Publications by authors named "Sunao Kaneko"

Mismatch negativity (MMN) is automatically elicited by incoming sound deviation compared to the neural representation of preceding homogenous sounds stored in the brain's auditory sensory memory. This study aimed to assess time-functional deviation sensitivity in auditory sensory memory associated with a temporal window of integration (TWI) of 160-170 msec in patients with schizophrenia. To this end, we measured the magnetic counterpart of the MMN (MMNm) in 20 patients with schizophrenia on medication and 20 healthy age-matched adults as a control group responding to an omitted tone segment incorporated into a complex sound of 176 ms duration corresponding to the TWI duration.

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Objective: To evaluate the long-term efficacy, safety, and tolerability of adjunctive perampanel for the treatment of patients with refractory focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), from the Asia-Pacific region.

Methods: Study 335 (NCT01618695) was a randomized, double-blind, placebo-controlled, Phase III study. Patients aged ≥12 years with refractory FOS who completed the Core Study could enter an open-label extension (OLEx) Phase (6-week Conversion and ≥46-week Maintenance Period).

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CUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated.

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Article Synopsis
  • Epilepsy syndromes are recognized as distinct patterns of symptoms with implications for treatment and prognosis, but there hasn’t been a universal classification system until now.
  • The International League Against Epilepsy (ILAE) Task Force was formed to create a formal classification and define what constitutes an epilepsy syndrome, including its clinical and EEG features.
  • The paper outlines the process for identifying syndromes in patients of all ages, categorizing them by onset age, types of seizures, and associated conditions, while providing definitions for each specific syndrome.
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Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees.

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Objective: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel.

Methods: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed.

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Objective: Neurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large-scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs.

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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.

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Background: Body weight (BW) gain may be induced by perampanel (PER) administration, similar to the well-known adverse effects of valproic acid and gabapentin. Intellectual disability (ID) and serum PER concentration may be risk factors of BW gain.

Purpose: This study investigated how ID and serum PER concentration are associated with PER-induced BW gain.

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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).

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Psychiatric comorbidities, including mood, anxiety, psychotic disorders, and autism spectrum disorder are common in patients with epilepsy (PWE), often occurring at rates 2-3-fold or higher than in the general population without epilepsy. Furthermore, an attention should be paid to psychiatric symptoms together with those caused by antiepileptic drug therapy, epilepsy surgery, and vagus nerve stimulation because these therapies sometimes induce psychiatric comorbidities. It is important to differentiate psychogenic non epileptic seizures (PNES) from epilepsy, and to provide patients with psychiatric treatment.

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Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the effects of SHBG on inflammation as well as lipid metabolism.

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Objective: Intellectual disability (ID) is associated with weight gain caused by antiepileptic drugs such as valproic acid. The present study analyzed the relationship between ID and weight loss caused by topiramate (TPM).

Methods: Seventy-eight patients with epilepsy (35 women, aged 18 to 70years) were enrolled in this prospective study.

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Background: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

Methods: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK).

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Aim: To unravel relationships between gastrointestinal (GI) symptoms impairing quality of life (QOL) and clinical profiles of diabetes mellitus (DM) patients.

Methods: We enrolled 134 outpatients with type 2 DM. Mean age was 64.

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Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan.

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Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein.

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Objectives: In the present study, we investigated the association between the severity of each symptom evaluated by the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and responsiveness to treatment in patients with major depressive disorder (MDD) to identify the items that predict treatment response.

Methods: The patients received a diagnosis of MDD if they had a score greater than 20 points on the MADRS. Following admission, 120 patients were enrolled in the study, and 89 patients completed the study.

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Objective: Evaluation of the efficacy of antiepileptic drugs (AEDs) used in the treatment of Dravet syndrome (DS) with different genotypes.

Methods: Patients with DS were recruited from different tertiary hospitals. Using a direct sequencing method and Multiplex Ligation-Dependent Probe Amplification (MLPA), genetic abnormalities were assessed within the exons and flanking introns of SCN1A gene, which encodes the α1 subunit of neuronal sodium channels.

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We generated a transgenic rat strain with a missense mutation in V286L (V286L-TG), in the gene encoding the neuronal nicotinic acetylcholine receptor β2 subunit (CHRNB2) found in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To confirm that V286L-TG rats exhibit seizures similar to those observed in humans, gene expression patterns and behavioral phenotypes were analyzed. In situ hybridization using a V286L Chrnb2-selective probe indicated that the transgene was expressed at higher levels in the cortex, hippocampus, and cerebellum of V286L-TG than wild-type littermates (non-TG).

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Previous studies have reported changes in the dimensions of the Temperament and Character Inventory (TCI) after patients with major depressive disorder are treated. We aimed to investigate the changes in the TCI dimensions after paroxetine treatment in patients with major depressive disorder. Forty-eight patients were enrolled in this study and were treated with 10-40 mg/day of paroxetine for 6 weeks.

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Article Synopsis
  • The study examined how age influences the initial and overall responses to paroxetine in patients with major depressive disorder (MDD).
  • 89 patients were divided into groups based on their response to treatment after 2 weeks and 6 weeks, using a specific depression rating scale for assessment.
  • Results showed that younger patients were more likely to be early responders, with key age thresholds identified for predicting responses at 42 years for early responders and 55 years for nonearly responders.
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Evidence from observational studies suggests that there is an association among depression and brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs), and folate; however, this association has yet to be examined in childhood and adolescent depression. The objective was to determine whether the BDNF, PUFAs, and folate in serum differ between first-episode childhood and adolescent depressed patients and healthy controls. We measured the serum levels of BDNF, PUFAs, and folate of cases admitted to the hospital for depression (n=24) and compared it to that of controls (n=26).

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