. Clonazepam and valproic acid were tapered and discontinued. In WES, c.1792C>T p.(Arg598Trp) missense variant in the CLCN2 gene was detected as heterozygous. In silico prediction algorithms showed that the variant had a destructive effect at the protein level. Written informed consent was obtained from the patient.
