Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media {SA}  

<jats:p>During her first year of junior high school, a 12-year-old Japanese girl with Down syndrome experienced dizziness, gait disruption, paroxysmal weakness in her hands, and sluggish speaking. Regular blood tests and a brain MRI revealed no abnormalities, and she was tentatively diagnosed with adjustment disorder. Nine months later, the patient experienced a subacute sickness of chest pain, nausea, sleep problem with night terrors, and delusion of observation. Rapid deterioration then developed with simultaneous fever, akinetic mutism, loss of facial expression, and urine incontinence. These catatonic symptoms improved after a few weeks after admission and treatment with lorazepam, escitalopram, and aripiprazole. After discharge, nonetheless, daytime slumber, empty eyes, paradoxical laughter, and declined verbal communication persisted. Upon confirmation of the cerebrospinal N-methyl-D-aspartate (NMDA) receptor autoantibody, methylprednisolone pulse therapy was tried, but it had little effect. Visual hallucinations and cenesthopathy, as well as suicidal thoughts and delusions of death, have predominated in the following years. Cerebrospinal IL-1ra, IL-5, IL-15, CCL5, G-CSF, PDGFbb, and VFGF were raised in the early stage of initial medical attention with nonspecific complaints, but were less prominent in the later stages of catatonic mutism and psychotic symptoms. We suggest a disease concept of progression from Down syndrome disintegrative disorder to NMDA receptor encephalitis, based on this experience.</jats:p>

DOI： 10.3389/fneur.2023.1200541

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

DOI： 10.1016/j.braindev.2022.10.005

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

The Drosophila behavior/human splicing protein family is involved in numerous steps of gene regulation. In humans, this family consists of three proteins: SFPQ, PSPC1, and NONO. Hemizygous loss-of-function (LoF) variants in NONO cause a developmental delay with several complications (e.g., distinctive facial features, cardiac symptoms, and skeletal symptoms) in an X-linked recessive manner. Most of the reported variants have been LoF variants, and two missense variants have been reported as likely deleterious but with no functional validation. We report three individuals from two families harboring an identical missense variant that is located in the nuclear localization signal, NONO: NM_001145408.2:c.1375C &gt; G p.(Pro459Ala). All of them were male and the variant was inherited from their asymptomatic mothers. Individual 1 was diagnosed with developmental delay and cardiac phenotypes (ventricular tachycardia and dilated cardiomyopathy), which overlapped with the features of reported individuals having NONO LoF variants. Individuals 2 and 3 were monozygotic twins. Unlike in Individual 1, developmental delay with autistic features was the only symptom found in them. A fly experiment and cell localization experiment showed that the NONO variant impaired its proper intranuclear localization, leading to mild LoF. Our findings suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.

DOI： 10.1038/s41598-023-27770-6

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Other Link： https://www.nature.com/articles/s41598-023-27770-6

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

DOI： 10.1111/ped.15594

PubMed

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Authorship：Last author  

DOI： 10.11251/ojjscn.55.52

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

DOI： 10.3805/eands.15.42

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/ped.15240

PubMed

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ped.15240

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

BACKGROUND: Marked decreases in serum creatine kinase levels have been noted in Duchenne and Becker muscular dystrophies as rare complications of autoimmune or autoinflammatory diseases. SUBJECTS AND METHODS: The influence of systemic inflammation on serum creatine kinase levels was reviewed from the charts of three subjects with Fukuyama congenital muscular dystrophy. RESULTS: A total of 30 infectious events were identified. Elevated serum C-reactive protein levels coincided with decreased creatine kinase levels on 19 occasions. In one subject, administration of 2 mg/kg/d prednisolone for bronchial asthma resulted in a decrease in creatine kinase level on six other occasions. CONCLUSION: Apart from an increase in endogenous cortisol secretion, certain inflammation-related molecules could play a role in mitigating muscle cell damage in Fukuyama congenital muscular dystrophy during febrile infectious episodes. Corticosteroids may be a promising agent for the treatment of muscular symptoms in this disorder.

DOI： 10.1016/j.braindev.2020.11.009

PubMed

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

AIM: To describe beneficial effects of callosotomy on KCNQ2-related intractable epilepsy. CASE REPORT: Our patient was a 10-year-old girl who had developed epilepsy during the neonatal period, accompanied by a suppression-burst pattern on the electroencephalography (EEG). The patient showed profound psychomotor developmental delay since early infancy. Daily seizures of versive posturing and ocular deviation were transiently controlled by carbamazepine and valproate at the age of 1 year; however, the seizures gradually increased to up to 50 times per day. Ictal EEG and positron emission tomography revealed an epileptic focus in the left frontal lobe at age 5 years. Total callosotomy resulted in marked reduction of epileptic seizures thereafter, as well as improved responses to external auditory and visual stimuli. Whole exome sequencing at age 9 identified a de novo missense variant in KCNQ2 (NM_172107.3:c.563A > C:p.(Gln188Pro)). CONCLUSION: This case supports that epilepsy surgery could benefit children with epileptic encephalopathy, even with the etiology of channelopathy.

DOI： 10.1016/j.braindev.2020.05.005

PubMed

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

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01232&link_issn=&doc_id=20200106260011&doc_link_id=%2Fcl1nohat%2F2020%2F005201%2F014%2F0047-0048%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl1nohat%2F2020%2F005201%2F014%2F0047-0048%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)総合医学社  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00643&link_issn=&doc_id=20190510470007&doc_link_id=%2Fag1snrsd%2F2019%2F007205%2F008%2F0621-0625%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2019%2F007205%2F008%2F0621-0625%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG Abs) are frequently detected in pediatric acquired demyelinating syndrome (ADS), and MOG-Ab-positive ADS differs from multiple sclerosis (MS) and aquaporin-4 (AQP4)-Ab-positive neuromyelitis optica spectrum disorder (NMOSD) in terms of age distribution, therapeutic response, and prognosis. METHODS: Based on medical records, we retrospectively evaluated patients with MOG-Ab-positive NMOSD treated in the acute phase who were followed up in the chronic phase at our hospital from January 2011 to December 2017. RESULTS: The patients comprised two boys and two girls aged 3-12 (median, 8) years. Peak MOG-Ab titers were 1:2048 to 1:32768 (median, 1:10240), and the relapse rate ranged from 0 to 1.25 times/year (median, 0.59 times/year); no sequelae were observed in any cases. Lesions other than those of optic neuritis were distributed at the cortex in one patient, subcortical white matter in four, deep white matter in three, and brainstem in one, all of which were disseminated lesions. No lesions were found in the corpus callosum, periventricular white matter, diencephalon, and regions adjacent to the third and fourth ventricles. The lesions tended to be asymptomatic, and two patients aged >5 years had well-demarcated lesions. CONCLUSION: All the patients showed disseminated lesions in the subcortical region to deep white matter, which were different from those found in MS and AQP4-Ab-positive NMOSD and were consistent with the characteristics of brain lesions in MOG-Ab-positive ADS, including other disease types.

DOI： 10.1016/j.braindev.2018.10.011

PubMed

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

Casein kinase 2 (CK2) is a serine threonine kinase ubiquitously expressed in eukaryotic cells and involved in various cellular processes. In recent studies, de novo variants in CSNK2A1 and CSNK2B, which encode the subunits of CK2, have been identified in individuals with intellectual disability syndrome. In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected two de novo variants in CSNK2A1 in two unrelated Japanese patients, a novel variant c.571C>T, p.(Arg191*) and a recurrent variant c.593A>G, p.(Lys198Arg), and two novel de novo variants in CSNK2B in Japanese and Malaysian patients, c.494A>G, p.(His165Arg) and c.533_534insGT, p.(Pro179Tyrfs*49), respectively. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures. This and previous studies have found a total of 20 CSNK2A1 variants in 28 individuals with syndromic intellectual disability. The hotspot variant c.593A>G, p.(Lys198Arg) was found in eight of 28 patients. Meanwhile, only five CSNK2B variants were identified in five individuals with neurodevelopmental disorders. We reviewed the previous literature to verify the phenotypic spectrum of CSNK2A1- and CSNK2B-related syndromes.

DOI： 10.1038/s10038-018-0559-z

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Language：Japanese   Publisher：(株)総合医学社  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00643&link_issn=&doc_id=20180529160007&doc_link_id=%2Fag1snrsd%2F2018%2F007106%2F008%2F1064-1070%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2018%2F007106%2F008%2F1064-1070%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：横浜市立大学医学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01499&link_issn=&doc_id=20180718460005&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001342%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001342%2F&type=%89%A1%95l%8Es%97%A7%91%E5%8Aw%81F%89%A1%95l%8Es%97%A7%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

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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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01232&link_issn=&doc_id=20160908410006&doc_link_id=%2Fcl1nohat%2F2016%2F004805%2F007%2F0347-0350%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl1nohat%2F2016%2F004805%2F007%2F0347-0350%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

DOI： 10.1111/ped.12288

PubMed

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

We describe the case of a 3-year-old boy diagnosed with the fulminant form of acute disseminated encephalomyelitis (ADEM). He developed general fatigue, fever, drowsiness and difficulty in walking. He had extensive multiple high-intensity lesions in the white matter of the cerebrum and cerebellum, which are typical findings of ADEM. He became comatose and developed decerebrate rigidity with severe brain edema despite high-dose methylprednisolone therapy, and then was subjected to mild hypothermia therapy, and given i.v. immunoglobulin. The patient recovered remarkably with the sequela of only mild action tremor. The patient was considered to have acute hemorrhagic leukoencephalitis (AHLE), an extremely severe form of ADEM, in terms of the rapidly deteriorating clinical course and neuroimaging features. It was speculated that AHLE and ADEM might be a continuous disease spectrum. It is considered that the severe brain edema associated with ADEM or AHLE is a suitable indication for mild hypothermia therapy.

DOI： 10.1111/ped.12180

PubMed

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

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01232&link_issn=&doc_id=20130108360011&doc_link_id=1390001205519049984&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205519049984&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

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

BACKGROUND AND PURPOSE: Influenza viral infection, which results in central nervous system dysfunction, is a major cause of acute encephalopathy (AE). The purpose of this study was to investigate the changes in the concentrations of brain metabolites in children with AE using single-voxel magnetic resonance spectroscopy (MRS) and to provide diagnostic information about the relationship between the symptoms of AE and metabolite concentrations. MATERIALS AND METHODS: The subjects were 10 children (mean age: 6.2 years; range: 1-13) with AE caused by the novel influenza A virus responsible for the 2009 influenza pandemic. The serial MRS data (TE/TR=30/5000 ms, 3 T) acquired from the basal ganglia (BG) and centrum semiovale (CS) of each patient were categorized into three periods: (1) initial neurological symptom presentation and the start of treatment (n=10), (2) short-term follow-up (n=9) and (3) long-term follow-up (n=3). As controls, the magnetic resonance (MR) spectra of eight age-matched children were also investigated. RESULTS: In both regions, the concentrations of the major metabolites (N-acetylaspartate, creatine, choline, myo-inositol, glutamate/glutamine complex and glutamate) only showed minor fluctuations between the three periods. On the other hand, higher levels of taurine (Tau) were observed in the BG during the second period (P=.005), and increased levels of glucose were observed in the CS during the first (P=.005) and second (P=.036) periods. CONCLUSIONS: Serial monitoring of brain metabolite changes was carried out with a clinical MR system. The concentrations of major metabolites only displayed very minor fluctuations in response to mild H1N1-related AE. However, a higher Tau concentration was found to be associated with neurological symptoms. Further studies are required to improve our understanding of the detailed activity of Tau in AE.

DOI： 10.1016/j.mri.2012.05.007

PubMed

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Language：Japanese   Publisher：神奈川県立こども医療センター  

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Language：Japanese   Publisher：神奈川県立こども医療センター  

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

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Language：Japanese   Publisher：神奈川県精神医学会  

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

DOI： 10.1111/j.1442-200x.2009.02829.x

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

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

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01232&link_issn=&doc_id=20120111410007&doc_link_id=1390001205518019584&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205518019584&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：Japanese   Publisher：神奈川県立こども医療センター  

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Language：Japanese   Publisher：神奈川県精神医学会  

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Language：Japanese   Publisher：(一社)日本薬剤疫学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：神奈川県立こども医療センター  

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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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