start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=561 end-page=566 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueTakushi en-aut-sei=Inoue en-aut-mei=Takushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, National Hospital Organization Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=abusive head trauma kn-keyword=abusive head trauma en-keyword=developmental and epileptic encephalopathy kn-keyword=developmental and epileptic encephalopathy en-keyword=epilepsy surgery kn-keyword=epilepsy surgery en-keyword=epileptic spasms kn-keyword=epileptic spasms en-keyword=hemispherotomy kn-keyword=hemispherotomy END start-ver=1.4 cd-journal=joma no-vol=107 cd-vols= no-issue= article-no= start-page=52 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comprehensive study of metabolic changes induced by a ketogenic diet therapy using GC/MS- and LC/MS-based metabolomics en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaigusaDaisuke en-aut-sei=Saigusa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishinumaEiji en-aut-sei=Hishinuma en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsukawaNaomi en-aut-sei=Matsukawa en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriAtsushi en-aut-sei=Mori en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiYuji en-aut-sei=Fujii en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MogamiYukiko en-aut-sei=Mogami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TokorodaniChiho en-aut-sei=Tokorodani en-aut-mei=Chiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuwaharaKozue en-aut-sei=Kuwahara en-aut-mei=Kozue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Numata-UematsuYurika en-aut-sei=Numata-Uematsu en-aut-mei=Yurika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=InoueKenji en-aut-sei=Inoue en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=4 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=5 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Shiga Medical Centre for Children kn-affil= affil-num=9 en-affil=Department of Paediatrics, Hiroshima City Funairi Citizens Hospital kn-affil= affil-num=10 en-affil=Department of Paediatric Neurology, Osaka Women's and Children's Hospital kn-affil= affil-num=11 en-affil=Department of Paediatrics, Kochi Health Sciences Centre kn-affil= affil-num=12 en-affil=Department of Paediatrics, Ehime Prefectural Central Hospital, kn-affil= affil-num=13 en-affil=Department of Paediatrics, Tohoku University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Shiga Medical Centre for Children kn-affil= affil-num=15 en-affil=Department of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amino acids kn-keyword=Amino acids en-keyword=Biomarkers kn-keyword=Biomarkers en-keyword=Intractable epilepsy kn-keyword=Intractable epilepsy en-keyword=Ketone bodies kn-keyword=Ketone bodies en-keyword=Organic acids kn-keyword=Organic acids END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=696882 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exclusion of the Possibility of "False Ripples" From Ripple Band High-Frequency Oscillations Recorded From Scalp Electroencephalogram in Children With Epilepsy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim 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. Methods 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). Results 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 (p < 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 (p < 0.0001). Discussion 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. Conclusion 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. en-copyright= kn-copyright= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=epilepsy kn-keyword=epilepsy en-keyword=child kn-keyword=child en-keyword=scalp EEG kn-keyword=scalp EEG en-keyword=false ripple kn-keyword=false ripple en-keyword=high-frequency oscillation (HFO) kn-keyword=high-frequency oscillation (HFO) en-keyword=fast oscillation (FO) kn-keyword=fast oscillation (FO) END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=100643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=NishizawaHitomi en-aut-sei=Nishizawa en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoYoshihiko en-aut-sei=Sato en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikawaMasumi en-aut-sei=Ishikawa en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArakawaYuko en-aut-sei=Arakawa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IijimaMari en-aut-sei=Iijima en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakanoKyoko en-aut-sei=Takano en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeAtsushi en-aut-sei=Watanabe en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoshoTomoki en-aut-sei=Kosho en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Department of Medicine, Shinshu University kn-affil= affil-num=2 en-affil=Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto kn-affil= affil-num=3 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=4 en-affil=Department of Dentistry and Oral Surgery, Shinshu University School of Medicine kn-affil= affil-num=5 en-affil=Department of Clinical Nutrition, Shinshu University Hospital kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=8 en-affil=Division of Clinical Genetics, Kanazawa University Hospital kn-affil= affil-num=9 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= en-keyword=Hypophosphatasia kn-keyword=Hypophosphatasia en-keyword=Alkaline phosphatase kn-keyword=Alkaline phosphatase en-keyword=Genetic disease kn-keyword=Genetic disease en-keyword=Asfotase alfa kn-keyword=Asfotase alfa en-keyword=Recombinant gene therapy kn-keyword=Recombinant gene therapy en-keyword=Motor function kn-keyword=Motor function END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue= article-no= start-page=33 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid.
Methods
Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations.
Results
We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain.
Conclusions
Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OboshiTaikan en-aut-sei=Oboshi en-aut-mei=Taikan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImaiKatsumi en-aut-sei=Imai en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshiharaNaoko en-aut-sei=Ishihara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DowaYuri en-aut-sei=Dowa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTakayoshi en-aut-sei=Koike en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoToshiyuki en-aut-sei=Yamamoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibasakiJun en-aut-sei=Shibasaki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShimboHiroko en-aut-sei=Shimbo en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukuyamaTetsuhiro en-aut-sei=Fukuyama en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakanoKyoko en-aut-sei=Takano en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShirakuHiroshi en-aut-sei=Shiraku en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakeshitaSaoko en-aut-sei=Takeshita en-aut-mei=Saoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkanishiTohru en-aut-sei=Okanishi en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=BabaShimpei en-aut-sei=Baba en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KubotaMasaya en-aut-sei=Kubota en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HamanoShin-ichiro en-aut-sei=Hamano en-aut-mei=Shin-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological Disorders kn-affil= affil-num=6 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurology, Gunma Children’s Medical Center kn-affil= affil-num=8 en-affil=Department of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological Disorders kn-affil= affil-num=9 en-affil=Institute of Clinical Genomics, Tokyo Women’s Medical University kn-affil= affil-num=10 en-affil=Department of Neonatology, Kanagawa Children’s Medical Center kn-affil= affil-num=11 en-affil=Clinical Institute, Kanagawa Children’s Medical Center kn-affil= affil-num=12 en-affil=Department of Pediatrics, Shinshu University kn-affil= affil-num=13 en-affil=Center for Medical Genetics, Shinshu University Hospital kn-affil= affil-num=14 en-affil=Department of Pediatrics, JA Toride Medical Center kn-affil= affil-num=15 en-affil=Department of Pediatrics, Yokohama City University Medical Center kn-affil= affil-num=16 en-affil=Department of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital kn-affil= affil-num=17 en-affil=Department of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital kn-affil= affil-num=18 en-affil=Division of Neurology, National Center for Child Health and Development kn-affil= affil-num=19 en-affil=Division of Neurology, Saitama Children’s Medical Center kn-affil= affil-num=20 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= en-keyword=ALDH7A1 kn-keyword=ALDH7A1 en-keyword=PLPBP kn-keyword=PLPBP en-keyword=PLPHP kn-keyword=PLPHP en-keyword=PROSC kn-keyword=PROSC en-keyword=Pyridoxal 5′-phosphate homeostasis protein deficiency kn-keyword=Pyridoxal 5′-phosphate homeostasis protein deficiency en-keyword=Pyridoxine-dependent epilepsy kn-keyword=Pyridoxine-dependent epilepsy END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=9 article-no= start-page=781 end-page=785 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differential diagnosis of nonepileptic twilight state with convulsive manifestations after febrile seizures en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakiKenji en-aut-sei=Waki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArakakiYoshio en-aut-sei=Arakaki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= en-keyword=Prolonged febrile seizure kn-keyword=Prolonged febrile seizure en-keyword=Acute encephalopathy with biphasic seizures and late reduced diffusion kn-keyword=Acute encephalopathy with biphasic seizures and late reduced diffusion en-keyword=Venous blood gas analysis kn-keyword=Venous blood gas analysis en-keyword=Electroencephalogram kn-keyword=Electroencephalogram en-keyword=Clinical characteristics kn-keyword=Clinical characteristics en-keyword=Venous blood gas kn-keyword=Venous blood gas END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=5 article-no= start-page=587 end-page=592 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions en-subtitle= kn-subtitle= en-abstract= kn-abstract=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 aged ≤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 seven patients who underwent abdominal CT, ECs or hematuria were found only in 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 increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkaMakio en-aut-sei=Oka en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=adrenocorticotropic hormone therapy kn-keyword=adrenocorticotropic hormone therapy en-keyword=calcium kn-keyword=calcium en-keyword=crystal kn-keyword=crystal en-keyword=renal tubular epithelial cell kn-keyword=renal tubular epithelial cell en-keyword=urinary sediment kn-keyword=urinary sediment END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=1-2 article-no= start-page=174 end-page=180 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pyridoxal 5′-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective To investigate the utility of serum pyridoxal 5′-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. Methods Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. Results Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. Conclusions The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubotaTakuo en-aut-sei=Kubota en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OzonoKeiichi en-aut-sei=Ozono en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MichigamiToshimi en-aut-sei=Michigami en-aut-mei=Toshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiDaisuke en-aut-sei=Kobayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeyariShinji en-aut-sei=Takeyari en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiyamaYuichiro en-aut-sei=Sugiyama en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NodaMasahiro en-aut-sei=Noda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaradaDaisuke en-aut-sei=Harada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NambaNoriyuki en-aut-sei=Namba en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzukiAtsushi en-aut-sei=Suzuki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UtoyamaMaiko en-aut-sei=Utoyama en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KitanakaSachiko en-aut-sei=Kitanaka en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UematsuMitsugu en-aut-sei=Uematsu en-aut-mei=Mitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitaniYusuke en-aut-sei=Mitani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsunamiKunihiro en-aut-sei=Matsunami en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakishimaShigeru en-aut-sei=Takishima en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OgawaErika en-aut-sei=Ogawa en-aut-mei=Erika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Osaka University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Bone and Mineral Research, Osaka Women's and Children's Hospital kn-affil= affil-num=5 en-affil=Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Department of Pediatrics, Osaka University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Pediatrics, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Showa General Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization kn-affil= affil-num=10 en-affil=Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization kn-affil= affil-num=11 en-affil=Department of Neonatology and Pediatrics, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=12 en-affil=Department of Pediatrics, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=13 en-affil=Department of Pediatrics, Graduate School of Medicine, University of Tokyo kn-affil= affil-num=14 en-affil=Department of Pediatrics, Tohoku University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Pediatrics, Kanazawa University Hospital kn-affil= affil-num=16 en-affil=Department of Pediatrics, Gifu Prefectural General Medical Center kn-affil= affil-num=17 en-affil=Department of Pediatrics, Soka Municipal Hospital kn-affil= affil-num=18 en-affil=Department of Pediatrics and Child Health, Nihon University School of Medicine kn-affil= affil-num=19 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Asfotase alfa kn-keyword=Asfotase alfa en-keyword=Liquid chromatography kn-keyword=Liquid chromatography en-keyword=Vitamin B6 kn-keyword=Vitamin B6 en-keyword=Diagnostic marker kn-keyword=Diagnostic marker en-keyword=Therapeutic monitoring kn-keyword=Therapeutic monitoring END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=5 article-no= start-page=402 end-page=407 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vitamin B6 in acute encephalopathy with biphasic seizures and late reduced diffusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TodaSoichiro en-aut-sei=Toda en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraNobusuke en-aut-sei=Kimura en-aut-mei=Nobusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MogamiYukiko en-aut-sei=Mogami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokorodaniChiho en-aut-sei=Tokorodani en-aut-mei=Chiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoTomoshiro en-aut-sei=Ito en-aut-mei=Tomoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Pediatrics, Sapporo City General Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=8 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= en-keyword=AESD kn-keyword=AESD en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Febrile seizure kn-keyword=Febrile seizure en-keyword=Pyridoxal 5′-phosphate kn-keyword=Pyridoxal 5′-phosphate en-keyword=Pyridoxal kinase kn-keyword=Pyridoxal kinase en-keyword=Risk factor kn-keyword=Risk factor END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=65 end-page=72 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metabolic Profiling of the Cerebrospinal Fluid in Pediatric Epilepsy en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaigusaDaisuke en-aut-sei=Saigusa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmedaKeiko en-aut-sei=Umeda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaijoReina en-aut-sei=Saijo en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoshibaSeizo en-aut-sei=Koshiba en-aut-mei=Seizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=3 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=5 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=6 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=7 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= en-keyword=antiepileptic drugs kn-keyword=antiepileptic drugs en-keyword=gas chromatography-tandem mass spectrometry kn-keyword=gas chromatography-tandem mass spectrometry en-keyword=metabolome analysis kn-keyword=metabolome analysis en-keyword=metabolomics kn-keyword=metabolomics END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue= article-no= start-page=100515 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and genetic aspects of mild hypophosphatasia in Japanese patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=YokoiKatsuyuki en-aut-sei=Yokoi en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoko en-aut-sei=Nakajima en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinkaiYasuko en-aut-sei=Shinkai en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SanoYoshimi en-aut-sei=Sano en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraMototaka en-aut-sei=Imamura en-aut-mei=Mototaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshikawaTetsushi en-aut-sei=Yoshikawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoTetsuya en-aut-sei=Ito en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University kn-affil= affil-num=4 en-affil=Department of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of Medicine kn-affil= affil-num=5 en-affil=Department of Plastic Surgery, Division of Pediatric Dentistry & Orthodontics, Fujita Health University of Medicine kn-affil= affil-num=6 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Fujita Health University School of Medicine kn-affil= affil-num=9 en-affil=Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University kn-affil= en-keyword=ALPL kn-keyword=ALPL en-keyword=Dominant-negative mutations kn-keyword=Dominant-negative mutations en-keyword=Hypophosphatasia kn-keyword=Hypophosphatasia en-keyword=Premature loss of deciduous kn-keyword=Premature loss of deciduous END