Publications by authors named "Hideaki Shiraishi"

102 Publications

Construction of a fiber-optically connected MEG hyperscanning system for recording brain activity during real-time communication.

PLoS One 2022 23;17(6):e0270090. Epub 2022 Jun 23.

Department of Child and Adolescent Psychiatry, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.

Communication is one of the most important abilities in human society, which makes clarification of brain functions that underlie communication of great importance to cognitive neuroscience. To investigate the rapidly changing cortical-level brain activity underlying communication, a hyperscanning system with both high temporal and spatial resolution is extremely desirable. The modality of magnetoencephalography (MEG) would be ideal, but MEG hyperscanning systems suitable for communication studies remain rare. Here, we report the establishment of an MEG hyperscanning system that is optimized for natural, real-time, face-to-face communication between two adults in sitting positions. Two MEG systems, which are installed 500m away from each other, were directly connected with fiber optic cables. The number of intermediate devices was minimized, enabling transmission of trigger and auditory signals with almost no delay (1.95-3.90 μs and 3 ms, respectively). Additionally, video signals were transmitted at the lowest latency ever reported (60-100 ms). We furthermore verified the function of an auditory delay line to synchronize the audio with the video signals. This system is thus optimized for natural face-to-face communication, and additionally, music-based communication which requires higher temporal accuracy is also possible via audio-only transmission. Owing to the high temporal and spatial resolution of MEG, our system offers a unique advantage over existing hyperscanning modalities of EEG, fNIRS, or fMRI. It provides novel neuroscientific methodology to investigate communication and other forms of social interaction, and could potentially aid in the development of novel medications or interventions for communication disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270090PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223398PMC
June 2022

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

Epilepsia Open 2022 May 28. Epub 2022 May 28.

Department of Neurosurgery, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Objective: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study.

Methods: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes.

Results: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10 % per case, p<0.001) and EEG monitoring (-3.81*10 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001).

Significance: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/epi4.12616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348370PMC
May 2022

Lacosamide monotherapy for the treatment of childhood epilepsy with centrotemporal spikes.

Brain Dev 2022 Jun 28;44(6):380-385. Epub 2022 Feb 28.

Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital Hamamatsu, Japan.

Objective: Childhood epilepsy with centrotemporal spikes (CECTS) is known as age-limited focal epilepsy syndrome in childhood. Lacosamide is a third-generation antiepileptic drug. This study aimed to evaluate the efficacy of lacosamide monotherapy for the treatment of CECTS.

Methods: We enrolled 18 patients (6 girls and 12 boys) who met the following criteria: 1) the age of onset of the seizures was between 3 and 13 years of age; 2) showing at least hemifacial and/or oropharyngeal seizures; 3) interictal discharges in central and/or middle temporal electrodes; 4) no intellectual disability; 5) treatment duration of lacosamide monotherapy over 6 months. We retrospectively collected and analyzed clinical data and treatment information. We evaluated the seizure occurrences during 0-3, 4-6, and 7-12 months from the treatment initiation and the last 6 months of the follow-up. We also evaluated the outcomes as seizure-free if the patients developed no seizures both over 6 months and 3 times of pretreatment mean seizure interval at the last follow-up.

Results: Of the patients, 39%, 67% and 72% were seizure-free during 0-3, 4-6, and 7-12 months from treatment initiation, respectively. Finally, 83% of the patients achieved seizure freedom. Seizure freedom was achieved in 72% during the first 4 months of treatment. All patients continued lacosamide monotherapy during the study, although four patients showed transient fatigue or somnolence.

Conclusions: Lacosamide showed good efficacy for controlling seizures with fewer adverse effects, and therefore may be a good candidate as a first-line medication for the treatment of new-onset CECTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2022.02.005DOI Listing
June 2022

Burden of seizures and comorbidities in patients with epilepsy: a survey based on the tertiary hospital-based Epilepsy Syndrome Registry in Japan.

Epileptic Disord 2022 Feb;24(1):82-94

Department of Pediatrics, School of Medicine, Shinshu University, Matsumoto, Japan.

Objective: To examine the current medical and psychosocial status of patients with epilepsy, aiming to facilitate appropriate application of the Intractable/Rare Diseases Act of Japan.

Methods: By analysing the cross-sectional data of patients registered in the tertiary hospital-based Epilepsy Syndrome Registry of Japan, we investigated the proportion of patients who met the severity criteria as defined by the Act (seizure frequency of at least once a month, or presence of intellectual/neurological/psychiatric symptoms, or both) and whether there are candidate syndrome/diseases to be added to the existing list in the Act.

Results: In total, 2,209 patients were registered. After excluding self-limited/idiopathic epilepsies, 1,851 of 2,110 patients (87.7%) met the severity criteria. The patients were classified into eight main epilepsy syndromes (594 patients), 20 groups based on aetiology (1,078 patients), and three groups without known aetiology (427 patients). Most of the groups classified by syndrome or aetiology had high proportions of patients satisfying the severity criteria (>90%), but some groups had relatively low proportions (<80%) resulting from favourable outcome of surgical therapy. Several small groups with known syndrome/aetiology await detailed analysis based on a sufficiently large enough number of patients registered, some of whom may potentially be added to the list of the Act.

Significance: The registry provides data to examine the usefulness of the severity criteria and list of diseases that are operationally defined by the Act. Most epilepsy patients with various syndromes/diseases and aetiology groups are covered by the Act but some are not, and the list of designated syndromes/diseases should be complemented by further amendments, as suggested by future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1361DOI Listing
February 2022

Sirolimus for epileptic seizures associated with focal cortical dysplasia type II.

Ann Clin Transl Neurol 2022 02 18;9(2):181-192. Epub 2022 Jan 18.

National Hospital Organization, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.

Objective: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II.

Methods: Sixteen patients (aged 6-57 years) with FCD type II received sirolimus at an initial dose of 1 or 2 mg/day based on body weight (FCDS-01). In 15 patients, the dose was adjusted to achieve target trough ranges of 5-15 ng/mL, followed by a 12-week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES-FCD) in which 60 patients with FCD type II were included as an external control group.

Results: The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1-4-, 5-8-, and 9-12-week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus-treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL-6 level was elevated over time.

Interpretation: The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862414PMC
February 2022

Adrenal function during long-term ACTH therapy for patients with developmental and epileptic encephalopathy.

Epilepsia Open 2022 03 14;7(1):194-200. Epub 2021 Dec 14.

Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin-releasing hormone (CRH) stimulation test during LT-ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life-threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT-ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT-ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/epi4.12566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886065PMC
March 2022

Alpha-actinin-4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas.

Cancer Sci 2022 Mar 20;113(3):1002-1009. Epub 2022 Jan 20.

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small-cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy (ADJ) according to real-world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were carried out. Formalin-fixed, paraffin-embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009-0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages: HR, 1.214; 95% CI, 0.848-1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side-effects of ADJ, and saving medical costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.15228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898703PMC
March 2022

Successful recovery from severe hypertension in a patient with Leigh syndrome.

Mol Genet Metab Rep 2020 Dec 29;25:100684. Epub 2020 Nov 29.

Department of Pediatrics, Teine-Keijinkai Hospital, Sapporo, Japan.

Hypertension is a rare complication of Leigh Syndrome (LS), but prognosis of patients with hypertension is poor and its presence is indicative of the terminal stage of the disease. Herein, we report a four-year-old girl case diagnosed with LS at 15 months of age who subsequently developed severe hypertension and respiratory failure. Physical examination and laboratory findings did not indicate a secondary cause of hypertension. Her respiratory failure was treated with non-invasive ventilation and hypertension controlled with enalapril, furosemide and spironolactone. To our knowledge, this is the first case of a patient with LS recovering from severe hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgmr.2020.100684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461110PMC
December 2020

Itpr1 regulates the formation of anterior eye segment tissues derived from neural crest cells.

Development 2021 08 26;148(16). Epub 2021 Aug 26.

Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan.

Mutations in ITPR1 cause ataxia and aniridia in individuals with Gillespie syndrome (GLSP). However, the pathogenic mechanisms underlying aniridia remain unclear. We identified a de novo GLSP mutation hotspot in the 3'-region of ITPR1 in five individuals with GLSP. Furthermore, RNA-sequencing and immunoblotting revealed an eye-specific transcript of Itpr1, encoding a 218amino acid isoform. This isoform is localized not only in the endoplasmic reticulum, but also in the nuclear and cytoplasmic membranes. Ocular-specific transcription was repressed by SOX9 and induced by MAF in the anterior eye segment (AES) tissues. Mice lacking seven base pairs of the last Itpr1 exon exhibited ataxia and aniridia, in which the iris lymphatic vessels, sphincter and dilator muscles, corneal endothelium and stroma were disrupted, but the neural crest cells persisted after completion of AES formation. Our analyses revealed that the 218-amino acid isoform regulated the directionality of actin fibers and the intensity of focal adhesion. The isoform might control the nuclear entry of transcriptional regulators, such as YAP. It is also possible that ITPR1 regulates both AES differentiation and muscle contraction in the iris.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.188755DOI Listing
August 2021

Chronic deep brain stimulation reduces cortical β-γ phase amplitude-coupling in patients with Parkinson's disease.

Parkinsonism Relat Disord 2021 08 16;89:148-150. Epub 2021 Jul 16.

Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. Electronic address:

We compared β-γ phase amplitude coupling (PAC) before and one year after chronic deep brain stimulation (DBS) in patients with Parkinson's disease using EEG and observed significant post-operative reduction of PAC values. Our findings suggest that the reduction in PAC due to DBS can be observed after chronic stimulation, which is not a transient phenomenon just after the start of DBS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2021.07.017DOI Listing
August 2021

Pseudocirrhosis due to liver metastasis from lung adenocarcinoma.

Thorac Cancer 2021 09 17;12(17):2407-2410. Epub 2021 Jul 17.

Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Pseudocirrhosis is a radiological diagnosis of cirrhosis without histological evidence and occurs as a complication of liver metastases from solid tumors. A 50-year-old man without any previous history of liver disease was diagnosed with adenocarcinoma of the left upper lung lobe and liver metastasis. After chemotherapy, the liver metastases shrank; however, over time, the liver shrank and showed cirrhosis-like morphological changes. His performance status deteriorated due to ascites and leg edema, and chemotherapy was terminated. Physicians treating lung adenocarcinoma with liver metastases should be aware that pseudocirrhosis is a rare but important complication that can worsen performance status (PS) and hinder treatment continuation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.14084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410515PMC
September 2021

Current medico-psycho-social conditions of patients with West syndrome in Japan.

Epileptic Disord 2021 Aug;23(4):579-589

Department of Pediatrics, School of Medicine, Shinshu University, Matsumoto, Japan.

Objective: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan.

Methods: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset.

Results: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%.

Significance: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1301DOI Listing
August 2021

A Single-Arm Open-Label Clinical Trial on the Efficacy and Safety of Sirolimus for Epileptic Seizures Associated with Focal Cortical Dysplasia Type II: A Study Protocol.

Kurume Med J 2021 Jul 15;66(2):115-120. Epub 2021 Jun 15.

Department of Pediatrics, Showa University School of Medicine.

Epileptic seizures are core symptoms in focal cortical dysplasia (FCD), a disease that often develops in infancy. Such seizures are refractory to conventional antiepileptic drugs (AED) and temporarily disappear in response to AED in only 17% of patients. Currently, surgical resection is an important option for the treatment of epileptic seizures in FCD. In 2015, Korean and Japanese groups independently reported that FCD is caused by somatic mosaic mutation of the MTOR gene in the brain tissue. Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. A single arm open-label clinical trial for FCD type II patients is being conducted in order to evaluate the efficacy and safety of sirolimus. The dose of sirolimus is fixed for the first 4 weeks and dose adjustment is achieved to maintain a blood level of 5 to 15 ng/mL during 8 to 24 weeks after initiation of administration, and it is kept within this level during a maintenance therapy period of 12 weeks. Primary endpoint is a reduction in the rate of incidence of focal seizures (including focal to bilateral tonic-clonic seizures) per 28 days during the maintenance therapy period from the observation period. To evaluate the frequency of epileptic seizures, registry data will be used as an external control group. We hope that the results of this trial will lead to future innovative treatments for FCD type II patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2739/kurumemedj.MS662007DOI Listing
July 2021

Development of a reading difficulty questionnaire for adolescents in Japanese.

Brain Dev 2021 Oct 26;43(9):893-903. Epub 2021 May 26.

Department of Child and Adolescent Psychiatry, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.

Background: Dyslexia is a neurodevelopmental disorder which occurs in childhood but continues to influence academic and occupational function in adulthood. Recently, a Japanese dyslexia questionnaire and diagnostic procedure was established for primary school children. However, there is currently no procedure for the diagnosis or screening of dyslexia in individuals at or above junior high school age; accordingly, we aimed to develop a questionnaire to screen for reading difficulties in those individuals.

Methods: A questionnaire with various candidate items was developed from two English questionnaires, one Japanese questionnaire, and newly devised items focusing on the Japanese writing system and the most appropriate 28 items were selected. In total, 462 adults and 127 junior high to high school students were enrolled. Of those, 191 participants also took part in reading tests. After the exploratory factor analysis, reliability and validity were evaluated using the above control participants and 12 adolescents with dyslexia.

Results: The questionnaire included three factors, i.e., silent reading sub-scale (four items), writing sub-scale (four items), and aloud reading sub-scale (three items). Five were newly devised items focusing on the Japanese writing system. Cronbach's alphas of the three factors were 0.706, 0.638, and 0.568, respectively, and the interclass correlation coefficients (2,1) were 0.743, 0.609, and 0.695, respectively. The silent reading and aloud reading sub-scales were positively correlated with word, non-word, and passage reading time.

Discussion: The newly developed questionnaire correlated well with actual reading performance and may be used to screen reading difficulty in Japanese individuals at or above junior high school age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2021.05.007DOI Listing
October 2021

Selective Eating in Autism Spectrum Disorder Leading to Hair Color Change.

Pediatr Neurol 2021 07 2;120:1-2. Epub 2021 Apr 2.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2021.03.001DOI Listing
July 2021

Appraisal of definition of baseline length for somatosensory evoked magnetic fields.

J Neurosci Methods 2021 07 2;359:109213. Epub 2021 May 2.

Department of Systems Neuroscience, School of Medicine, Sapporo Medical University, South 1, West 17, Chuo-ku, Sapporo, 060-8556, Japan. Electronic address:

Background: The baseline (BL) segment in the prestimulus period is generally assigned as a reference of evoked activities. However, an experimenter empirically defines its length in each condition. So far, the criterion for the length of a BL segment has not been established.

New Method: We evaluated the effect of the length of the BL segment by recording somatosensory evoked magnetic fields (SEFs) under fixed stimulus onset asynchrony (SOA). For the evaluation of the length of the BL segment in the prestimulus period, five proportions in relation to SOA were used as the BL segment. In addition, we adopted other two types of BL segment which were the single data point measured from the value of stimulus onset (BL0) and the mean value of the whole raw data throughout the recording (DC mean). We investigated the influence of the BL segments on SEFs by utilizing two indicators: normalized N20 m amplitudes and estimated locations of corresponding equivalent current dipoles (ECDs).

Results: Both indicators did not show any significant differences, based on the factor of BL segments, in any SOA conditions.

Comparison With Existing Method: The BL0 had by far the largest variation in the ECD locations.Therefore, utilizing stimulus onset as the BL segment should be avoided. In addition, considering that other BL segments provided comparable values by the two indicators, the DC mean can reasonably be adopted.

Conclusions: We suggest that utilizing the DC mean could be employed as the BL segment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneumeth.2021.109213DOI Listing
July 2021

The use of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide-based colorimetric assay in the viability analysis of the filamentous cyanobacterium Arthrospira platensis.

Biosci Biotechnol Biochem 2021 Feb;85(3):739-742

Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

The applicability of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to an industrially valuable filamentous cyanobacterium Arthrospira platensis was examined. When it was applied to A. platensis NIES-39, as few as 10 viable trichomes were quantitatively detected. However, depending on the experimental conditions, it also generated artifactual viability signals. The results should help clarify the scope and limits of the MTT assay in viability analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bbb/zbaa050DOI Listing
February 2021

Selective Eating in Autism Spectrum Disorder Leading to Kwashiorkor and Brain Edema.

Pediatr Neurol 2021 03 26;116:55-56. Epub 2020 Dec 26.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2020.12.007DOI Listing
March 2021

Variance in the pathophysiological impact of the hemizygosity of gamma-aminobutyric acid type A receptor subunit genes between Prader-Willi syndrome and Angelman syndrome.

Brain Dev 2021 Apr 5;43(4):521-527. Epub 2021 Jan 5.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. Electronic address:

Introduction: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are neurodevelopmental disorders caused by loss of function of maternally expressed UBE3A and paternally expressed contiguous genes on chromosome 15q11-13, respectively. A majority of these syndromes suffer from a large deletion of the relevant chromosome (AS Del or PWS Del), which includes biallelically expressed gamma-aminobutyric acid type A receptor subunit (GABAaR) genes, while remaining individuals present without the deletion (AS non-Del or PWS non-Del). We previously reported that AS Del, but not AS non-Del individuals, show aberrantly desynchronized somatosensory-evoked magnetic fields (SEFs) and speculated that it might reflect GABAergic dysfunction due to the hemizygosity of GABAaR genes. To verify its pathophysiological impact on PWS and AS, we analyzed the SEFs of PWS individuals.

Method: SEFs were recorded from eight PWS Del and two PWS non-Del individuals. The latency and strength of the first peak (N1m) were compared with those of AS Del/non-Del individuals and controls, most of which were obtained earlier.

Results: In contrast to AS, both PWS Del and PWS non-Del showed normal SEF waveforms. Desynchronized response with delayed N1m peak latency was exclusively indicated in AS Del. N1m strength was statistically higher in AS Del and AS non-Del, but not in PWS Del and PWS non-Del.

Conclusions: Our results indicate that the pathophysiological impact of the hemizygosity of GABAaR genes is lower in PWS than AS. UBE3A deficiency and the hemizygosity of GABAaR genes could synergistically deteriorate neuronal function, resulting in aberrant SEFs in AS Del.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.12.014DOI Listing
April 2021

Flurothyl-induced seizure paradigm revealed higher seizure susceptibility in middle-aged Angelman syndrome mouse model.

Brain Dev 2021 Apr 4;43(4):515-520. Epub 2021 Jan 4.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. Electronic address:

Introduction: Epilepsy is one of the main clinical problems in Angelman syndrome (AS). Seizures typically start in early childhood then decrease or are often alleviated by young adulthood. Several studies using AS model mice showed comparable seizure susceptibility during young adulthood. In contrast, the course of epilepsy post young adulthood differs from persistently relieved to rerising among reports. To elucidate this, we evaluated the seizure susceptibility of AS model mice of two different ages.

Methods: Mice lacking maternal Ube3a gene (Ube3a) of C57BL/6 background or their littermate wild type (WT) were divided into two groups by age, 2 to 3 months (2-3 M) and 6 to 12 months (6-12 M), corresponding to adolescent to young adult aged and middle aged humans, respectively. Seizure susceptibility was evaluated by flurothyl inhalation or intraperitoneal injection of pentylenetetrazole (PTZ IP)-induced acute seizure protocol.

Results: In the flurothyl-induced seizure paradigm, the latency to seizure occurrence had a significant interaction with genotype and age. Post-hoc analysis revealed that the latency was significantly shorter at 6-12 M than at 2-3 M in Ube3a mice, and in Ube3a mice than in WT mice at 6-12 M. No significant interaction or difference was observed by PTZ IP.

Conclusion: The flurothyl-induced seizure paradigm revealed that seizure susceptibility of Ube3a mice increased with age, similar to clinical studies reporting the reappearance of epilepsy in older age. The flurothyl-induced seizure paradigm applied to middle-aged Ube3a mice could be a suitable protocol for screening drugs against seizures in AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.12.011DOI Listing
April 2021

Reinterpretation of magnetic resonance imaging findings with magnetoencephalography can improve the accuracy of detecting epileptogenic cortical lesions.

Epilepsy Behav 2021 01 13;114(Pt A):107516. Epub 2020 Dec 13.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Electronic address:

Objective: This study examined whether the application of magnetoencephalography (MEG) to interpret magnetic resonance imaging (MRI) findings can aid the diagnosis of intractable epilepsy caused by organic brain lesions.

Methods: This study included 51 patients with epilepsy who had MEG clusters but whose initial MRI findings were interpreted as being negative for organic lesions. Three board-certified radiologists reinterpreted the MRI findings, utilizing the MEG findings as a guide. The degree to which the reinterpretation of the imaging results identified an organic lesion was rated on a 5-point scale.

Results: Reinterpretation of the MRI data with MEG guidance helped detect an abnormality by at least one radiologist in 18 of the 51 patients (35.2%) with symptomatic localization-related epilepsy. A surgery was performed in 7 of the 51 patients, and histopathological analysis results identified focal cortical dysplasia in 5 patients (Ia: 1, IIa: 2, unknown: 2), hippocampal sclerosis in 1 patient, and dysplastic neurons/gliosis in 1 patient.

Conclusions: The results of this study highlight the potential diagnostic applications of MEG to detect organic epileptogenic lesions, particularly when radiological visualization is difficult with MRI alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107516DOI Listing
January 2021

Reply to the letter: "Perampanel may be beneficial in leigh syndrome by its anti-oxidative but not anti-epileptic effect".

Brain Dev 2021 02 13;43(2):361-362. Epub 2020 Dec 13.

Department of Pediatrics, Teine Keijinkai Hospital, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.10.008DOI Listing
February 2021

Short-latency somatosensory-evoked potentials demonstrate cortical dysfunction in patients with Angelman syndrome.

eNeurologicalSci 2021 Mar 1;22:100298. Epub 2020 Dec 1.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.

Background: Angelman syndrome (AS) is neurodevelopmental disorder, causal gene of which is maternally expressed . A majority of patients results from the large deletion of relevant chromosome which includes GABA receptor subunit genes (GABARs) as well as (AS Del) We previously reported aberrantly desynchronized primary somatosensory response in AS Del by using magnetoencephalography. The purpose of this study is to estimate cortical and subcortical involvement in the deficit of primary somatosensory processing in AS.

Methods: We analyzed short-latency somatosensory-evoked potentials (SSEPs) in 8 patients with AS Del. SSEPs were recorded on a 4-channel system comprising of two cortical electrodes which were placed on the frontal and centro-parietal areas. The peak and onset latency of each component were measured to compare latency and interval times.

Results: The first-cortical peak latency (N20, P20), and N13-N20 peak interval times were significantly prolonged in AS Del compared to healthy controls. In contrast, there was no difference in latencies between subcortical components up to N20 onset or for N11-N20 onset interval times.

Conclusion: Highly desynchronized first-cortical SSEP components and normal latencies of subcortical components indicated cortical dysfunction rather than impairment of afferent pathways in AS Del patients, which might be attributed to GABAergic dysfunction due to loss of function and heterozygosity of GABARs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ensci.2020.100298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721653PMC
March 2021

Brigatinib and lorlatinib: their effect on ALK inhibitors in NSCLC focusing on resistant mutations and central nervous system metastases.

Jpn J Clin Oncol 2021 Jan;51(1):37-44

Department of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.

Major issues in anaplastic lymphoma kinase-positive non-small cell lung carcinoma are acquired resistance against anaplastic lymphoma kinase inhibitors and control of central nervous system metastasis. The development of these inhibitors has changed therapeutic strategy in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Brigatinib and lorlatinib were designed to penetrate the blood-brain barrier and to inhibit resistant mutations against anaplastic lymphoma kinase inhibitors. We review the clinical data supporting treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma with brigatinib and lorlatinib. Brigatinib has shown promising antitumour activity, including substantial activity against central nervous system metastases, in crizotinib-treated (ALTA trial) patients and crizotinib-naïve (ALTA-1L trial) patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. In addition, brigatinib improved progression-free survival compared with crizotinib in anaplastic lymphoma kinase inhibitor-naïve patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Lorlatinib has demonstrated clinical antitumour activity against both intracranial and extracranial lesions in patients with anaplastic lymphoma kinase- or c-ros oncogene 1 (ROS1)-positive non-small cell lung carcinoma. Ongoing trials and further studies of these agents' biological and clinical properties would provide insight into the optimal therapeutic strategy for administering them to achieve the best survival benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyaa192DOI Listing
January 2021

Semi-automated brain responses in communication: A magnetoencephalographic hyperscanning study.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:2893-2896

Face to face communication is interactive, and involves continuous feedforward and feedback of information, thoughts, and feelings to the opposite party. To accurately assess the neural processing underlying these interactions, synchronous and simultaneous recording of the brain activity from both parties is needed, a method known as hyperscanning. Here, we investigated the neural processing underlying nonverbal face-to-face communication using a magnetoencephalographic (MEG) hyperscanning system, comprising two fiber optically connected MEGs. Eight pairs of subjects participated. Each individual in each pair viewed a combined 80 randomized 20 s trials of 40 real-time and 40 recorded (hereafter, real and simulated, respectively) videos of the opposite party's face. Non-verbal communication through actions such as gaze, eye blinks, and facial expression was intrinsically only possible during real videos. After each trial, subjects individually subjectively discriminated whether the viewed video was real or simulated. Overall subjective discrimination accuracies were slightly but significantly above chance level. Statistical analysis of brain activity revealed a significant three way interaction between theta-band rhythm amplitude, video type, and subjective discrimination response in the right frontal cortex. Additionally, when subjects responded that videos were simulated, theta activity was significantly lower for real videos compared with simulated videos (p = 0.01). This result not only demonstrates the importance of right frontal theta activity during non-verbal communication, but also indicates the existence of unconscious, semi-automated neural processing during non-verbal communication that underlies one's ability to subjectively discriminate whether or not the opposite party is real.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9176538DOI Listing
July 2020

Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease.

PLoS One 2020 17;15(9):e0232808. Epub 2020 Sep 17.

Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Studies on evoked responses in Parkinson's disease (PD) may be useful for elucidating the etiology and quantitative evaluation of PD. However, in previous studies, the association between evoked responses and detailed motor symptoms or cognitive functions has not been clear. This study investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson's disease (PD), and the correlations between evoked fields and the patient's clinical characteristics, motor symptoms, and cognitive functions. Twenty patients with PD and 10 healthy controls (HCs) were recruited as participants. We recorded VEF, AEF, and SEF, collected clinical characteristics, performed physical examinations, and administered 10 cognitive tests. We investigated differences in the latencies of the evoked fields between patients with PD and HCs. We also evaluated the correlation of the latencies with motor symptoms and cognitive functioning. There were significant differences between the two groups in 6 of the cognitive tests, all of which suggested mild cognitive impairment in patients with PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in the patients with PD than in the HCs. The latencies mainly correlated with medication and motor symptoms, less so with cognitive tests, with some elements of the correlations remaining significant after Bonferroni correction. In conclusion, the latencies of the VEF, AEF, and SEF were greater in PD patients than in HCs and were mainly correlated with medication and motor symptoms rather than cognitive functioning. Findings from this study suggest that evoked fields may reflect basal ganglia functioning and are candidates for assessing motor symptoms or the therapeutic effects of medication in patients with PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232808PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498017PMC
October 2020

Myocardial T-mapping and Extracellular Volume Quantification in Patients and Putative Carriers of Muscular Dystrophy: Early Experience.

Magn Reson Med Sci 2021 Sep 7;20(3):320-324. Epub 2020 Sep 7.

Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

To assess myocardial fibrosis associated with muscular dystrophy, T-mapping and extracellular volume fraction (ECV) quantification was prospectively performed using cardiovascular MR (CMR) imaging in 6 male patients with muscular dystrophy and 5 female putative carriers of Duchenne or Becker muscular dystrophy. Five patients and all putative carriers had an elevated ECV (>29.5% for men and >35.2% for women), suggesting that ECV has a potential to detect diffuse fibrotic changes in patients and putative carriers of muscular dystrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2463/mrms.bc.2020-0069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424027PMC
September 2021

Efficacy of bezafibrate for preventing myopathic attacks in patients with very long-chain acyl-CoA dehydrogenase deficiency.

Brain Dev 2021 Feb 11;43(2):214-219. Epub 2020 Aug 11.

Hokkaido University Hospital Clinical Research and Medical Innovation Center, Research and Development Division, Japan.

Background: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks.

Patients And Methods: We conducted an open-label, non-randomized, multi-center study into the effects of bezafibrate on five patients with VLCADD. Bezafibrate was administered for 4 years, and we analyzed the number of myopathic attacks requiring hospitalization and treatment infusions.

Results: The number of myopathic attacks requiring infusions of 24 h or longer significantly decreased during the study period. The patients' ability to conduct everyday activities was also improved by the treatment.

Conclusion: Our findings show the potential long-term efficacy of bezafibrate in preventing myopathic attacks for patients with VLCADD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.07.019DOI Listing
February 2021

Efficacy of perampanel for epileptic seizures and daily behavior in a patient with Leigh syndrome: A case report.

Brain Dev 2021 Jan 29;43(1):157-159. Epub 2020 Jul 29.

Department of Pediatrics, Nikko Memorial Hospital, Japan.

Background: Leigh syndrome (LS) is a mitochondrial disorder that shows abnormal basal ganglia lesion and psychomotor regression. Although vitamins have been used for LS, we have not found any effective drug.

Case Presentation: A 26-year-old man who showed psychomotor delay and short stature at the age of 1 year was diagnosed with LS according to the results of cerebrospinal fluid and high signal intensity in the bilateral striatum on T2-weighted magnetic resonance imaging. He demonstrated psychomotor delay and breathing disorders, but the progression was very slow. His symptoms suddenly worsened at the age of 24 years after acute epididymitis. He showed epileptic seizures simultaneously and his activities of daily living (ADL) significantly worsened. Several antiepileptic drugs were ineffective, but his seizures were suppressed by a low dose of perampanel and his ADL improved.

Conclusion And Discussion: Our case showed that low-dose perampanel could be a drug for epileptic seizures and improvement of ADL in patients with LS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.07.008DOI Listing
January 2021

Correlation between the expression of folate receptor alpha (FRα) and clinicopathological features in patients with lung adenocarcinoma.

Lung Cancer 2020 07 11;145:152-157. Epub 2020 May 11.

Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Objectives: Folate receptor alpha (FRα) is expressed on the cell surface, mediates its intracellular transport via receptor-mediated endocytosis, and is involved in cell division. Whether FRα could be a potential therapeutic target in FRα-expressing cancers remains unknown. Here, we retrospectively investigated the correlations between tumor FRα expression in lung adenocarcinoma (LADC) and clinicopathological features.

Materials And Methods: FRα expression was evaluated using a tissue microarray (TMA) constructed from surgical specimens of LADC and compared with clinicopathological features including the EGFR mutation status and the expressions of PD-L1, PD-L2, PD-1, CD4, CD8, CD204, and αSMA. If the proportion of positively stained tumor cells was greater than or equal to 5%, the tumor was considered to show FRα expression; if the H-score was more than or equal to 60, the tumor was considered to show high FRα expression.

Results: Overall, 466 TMA cores created from 233 LADC patients were evaluated: FRα-positive expression (FRα-pos)/negative (FRα-neg), 222/11; FRα high expression (FRα-HE)/low (FRα-LE), 190/43. AnEGFR mutation was present in 53.2 % of the patients. The median H-score of FRα expression, FRα-pos rate, and FRα-HE rate for EGFR mutation/wild type were 159/104 (p = 0.0002), 97.6/92.7 % (p = 0.0773), and 88.7/73.4 % (p = 0.0026), respectively. The H-scores for FRα had mild correlations with the proportion of tumor cells with positive staining for PD-L1 (r=-0.2557, p < 0.0001), the number of CD8-positive cells per square millimeter (r=-0.1767, p = 0.0069), and the area with positive staining for αSMA (r = 0.2049, p = 0.0017). No correlations were seen between FRα expression and other cancer-immunity markers.

Conclusion: Tumor FRα expression was significantly higher in LADCs withEGFR mutation than in those with wild-type EGFR. This study suggested that FRα expression was related to cancer and microenvironment-immunity markers such as PD-L1 expression, CD8 cells, and αSMA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2020.05.002DOI Listing
July 2020
-->