Synaptic vesicle glycoprotein 2A (SV2A) is a membrane protein specifically expressed in synaptic vesicles. SV2A is found to regulate the release of neurotransmitters by modulating exocytosis processes such as fusion of the releasable neurotransmitter pool, priming processes, and synaptotagmin-1 interactions. The role of SV2A in epileptogenesis has become a research focus since SV2A was found to be the brain-binding site of the antiepileptic drug levetiracetam. SV2A in inhibitory neurons is believed to be involved in epileptogenesis because the expression levels of SV2A in these neurons are decreased in epilepsy disease models and human patients. However, studies on the anti-epileptic mechanism of levetiracetam suggest that it acts by modulating the function of SV2A in excitatory neurons. It is difficult to clearly identify the role of SV2A in epileptogenesis because SV2A exists in both excitatory and inhibitory synapses and is expressed at different levels in various experimental systems and background diseases. Future studies will be needed to elucidate the physiological role of SV2A and the related pathology.

This clinical study is to evaluate the long-term safety and efficacy of vigabatrin (VGB) in Japanese patients with infantile spasms. A total of 17 patients were treated (maximum treatment duration: 1,380 days), including 7 patients transitioned from the preceding phase III study, 2 patients administered VGB outside of clinical trials, and 8 patients who initiated VGB in this study. In these 8 patients, the daily dose was set during a dose adjustment phase. In the other patients, the daily dose was the same as at the start of the study (≤150 mg/kg/day). Nine patients discontinued the study because of treatment change (7 patients) and adverse drug reactions (2 patients). Adverse drug reactions occurred in 76.5% (13/17 patients) of patients. Notable adverse drug reactions included mild retinal abnormalities (2 patients, unrecovered), asymptomatic magnetic resonance imaging abnormality (1 patient, recovering), and encephalopathy (1 patient, recovered). However, the long-term administration of VGB was generally well tolerated. Spasms disappeared in 6 of 8 patients who completed the study. Follow-up including periodic ophthalmic examination is necessary to address adverse drug reactions such as retinal disorder observed in long-term administration of VGB in patients with infantile spasms. (Funded by Alfresa Pharma Corporation and Sanofi KK)

Haemophilus influenzae type b (Hib) vaccine and Streptococcus pneumoniae conjugated vaccine (PCV) have been widely used in Japan since 2010. However, whether the incidences of bacterial meningitis and post-symptomatic epilepsy have actually decreased remains unclear. This study investigated sequential changes in the incidences of pediatric bacterial meningitis and post-symptomatic epilepsy before and after the implementation of Hib vaccine and PCV programs. Patients under 15 years old with bacterial meningitis in Yamanashi prefecture between 2004 and 2016 were recruited. A total of 51 pediatric patients were enrolled. The number of patients from 2004 to 2010 (pre-vaccine era) was 45 (6.4 cases per year). Among these, three cases developed symptomatic epilepsy. In contrast, the number of patients from 2011 to 2016 (post-vaccine era) was 6 (1.0 cases per year), of whom none developed symptomatic epilepsy. The 3 patients who developed symptomatic epilepsy in the pre-vaccine era presented with a significantly longer fever period and refractory status epilepticus in the acute phase compared to the remaining 48 patients. These findings suggest that Hib vaccine and PCV may be effective interventions to prevent not only bacterial meningitis, but also symptomatic epilepsy after bacterial meningitis.

We conducted a survey of nursery schooling and parental employment in Dravet syndrome and West syndrome, to clarify the status of patients with infantile-onset intractable epilepsy in Japan. The survey was returned from 70 of 120 patients (58.3%) with Dravet syndrome and 136 of 244 (55.7%) with West syndrome. Enrollment rates in nursery school under 6 years old at the time of the survey were 25.0% and 36.8%, respectively (vs. 0% for patients requiring special medical care and 42.4% for all Japanese children); some restrictions were present in 66.7% and 19.6%, with denial of permission for administration of regularly-prescribed medication in 10.5% and 19.6%, and for emergency use in 36.8% and 16.7%, respectively. Epileptic seizures during school hours were experienced in 85.0% and 44.0%, and status epilepticus had occurred in 20.0% and 4.5%, respectively. Employment rates were 20.8% and 26.4% in mothers (vs. 47.3-61.2% for all Japanese mothers), and 98.0% and 95.2% in fathers, respectively. Therefore, these children have low enrollment rates and high restriction rates in nursery school, and low maternal employment rates.

When diagnosing childhood absence epilepsy and juvenile absence epilepsy, it is important to take into consideration the age at onset, the type of seizure, and the bilateral synchronic 3-Hz generalized spike-and-wave complexes on EEG. Absence seizure is usually observed in children and juveniles. Here, we report a case of absence epilepsy which was diagnosed for the first time over the age of 30. A 39-year-old woman presented with three or four episodes of momentary loss of consciousness. She was otherwise healthy and had no clinical history of loss of consciousness. EEG showed bilateral synchronic 3.5-4 Hz generalized spike-and-wave complexes persisting 7-8 seconds during hyperventilation, and she displayed a pause during the EEG abnormality which we consider to indicate loss of consciousness. We diagnosed her with absence epilepsy. Although absence epilepsy in adults is rare, a few cases of absence epilepsy with an age of onset over 30 have been reported. We emphasize that it is important to examine EEG, including activations, even when the case is late onset.