A post hoc analysis of the long-term safety and efficacy of perampanel in Asian patients with epilepsy.

This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline.

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study.

Objective: To present the baseline data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with emphasis on the characteristics of epilepsies associated with tuberous sclerosis complex (TSC).

Methods: Retrospective and prospective patients' data on all aspects of TSC were collected from multiple countries worldwide. Epilepsy variables included seizure type, age at onset, type of treatment, and treatment outcomes and association with genotype, seizures control, and intellectual disability.

Further corroboration of distinct functional features in SCN2A variants causing intellectual disability or epileptic phenotypes.

Background: Deleterious variants in the voltage-gated sodium channel type 2 (Na1.2) lead to a broad spectrum of phenotypes ranging from benign familial neonatal-infantile epilepsy (BFNIE), severe developmental and epileptic encephalopathy (DEE) and intellectual disability (ID) to autism spectrum disorders (ASD). Yet, the underlying mechanisms are still incompletely understood.

Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations.

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine.

Different types of suppression-burst patterns in patients with epilepsy of infancy with migrating focal seizures (EIMFS).

Purpose: In rare cases, patients with epilepsy of infancy withmigrating focal seizures (EIMFS) exhibit suppression-burst (SB) patterns on electroencephalography (EEG), similar to the findings observed in patients with Ohtahara syndrome and early myoclonic encephalopathy. In this report, we discuss six cases of EIMFS in which patients exhibited two types of SB patterns.

Methods: We evaluated six patients with EIMFS who had been admitted to the NHO Shizuoka Institute of Epilepsy and Neurological Disorders between 2011 and 2018.

Is additional mesial temporal resection necessary for intractable epilepsy with cavernous malformations in the temporal neocortex?

Purpose: Cavernous malformation (CM) in the temporal neocortex causes intractable epilepsy. Whether to resect additional mesial temporal structures in addition to the lesionectomy is a still controversial issue. To clarify the need for the procedure, we retrospectively analyzed pre- and postoperative clinical data of patients with surgically removed CM.

Phenotypic features of 1q41q42 microdeletion including WDR26 and FBXO28 are clinically recognizable: The first case from Japan.

1q41q42 microdeletion syndrome has been established in 2007. Since then, more than 17 patients have been reported so far. The reported deletions showed random breakpoints and deletion regions are aligned as roof tiles.

Everolimus for treatment-refractory seizures in TSC: Extension of a randomized controlled trial.

Background: EXamining everolimus In a Study of Tuberous sclerosis 3 (EXIST-3) demonstrated significantly reduced seizure frequency (SF) with everolimus vs placebo. In this study, we evaluate the long-term efficacy and safety of everolimus for tuberous sclerosis complex (TSC)-associated treatment-refractory seizures.

Methods: After completion of the core phase, patients could enter an open-label extension phase and receive everolimus (target exposure, 3-15 ng/mL) for ≥48 weeks.

Adjunctive levetiracetam in the treatment of Chinese and Japanese adults with generalized tonic-clonic seizures: A double-blind, randomized, placebo-controlled trial.

Objective: To assess the efficacy, safety, and tolerability of adjunctive levetiracetam (LEV) in Chinese and Japanese adults with generalized tonic-clonic (GTC) seizures (N01159; NCT01228747).

Methods: This double-blind, randomized, placebo-controlled, multicenter phase III trial comprised: 4-week retrospective and 4-week prospective baseline, 12-week dose-adjustment, and 16-week evaluation periods. Chinese and Japanese patients ≥16 years old with idiopathic generalized, symptomatic generalized, or undetermined epilepsy with GTC seizures received a single-blind placebo during the prospective baseline, and then were randomized 1:1 to placebo or LEV 1,000 mg/day administered twice daily.

Chronic dysfunction of blood-brain barrier in patients with post-encephalitic/encephalopathic epilepsy.

Purpose: This study aimed to elucidate the characteristics and effects of chronic blood-brain barrier (BBB) dysfunction in patients with post-encephalitic/encephalopathic epilepsy (PEE), using brain images and the cerebral spinal fluid (CSF)/serum albumin ratio (albumin quotient, QAlb) as a marker of BBB function.

Methods: We examined the albumin levels in CSF and serum samples from 312 patients with refractory epilepsy in our center between 2004 and 2015. Sixty samples from patients with PEE and 97 samples from age- and sex-matched disease controls (DC) were evaluated.

Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software.

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive neuroscience. Intracranial electroencephalography (EEG) can directly record electrical neural activity and has the unique potential to accomplish this goal. Traditionally, averaging analysis has been applied to analyze intracranial EEG data; however, several new techniques are available for depicting neural activity and intra- and inter-regional connectivity.

Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy.

Purpose: To evaluate long-term tolerability, safety and efficacy of adjunctive perampanel in a Phase II, multicentre, open-label, dose-ascending Study 231 (NCT00849212) and its extension (Study 233; NCT00903786) in Japanese patients with refractory partial-onset seizures (POS), with/without secondarily generalised seizures.

Methods: In Study 231, patients received adjunctive perampanel ≤12 mg/day during a 10-week treatment period. Patients completing Study 231 could enter Study 233 (≤316-week treatment period).

TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study.

Background: Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations.

Results: The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015).

Toxic Epidermal Necrolysis in a Patient with Autoimmune Limbic Encephalitis with Anti-Glutamate Receptor Antibodies.

We report on a 44-year-old woman who was diagnosed with toxic epidermal necrolysis (TEN) during the recovery phase from autoimmune limbic encephalitis with anti-glutamate receptor antibodies. Both, autoimmune limbic encephalitis and TEN are very rare diseases. The co-existence of the two diseases has not yet been reported.

Improvement in anti--methyl-d-aspartate receptor antibody-mediated temporal lobe epilepsy with amygdala enlargement without immunotherapy.

Focal neuroinflammation is considered one of the hypotheses for the cause of temporal lobe epilepsy (TLE) with amygdala enlargement (AE). Here, we report a case involving an adult female patient with TLE-AE characterized by late-onset seizures and cognitive impairment. Anti--methyl-d-aspartate receptor (NMDAR) antibodies were detected in her cerebrospinal fluid.

Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice.

Mutations in the gene encoding a voltage-gated sodium channel Nav1.2 are associated with epilepsies, intellectual disability, and autism. gain-of-function mutations cause early-onset severe epilepsies, while loss-of-function mutations cause autism with milder and/or later-onset epilepsies.

Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial.

Background: Epilepsy occurs in 70-90% of patients with tuberous sclerosis complex. We aimed to assess the efficacy and safety of adjunctive everolimus for treatment-refractory seizures associated with tuberous sclerosis complex in paediatric patients enrolled in the EXIST-3 trial, a double-blind, placebo-controlled, randomised, phase 3 study.

Methods: This post-hoc analysis focused on paediatric patients (age <18 years) in the EXIST-3 trial, which consisted of baseline (8 weeks), core (18 weeks), and extension phases (≥48 weeks) and was done at 99 centres in 25 countries worldwide.

Working memory deficit in drug-resistant epilepsy with an amygdala lesion.

This study compared temporal lobe epilepsy (TLE) patients with amygdala lesion (AL) without hippocampal sclerosis (HS) (TLE-AL) with patients with TLE and HS without AL (TLE-HS). Both subtypes of TLE arose from the right hemisphere. The TLE-AL group exhibited a lower Working Memory Index (WMI) on the Wechsler Adult Intelligence Scale, third edition (WAIS-III), indicating that the amygdala in the right hemisphere is involved in memory-related function.

Surgical Resection of Amygdala and Uncus.

The amygdala and uncus are located close to important neurovascular structures. We describe a safe technique for resection of amygdala and uncus. Under general anesthesia, the patient is positioned supine, with the head rotated approximately 20 degrees to the unoperated side and slightly extended.

Influence of Inflammation on the Pharmacokinetics of Perampanel.

Background: It is well-known that the pharmacokinetics of various drugs are influenced by inflammation. This study evaluated the relationship between C-reactive protein (CRP; an inflammation marker) and the pharmacokinetics of perampanel.

Methods: Among 111 patients who underwent measurement of both CRP and perampanel, 23 patients had a serum CRP level exceeding 1.

Independent occurrence of de novo and variants in brothers with different neurological disorders - leukodystrophy and autism.

Consecutive occurrence of de novo variants in the same family is an extremely rare phenomenon. Two siblings, a younger brother with hypomyelinating leukodystrophy and an elder brother with severe intellectual disability and autistic features, had independent de novo variants of c.139T > G (p.

A recurrent homozygous variant in siblings with Lafora disease.

We report a case of two siblings with progressive myoclonus epilepsy whose parents were not consanguineous. Their clinical symptoms were typical of Lafora disease (LD), but skin biopsies revealed no Lafora bodies. Whole-exome sequencing identified a recurrent homozygous frameshift variant in the gene in both siblings.