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

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

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

DOI： 10.1016/j.seizure.2023.03.014

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Language：Japanese   Publisher：(株)日本臨床社  

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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

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

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Language：English  

Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

DOI： 10.18926/AMO/63742

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

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

BACKGROUND: Infantile apneic seizures (IASs) are unexpected life-threatening events. We aimed to determine the utility of prolonged video-electroencephalography (vEEG) and heart rate variability (HRV) in IAS. METHODS: The study included seven infants with apneic seizures captured by vEEG, percutaneous oxygen saturation (SpO2), and electrocardiography (ECG). Interictal, preictal, and postictal HRV of patients and N2 sleep HRV of 10 age-matched controls were determined. RESULTS: We analyzed seven vEEGs (duration = 17 to 87 hours) of seven patients aged three to 13 months (mean onset age of apneic event = 6.3 months). Fifteen apneic seizures (one to five per infant) were captured. The initial apneic seizure was captured at 7.5 to 76 hours (mean = 36.6 hours) after vEEG initiation. Ictal rhythmic delta/theta/fast waves were seen over temporal (five patients), central (one), and diffuse areas (one). Ictal SpO2 decreased between 1.5% and 90% (mean = 47.9%). Ictal decreased heart rate (HR) (six seizures) and ictal increased HR (14) was detected. Both decreased and increased HR was observed (five). The preictal low-frequency (LF)/high-frequency (HF) ratio was significantly higher than the interictal LF/HF ratio (P = 0.048). Preictal (P = 0.048), and postictal (P = 0.019) root mean square of successive differences (RMSSDs) of patients were lower than the sleep RMSSD of controls. These results indicated dominant sympathetic activity. RMSSD from interictal to preictal periods tended to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.066). The postictal RMSSD showed tendency to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.088). The decreased HR and increased RMSSD suggested not only sympathetic activity but also escalated parasympathetic activity in IAS. CONCLUSIONS: Infants with unexpected apneic events should be monitored with prolonged vEEG, SpO2, and ECG. Abnormal HRV in infants with apneic seizures might indicate additional autonomic dysregulation in IAS.

DOI： 10.1016/j.pediatrneurol.2021.11.007

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

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

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

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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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/wnf.0000000000000443

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Neurosurgery Publishing Group (JNSPG)  

<sec>
<title>OBJECTIVE</title>
Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgical option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes.


</sec>
<sec>
<title>METHODS</title>
The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non–rapid eye movement sleep. The MI of the gamma (30–70 Hz) amplitude and delta (0.5–4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes.


</sec>
<sec>
<title>RESULTS</title>
The median age at first surgery was 2.3 years (range 10 months–9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5–54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 seizure-free patients than in the 6 patients with residual ESs (p &lt; 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p &lt; 0.001).


</sec>
<sec>
<title>CONCLUSIONS</title>
In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.


</sec>

DOI： 10.3171/2020.9.peds20520

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Other Link： https://thejns.org/downloadpdf/journals/j-neurosurg-pediatr/27/5/article-p572.xml

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

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

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

DOI： 10.1016/j.neulet.2020.135211

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

DOI： 10.1016/j.yebeh.2019.106688

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Pediatric Endocrinology  

DOI： 10.1297/cpe.28.155

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

Anti-NMDAR encephalitis is increasingly recognized as one etiology of psychiatric symptoms, but there is not enough evidence on patients with mood disorder. We assayed anti-NR1/NR2B IgG antibodies in serum and/or cerebrospinal fluid of 62 patients initially diagnosed with mood disorder by a cell-based assay. We also investigated the specific patient characteristics and psychotic symptoms. At first admission, the patients showed only psychiatric symptoms without typical neurological signs or abnormal examination findings. Four of the 62 patients had anti-NR1/NR2B IgG antibodies. The anti-NR1/NR2B IgG antibody-positive patients showed more super- or abnormal sensitivity (P = 0.00088), catatonia (P = 0.049), and more conceptual disorganization (P < 0.0001), hostility (P = 0.0010), suspiciousness (P < 0.0001), and less emotional withdrawal (P < 0.0001) and motor retardation (P < 0.0001) on the Brief Psychiatric Rating Scale than the antibody-negative patients. During the clinical course, anti-NR1/NR2B IgG antibody-positive patients showed more catatonia (P = 0.0042) and met Graus's criteria for diagnosis of anti-NMDAR encephalitis, but negative patients did not. Immunotherapy was effective for anti-NR1/NR2B IgG antibody-positive patients, and there was the weak relationship (R² = 0.318) between the anti-NR1/NR2B IgG antibody titer in the cerebrospinal fluid and the Brief Psychiatric Rating Scale score.

DOI： 10.1016/j.euroneuro.2019.07.137

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

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Language：Japanese   Publishing type：Research paper (other academic)   Publisher：(一社)日本小児神経学会  

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

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

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens-Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

DOI： 10.1111/1346-8138.14253

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

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens-Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

DOI： 10.1111/1346-8138.14253

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

OBJECTIVE: We explored fast (40-150 Hz) oscillations (FOs) from the ictal scalp electroencephalogram (EEG) data of myoclonic seizures in pediatric patients to obtain insight into the pathophysiological mechanisms involved in the generation of myoclonic seizures. SUBJECTS AND METHODS: The participants were 21 children (11 boys, 10 girls; age ranging from 5 months to 17 years 2 months) with myoclonic seizures associated with generalized (poly)spike-wave bursts in the ictal EEG data. The patients had heterogeneous etiologies and epilepsy diagnoses. In the ictal data, we detected FOs that clearly showed oscillatory morphology in filtered EEG traces and an outstanding spectral blob in time-frequency analysis. RESULTS: We identified FOs in 61 (88.4%) of all 69 myoclonic seizures. Every patient had at least one myoclonic seizure-associated FO. The observed FOs were embedded in the spike component of (poly)spike-wave discharges, and they had a focal distribution with frontal predominance. They ranged in frequency from 41.0 to 123.0 Hz and involved both the gamma and ripple bands, and their spectral peak frequencies were higher in the group of patients with a genetic background free of apparent fundamental brain pathology than in the group of other patients (p = 0.019). CONCLUSION: FOs were found to represent at least part of the cortical pathophysiological process in the generation of myoclonic seizures that should involve the thalamocortical network system.

DOI： 10.1016/j.braindev.2018.01.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/hmg/ddy052

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

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Georg Thieme Verlag KG  

<title>Abstract</title>Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) is a disorder resulting from shortage of energy in the brain caused by reduced GLUT1 activity. Its common clinical symptoms include seizures, microcephaly, intellectual disability, abnormal ocular movements, ataxia, and dystonia. We report a case of GLUT1DS with unusual symptoms, including periventricular calcification. The patient is a Japanese girl, whose seizures had always evolved into status epilepticus since she was 4 months old. She also had cataracts and horizontal nystagmus. Neuroimaging studies showed periventricular calcification and brain atrophy. Laboratory data revealed pseudohyperkalemia, reticulocyte increase, and hypoglycorrhachia. A mutation of c1306_1308delATC (p.Ile436del) was identified in the SLC2A1 gene, and she was thus diagnosed with GLUT1DS. A case with the identical SLC2A1 gene mutation and similar clinical findings was previously reported by Bawazir et al (2012). The leak of monovalent cations through the red cell membrane causes hemolysis in such patients, and a similar phenomenon may occur at the blood–brain barrier and the lens epithelium. After commencing ketogenic diet therapy, the electroencephalogram (EEG) abnormalities improved markedly and the patient's development advanced. Clinicians should be aware of atypical GLUT1DS.

DOI： 10.1055/s-0037-1603520

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

BACKGROUND: We quantified pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) in paired serum and cerebrospinal fluid (CSF) samples from children and investigated the effect of age on the concentrations and CSF-to-serum ratios of these vitamers. METHODS: Serum and CSF samples prospectively collected from 49 pediatric patients were analyzed. PLP, PL, and PA were measured using high-performance liquid chromatography with fluorescence detection, using pre-column derivatization by semicarbazide. Effects of age on these vitamers, the PLP-to-PL ratio, CSF-to-serum PLP ratio, and CSF-to-serum PL ratio were evaluated using correlation analysis. RESULTS: The PLP, PL, and PA concentrations in the serum and CSF were higher at younger ages, except for CSF PA concentrations that were mostly below the limit of detection (<1.2nmol/l). The PLP-to-PL ratios in the serum and CSF correlated positively with age. The CSF-to-serum PLP ratio and CSF-to-serum PL ratio were independent of age. CONCLUSIONS: Age-related changes in PLP, PL, and PA in serum and in CSF from pediatric patients and CSF-to-serum ratios of PLP and PL demonstrated in this study will provide valuable information for evaluating PLP supply to the central nervous system from the peripheral blood.

DOI： 10.1016/j.cca.2017.07.032

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

DOI： 10.1002/epi4.12043

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

DOI： 10.1016/j.cca.2016.12.027

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

BACKGROUND: We describe a new method for simultaneous measurement of monoamine metabolites (3-O-methyldopa [3-OMD], 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], 5-hydroxyindoleacetic acid [5-HIAA], and homovanillic acid [HVA]) and 5-methyltetrahydrofolate (5-MTHF) and its use on cerebrospinal fluid (CSF) samples from pediatric patients. METHODS: Monoamine metabolites and 5-MTHF were measured by high-performance liquid chromatography with fluorescence detection. CSF samples were prospectively collected from children according to a standardized collection protocol in which the first 1-ml fraction was used for analysis. RESULTS: Monoamine metabolites and 5-MTHF were separated within 10min. They showed linearity from the limit of detection to 1024nmol/l. The limit of quantification of each metabolite was sufficiently low for the CSF sample assay. In 42 CSF samples after excluding cases with possibly altered neurotransmitter profiles, the concentrations of 3-OMD, MHPG, 5-HIAA, HVA, and 5-MTHF showed significant age dependence and their ranges were comparable with the reference values in the literature. The metabolite profiles of aromatic l-amino acid decarboxylase deficiency, Segawa disease, and folate receptor α defect by this method were compatible with those in the literature. CONCLUSIONS: This method is a simple means of measuring CSF monoamine metabolites and 5-MTHF, and is especially useful for laboratories not equipped with electrochemical detectors.

DOI： 10.1016/j.cca.2016.12.005

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

β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation, and it is caused by a mutation in the UPB1 gene. Approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. Non-neurological symptoms have been rarely reported. We describe a case of this disease with developmental delay and dysmorphic features. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant (⩾+4.5 standard deviation after logarithmic transformation) elevations of β-ureidopropionic acid and β-ureidoisobutyric acid, strongly suggesting a diagnosis of β-ureidopropionase deficiency. Subsequent quantitative analysis of pyrimidines by liquid chromatography-tandem mass spectrometry supported this finding. Genetic testing of the UPB1 gene confirmed compound heterozygosity of a novel mutation (c.976C>T) and a previously-reported mutation (c.977G>A) that is common in East Asians. β-Ureidopropionase deficiency is probably underdiagnosed, considering a wide phenotypical variability, non-specific neurological presentations, and an estimated prevalence of 1/5000-6000. Urine metabolomics should be considered for patients with unexplained neurological symptoms.

DOI： 10.1016/j.braindev.2016.08.001

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (&lt;0.1 Hz) to traditional frequency bands (e.g., the approx. 10 Hz alpha rhythm) to high-frequency bands of up to 500 Hz. High-frequency oscillations (HFOs) including ripple and fast ripple oscillations (80-200 Hz and &gt;200/250 Hz, respectively) are particularly of note due to their very close relationship to epileptogenicity, with the possibility that they could function as a surrogate biomarker of epileptogenicity. In contrast, physiological high-frequency activity plays an important role in higher brain functions, and the differentiation between pathological/epileptic and physiological HFOs is a critical issue, especially in epilepsy surgery. HFOs were initially recorded with intracranial electrodes in patients with intractable epilepsy as part of a long-term invasive seizure monitoring study. However, fast oscillations (FOs) in the ripple and gamma bands (40-80 Hz) are now noninvasively detected by scalp EEG and magnetoencephalography, and thus the scope of studies on HFOs/FOs is rapidly expanding.

DOI： 10.18926/AMO/55201

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

DOI： 10.1002/epi4.12014

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

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

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder that affects the degradation of gamma-aminobutyric acid and leads to the accumulation of gamma-hydroxybutyric acid (GHB) in body fluids. Diagnosis of SSADH deficiency is challenging, since the neurological symptoms are non-specific. CASE: The patient is a nine-year-old Japanese boy who presented with developmental delay, autism, epilepsy, and episodic gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the bilateral thalami, globus pallidi, substantia nigra, and dentate nuclei. Urine metabolome analysis revealed elevated GHB, which led to a biochemical diagnosis of SSADH deficiency. Genetic analysis of the ALDH5A1 gene revealed a novel missense mutation c.1586G>A inherited from his father. It also demonstrated three single nucleotide polymorphisms (SNPs) (c.106G>C, c.538C>T, and c.545C>T), all of which were inherited from his mother and are known to reduce SSADH enzyme activity. There were no duplications or deletions in other exons in the patient or his parents. No variants in the upstream, intronic, or downstream regions of the ALDH5A1 gene were found in the patient. Enzymatic assay revealed a marked reduction of SSADH enzyme activity (≈2% of the lower limit of the normal range). CONCLUSION: Although other mechanisms cannot be fully excluded, the clinical manifestation of SSADH deficiency in this patient may be attributed to the combined effect of the mutation and the three enzyme activity-reducing SNPs. Urine metabolome analysis effectively detected his elevated GHB and is thus considered to be a good screening method for this underdiagnosed and potentially manageable metabolic disorder.

DOI： 10.1016/j.braindev.2016.03.008

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Language：English   Publisher：JOHN LIBBEY EUROTEXT LTD  

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features-warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence.
The term "benign" is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research.A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence-free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice.
Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the "unknown cause" classification and strongly suggest a genetic aetiology. The IFE are strongly age-related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age-related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored.
The symposium led to the formation of internationalworking groups under the umbrella of "Luke's Idiopathic Focal Epilepsy Project" to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.

DOI： 10.1684/epd.2016.0839

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

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

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

BACKGROUND: Mutations of the SCN4A gene cause several skeletal muscle channelopathies and overlapping forms of these disorders. However, the variability of the clinical presentation in childhood is confusing and not fully understood among pediatric neurologists. PATIENTS: We found three different mutations (p.V445M, p.I693L, and a novel mutation, p.V1149L) in SCN4A but not in the CLCN1 gene. The patient with p.V445M showed the clinical phenotype of sodium channel myotonia, but her clear symptoms did not appear until 11 years of age. Her younger sister and mother, who have the same mutation, displayed marked intrafamilial phenotypic heterogeneity from mild to severe painful myotonia with persistent weakness. The patient with p.I693L exhibited various symptoms that evolved with age, including apneic episodes, tonic muscular contractions during sleep, fluctuating severe episodic myotonia, and finally episodic paralyses. The patient with the novel p.V1149L mutation exhibited episodic paralyses starting at 3 years of age, and myotonic discharges were detected at 11 years of age for the first time. CONCLUSION: The present cohort reveals the complexity, variability, and overlapping nature of the clinical features of skeletal muscle sodium channelopathies. These are basically treatable disorders, so it is essential to consider genetic testing before the full development of a patient's condition.

DOI： 10.1016/j.pediatrneurol.2015.01.014

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

Purpose: Benign childhood epilepsy with centro-temporal spikes (BECTS) and Panayiotopoulos syndrome (PS) have different pathophysiologies and show different types of seizures, yet they overlap in some important respects. In an attempt to understand the ways in which they differ from each other and overlap each other, we performed a detailed investigation on patients who had both characteristic types of seizure manifestations, namely, sylvian seizures and emetic seizures. Subjects and methods: We recruited consecutive subjects from the EEG database of outpatients who had visited our hospital between 2008 and 2010 and who had been diagnosed with BECTS or PS. As a result, 45 patients with BECTS and 50 patients with PS were selected from the database. Viewing the clinical records of these 95 patients, five patients were selected who had experienced both sylvian seizures and emetic seizures. Next, the clinical features and EEG findings of these five patients were retrospectively observed at the date of investigation: October 1, 2011. Results: We found that all the patients showed rolandic spikes when they had sylvian seizures, and occipital spikes or multifocal spikes when they had emetic seizures. We also report in detail on one patient who showed two different types of ictal EEG patterns: one of which started in the occipital area and the other of which was located in the rolandic area. Conclusion: Based on these findings, we conclude that widespread cortical hyperexcitability that includes the occipital area is necessary to produce the autonomic seizure manifestations seen in PS. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.braindev.2014.01.013

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Child Neurology  

We report a 10-month-oIcI girl who had brief epileptic negative myoclonus during the course of West syndrome. She began to have epileptic spasms in series at the age of 8 months. Video-elcctroencephalograph (EEG) monitoring revealed that she also had brief epileptic negative myoclonus when she was 10 months old. Brief atonia of limbs occurred in isolation or in a cluster during drowsiness or sleep. The ictal EEG exhibited diffuse polyspikes and waves or diffuse high-voltage slow waves that were overlapped by low-voltage fast waves. 3 to 4 hundred milliseconds of silent periods were observed in the bilateral deltoid electromyograms, which correspond to the EEG patterns.
The occurrence of other types of seizures, partial seizures in particular, accompanied by epileptic spasms has been fully investigated. This is the first case report of a patient with West syndrome whose coexisting epileptic negative myoclonus was confirmed by a silent electromyogram pattern.

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

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

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

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

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

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

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

Purpose: To clarify the clinical implications of the preceding positive spikes (PPSs) observed primarily in rolandic spikes, we analyzed PPSs in the rolandic and occipital spikes observed in the electroencephalograms (EEGs) of patients with two types of benign partial epilepsies (benign childhood epilepsy with centro-temporal spikes [BECT] and Panayiotopoulos syndrome [PS]) and febrile seizures (FS). Subjects and methods: We identified patients from our outpatient EEG database that were seen between 2006 and 2008 that had BECT, PS, and FS with rolandic or occipital spikes. We generated an averaged spike for each patient from the rolandic and occipital spikes that were detected using an automatic spike detection and clustering system. We compared the presence rate of the averaged spikes with the PPS among the three groups (BECT vs. PS vs. FS) using sequential mapping. Results: We identified 25 BECT, 18 PS, and 15 FS patients with rolandic spikes. Fifteen BECT and nine PS patients exhibited a PPS in their averaged rolandic spikes, whereas only four FS patients did. Three of these four FS patients later developed afebrile seizures, and one of them was diagnosed as having PS. We analyzed eight PS and six FS patients with occipital spikes. Five PS patients exhibited a PPS in their averaged occipital spikes, whereas only one FS patient did. This FS patient later developed prolonged autonomic febrile seizures. Conclusion: PPSs are observed not only in rolandic spikes associated with BECT that is related strictly to sylvian seizures, but also in rolandic and occipital spikes associated with PS. Although PPSs are rare in such spikes observed in FS, patients with FS and PPSs may have an increased risk of developing afebrile seizures or prolonged autonomic febrile seizures. Further studies are warranted to determine the diagnostic utility of PPSs as a marker of the future development of epilepsy when they are observed in FS patients. (C) 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.braindev.2012.06.006

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

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We observed characteristic involuntary movements in premature babies during early infancy. These movements consisted of asymmetrical irregular banging of the extremities, similar to chorea, ballisms, or jitteriness. We investigated the clinical characteristics and neuroimaging findings of the patients with these peculiar involuntary movements to clarify their pathophysiological mechanisms and to find a treatment. In our sequential follow-up study on 90 premature infants with various pre-and perinatal brain insults, we found various types of cerebellar injuries in 28 patients. In 19 of these, the prominent injuries were observed in the inferior cerebellar hemispheres. These cerebellar injuries were often observed in patients born before the gestational age of 27 weeks. Fourteen of the 28 patients with cerebellar injuries displayed the above-mentioned characteristic involuntary movements. Twelve of these 14 patients with both cerebellar injury and involuntary movements were born before the gestational age of 27 weeks. On the contrary, 10 patients with cerebellar injury bom after the gestational age of 27 weeks did not display these peculiar involuntary movements. It is noteworthy that cerebral injuries were not associated with the occurrence of these involuntary movements. Two patients with asymmetrical cerebellar deformity caused by compression due to a cystic lesion did not show these involuntary movements. The movements appeared around the corrected age of 3 months, and they disturbed the patients' acquisition of sitting ability. Nine patients with these involuntary movements developed severe athetotic cerebral palsy. These movements showed drug resistance, however, benzodiazepines had a partial effect in some patients. Recently, cerebellar injury in premature infants has received a lot of attention. We believe that the peculiar involuntary movements we observed in the present patient group may be caused by a particular type of cerebellar damage specific to premature infants born before 27 weeks of gestational age.

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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

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

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

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

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

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

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

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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

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

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

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Language：Japanese   Publisher：Japanese Congress of Neurological Surgeons  

Intracranial electroencephalography (IEEG) is useful as an evaluation component of resective surgery when the results of noninvasive tests are incongruent in patients with refractory neocortical epilepsy. High-frequency oscillations (HFOs&gt
80 Hz) have recently been recognized as having a strong relationship to the epileptogenic zone, and the complete resection of HFOs has been considered a favorable prognostic indicator for surgical outcome. It is sometimes difficult, however, to comprehend dynamic changes in ictal HFOs recorded via subdural electrodes. We performed surgical treatment on a medically intractable patient diagnosed with occipital lobe epilepsy after analyzing the patient's HFOs with IEEG using the original program. The patient has achieved seizure-free status one year after surgery. Our method of creating a brain surface topographic map of interictal HFOs and a topographic movie of ictal HFOs was useful for easy understanding of seizure onset zone and epileptic HFOs propagation. It may also be helpful for determining the necessary extent of surgical resection to include the epileptogenic zone, thus promoting better postsurgical seizure outcomes.

DOI： 10.7887/jcns.24.32

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

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DOI： 10.11251/ojjscn.44.239

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Event date： 2021.6.24

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Event date： 2021.5.29

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Event date： 2020.11.26 - 2020.11.28

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2020.6.19 - 2020.6.21

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Event date： 2019.12.6 - 2019.12.10

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Event date： 2018.11.8 - 2018.11.10

Presentation type：Poster presentation  

Venue：東京  

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Event date： 2018.10.25 - 2018.10.27

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Event date： 2018.5.31 - 2018.6.2

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Event date： 2018.5.31 - 2018.6.2

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Venue：千葉  

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Event date： 2018.2.19

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Venue：岡山  

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Event date： 2018.2.17

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Event date： 2018.2.10 - 2018.2.11

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Venue：新潟  

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Event date： 2017.7.15

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Event date： 2017.6.15 - 2017.6.17

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Event date： 2016.12.4

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Event date： 2016.10.27 - 2016.10.29

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Event date： 2016.7.16

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