研究者詳細 - 秋山　倫之

A case of vitamin B6-responsive West syndrome caused by severe traumatic brain injury 査読国際誌

Inoue T, Akiyama T, Hanaoka Y, Oka M, Kobayashi K

Epilepsy & Seizure 10 ( 1 ) 114 - 119 2019年2月

Detection of fast (40-150 Hz) oscillations from the ictal scalp EEG data of myoclonic seizures in pediatric patients. 査読

Kobayashi K, Ohuchi Y, Shibata T, Hanaoka Y, Akiyama M, Oka M, Endoh F, Akiyama T

Brain & development 40 ( 5 ) 397 - 405 2018年5月

Strong coupling between slow oscillations and wide fast ripples in children with epileptic spasms: Investigation of modulation index and occurrence rate 査読

Yasushi Iimura, Kevin Jones, Lynne Takada, Itsuki Shimizu, Misaki Koyama, Kyoko Hattori, Yushi Okazawa, Yutaka Nonoda, Eishi Asano, Tomoyuki Akiyama, Cristina Go, Ayako Ochi, O. Carter Snead, Elizabeth J. Donner, James T. Rutka, James M. Drake, Hiroshi Otsubo

Epilepsia 59 ( 3 ) 544 - 554 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing Inc.

Objective: Epileptic spasms (ES) often become drug-resistant. To reveal the electrophysiological difference between children with ES (ES+) and without ES (ES−), we compared the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI) of coupling between slow and fast oscillations. In ES+, we hypothesized that (1) pathological HFOs are more widely distributed and (2) slow oscillations show stronger coupling with pathological HFOs than in ES−. Methods: We retrospectively reviewed 24 children with drug-resistant multilobar onset epilepsy, who underwent intracranial video electroencephalography prior to multilobar resections. We measured the OR of HFOs and determined the electrodes with a high rate of HFOs by cluster analysis. We calculated MI, which reflects the degree of coupling between HFO (ripple/fast ripple [FR]) amplitude and 5 different frequency bands of delta and theta activities (0.5-1 Hz, 1-2 Hz, 2-3 Hz, 3-4 Hz, 4-8 Hz). Results: In ES+ (n = 10), the OR( FR s), the number of electrodes with high-rate FRs, and the MI( FR s &amp
3-4 Hz) in all electrodes were significantly higher than in ES− (n = 14). In both the ES+ and ES− groups, MI(ripples/ FR s &amp
3-4 Hz) was the highest among the 5 frequency bands. Within the good seizure outcome group, the OR( FR s) and the MI( FR s &amp
3-4 Hz) in the resected area in ES+ were significantly higher than in ES− (OR[FR s], P =.04
MI[ FR s &amp
3-4 Hz], P =.04). Significance: In ES+, the larger number of high-rate FR electrodes indicates more widespread epileptogenicity than in ES−. High values of OR( FR s) and MI( FR s &amp
3-4 Hz) in ES+ compared to ES− are a signature of the severity of epileptogenicity. We proved that ES+ children who achieved seizure freedom following multilobar resections exhibited strong coupling between slow oscillations and FRs.

DOI： 10.1111/epi.13995

Scopus

A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: clinical course and review of the literature. 査読

Oyachi M, Harada D, Sakamoto N, Ueyama K, Kondo K, Kishimoto K, Izui M, Nagamatsu Y, Kashiwagi H, Yamamuro M, Tamura M, Kikuchi S, Akiyama T, Michigami T, Seino Y, Namba N

Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 27 ( 3 ) 179 - 186 2018年

Differential diagnosis of nonepileptic twilight state with convulsive manifestations after febrile seizures 査読

Hiroyuki Miyahara, Tomoyuki Akiyama, Kenji Waki, Yoshio Arakaki

Brain and Development 40 ( 9 ) 781 - 785 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier B.V.

Background: Nonepileptic twilight state with convulsive manifestations (NETC) is a nonepileptic state following a febrile seizure (FS), which may be misdiagnosed as a prolonged seizure and result in overtreatment. We aimed to describe clinical manifestations of NETC and to determine characteristics that are helpful to distinguish NETC from other pathological conditions. Methods: We conducted a retrospective chart review from January 2010 to December 2016 and selected the patients who presented with symptoms resembling status epilepticus with fever and a confirmed diagnosis using an electroencephalogram (EEG). We compared the NETC clinical features and venous blood gas analysis results with those of other conditions that mimic NETC. We also compared the characteristics of NETC with past reports. Results: Our NETC patients presented with short durations of the preceding generalized convulsions followed by tonic posturing, closed eyes, no cyanosis, responsiveness to painful stimulation, and no accumulation of CO2 in the venous blood gas. Most of these characteristics were consistent with past reports. Prolonged FS or acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) showed several of these features, but all the characteristics were not consistent with our study. Conclusions: Prolonged FS and AESD need to be differentiated from NETC, and close clinical observation makes it possible to partially distinguish NETC from the other conditions. EEG is recommended for patients with symptoms that are inconsistent with these features.

DOI： 10.1016/j.braindev.2018.05.014

Scopus

Pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid in the paired serum and cerebrospinal fluid of children 査読

Tomoyuki Akiyama, Yumiko Hayashi, Yoshiyuki Hanaoka, Takashi Shibata, Mari Akiyama, Hiroki Tsuchiya, Tokito Yamaguchi, Katsuhiro Kobayashi

CLINICA CHIMICA ACTA 472 118 - 122 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE 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 (< 1.2 nmo1/1). 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-toserum 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

Epileptogenic high-frequency oscillations skip the motor area in children with multilobar drug-resistant epilepsy 査読

Yasushi Iimura, Kevin Jones, Kyoko Hattori, Yushi Okazawa, Atsuko Noda, Kana Hoashi, Yutaka Nonoda, Eishi Asano, Tomoyuki Akiyama, Cristina Go, Ayako Ochi, O. Carter Snead, Elizabeth J. Donner, James T. Rutka, James M. Drake, Hiroshi Otsubo

CLINICAL NEUROPHYSIOLOGY 128 ( 7 ) 1197 - 1205 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

Objective: Subtotal hemispherectomy involves the resection of multiple lobes in children with drug-resistant epilepsy, skipping the motor area (MA). We determined epileptogenicity using the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI), demonstrating strength of coupling between HFO and slow wave. We hypothesized that epileptogenicity increased over the multiple lobes but skipped the MA.
Methods: We analyzed 23 children (14 subtotal hemispherectomy; 9 multilobar resections). Scalp video-EEG and magnetoencephalography were performed before surgery. We analyzed the OR(HFO) and MI(5 (phases= 0.5-8) (Hz)) on electrodes of total area, resection areas, and MA. We compared the data between good [International League Against Epilepsy (ILAE) class I-II] and poor (III-VI) seizure outcome groups.
Results: ILAE class Ia outcome was achieved in 18 children. Among the MI(5 phases) in the resection areas, MI(3-4 (Hz)) was the highest. The OR(HFO) and MI(3-4 (Hz)) in both total area and resection areas were significantly higher in the good seizure outcome group than in the poor outcome group. The OR(HFO) and MI(3-4 (Hz)) in resection areas were significantly higher than in the MA.
Conclusions: Our patients with multilobar drug-resistant epilepsy showed evidence of multifocal epileptogenicity that specifically skipped the MA. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.clinph.2017.03.031

Complex observation of scalp fast (40-150 Hz) oscillations in West syndrome and related disorders with structural brain pathology. 査読国際誌

Kobayashi K, Endoh F, Agari T, Akiyama T, Akiyama M, Hayashi Y, Shibata T, Hanaoka Y, Oka M, Yoshinaga H, Date I

Epilepsia open 2 ( 2 ) 260 - 266 2017年6月

Measurement of pyridoxal 5 '-phosphate, pyridoxal, and 4-pyridoxic acid in the cerebrospinal fluid of children 査読

Tomoyuki Akiyama, Mari Akiyama, Yumiko Hayashi, Takashi Shibata, Yoshiyuki Hanaoka, Soichiro Toda, Katsumi Imai, Shin-ichiro Hamano, Tohru Okanishi, Harumi Yoshinaga, Katsuhiro Kobayashi

CLINICA CHIMICA ACTA 466 1 - 5 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Background: We quantified pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) in the cerebrospinal fluid (CSF) of children and to investigate the effect of age, sex, epilepsy, and anti-epileptic drug (AED) therapy on these vitamers.
Methods: CSF samples prospectively collected from 116 pediatric patients were analyzed. PLP, PI, and PA were measured using high-performance liquid chromatography with fluorescence detection, using pre-column derivatization by semicarbazide. Effects of age, sex, epilepsy, and AEDs on these vitamers and the PLP/PL ratio were evaluated using multiple linear regression models.
Results: The PLP, PL, and PA concentrations were correlated negatively with age and the PLP/PL ratio was correlated positively with age. Multiple regression analysis revealed that the presence of epilepsy was associated with lower PLP concentrations and PLP/PL ratios but sex and AED therapy had no influence on these values. The observed ranges of these vitamers in epileptic and non-epileptic patients were demonstrated.
Conclusions: We showed the age dependence of PLP and PL in CSF from pediatric patients. Epileptic patients had lower PLP concentrations and PLP/PL ratios than non-epileptic patients, but it is unknown whether this is the cause, or a result, of epilepsy. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.cca.2016.12.027

Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency 査読

Yu Kobayashi, Jun Tohyama, Tomoyuki Akiyama, Shinichi Magara, Hideshi Kawashima, Noriyuki Akasaka, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto

BRAIN & DEVELOPMENT 39 ( 3 ) 266 - 270 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy. Nerve conduction studies revealed both axonal degeneration and demyelinating features. A diagnosis of cerebral folate deficiency was confirmed by a homozygous c.466T>G (p.W156G) mutation in FOLR1, coupled with extremely low cerebrospinal fluid levels of 5-methyltetrahydrofolate. Her symptoms, neuroradiological findings, and polyneuropathy were alleviated by oral folinic acid treatment in conjunction with intravenous and intramuscular administration therapy. Our patient shows that folinic acid therapy can ameliorate the clinical symptoms, white matter disturbances, cortical insults, and peripheral neuropathy of cerebral folate deficiency caused by FOLR1 mutation. It is important to recognize these clinical symptoms and make a precise diagnosis early on, because cerebral folate deficiency is treatable. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.braindev.2016.09.011

Simultaneous measurement of monoamine metabolites and 5-methyltetrahydrofolate in the cerebrospinal fluid of children 査読

Tomoyuki Akiyama, Yumiko Hayashi, Yoshiyuki Hanaoka, Takashi Shibata, Mari Akiyama, Kazuyuki Nakamura, Yu Tsuyusaki, Masaya Kubota, Harumi Yoshinaga, Katsuhiro Kobayashi

CLINICA CHIMICA ACTA 465 5 - 10 2017年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Background: We describe a new method for simultaneous measurement of monoamine metabolites (3-0-methyldopa [3-0MD],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 10 min. They showed linearity from the limit of detection to 1024 nmol/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 alpha 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. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.cca.2016.12.005

Importance of the multisystem follow-up in patients with tuberous sclerosis complex. 査読

A Japanese case of β-ureidopropionase deficiency with dysmorphic features. 査読

Akiyama T, Shibata T, Yoshinaga H, Kuhara T, Nakajima Y, Kato T, Maeda Y, Ohse M, Oka M, Kageyama M, Kobayashi K

Brain & development 39 ( 1 ) 58 - 61 2017年1月

Yoshinaga H, Oka M, Akiyama T, Endoh F, Akiyama M, Hayashi Y, Shibata T, Hanaoka Y, Kobayashi K

No to hattatsu = Brain and development 5-9 ( 1 ) 5 - 9 2017年1月

記述言語：日本語出版者・発行元：一般社団法人日本小児神経学会

<p> 【目的】結節性硬化症 (TSC) は多臓器に過誤組織を発生する疾患である. したがって多くの診療科が協力して診療に当たる必要がある. そこで, その実態を把握するために以下の検討を行った. 【方法】対象は岡山大学病院小児神経科を受診したTSC症例のうち複数年にわたって来院歴のある38例とした. 各臓器のフォローアップ状況を小児群と成人群に分けて後方視的に検討した. 【結果】小児期には比較的どの臓器も確実にフォローが行われていた. 成人群では脳の画像のフォローは上衣下巨星細胞腫 (SEGA) のある症例も含めて不完全であった. 腎臓は, 成人群では異常のあった7例においても5年以上フォローがされていなかった. 肺はリンパ脈管筋腫 (LAM) の合併率の高くなる18歳以上の女性においても検査率は50%であった. 心臓は小児群では横紋筋腫のある12例中10例が1～3年ごとのエコー検査を受けていたが, 一方で伝導障害に関しての心電図の施行は全年齢でおろそかであった. 【結論】欧米でのガイドラインに照らし合わせてみると, フォローアップ体制は特に成人群において不完全であることが明らかとなった. TSCボードなどの多数科の医療連携体制の場が必要と考えられた.</p>

DOI： 10.11251/ojjscn.49.5

CiNii Article

Significance of High-frequency Electrical Brain Activity 査読

Katsuhiro Kobayashi, Tomoyuki Akiyama, Takashi Agari, Tatsuya Sasaki, Takashi Shibata, Yoshiyuki Hanaoka, Mari Akiyama, Fumika Endoh, Makio Oka, Isao Date

ACTA MEDICA OKAYAMA 71 ( 3 ) 191 - 200 2017年

記述言語：英語出版者・発行元：OKAYAMA UNIV MED SCHOOL

Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (<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 >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

A study on spike focus dependence of high-frequency activity in idiopathic focal epilepsy in childhood. 査読

Shibata T, Yoshinaga H, Akiyama T, Kobayashi K

Epilepsia open 1 ( 3-4 ) 121 - 129 2016年12月

Fast (40-150 Hz) oscillations are associated with positive slow waves in the ictal EEGs of epileptic spasms in West syndrome 査読

Katsuhiro Kobayashi, Tomoyuki Akiyama, Makio Oka, Fumika Endoh, Harumi Yoshinaga

BRAIN & DEVELOPMENT 38 ( 10 ) 909 - 914 2016年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Objective: To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40-150 Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs.
Methods: In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, TT) of identical EEG data in a referential montage. Among six EEG data sections defined according to TT, the number of FOs, peak power values, and peak frequencies were compared.
Results: We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at TT. The number of gamma oscillations in the 1 s epoch including TT was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections.
Conclusions: The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights

DOI： 10.1016/j.braindev.2016.05.005

Magnetoencephalography spike sources interrelate the extensive epileptogenic zone of tuberous sclerosis complex 査読

Tohru Okanishi, Tomoyuki Akiyama, Ellen Mayo, Yasunori Honda, Chihiro Ueda-Kawada, Midori Nakajima, Yoichiro Homma, Ayako Ochi, Cristina Go, Elysa Widjaja, Sylvester H. Chuang, James T. Rutka, James Drake, O. Carter Snead, Hiroshi Otsubo

EPILEPSY RESEARCH 127 302 - 310 2016年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Objective: We hypothesized that the extensive epileptic network in patients with tuberous sclerosis complex (TSC) manifests as clustered and scattered distributions of magnetoencephalography spike sources (MEGSS).
Methods: We retrospectively analyzed pre-surgical MEG in 15 patients with TSC. We performed single moving dipole analysis to localize and classify clustered and scattered MEGSS. We compared the number of electrodes within the resected area (RA) and the proportions of clustered and scattered MEGSS within RA with the seizure outcome.
Results: The number of electrodes within RA ranged from 29 to 83 (mean = 51). The MEGSS were distributed over multiple lobes (3-8; mean = 5.9) and bilaterally in 14 patients. Clusters of MEGSS ranged from 1 to 4 (mean = 1.4). The number of MEGSS ranged in total from 28 to 139 (mean = 70); in the clusters, 10-128 (mean = 49); and in the scatters, 0-45 (mean = 21). Four patients achieved an Engel class I surgical outcome, four, a class II outcome; five, a class III outcome; and two, a class IV outcome. The proportion of MEGSS ranged in total from 0 to 92% (mean = 57%) within RA; 0-100% (mean = 67%) in the resection hemisphere; 0-100% (mean = 63%) in the clusters; and 0-81% (mean = 28%) in the scatters. Univariate ordinal logistic regression analyses showed that the proportion of scattered MEGSS within RA (p = 0.049) significantly correlated with seizure outcomes. Multivariate analyses using three covariates (number of electrodes, proportions of clustered and scattered MEGSS within RA) showed that only the proportion of scattered MEGSS within RA significantly correlated with seizure outcomes (p = 0.016).
Significance: MEG data showed a wide distribution of multilobar MEGSS in patients with TSC. The seizure outcome was not related to the clustered MEGSS within RA, since the grids were essentially planned to cover and resect the clustered MEGSS surrounding tubers. The maximal possible resection of scattered MEGSS correlated with improved seizure outcome in TSC. Some parts of the epileptogenic zone disrupted by multiple tubers did not have a sufficiently large area to produce clustered MEGSS. Although the wide distribution of scattered MEGSS is not interpreted as epileptogenic, they might be interrelated with clustered MEGSS to project a complex epilepsy network and be part of the extensive epileptogenic zones found in TSC. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.eplepsyres.2016.09.007