Language：English   Publishing type：Research paper (scientific journal)  

Fast ripples (FRs) (250-500 Hz) on the electroencephalogram (EEG) are closely related to epileptogenicity and are important to determine cortical regions resected in epilepsy surgery. However, FR-related epileptogenicity may be variable, and may depend on information associated with FRs. We enrolled nine epilepsy patients who had undergone intracranial 5 kHz-sampling-rate EEG for surgical treatment and had final Engel class I outcomes. Three electrodes were selected from each epileptogenic area (EA) and the unlikely EA (the region outside the EA) in each patient. Up to 100 candidate FRs were automatically detected from interictal nocturnal EEG at each of the selected electrodes and were visually reviewed independently by two researchers. Multivariate logistic regression analysis was performed using the frequency and log-power value of the corresponding FRs, presence of concurrent spike, ripple, very-high-frequency oscillations (vHFO)1 (500-600 Hz), and vHFO2 (600-1200 Hz), and whether the timing of the spectral peak of corresponding FRs was in the peak-trough or trough-peak transition of each slow activity (0.5-1, 1-2, 2-3, 3-4, and 4-8 Hz) as independent variables. Factors significantly related to epileptogenicity were FR power, the concurrent presence of spike and vHFO2, coupling with 0.5-1 and 1-2 Hz slow waves in the peak-trough transition, and coupling with 3-4 and 4-8 Hz slow waves in the trough-peak transition. Multifactorial analysis of FRs may increase their usefulness, potentially leading to improved treatment outcomes in epilepsy surgery.

DOI： 10.1016/j.ebr.2025.100776

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

GNAO1 variant affects primarily the brain and neurodevelopment, leading to a range of motor disorders including seizures beginning in infancy and involuntary movements such as dyskinesia and dystonia. Our patient, a 15-year-old Japanese female, began exhibiting involuntary movements at age 4. A de novo missense mutation (NM_020988.3: c.228C>G, NP_066268.1: p.(Asn76Lys)) in the GNAO1 gene was identified when the patient was 15, and during the same year she developed influenza pneumonia, accompanied by dystonic storm. She required intensive care with mechanical ventilation and underwent a tracheostomy. She also developed posterior reversible encephalopathy syndrome. Globus pallidal stimulation was administered, leading to an improvement in the dystonic storm. Early consideration of globus pallidal stimulation is recommended when treating difficult-to-manage dystonic storms.

DOI： 10.18926/AMO/69156

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ajmg.a.64030

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy characterized by drug-resistant seizures and multiple comorbidities. It has been reported that in adulthood, it may be accompanied by parkinsonism, but the pathogenesis of this condition remains unclear. We performed dopamine transporter single-photon emission computed tomography (DAT SPECT) and measured monoamine metabolite levels in the cerebrospinal fluid (CSF) in two adult patients with DS who developed parkinsonism around the age of 30 years. DAT SPECT showed no abnormalities in either patient, whereas CSF tests revealed significant decreases in the levels of homovanillic and 5-hydroxyindoleacetic acids. One patient with severe symptoms was treated with levodopa-carbidopa, which improved parkinsonism manifestations. The other patient initiated treatment with a low dose and has been continuing the treatment without any reported side effects. In conclusion, CSF testing can detect a decrease in dopamine synthesis and may be useful in monitoring the efficacy of levodopa treatment in patients with DS and parkinsonism. PLAIN LANGUAGE SUMMARY: Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy. DS can lead to the development of parkinsonism in adulthood, a clinical syndrome characterized by tremor, slowed movements, and rigidity. Although parkinsonism is a significant issue for patients, its underlying pathology has not yet been elucidated. In this study, we confirmed that the levels of monoamine metabolites in the CSF were low in two patients, potentially shedding light on the pathology involved.

DOI： 10.1002/epi4.70034

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The use of asfotase alfa, a bone-targeted recombinant alkaline phosphatase (ALP) enzyme, for the treatment of adult-onset hypophosphatasia (HPP) remains controversial, particularly in patients without evident bone abnormalities. We report the case of a 41-year-old woman with a history of Graves' disease, who presented with progressive joint pain and severe fatigue. Despite the absence of bone lesions, the patient was diagnosed with HPP based on persistently low alkaline phosphatase levels, family history, and a novel heterozygous ALPL variant (p.Ala205Thr). Functional analysis revealed a dominant-negative effect for this variant. Her symptoms significantly interfered with her daily activities owing to uncontrolled pain and loss of motor function and were so exacerbated that high doses of acetaminophen and NSAIDs were ineffective. Treatment with asfotase alfa was initiated based on multidisciplinary team consensus. Within 3 months of treatment initiation, her pain improved significantly, as indicated by reduced scores on the visual analog scale from 6.6 to 0.9, and elimination of the need for analgesics. Additionally, her grip strength increased, and her urinary phosphoethanolamine levels and serum pyridoxal 5'-phosphate/pyridoxal ratio decreased from 90.4 to 57.8 μmol/g·creatinine and from 4.6 to 0.4, respectively. These improvements have been maintained for more than 2 years. This case highlights the potential of asfotase alfa in effectively alleviating symptoms in patients with adult-onset HPP without bone lesions, emphasizing the importance of patient selection and outcome monitoring. We also discuss the key considerations for future treatment, supported by a literature review of asfotase alfa in adult patients with HPP.

DOI： 10.1507/endocrj.EJ24-0431

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE. REVIEW: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms. CONCLUSION: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine.

DOI： 10.1016/j.braindev.2024.104318

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

SUMMARY: Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5'-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. LEARNING POINTS: A diagnosis of adult HPP without bone-related symptoms can be challenging. A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia. Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.

DOI： 10.1530/EDM-24-0121

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t1: at which the seizure should be regarded as an "abnormally prolonged seizure"; and t2: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the "Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023" (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.

DOI： 10.1016/j.braindev.2024.104306

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Post-operative complications of corpus callosotomy (CC) in children, prolonged hospitalization due to inactivity as acute disconnection syndrome is occasionally experienced. We aimed to clarify this issue and its risk factors with a hypothesis that electroencephalogram (EEG) findings as measures of functional lateralization may be among prognostic factors for post-operative recovery. MATERIALS AND METHODS: Twenty-three patients with childhood-onset drug-resistant epilepsy who underwent total CC between April 2017 and December 2023 were included in the study and they were divided into two groups based on the duration of post-operative hospitalization as an indicator of recovery of daily living activity. We compared scalp EEG findings and the other factors including clinical characteristics between the two groups. RESULTS: Of 22 patients (14 males) without specific complications, post-operative hospitalization clustered in 9-14 days in 15 patients (Group A) with range 16-118 days in seven patients (Group B). The ratios of patients with non-lateralized spikes on pre-operative EEG and that of patients with symmetric background activity on post-operative EEG were significantly greater in Group B (7/7, 100 %; 6/7, 86 %, respectively) than in Group A (8/15, 53 %; 4/15, 27 %, respectively) (p = 0.038; p = 0.020, respectively, by Fisher's exact test), while other factors were not significantly different between the two groups. CONCLUSIONS: Delayed recovery of living activity should be anticipated, especially in patients with non-lateralized epileptic discharges on pre-operative EEG.

DOI： 10.1016/j.braindev.2024.09.006

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

DOI： 10.1007/s00277-024-06000-7

PubMed

researchmap

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bdcasr.2024.100033

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: In developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS), the thalamocortical network is suggested to play an important role in the pathophysiology of the progression from focal epilepsy to DEE-SWAS. Ethosuximide (ESM) exerts effects by blocking T-type calcium channels in thalamic neurons. With the thalamocortical network in mind, we studied the prediction of ESM effectiveness in DEE-SWAS treatment using phase-amplitude coupling (PAC) analysis. METHODS: We retrospectively enrolled children with DEE-SWAS who had an electroencephalogram (EEG) recorded between January 2009 and September 2022 and were prescribed ESM at Okayama University Hospital. Only patients whose EEG showed continuous spike-and-wave during sleep were included. We extracted 5-min non-rapid eye movement sleep stage N2 segments from EEG recorded before starting ESM. We calculated the modulation index (MI) as the measure of PAC in pair combination comprising one of two fast oscillation types (gamma, 40-80 Hz; ripples, 80-150 Hz) and one of five slow-wave bands (delta, 0.5-1, 1-2, 2-3, and 3-4 Hz; theta, 4-8 Hz), and compared it between ESM responders and non-responders. RESULTS: We identified 20 children with a diagnosis of DEE-SWAS who took ESM. Fifteen were ESM responders. Regarding gamma oscillations, significant differences were seen only in MI with 0.5-1 Hz slow waves in the frontal pole and occipital regions. Regarding ripples, ESM responders had significantly higher MI in coupling with all slow waves in the frontal pole region, 0.5-1, 3-4, and 4-8 Hz slow waves in the frontal region, 3-4 Hz slow waves in the parietal region, 0.5-1, 2-3, 3-4, and 4-8 Hz slow waves in the occipital region, and 3-4 Hz slow waves in the anterior-temporal region. SIGNIFICANCE: High MI in a wider area of the brain may represent the epileptic network mediated by the thalamus in DEE-SWAS and may be a predictor of ESM effectiveness.

DOI： 10.1016/j.eplepsyres.2024.107359

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本内分泌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Hypophosphatasia (HPP) is a rare skeletal dysplasia caused by variants in the alkaline phosphatase (ALPL) gene. More than 400 pathogenic variants of the ALPL gene have been registered in the ALPL gene variant database. Here, we describe the case of a Japanese child with odonto-hypophsphatasia (odonto-HPP) and a novel ALPL variant. CASE PRESENTATION: At the age of 2 years and 1 month, he prematurely lost one deciduous tooth, with the root intact, when he fell and hit his face lightly. Three months later, he lost another adjacent deciduous tooth without incentive. His serum alkaline phosphatase (ALP) level was 72 U/L. His urine phosphoethanolamine (PEA) level was extremely high at 938 μmol/mg·Cre. The serum pyridoxal 5'-phosphaye (PLP) level was 255.9 nmol/L. Based on the clinical symptoms and laboratory findings, the patient was clinically diagnosed with odonto-HPP. Genetic analysis of the ALPL gene revealed a heterozygous variant (NM_000478.6:c.1151C>A, p.Thr384Lys). CONCLUSIONS: We report a case of odonto-HPP with a novel variant in the ALPL gene. HPP is a rare disease, and the heterozygous mutation in the ALPL gene highlights the novelty of this case.

DOI： 10.1515/jpem-2023-0549

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics. METHODS: This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups. CONCLUSIONS: Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.

DOI： 10.1016/j.braindev.2023.12.004

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Institute of Electrical and Electronics Engineers (IEEE)  

DOI： 10.1109/access.2024.3487637

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

DOI： 10.18926/AMO/65980

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: MECP2 is a well-known causative gene for Rett syndrome but other phenotypes have also been reported. Here, we report a case of a female patient with adolescent-onset progressive myoclonus epilepsy (PME) carrying a novel truncating mutation in the MECP2 gene. CASE REPORT: The patient was a 29-year-old woman with infantile-onset intellectual disability of unspecified cause. She had demonstrated slow but steady development with moderate intellectual disability until the age of 16, when she started having epileptic seizures. Her epilepsy progressed intractably with multiple seizure types accompanied by myoclonus, tremor, and gradual regression. She is currently apathetic and requires extensive assistance in all aspects of life. After an extensive work-up for underlying diseases for PME turned out negative, whole-exome sequencing revealed a de novo 113-bp deletion and 3-bp insertion in MECP2, a variant of NM_004992.4:c.1099_1211delinsGGG, p.(His367Glyfs*32). CONCLUSIONS: The clinical presentation of this case was inconsistent with Rett syndrome, and the rapid regression in the patient's twenties was considered characteristic. Mutations of MECP2 may result in variable neurodevelopmental phenotypes and may also be considered a causative gene for adolescent-onset PME.

DOI： 10.1016/j.braindev.2023.07.006

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Children with a congenital heart disease (CHD) are at a higher risk of developing epilepsy than the general population, but detailed characteristics of CHD-associated epilepsy have not been clarified. The purposes of this study were to determine the risk factors for developing epilepsy associated with CHD and to elucidate the characteristics of such epilepsy. METHODS: We performed a retrospective cohort study based on medical records of pediatric patients with CHD who were born between January 2006 and December 2016, underwent cardiac surgery at Okayama University Hospital, and were followed up until at least age three years. Multivariate logistic regression analysis was used to determine factors particularly associated with epilepsy occurrence. In patients who developed epilepsy, clinical data on seizure characteristics were further investigated. RESULTS: We collected data from 1024 patients, and 41 (4.0%) developed epilepsy. The presence of underlying disease (odds ratio [OR]: 2.413; 95% confidence interval [CI]: 1.150 to 4.883) and the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category 2 (OR: 4.373; 95% CI: 1.090 to 29.150) and category 5 (OR: 10.385; 95% CI: 1.717 to 89.016) were significantly related to epilepsy occurrence. Of the 41 patients with epilepsy, 15 (including nine with hypoplastic left heart syndrome) had focal impaired awareness seizures specified as autonomic seizures with vomiting, which tends to escape detection. CONCLUSIONS: We clarified the risk factors for developing epilepsy in children with CHD. We also found that autonomic seizure with vomiting is an important symptom in these children.

DOI： 10.1016/j.pediatrneurol.2023.07.004

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

OBJECTIVE: The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets. METHODS: Subjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2-4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS: Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated. CONCLUSIONS: The metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications.

DOI： 10.1016/j.seizure.2023.03.014

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We developed an artificial intelligence (AI) technique to identify epileptic discharges (spikes) in pediatric scalp electroencephalograms (EEGs). We built a convolutional neural network (CNN) model to automatically classify steep potential images into spikes and background activity. For the CNN model' training and validation, we examined 100 children with spikes in EEGs and another 100 without spikes. A different group of 20 children with spikes and 20 without spikes were the actual test subjects. All subjects were ≥ 3 to < 18 years old. The accuracy, sensitivity, and specificity of the analysis were >0.97 when referential and combination EEG montages were used, and < 0.97 with a bipolar montage. The correct classification of background activity in individual patients was significantly better with a referential montage than with a bipolar montage (p=0.0107). Receiver operating characteristic curves yielded an area under the curve > 0.99, indicating high performance of the classification method. EEG patterns that interfered with correct classification included vertex sharp transients, sleep spindles, alpha rhythm, and low-amplitude ill-formed spikes in a run. Our results demonstrate that AI is a promising tool for automatically interpreting pediatric EEGs. Some avenues for improving the technique were also indicated by our findings.

DOI： 10.18926/AMO/64111

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Sepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported. METHODS: We developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients. RESULTS: In the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L). CONCLUSIONS: The simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.

DOI： 10.1016/j.cca.2022.07.016

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Objective: The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5-methyltetrahydrofolic acid (5MTHF) across the blood-cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with CFD to support this hypothesis. Methods: We measured CSF and serum 5MTHF concentrations in a patient with Kearns-Sayre syndrome (KSS) and a patient homozygous for MTHFR C677T polymorphism before and during folate supplementation therapy. To evaluate these 5MTHF concentrations, we also analyzed CSF and serum samples in pediatric patients without folate supplementation. Results: Both patients had low CSF 5MTHF before treatment and high-dose FA therapy did not normalize CSF 5MTHF. There was a dissociation between serum total folate and 5MTHF concentrations during FA therapy, which was considered to be due to the appearance of unmetabolized FA. The addition of folinic acid did not improve low CSF 5MTHF in the KSS patient and the cessation of FA resulted in the normalization of CSF 5MTHF. In the patient homozygous for MTHFR C677T, minimization of the FA dosage resulted in the normalization of CSF 5MTHF and an increased CSF-to-serum 5MTHF ratio. Conclusions: Our data suggest that excess supplementation of FA impaired 5MTHF transport across the blood-CSF barrier. In the treatment of CFD, supplementation of folinic acid or 5MTHF (in cases of impaired 5MTHF synthesis) is preferred over the use of FA. The reference values of CSF 5MTHF concentration based on 600 pediatric cases were also provided.

DOI： 10.1002/jmd2.12321

PubMed

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmd2.12321

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

researchmap

Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The severity of HPP is widely diverse from the perinatal form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to pneumonia which was caused by severe hypomineralization of the bones-such as chest deformity and fractured ribs-and muscle weakness. Enzyme replacement therapy using asfotase alfa (AA) was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of AA experience in ten cases of pediatric-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 [7.6-12.5] years; 60% male). This is a study of a single-center cohort describing the clinical course of patients with HPP, mainly consisting of the mild childhood form of HPP, treated with AA in Japan. RESULTS: One case of perinatal form of HPP, two cases of benign prenatal form, and seven cases of childhood form were observed. The most common symptom at onset was pain. All patients had low serum alkaline phosphatase levels as compared to the age-matched reference range before the commencement of AA. All HPP patients seem to have responded to AA treatment, as evidenced by pain alleviation, increased height standard deviation, improvement in respiratory condition and 6-min walk test result improvement, disappearance of kidney calcification, alleviation of fatigue, and/or increases in bone mineralization. There were no serious adverse events, but all patients had an injection site reaction and skin changes at the injection sites. Genetic analysis showed that eight out of ten patients had compound heterozygosity. CONCLUSIONS: AA may be effective in patients with mild to severe pediatric-onset forms of HPP.

DOI： 10.1186/s13023-022-02230-y

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1002/acn3.51505

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English  

Early-onset isolated (DYT1) dystonia is one of the most common forms of primary dystonia in childhood, and deep brain stimulation of the globus pallidus internus (GPi-DBS) is a highly effective treatment for it. However, the effectiveness of GPi-DBS in monozygotic twins with DYT1 dystonia has never been reported globally. Here, we report the cases of monozygotic twins with DYT1 dystonia who were treated using GPi-DBS, and we include a literature review. The younger brother showed an abnormal gait, with external rotation of the right lower leg at 6 years old. The symptoms gradually became so severe that he had difficulty walking on his own at 9 years of age. Treatment with levodopa-carbidopa partially resolved his symptoms, but most of the symptoms remained. Meanwhile, the older brother developed dystonia in both upper limbs at 8 years of age, with gradual symptom progression. At 13 years of age, they were diagnosed with DYT1 dystonia. Bilateral GPi-DBS was performed in both patients at 16 years of age. Their symptoms remarkably improved after surgery. The Burke-Fahn-Marsden dystonia rating scale (BFMDRS) movement score was reduced from 52 to 2 points for the younger brother and from 35 to 1 point for the older brother. Even if monozygotic twins have the same genes, the onset and severity of symptoms might vary in accordance with differences in epigenomic profiles. However, GPi-DBS treatment was very effective for the two cases; thus, we should consider the surgical interventions for each patient.

DOI： 10.2176/jns-nmc.2022-0084

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

In this paper, we propose a time-series stochastic model based on a scale mixture distribution with Markov transitions to detect epileptic seizures in electroencephalography (EEG). In the proposed model, an EEG signal at each time point is assumed to be a random variable following a Gaussian distribution. The covariance matrix of the Gaussian distribution is weighted with a latent scale parameter, which is also a random variable, resulting in the stochastic fluctuations of covariances. By introducing a latent state variable with a Markov chain in the background of this stochastic relationship, time-series changes in the distribution of latent scale parameters can be represented according to the state of epileptic seizures. In an experiment, we evaluated the performance of the proposed model for seizure detection using EEGs with multiple frequency bands decomposed from a clinical dataset. The results demonstrated that the proposed model can detect seizures with high sensitivity and outperformed several baselines.

DOI： 10.1109/EMBC46164.2021.9630840

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Fast oscillations (FOs) &amp;gt;40 Hz in electroencephalograms (EEGs) are associated with ictogenesis and epileptogenesis in adults and children with epilepsy. However, only a few previous studies showed FOs in neonates. Reported frequencies of such neonatal FOs were in the low-gamma (&amp;lt;60 Hz) band and, therefore, they were not high compared to those in pediatric patients. We herein report a newborn patient with severe hypoxic–ischemic encephalopathy (HIE), who showed pathological FOs with a frequency in the high-gamma band. She was born at a gestational age of 39 weeks 4 days by emergency cesarean section because of non-reassuring fetal status. She had focal motor seizures involving unilateral upper and lower limbs lasting for tens of seconds on days 0, 1, 4, 5, 8, and 9 and subclinical seizures on days 4–11. Phenobarbital (PB) was intravenously administered on days 0, 2, 4, 5, and 6. We found FOs that were superimposed on the ictal delta activities using visual inspection and time–frequency analysis on 8–11 days of age. Among them, we detected high-gamma (71.4–100 Hz) oscillations that appeared to be temporally independent of low-gamma activities in the ictal EEG on 11 days of age. To the best of our knowledge, this is one of the earliest reports showing pathological FOs with a frequency of &amp;gt;60 Hz in the high-gamma band in human neonatal seizures, which were previously observed in animal studies. Further studies are needed to elucidate the pathophysiology of ictal FOs in neonatal seizures.

DOI： 10.3389/fped.2021.679771

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.2739/kurumemedj.MS662007

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: DYT-TOR1A is caused by a GAG deletion in the TOR1A gene. While it usually manifests as early-onset dystonia, its phenotype is extremely diverse, even within one family. Recent reports have revealed that some DYT-TOR1A cases have novel mutations in the TOR1A gene while others have mutations in both TOR1A and another DYT gene (THAP1 or SGCE). Our understanding of the correlation between genotype and phenotype is becoming increasingly complicated. CASE PRESENTATIONS: Here, we report on monozygotic twins who developed dystonia in childhood. The two children had different presentations in terms of onset age and dominant disturbances, but both exhibited marked diurnal fluctuation and jerking movements of the limbs as well as levodopa/levodopa-carbidopa responsiveness. These features are commonly associated with DYT/PARK-GCH1 and DYT-SGCE, yet these twins had no mutations in the GCH1 or SGCE genes. Whole exome sequencing eventually revealed a single GAG deletion in the TOR1A gene. CONCLUSION: Monozygotic twins whose only mutation was a GAG deletion in TOR1A exhibited DYT/PARK-GCH1-asssociated features and jerking movements reminiscent of myoclonus. This finding may expand the spectrum of phenotypes associated with DYT-TOR1A, and suggests that levodopa has potential as a treatment for DYT-TOR1A with DYT/PARK-GCH1-associated features.

DOI： 10.1016/j.braindev.2021.03.005

PubMed

researchmap

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

<sec><title>Aim</title>Ripple-band epileptic high-frequency oscillations (HFOs) can be recorded by scalp electroencephalography (EEG), and tend to be associated with epileptic spikes. However, there is a concern that the filtration of steep waveforms such as spikes may cause spurious oscillations or “false ripples.” We excluded such possibility from at least some ripples by EEG differentiation, which, in theory, enhances high-frequency signals and does not generate spurious oscillations or ringing.

</sec><sec><title>Methods</title>The subjects were 50 pediatric patients, and ten consecutive spikes during sleep were selected for each patient. Five hundred spike data segments were initially reviewed by two experienced electroencephalographers using consensus to identify the presence or absence of ripples in the ordinary filtered EEG and an associated spectral blob in time-frequency analysis (Session A). These EEG data were subjected to numerical differentiation (the second derivative was denoted as EEG″). The EEG″ trace of each spike data segment was shown to two other electroencephalographers who judged independently whether there were clear ripple oscillations or uncertain ripple oscillations or an absence of oscillations (Session B).

</sec><sec><title>Results</title>In Session A, ripples were identified in 57 spike data segments (Group A-R), but not in the other 443 data segments (Group A-N). In Session B, both reviewers identified clear ripples (strict criterion) in 11 spike data segments, all of which were in Group A-R (<italic>p</italic> &amp;lt; 0.0001 by Fisher’s exact test). When the extended criterion that included clear and/or uncertain ripples was used in Session B, both reviewers identified 25 spike data segments that fulfilled the criterion: 24 of these were in Group A-R (<italic>p</italic> &amp;lt; 0.0001).

</sec><sec><title>Discussion</title>We have demonstrated that real ripples over scalp spikes exist in a certain proportion of patients. Ripples that were visualized consistently using both ordinary filters and the EEG″ method should be true, but failure to clarify ripples using the EEG″ method does not mean that true ripples are absent.

</sec><sec><title>Conclusion</title>The numerical differentiation of EEG data provides convincing evidence that HFOs were detected in terms of the presence of such unusually fast oscillations over the scalp and the importance of this electrophysiological phenomenon.

</sec>

DOI： 10.3389/fnhum.2021.696882

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Physiological gamma and ripple activities may be linked to neurocognitive functions. This study investigated the relationship between development and non-epileptic, probably physiological, fast (40-200 Hz) oscillations (FOs) including gamma (40 - 80 Hz) and ripple (80 - 200 Hz) oscillations in scalp EEG in children with neurodevelopmental disorders. METHODS: Participants were 124 children with autism spectrum disorder (ASD) and/or attention deficit/hyperactivity disorder (ADHD). Gamma and ripple oscillations were explored from 60-second-long sleep EEG data in each subject using a semi-automatic detection tool supplemented with visual confirmation and time-frequency analysis. RESULTS: Gamma and ripple oscillations were detected in 25 (20.2%) and 22 (17.7%) children, respectively. The observation of one or more occurrence(s) of ripple oscillations, but not gamma oscillations, was significantly related to lower age at EEG recording (odds ratio, OR: 0.727 [95% confidence interval, CI: 0.568-0.929]), higher intelligence/developmental quotient (OR: 1.041, 95% CI: 1.002-1.082), and lack of a diagnosis with ADHD (OR: 0.191, 95% CI: 0.039 - 0.937) according to a binominal logistic regression analysis that included diagnosis with ASD, sex, history of perinatal complications, history of febrile seizures, and use of a sedative agent for the EEG recording as the other non-significant parameters. Diagnostic group was not related to frequency or power of spectral peaks of FOs. CONCLUSION: The production of non-epileptic scalp ripples was confirmed to be associated with brain development and function/dysfunction in childhood. Further investigation is necessary to interpret all of the information on higher brain functions that may be embedded in scalp FOs.

DOI： 10.1016/j.braindev.2021.05.004

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English  

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disorder caused by mutations in either TSC1 on chromosome 16 or TSC2 on chromosome 9, clinically characterized mainly by facial angiofibroma, epilepsy, and intellectual disability. Cortical dysplasias, subependymal nodules, and subependymal giant cell astrocytoma are characteristic central nervous system lesions among 11 major features in the current clinical diagnostic criteria for TSC. We encountered an unusual case of genetically confirmed TSC1 presenting with symptomatic West syndrome due to an isolated cortical dysplasia in the left occipital lobe of a six-month-old male infant who did not meet the clinical diagnostic criteria for TSC. The patient underwent left occipital lesionectomy at age 11 months and has been seizure-free for nearly six years since then. Histological examination of the resection specimen revealed cortical neuronal dyslamination with abundant dysmorphic neurons and ballooned cells, consistent with focal cortical dysplasia (FCD) type IIb. However, the lesion was also accompanied by unusual features, including marked calcifications, dense fibrillary gliosis containing abundant Rosenthal fibers, CD34-positive glial cells with abundant long processes confined to the dysplastic cortex, and multiple nodular lesions occupying the underlying white matter, consisting exclusively of ballooned cell and/or balloon-like astrocytes with focal calcifications. Genetic testing for TSC1 and TSC2 using the patient's peripheral blood revealed a germline heterozygous mutation in exon 7 (NM_000368.5: c.526dupT, p.Tyr176fs) in TSC1. Isolated FCD with unusual features such as calcification, dense fibrillary gliosis, Rosenthal fibers and/or subependymal nodule-like lesions in the white matter may indicate the possibility of a cortical tuber even without a clinical diagnosis of TSC. Identification of such histopathological findings has significant implications for early and accurate diagnosis and treatment of TSC, and is likely to serve as an important supplementary feature for the current clinical diagnostic criteria for TSC.

DOI： 10.1111/neup.12700

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Hypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET®2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph®) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP.

DOI： 10.1016/j.ymgmr.2020.100643

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Epilepsy associated with tuberous sclerosis complex (TSC) has very complex clinical characteristics. Scalp electroencephalogram (EEG) fast (40-200 Hz) oscillations (FOs) were recently suggested to indicate epilepsy severity. Epileptic FOs may undergo age-dependent longitudinal change in individual patients, however, and the typical pattern of such change is not yet fully clarified. We therefore investigated the age-related correspondence between clinical courses and FOs in pediatric patients with TSC-associated epilepsy. SUBJECTS AND METHODS: FOs were semi-automatically detected from scalp sleep EEG data recorded from 23 children (15 boys, 8 girls; initial data obtained at <10 years of age) with TSC-associated epilepsy. RESULTS: The number of FOs per patient that were associated with spikes was significantly greater than that of FOs unassociated with spikes (median 145 and 5, respectively; p = 0.0001 by the Wilcoxon signed-rank test). In the eight patients who had West syndrome (WS) in infancy, FOs associated with spikes were abundant during the WS period prior to adrenocorticotropic hormone therapy, with significantly greater numbers of FOs compared to the post-WS period (median 242 and 0, respectively; p = 0.0078). As there was no such time-dependent difference regarding FOs unassociated with spikes, FOs associated with spikes were identified as epileptic. The detected FOs included both gamma and ripple oscillations with no consistent age-dependent shifts in dominant frequency. There were no apparent age-related changes in FO duration. CONCLUSIONS: Epileptic scalp FOs are confirmed to correspond to severity of epileptic encephalopathy, particularly in WS, even during the long-term evolutional courses of TSC-associated epilepsy.

DOI： 10.1016/j.braindev.2020.06.001

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Epilepsy Society  

DOI： 10.3805/JJES.38.36

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The detection of epileptic seizures from scalp electroencephalogram (EEG) signals can facilitate early diagnosis and treatment. Previous studies suggested that the Gaussianity of EEG distributions changes depending on the presence or absence of seizures; however, no general EEG signal models can explain such changes in distributions within a unified scheme. METHODS: This paper describes the formulation of a stochastic EEG model based on a multivariate scale mixture distribution that can represent changes in non-Gaussianity caused by stochastic fluctuations in EEG. In addition, we propose an EEG analysis method by combining the model with a filter bank and introduce a feature representing the non-Gaussianity latent in each EEG frequency band. RESULTS: We applied the proposed method to multichannel EEG data from twenty patients with focal epilepsy. The results showed a significant increase in the proposed feature during epileptic seizures, particularly in the high-frequency band. The feature calculated in the high-frequency band allowed highly accurate classification of seizure and non-seizure segments [area under the receiver operating characteristic curve (AUC) = 0.881] using only a simple threshold. CONCLUSION: This paper proposed a multivariate scale mixture distribution-based stochastic EEG model capable of representing non-Gaussianity associated with epileptic seizures.Experiments using simulated and real EEG data demonstrated the validity of the model and its applicability to epileptic seizure detection. SIGNIFICANCE: The stochastic fluctuations of EEG quantified by the proposed model can help detect epileptic seizures with high accuracy.

DOI： 10.1109/TBME.2020.3006246

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01742&link_issn=&doc_id=20200715050005&doc_link_id=10.3805%2Fjjes.38.36&url=https%3A%2F%2Fdoi.org%2F10.3805%2Fjjes.38.36&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD. METHODS: We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection. RESULTS: The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS. CONCLUSIONS: Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation.

DOI： 10.1016/j.braindev.2020.02.002

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.3298-19

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

<jats:title>Abstract</jats:title>
<jats:p>Pyridoxine-dependent epilepsy (PDE) is a rare autosomal-recessive disorder typically presenting with neonatal seizures and is sometimes difficult to diagnose, because the clinical features mimic those of birth asphyxia. A Japanese newborn boy presented with pulmonary haemorrhage and convulsions on the day of birth. Brain computed tomography showed diffuse, but mild, low-density cerebral white matter and a thin subdural hematoma in the posterior fossa. He did not have thrombocytopenia or coagulopathy. His respiratory status improved with conservative treatment, but his convulsions were persistent even after prescription of several antiepileptic drugs. His serum and cerebrospinal fluid showed decreased vitamin B6 vitamers and increased upstream metabolites of α-aminoadipic semialdehyde dehydrogenase, strongly suggesting a diagnosis of PDE; the epileptic spasms ceased after administration of intravenous pyridoxal phosphate hydrate. Gene analysis revealed novel compound heterozygous mutations in ALDH7A1 that included NM_001182.4:[c.1196G &amp;gt; T] and [c.1200 + 1G &amp;gt; A]. Atypical birth asphyxia with persistent neonatal seizure should prompt vitamin B6/metabolite screening.</jats:p>

DOI： 10.1093/omcr/omaa008

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

To characterize metabolic profiles within the central nervous system in epilepsy, we performed gas chromatography-tandem mass spectrometry (GC-MS/MS)-based metabolome analysis of the cerebrospinal fluid (CSF) in pediatric patients with and without epilepsy. The CSF samples obtained from 64 patients were analyzed by GC-MS/MS. Multivariate analyses were performed for two age groups, 0-5 years of age and 6-17 years of age, to elucidate the effects of epilepsy and antiepileptic drugs on the metabolites. In patients aged 0-5 years (22 patients with epilepsy, 13 without epilepsy), epilepsy patients had reduced 2-ketoglutaric acid and elevated pyridoxamine and tyrosine. In patients aged 6-17 years (12 with epilepsy, 17 without epilepsy), epilepsy patients had reduced 1,5-anhydroglucitol. Valproic acid was associated with elevated 2-aminobutyric acid, 2-ketoisocaproic acid, 4-hydroxyproline, acetylglycine, methionine, N-acetylserine, and serine. Reduced energy metabolism and alteration of vitamin B6 metabolism may play a role in epilepsy in young children. The roles of 1,5-anhydroglucitol in epilepsy in older children and in levetiracetam and zonisamide treatment remain to be explained. Valproic acid influenced the levels of amino acids and related metabolites involved in the metabolism of serine, methionine, and leucine.

DOI： 10.18926/AMO/57955

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high-risk cases with renal calcified lesions are yet to be clarified. METHODS: In this study, 43 patients with West syndrome ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography. RESULTS: After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the 7 patients who underwent abdominal CT, ECs or hematuria were found only those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions. CONCLUSIONS: The risk of renal calcified lesions increases after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy.

DOI： 10.1111/ped.14158

PubMed

researchmap

Language：English  

Hypophosphatasia (HPP) is a rare skeletal disorder caused by loss-of-function mutations in Alkaline Phosphatase, Biomineralization associated (ALPL) gene that encodes tissue-nonspecific alkaline phosphatase. Odontohypophosphatasia (odonto-HPP), a mild form of HPP, is characterized only by oral manifestations including premature exfoliation of deciduous teeth. Enzyme replacement therapy (ERT) is effective in severe HPP cases; however, information about its efficacy for odonto-HPP is limited. A 2-yr-old girl was referred to our hospital for mobility of her deciduous teeth with low serum alkaline phosphatase (ALP) level of 253 U/L (reference range: 410-1,150 U/L) and high urine phosphoethanolamine level of 1,419.9 µmol/g·Cre (7-70 µmol/g·Cre). She had no history of bone fractures; however, several members of her family had low serum ALP levels with a history of pathological fractures. She had a novel heterozygous missense mutation (c.1183A>T, p.Ile395Phe) in ALPL, and therefore, was diagnosed with odonto-HPP. After she was provided ERT to prevent premature exfoliation, no tooth mobility was observed. However, two deciduous teeth exfoliated two months after starting ERT, which was possibly triggered by a bout of common cold. Starting ERT following tooth mobility might be relatively late. Previous studies on experimental mice showed that starting ERT at birth may be effective in preventing premature exfoliation of deciduous teeth.

DOI： 10.1297/cpe.29.115

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP. Methods: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent. Results: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant. Discussion: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function.

DOI： 10.1016/j.ymgmr.2019.100515

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recently, many genes related to neurodevelopmental disorders have been identified by high-throughput genomic analysis; however, a comprehensive understanding of the mechanism underlying neurodevelopmental disorders remains to be established. To further understand these underlying mechanisms, we performed a comprehensive genomic analysis of patients with undiagnosed neurodevelopmental disorders. METHODS: Genomic analysis using next-generation sequencing with a targeted panel was performed for a total of 133 Japanese patients (male/female, 81/52) with previously undiagnosed neurodevelopmental disorders, including developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy. Genomic copy numbers were also analyzed using the eXome Hidden Markov Model (XHMM). RESULTS: Thirty-nine patients (29.3%) exhibited pathogenic or likely pathogenic findings with single-gene variants or chromosomal aberrations. Among them, 20 patients were presented here. Pathogenic or likely pathogenic variants were identified in 18 genes, including ACTG1, CACNA1A, CHD2, CDKL5, DNMT3A, EHMT1, GABRB3, GABRG2, GRIN2B, KCNQ3, KDM5C, MED13L, SCN2A, SHANK3, SMARCA2, STXBP1, SYNGAP1, and TBL1XR1. CONCLUSION: A diagnostic yield of 29.3% in this study was nearly the same as that previously reported from other countries. Thus, we suggest that there is no difference in genomic backgrounds in Japanese patients with undiagnosed neurodevelopmental disabilities. Although most of the patients possessed de novo variants, one of the patients showed an X-linked inheritance pattern. As X-linked recessive disorders exhibit the possibility of recurrent occurrence in the family, comprehensive molecular diagnosis is important for genetic counseling.

DOI： 10.1016/j.braindev.2019.05.007

PubMed

researchmap

DOI： 10.1016/j.clinph.2019.08.001

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000502568

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Hypophosphatasia (HPP) is a rare disorder caused by low serum tissue non-specific alkaline phosphatase (ALP) activity due to hypomorphic mutations in the ALPL gene. HPP is characterized by defective bone mineralization. It frequently accompanies pyridoxine-responsive seizures. Because alkaline phosphatase change pyridoxal 5' phosphate (PLP) into pyridoxal (PL), which can cross the blood brain barrier and regulates inhibitory neurotransmitter gamma-aminobutyric acid. The female patient was born at a gestational age of 37 weeks 2 days. She presented severe respiratory disorder due to extreme thoracic hypoplasia. With the extremely low serum ALP value (14 IU/L), she was clinically diagnosed as HPP. The diagnosis was confirmed with genetic testing. On day1, the subclinical seizures were detected by aEEG. Together with enzyme replacement therapy by asfotase alfa, pyridoxine hydrochloride was administered, then the seizures were rapidly controlled. While confirming that there was no seizure by aEEG monitoring, pyridoxine hydrochloride was gradually discontinued after 1 month. Before administration of pyridoxine hydrochloride, PL was extremely low (4.7 nM) and PLP was increased (1083 nM). After the withdrawal, PL was increased to 84.9 nM only by enzyme replacement. Monitoring with aEEG enabled early intervention for pyridoxine responsive seizures. Confirming increased serum PL concentration is a prudent step in determining when to reduce or discontinue pyridoxine hydrochloride during enzyme replacement therapy.

DOI： 10.1016/j.braindev.2019.03.015

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.braindev.2019.07.006

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Dihydropyrimidinase deficiency is a rare autosomal recessive disease affecting the second step of pyrimidine degradation. It is caused by mutations in the DPYS gene. Only approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. We report a case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant elevations of dihydrouracil and dihydrothymine, which were subsequently confirmed by a quantitative analysis using liquid chromatography-tandem mass spectrometry. Genetic testing of the DPYS gene revealed two mutations: a novel mutation (c.175G > T) and a previously reported mutation (c.1469G > A). Dihydropyrimidinase deficiency is probably underdiagnosed, considering its wide phenotypical variability, nonspecific neurological presentations, and an estimated prevalence of 2/20,000. As severe 5-fluorouracil-associated toxicity has been reported in patients and carriers of congenital pyrimidine metabolic disorders, urinary pyrimidine analysis should be considered for those who will undergo 5-fluorouracil treatment.

DOI： 10.1016/j.braindev.2018.10.005

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3805/eands.10.114

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

DOI： 10.1016/j.braindev.2018.01.004

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Inc.  

DOI： 10.1111/epi.13995

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Hypophosphatasia (HPP) is a metabolic bone disease characterized by failure of bone calcification and vitamin B6 dependent seizures. It is caused by loss-of-function mutations in the ALPL gene. A newborn girl required respiratory support by nasal-directional positive airway pressure at birth, and pyridoxine hydrochloride administration for vitamin B6-dependent seizures observed from day two. Umbilical cord blood showed low alkaline phosphatase (ALP) activity and high pyridoxal phosphate levels. Radiographs showed severe rickets-like appearance of the bones. Genetic analysis of the ALPL gene revealed compound heterozygous mutations, c.1559delT/p.Ser188Pro. We diagnosed her with perinatal severe HPP, and started the patient on asfotase alfa from day six. Following enzyme replacement therapy (ERT), skeletal mineralization and respiratory insufficiency improved with no remarkable side-effects. Crying vital capacity (CVC) was used to evaluate respiratory status, which continuously improved from 13.3 mL/kg (day 22) to 20.6 mL/kg (day 113). Since no seizures occurred, pyridoxine hydrochloride was tapered off at one year of age. Strategies to manage perinatal severe HPP cases following ERT have not been established till date. A review of the literature shows that CVC may be a good indicator for weaning from ventilatory support. In addition, ERT will most likely enable withdrawal of pyridoxine treatment.

DOI： 10.1297/cpe.27.179

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

DOI： 10.1016/j.braindev.2018.05.014

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.cca.2017.07.032

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2017.03.031

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We investigated the relationship between the scalp distribution of fast (40-150 Hz) oscillations (FOs) and epileptogenic lesions in West syndrome (WS) and related disorders. Subjects were 9 pediatric patients with surgically confirmed structural epileptogenic pathology (age at initial electroencephalogram [EEG] recording: mean 7.1 months, range 1-22 months). The diagnosis was WS in 7 patients, Ohtahara syndrome in 1, and a transitional state from Ohtahara syndrome to WS in the other. In the scalp EEG data of these patients, we conservatively detected FOs, and then examined the distribution of FOs. In five patients, the scalp distribution of FOs was consistent and concordant with the lateralization of cerebral pathology. In another patient, FOs were consistently dominant over the healthy cerebral hemisphere, and the EEG was relatively low in amplitude over the pathological atrophic hemisphere. In the remaining 3 patients, the dominance of FOs was inconsistent and, in 2 of these patients, the epileptogenic hemisphere was reduced in volume, which may result from atrophy or hypoplasia. The correspondence between the scalp distribution of FOs and the epileptogenic lesion should be studied, taking the type of lesion into account. The factors affecting scalp FOs remain to be elucidated.

DOI： 10.1002/epi4.12043

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.cca.2016.12.027

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2016.09.011

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.cca.2016.12.005

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2016.08.001

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Society of Child Neurology  

<p>  Objective: Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by the formation of hamartoma in multiple organ systems of the body. However, without a well-established cooperative system involving related departments, some organ lesions might be overlooked until symptoms appear or even until the disorder progresses. Therefore, the purpose of this study is to investigate the current status of follow-ups in the TSC patients in the Department of Child Neurology at Okayama University Medical Hospital. Methods: We performed a retrospective chart review of 38 patients with TSC who visited our hospital at least twice between January 2005 and December 2014. Patients were between 3 years and 48 years of age at their latest visit. We divided the patients into a child group and an adult group, and investigated the patients' follow-up data while focusing on the various multiorgan systems. Results: The follow-ups were well conducted in the child group in terms of every organ. In the adult group, neuroimaging tests were unsatisfactorily performed. The kidney has not been examined in seven patients more than five years even though these patients all had kidney lesions. The lung was not been examined in 7 out of 14 female patients over 18 years of age who are most at risk for lymphangioleiomyomatosis (LAM). In 12 out of 18 child patients, echocardiograms were performed every few years, while electrocardiograms to assess underlying conduction defects were rarely performed in either age group. Conclusions: In Europe, guidelines for the management of TSC have been well established. However, in our hospital, the multiorgan system follow-up is not satisfactorily performed especially in adult patients. We decided the establishment of a TSC board in our hospital for the management of this multiorgan disorder.</p>

DOI： 10.11251/ojjscn.49.5

PubMed

CiNii Article

researchmap

Language：English  

DOI： 10.18926/AMO/55201

Web of Science

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/epi4.12014

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2016.05.005

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2016.09.007

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2016.03.008

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.1684/epd.2016.0839

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.cca.2016.06.032

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.1016/j.parkreldis.2016.04.021

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2015.05.012

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1515/cclm-2015-0208

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2014.12.005

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ejmg.2015.05.006

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2014.08.010

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.pediatrneurol.2015.01.014

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2014.08.006

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ana.24299

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2014.01.013

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Novel PLA2G6 mutations associated with p.Asp283Asn and a unique intragenic deletion of exons 4 and 5 due to non-allelic homologous recombination were identified in a Japanese female patient with typical infantile neuroaxonal dystrophy. The patient showed progressive tetraplegia beginning at 9 months. An electroencephalogram showed a diffuse increase in fast waves, and brain magnetic resonance imaging showed progressive brain atrophy and T2 hypointensity in the globus pallidus.

DOI： 10.1038/hgv.2015.48

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/epi.12761

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2013.11.011

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1212/WNL.0000000000000102

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.expneurol.2013.10.019

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2012.12.001

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis resulting in cerebral creatine depletion. We present a 38-year-old patient, the first Japanese case of GAMT deficiency. Developmental delay started after a few months of age with a marked delay in language, which resulted in severe intellectual deficit. She showed hyperactivity and trichotillomania from childhood. Epileptic seizures appeared at 18 months and she had multiple types of seizures including epileptic spasms, brief tonic seizures, atypical absences, complex partial seizures with secondary generalization, and "drop" seizures. They have been refractory to multiple antiepileptic drugs. Although there have been no involuntary movements, magnetic resonance imaging revealed T2 hyperintense lesions in bilateral globus pallidi. Motor regression started around 30 years of age and the patient is now able to walk for only short periods. Very low serum creatinine levels measured by enzymatic method raised a suspicion of GAMT deficiency, which was confirmed by proton magnetic resonance spectroscopy and urinary guanidinoacetate assay. GAMT gene analysis revealed that the patient is a compound heterozygote of c.578A>G, p.Gln193Arg and splice site mutation, c.391G>C, p.Gly131Arg, neither of which have been reported in the literature. We also identified two aberrant splice products from the patient's cDNA analysis. The patient was recently started on supplementation of high-dose creatine and ornithine, the effects of which are currently under evaluation. Although rare, patients with developmental delay, epilepsy, behavioral problems, and movement disorders should be vigorously screened for GAMT deficiency, as it is a treatable disorder.

DOI： 10.1007/8904_2013_245

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/jn.00034.2013

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2012.12.012

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2012.06.006

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0039326

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2011.12.015

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2011.03.009

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2011.05.026

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2011.08.003

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2011.03198.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2011.03199.x

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2011.03068.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2011.02.006

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.1177/0883073810378536

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2010.02776.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/hbm.20963

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2009.07.006

Web of Science

researchmap

Language：Japanese  

PubMed

CiNii Article

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2010177522

Language：English  

DOI： 10.1016/j.braindev.2009.10.003

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2009.7.PEDS09198

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2007.12.014

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2007.12.007

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2007.00923.x

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1528-1167.2006.00823.x

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.1111/j.1528-1167.2006.00843_5.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2006.02.003

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2005.11.017

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinph.2005.08.029

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.pediatrneurol.2004.05.006

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.0013-9580.2004.45703.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0387-7604(03)00101-3

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.0013-9580.2004.458004.x

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S1388-2457(02)00047-0

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S1388-2457(02)00046-9

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/S0531-5131(01)00713-0

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1442-200X.1998.tb02005.x

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

researchmap

Total pages：xvi, 253p   Language：Japanese

CiNii Books

researchmap

Total pages：178  

ASIN

researchmap

Total pages：xix, 97p   Language：Japanese

CiNii Books

researchmap

Total pages：141p   Language：Japanese

CiNii Books

researchmap

Total pages：xvi, 362p   Language：Japanese

CiNii Books

researchmap

Total pages：xvi, 259p   Language：Japanese

CiNii Books

researchmap

Total pages：xvi, 671p   Language：Japanese

CiNii Books

researchmap

Total pages：268p   Language：Japanese

CiNii Books

researchmap

Language：Japanese   Publisher：日本遺伝カウンセリング学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：English   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(株)日本小児医事出版社  

CiNii Article

CiNii Books

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：日本先天代謝異常学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

DOI： 10.11251/ojjscn.49.5

CiNii Article

researchmap

Language：Japanese   Publisher：Japanese Society of Clinical Neurophysiology  

&lt;p&gt;High-frequency oscillations (HFOs) are defined as electroencephalographic activity at frequencies over 80 Hz. To record HFOs, a sampling frequency at or above 2 kHz and anti-alias filtering at or above 600 Hz is recommended. HFOs can be recorded using clinical macroelectrodes. Visual identification of HFOs can be achieved by high-pass filtering, increasing sensitivity, and temporally expanding the electroencephalogram (EEG). Interictal HFOs in intracranial EEGs suggest the localization of the seizure onset zone and epileptogenic zone. Ictal-onset HFOs in intracranial EEGs may be helpful in improving seizure outcome after epilepsy surgery. Epileptic encephalopathies in children show many interictal HFOs in scalp EEGs, and these HFOs may contribute to the development of cognitive deficits in this condition. Clues for differentiating pathological HFOs from physiological HFOs include the presence or absence of accompanying spikes, a different coupling pattern with slow waves, and different suppression patterns during rapid-eye-movement sleep.&lt;/p&gt;

DOI： 10.11422/jscn.45.525

CiNii Article

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：日本先天代謝異常学会  

researchmap

Language：Japanese   Publisher：日本先天代謝異常学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(株)中外医学社  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：日本先天代謝異常学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：日本脳循環代謝学会  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J02631&link_issn=&doc_id=20150928450026&doc_link_id=10.16977%2Fcbfm.26.2_163&url=https%3A%2F%2Fdoi.org%2F10.16977%2Fcbfm.26.2_163&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：一般社団法人 日本てんかん学会  

The amount of information exists in the scalp and intracranial EEG. It is a hard work to find out the suitable information for out aims, especially the epileptogenic focus in the focal onset epilepsy. Yet, there are some specific points guiding to review EEG regarding the epileptogenic zone or hemisphere regarding the resective surgery. This paper introduces six topics consisting of 1), ECG like rhythmic spike and waves of focal cortical dysplasia (FCD); 2), lateralizing sign of generalized paroxysmal fast activity (GPFA); 3), lateralized epileptogenic spikes during REM sleep; 4), ECG change before and after EEG seizure onset indicating laterality in the temporal lobe epilepsy; 5), EMG change indicating laterality; 6), preictal change between high frequency oscillation in the spike and post-spike slow wave in FCD type II. The six topics can promise the EEG readers to lead the epileptogenic zone away from the EEG labyrinth.

DOI： 10.3805/jjes.33.126

CiNii Article

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：Japanese Society of Clinical Neurophysiology  

&lt;p&gt;High-frequency oscillations (HFOs) are defined as electroencephalographic activity at a frequency above 80 Hz. Activity of this type has drawn attention as a surrogate marker of the epileptogenic zone, and its use as such may help improve seizure outcome after epilepsy surgery. The methods by which HFOs are recorded and interpreted varies significantly among epilepsy centers, however. For recording HFOs, a sampling frequency at or over 2 kHz and an antialiasing filter at or over 600 Hz should be used. The use of intracranial electrodes with a surface contact area of 0.2 to 5 mm&lt;sup&gt;2&lt;/sup&gt; is recommended. For appropriate display of HFOs using the viewing software by Nihon Kohden Co., the use of a monitor with at least 1,920 pixels in the horizontal direction is recommended. The high-cut filter should be turned off, a time constant of 0.001 to 0.003 s (corresponding to the low-cut filter at 53 to 160 Hz) should be used, the sensitivity should be set to 1 to 5 &amp;mu;V/mm, and the time scale should be set to 0.5 to 1 s/page. Computerized spectral analysis and automated detection of HFOs are also described.&lt;/p&gt;

DOI： 10.11422/jscn.43.499

CiNii Article

researchmap

Language：Japanese   Publisher：The Japanese Society of Cerebral Blood Flow and Metabolism  

In epileptic encephalopathy, epileptic activity itself may contribute to severe cognitive and behavioral impairments, and it is a case in severe epilepsies in infancy and early childhood. Epilepsies caused by cortical dysplasia are intractable and hence surgical treatment is recommended for them during early childhood when brain functional plasticity is still expected. MRI is generally difficult to interpret because of poor contrast in infancy. Therefore positron emission tomography (PET) and single photon emission computed tomography (SPECT) are useful to identify seizure focus, and SISCOM (Subtraction Ictal SPECT CO-registered to MRI) is particularly important. Eight patients with severe epilepsies underwent a hemispherectomy during infancy and early childhood at the Epilepsy Center of Okayama University Hospital. In two patients, MRI showed uncertain abnormalities, and SISCOM and PET disclosed pathological cortical regions, demonstrating the validity of functional neuroimaging techniques related to brain circulation and metabolism in the evaluation of very young candidate patients for epilepsy surgery.

DOI： 10.16977/cbfm.26.2_163

CiNii Article

researchmap

Language：Japanese   Publisher：Japanese Congress of Neurological Surgeons  

DOI： 10.7887/jcns.24.32

Scopus

CiNii Article

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：金原出版  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：(一社)日本医学教育学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：The Japanese Society of Child Neurology  

&amp;emsp;難治てんかん患者を診たら, てんかん診断の再確認と基礎疾患の確認のための精査を行う. 同時に外科治療の可能性も考える. 焦点切除術の適応例では, 発作抑制効果は外科治療の方が高い. 精査が困難な場合, 専門施設への紹介を考慮されたい. まず発作時ビデオ脳波とMRIを行う. MRIは, 微細な病変の見落としを最小限にするため, てんかんに特化した撮影条件を神経放射線科医との協力で作成して用いる. 必要に応じてPET, SPECT, 脳磁図等を行い, 手術適応を決定する. 術後の発達の最終転帰は術前の発達レベルに規定される. 発達レベルが落ちてしまう前に外科治療の可能性を見つけ出すことが, 小児神経科医の重要な役割である.

DOI： 10.11251/ojjscn.45.211

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：(一社)日本てんかん学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本小児科学会  

researchmap

researchmap

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

researchmap

Language：English   Publisher：(一社)日本てんかん学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

DOI： 10.1016/j.eplepsyres.2010.07.018

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：メディカルレビュー社  

CiNii Article

researchmap

Language：Japanese   Publisher：Japan Epilepsy Society  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：メディカルレビュー社  

CiNii Article

researchmap

Language：Japanese   Publisher：永井書店  

CiNii Article

CiNii Books

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：脳と発達  

DOI： 10.11251/ojjscn1969.39.236

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：診断と治療社  

CiNii Article

CiNii Books

researchmap

Language：Japanese  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：Japan Epilepsy Society  

CiNii Article

CiNii Books

researchmap

Language：English   Publisher：日本てんかん学会  

CiNii Article

CiNii Books

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap