Vigabatrin (VGB), an effective antiepileptic drug for epileptic spasms, was approved for clinical use in Japan in 2016. Visual field defect is the most important adverse effect of VGB. Herein, we present a single center's experience of treatment with VGB. This study enrolled 33 patients between 2016 and 2019. VGB was effective in 30.3% (10/33) patients. The efficacy of VGB in the group in which adrenocorticotropic hormone (ACTH) therapy preceded VGB was 18.2% (2/11). Adverse effects were observed in 27.3% (9/33) patients. Most patients experienced mild sedation and respiratory complications; however, all patients recovered after VGB discontinuation. Two patients (6.5%, 2/31) presented with a transitory decline in ERG amplitude. VGB is a relatively safe and effective oral administrative anti-epileptic drug; however we may need to be careful with the administration of VGB when you undergoing VGB in patients in whom ACTH therapy was ineffective.

Online medical consultations were conducted for epilepsy patients living in remote areas seeking a second opinion. The 6 patients included in the study were aged 2 to 25 years and visited our online outpatient service between July 2019 and February 2020. Five lived in various prefectures in Japan and 1 lived overseas. There were a total of 9 sessions; the first session lasting 52 to 83 minutes for each patient. The medical advice given to the patients included epilepsy diagnosis confirmation for 2, epilepsy surgery recommendation for 3, and medication strategies for 3, with overlapping. The doctor-to-patient (D to P) type of session was mostly used, or with the attendance of the primary care doctor (D to P with D). Two patients seeking surgical treatment received explanations of the surgical procedure and possible complications, online, from the epilepsy neurosurgeon in our hospital at their 2nd session. The direct correspondence with the primary care doctor without the patient (D to D) was done after the online D to P session for 1 patient.

The major seizure type of Ring chromosome 20 syndrome [r (20) ] is non-convulsive seizures. Among the 10 patients with refractory epilepsy and NCS, which were under the care of the Department of Child Neurology, NCNP and suspected of r (20), the ictal EEG with spike and slow-wave complex were analyzed for the frequency variation of slow-wave and the amplitude of spike-wave compared with slow-wave. Of 5 cases with r (20), all 5 cases had frequency variation and 4 cases had the slow-wave dominant type of ictal EEG, whereas there were 2 cases with frequency variation and no case with slow-wave dominant type among 5 non-r (20) cases. We concluded that these two specific factors are important for diagnosis of r (20). We also speculated that the dysfunction of thalamus and basal ganglia might be responsible for the mechanism of refractory epilepsy with r (20).

Epilepsy is a common feature of Angelman syndrome. Patients with Angelman syndrome have an increased risk of developing a nonconvulsive status epilepticus, and up to 50% patients have nonconvulsive status epilepticus (NCSE) with myoclonic or atypical absence status. While intravenous medications are used for inpatient treatment of critical illness-related NCSE, there is no consensus on treatment of ambulatory NCSE. We report two cases of Angelman syndrome presenting with NCSE, which was controlled with the administration of topiramate. They had previously been diagnosed with Angelman syndrome by FISH. Following diagnosis they had developed epilepsy and had been treated with multiple antiepileptic drugs. We diagnosed them with NCSE when they were 4 and 5 years old, respectively. In case 1, no therapeutic effects of intravenous midazolam or oral diazepam were observed, and in case 2, no therapeutic effects of intravenous midazolam or levetiracetam were observed. We then administered topiramate to both patients, which led to their NCSE resolving 3 weeks after commencement. Therefore, we believe that topiramate is effective for NCSE ambulatory treatment of Angelman syndrome. Further studies are needed to evaluate the efficacy and safety of topiramate for Angelman syndrome with NCSE.

Perampanel (PER) is a new antiepileptic drug (AED) and a selective non-competitive antagonist against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. The effects of PER on Lennox-Gastaut syndrome (LGS) have not been established, and because of its adverse effects of irritability, detrimental effects on cognition and behavior should be anticipated upon its usage for LGS. We report a 22-year-old male patient who had West syndrome at 5 months of age and whose epilepsy was thereafter very resistant to ACTH therapy and numerous AEDs. Tonic seizures began to occur at 2 years of age with the appearance of slow spike-wave complexes and generalized paroxysmal fast activity on electroencephalogram (EEG), which indicated a transition from West syndrome to LGS. At 5 years of age, behavior disorders such as irritability and violent aggressiveness emerged. Occasional focal impaired awareness seizures and myoclonic seizures began at 9 years of age. At 18 years of age, PER was cautiously introduced with a dramatic reduction of seizure frequency and associated improvement of behavioral disorders. In this case, we believe that the amelioration of irritability and aggressive behavior was brought about by the decrease of seizure frequency through the antiepileptic effects of PER, despite its potential to cause irritability.

A psychoeducational program for children with epilepsy and their parents "famoses" (modular service package epilepsy for families) was developed in European Union to help children with epilepsy and their parents achieve a better understanding of their disease, gain more self-confidence, and reduce specific fears regarding epilepsy. "famoses" comprises two different educational programs: a program for children with epilepsy and another for their parents. The programs are designed to be interactive among the participants and trainers.

The aims of our study were to introduce "famoses" into Japan and evaluate the efficacy of the program.

We introduced "famoses" a year ago and performed "famoses" courses three times (parent course; n=17, children course; n=9).

The epilepsy-specific knowledge, coping, and encouragement of the child's autonomy were significantly improved, and the stress for some epilepsy related factors was significantly decreased in the parents' group. Some items in the QOL domain tended to be improved in the patients with well social and communication skill. The satisfaction with the "famoses" course was high in both groups. In conclusion, "famoses" can be well performed in Japan and useful for children with epilepsy and their families.

Psychiatric comorbidities of epilepsy often have a critical impact on patients' quality of life, and the underlying neural mechanisms are still unclear, while the relationship is supposed to be bidirectional. Despite the high prevalence, little is known about the neural correlates in comorbid anxiety in epilepsy, and further investigation is needed. This research project investigated the relationships between anxiety symptoms and neural activities in patients with temporal lobe epilepsy (TLE) during verbal and facial stimuli in functional MRI. As a result, anxiety symptoms in TLE reduced the neural response to verbal stimuli in posterior default-mode areas, and the reduced neural response to fearful stimuli was also found in similar areas. Considering the functions of posterior default-mode, anxiety in TLE may be associated with anxious arousal, memory, and/or hippocampal formation.

The juvenile-onset dentatorubural-pallidoluysian atrophy (DRPLA) presents progressive myoclonic epilepsy (PME): ataxia, myoclonus, seizure, and progressive intellectual deterioration. DRPLA is caused by an expanded polyglutamine tract within the atrophin-1 and an autosomal dominant fatal disease. There are no disease-modifying therapies at present. Recently, perampanel (PER), a selective non-competitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, was reported to be effective for PME. In this study, we investigated the effectiveness of PER to the DRPLA transgenic model mice that present PME. PER was administrated every day at the doses of 2.5 mg/kg, 5 mg/kg, or 10 mg/kg to the DRPLA transgenic mice carrying the full-length human atrophin-1 with either Q113 or Q129 via oral gavage from the early stage. The control DRPLA transgenic mice received the same volume of methyl cellulose solution. We observed myoclonus and seizure with video. We analyzed motor function by rotarod task. Western blotting and immunohistochemical analysis of brain tissues were performed using antibodies against GluA1 and phosphorylated GluA1. In the results, PER was effective for myoclonus, seizure, and motor function. In immunohistochemical and biological analyses, PER treatment increased expression levels of the phosphorylated GluA1. In conclusion, the phosphorylation of GluA1 may contribute to improve myoclonus, seizure, and motor function.

As with determining a seizure focus, precise cortical motor mapping to minimize postoperative functional deficits remains a major challenge during brain surgery. However, little evidence is available with regards to quantifying the likelihood of postoperative functional deficits even with an electrical cortical stimulation (ECS) mapping that is currently the gold standard for determining the eloquent cortex. Recently, intrinsic brain activities which could be recorded by wide-band ECoG (electricalcorticography), as a non-stimulus mapping technique, allow clinicians to map the brain. Given the plasticity of brain function due to the individual pathological condition in patients with epilepsy, systematical and comprehensive brain mapping is necessary for each patient. Thus, our mapping approach that utilizes the multi-spectrum intrinsic brain activities is useful for mapping the motor cortex exhaustively, potentially identifying the threshold of brain activity for postoperative functional deficits. Since this approach can compensate for the limitations of ECS, it could become widely applicable for the pre-surgical brain mapping.

Visual inspection of interictal epileptiform discharges (IEDs) in multi-channel magnetoencephalography (MEG) requires a time-consuming evaluation process and often leads to inconsistent results among interpreters. In most clinical situations, the application of independent component analysis is restricted to artifact rejection. Here, we propose a novel extraction method for IEDs using a T/k type of blind source separation (BSS_T/k). We conducted comparisons of the results of BSS components with those obtained by visual inspection in sensor-space analysis for seven patients with focal epilepsy. BSS_T/k provided better signal decomposition of variable IEDs in one dominant component compared with sensor-space analysis. The dominant component was able to uncover IEDs that could not be detected by visual inspection, showing sufficient sensitivity along with high specificity. BSS_T/k was able to visualize the spreading signals over multiple channels into a single component from a single epileptogenic zone. BSS_T/k can be applied to focal epilepsy with a simple parameter setting. Based on the above results, we plan to develop the support analysis tool for visual identification of IEDs in future.

Sudden unexpected death in epilepsy (SUDEP) typically occurs following postictal respiratory depression and cardiac abnormalities. Additionally, abnormal interictal heart rate variability (HRV), which reflects autonomic dysregulation, may have potential as a biomarker of SUDEP risk. Daily monitoring of heart rate and respiratory condition would contribute to SUDEP risk assessment and effective preventative strategies in patients with intractable epilepsy. Therefore, we have been examining the usefulness of wearable heart rate monitoring systems with garment-type electrocardiogram (ECG) sensors and their potential for clinical application in SUDEP risk assessment. Combining garment-type sensor with multiple-lead electrodes and anti-noise transmitter would optimize the accuracy in accordance with individual differences in body structure and movement. The ring-figured pulse oximeter confers a reduced feeling of restriction than that conferred by conventional oximeters; thus, the former may be a useful option for detecting respiratory disturbances.