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

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on the advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. Thirty-one individuals aged 47-87 years were randomly assigned to receive either 5 g/day fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups' blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (HOMA-R) than the placebo group. In addition, the % changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

DOI： 10.1093/bbb/zbad065

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

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

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DOI： 10.3390/biomedicines11041092

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In an open pilot trial, six patients with various hereditary forms of spinocerebellar ataxia (SCA) were assigned to topiramate (50 mg/day) for 24 weeks. Four patients completed the protocol without adverse events. Of these four patients, topiramate was effective for three patients. Some patients with SCA could respond to treatment with topiramate.

DOI： 10.1002/ccr3.6980

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Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, also known as amyotrophic lateral sclerosis 14, is an autosomal dominant, progressive neurodegenerative disorder caused by various mutations in the valosin-containing protein gene. In this report, we examined a 51-year-old female Japanese patient with frontotemporal dementia and amyotrophic lateral sclerosis. The patient began noticing gait disturbances at the age of 45 years. Neurological examination at the age of 46 years met the Awaji criteria for clinically probable amyotrophic lateral sclerosis. At the age of 49 years, she tended to have poor mood and an aversion to activity. Her symptoms gradually worsened. She required a wheelchair for transport and had difficulty communicating with others because of poor comprehension. She then began to frequently exhibit irritability. Eventually, she was admitted to the psychiatric hospital because uncontrollable violent behavior throughout the day. Longitudinal brain magnetic resonance imaging revealed progressive brain atrophy with temporal dominance, non-progressive cerebellar atrophy, and some non-specific white matter intensities. Brain single photon emission computed tomography showed hypoperfusion in the bilateral temporal lobes and cerebellar hemispheres. Clinical exome sequencing revealed the presence of a heterozygous nonsynonymous variant (NM_007126.5, c.265C>T; p.Arg89Trp) in the valosin-containing protein gene, which was absent in the 1000 Genomes Project, the Exome Aggregation Consortium Database, and the Genome Aggregation Database, and was predicted to be "damaging" by PolyPhen-2 and "deleterious" using SIFT with a Combined Annotation Dependent Depletion score of 35. We also confirmed the absence of this variant in 505 Japanese control subjects. Therefore, we concluded that the variant in the valosin-containing protein gene was responsible for the symptoms of this patient.

DOI： 10.3389/fgene.2023.1155998

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Language：Japanese   Publisher：(一社)日本老年医学会  

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

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

Abstract

Dystonia (DYT) is a heterogeneous neurological disorder, and there are many types of DYT depending on the responsible genes. DYT11 is an autosomal dominant DYT caused by functional variants in the SGCE gene. We examined a Japanese patient with myoclonic dystonia. By using exome analysis, we identified a rare variant in the SGCE gene, NM_003919.3: c.304C > T [Arg102*], in this patient. Therefore, this patient has been molecularly diagnosed with DYT11. By Sanger sequencing, we confirmed that this variant was paternally inherited in this patient. By allele-specific PCR, we confirmed that the maternally inherited normal allele of SGCE was silenced, and only the paternally inherited variant allele was expressed in this patient. Despite the pathogenicity, identical variants have been recurrently reported in eight independent families from different ethnicities, suggesting recurrent mutations at this mutational hotspot in SGCE.

DOI： 10.1038/s41439-022-00207-8

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Other Link： https://www.nature.com/articles/s41439-022-00207-8

Language：Japanese   Publisher：別府大学短期大学部  

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先行研究により乾しいたけエキスを PC―１２細胞に暴露したところ神経突起伸長および細胞増殖に影響を与えている可能性があることが分かった。本研究では乾しいたけのうま味成分であるグアニル酸に着目し、グアニル酸を PC―１２細胞に暴露して神経突起伸長および細胞増殖を調べた。結果として細胞体から伸びる神経突起の伸長数にわずかな変化が認められた。また、グアニル酸は濃度依存的に細胞増殖を抑制していることも分かった。別の主要うま味成分であるグルタミン酸についても同様に実施したが調整した濃度の範囲内での変化は認められなかった。

DOI： 10.32289/tk04107

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032281638

Language：English   Publisher：(一社)日本脳神経超音波学会  

下顎窓から測定した、内頸動脈(ICA)における脳血管反応性(CVR)診断の有用性について検討した。有効な側頭窓が確認された健常者25例(男性13例、女性12例、平均年齢39.9±13.7歳)を対象に、息こらえ試験を行い、CVR指標としてbreath holding index(BHI)を用い、息こらえ前後の平均血流速度からBHIを算出し、ICAで測定したBHI(BHIi)と同側中大脳動脈で測定したBHI(BHIm)との相関性を評価した。その結果、BHImおよびBHIiはそれぞれ平均0.93±0.29および平均0.92±0.32で、BHImとBHIiのSpearman相関係数は0.665であった。また、BHImにより決定されたCVR障害に対するBHIiのカットオフポイントは0.71で、感度と特異度はともに80%得られた。以上の結果から、側頭窓からの測定が不十分である場合には、下顎窓からのBHI測定が代替測定として有用であることが明らかにされた。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02558&link_issn=&doc_id=20220113570003&doc_link_id=%2Fcn7neuro%2F2021%2F003403%2F003%2F0142-0147%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcn7neuro%2F2021%2F003403%2F003%2F0142-0147%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本老年医学会  

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

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

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Essential tremor (ET) is one of the most common movement disorders. However, there are currently no accepted biomarkers for ET. This report suggested that concentration of plasma glutamic acid, aspartic acid, and taurine could be biomarkers for ET.

DOI： 10.1002/ccr3.4580

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BACKGROUND: Impairment of cerebrovascular reactivity (CVR) has been reported in patients with multiple sclerosis (MS). Chronic inflammation and endothelial dysfunction are possible mechanisms underlying this hemodynamic impairment. This study aimed to evaluate CVR and endothelial function in patients with MS and explore their relationships with disease progression using functional sonographic procedures. METHODS: Patients with MS and age-/sex-matched healthy controls were assessed for endothelial function, determined by flow-mediated dilation (FMD), and CVR, measured using the breath-holding index (BHI). RESULTS: Twenty-seven patients with MS and 24 healthy controls were enrolled. FMD was significantly lower in MS subjects than in control subjects (6.0 ± 0.6 vs. 8.6 ± 0.7, p = 0.006); furthermore, BHI was similarly lower in MS than in controls, but insignificant. Remarkably, FMD was significantly lower in secondary progressive MS subjects than in relapse-remitting MS subjects (3.7 ± 1.3 vs. 6.7 ± 0.7, p = 0.045). In addition, FMD was inversely correlated with the disability score as per the expanded disability status scale (R2 = 0.170, p = 0.033) and modified Rankin scale (R2 = 0.187, p = 0.027). CONCLUSION: In patients with MS, endothelial dysfunction was more noticeable than CVR impairment, correlating with the severity and progression of MS.

DOI： 10.1016/j.msard.2021.103135

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Language：Japanese   Publisher：日本脳神経超音波学会・日本栓子検出と治療学会  

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DOI： 10.1016/j.ensci.2021.100346

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Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a "likely pathogenic" variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.

DOI： 10.1038/s41439-021-00153-x

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Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by episodic involuntary movement attacks triggered by sudden movements, acceleration, or intention to move. We ascertained two Japanese familial cases with PKD. The proband is a 22-year-old woman who had noted sudden brief (<30 s) of involuntary movements provoked by kinesigenic trigger such as starting to run, getting on a train, picking up a telephone receiver and so on at the age of 14. Interictal brain single photon emission computed tomography (SPECT) showed hyperperfusion in the left thalamus. A 46-year-old woman, the mother of the proband was also suffering from brief attacks triggered by starting to run in her high school days. On neurological examination, both showed no abnormality. Whole exome sequencing combined with rigorous filtering revealed two heterozygous nonsynonymous variants (NM_001447: c.8976G > C [p.Gln2992His] in FAT2 and NM_015678: c.8596C > T [p.Arg2866Trp] in NBEA). Real time quantitative PCR analysis of Nbea mRNA levels in the developing rat brain revealed peak at postnatal day 28 and decline at postnatal day 56. This result might match the most common clinical course of PKD from the point of view of the most common age at remission. NBEA has been reported to be responsible for neurodevelopmental disease accompanied by epilepsy. We concluded the variant in NBEA most likely to be responsible for our familial cases of PKD.

DOI： 10.1038/s10038-021-00914-0

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

We have previously reported a novel homozygous 4-bp deletion in DDHD1 as the responsible variant for spastic paraplegia type 28 (SPG28; OMIM#609340). The variant causes a frameshift, resulting in a functionally null allele in the patient. DDHD1 encodes phospholipase A1 (PLA1) catalyzing phosphatidylinositol to lysophosphatidylinositol (LPI). To clarify the pathogenic mechanism of SPG28, we established Ddhd1 knockout mice (Ddhd1[-/-]) carrying a 5-bp deletion in Ddhd1, resulting in a premature termination of translation at a position similar to that of the patient. We observed a significant decrease in foot-base angle (FBA) in aged Ddhd1(-/-) (24 months of age) and a significant decrease in LPI 20:4 (sn-2) in Ddhd1(-/-) cerebra (26 months of age). These changes in FBA were not observed in 14 months of age. We also observed significant changes of expression levels of 22 genes in the Ddhd1(-/-) cerebra (26 months of age). Gene Ontology (GO) terms relating to the nervous system and cell-cell communications were significantly enriched. We conclude that the reduced signaling of LPI 20:4 (sn-2) by PLA1 dysfunction is responsible for the locomotive abnormality in SPG28, further suggesting that the reduction of downstream signaling such as GPR55 which is agonized by LPI is involved in the pathogenesis of SPG28.

DOI： 10.1042/BSR20204171

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

BACKGROUND: Glomus tumors are soft tissue neoplasms comprised of glomus cells, vasculature, and smooth muscle cells, which occur commonly in a single subungual area of the digits, and their main clinical features include severe paroxysmal pain, localized tenderness, and cold hypersensitivity. CASE PRESENTATION: A 47-year-old Japanese man had suffered from chronic progressive paroxysmal shooting pain in his right leg since childhood. He avoided putting weight on his right foot whenever he walked. The frequency of paroxysmal pain and the number of tender points both gradually increased with age, and his right leg gradually atrophied. Magnetic resonance imaging of the lower extremity demonstrated multiple gadolinium-enhanced nodules that corresponded with his tender points. Excisional biopsy relieved his pain and provided a histopathological diagnosis of glomus tumors. CONCLUSION: This case suggests that small glomus tumors located in deep tissue may cause disuse atrophy because of their long delay before diagnosis. Clinicians should consider the potential for glomus tumors when patients exhibit unilateral lower limb muscular atrophy with pain.

DOI： 10.1186/s13256-020-02616-1

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Authorship：Lead author,　Corresponding author   Language：English  

We describe a 61-year-old woman with bilateral parkinsonism caused by unilateral infarction limited to the territory of the lenticulostriate arteries. Although dopamine transporter imaging with single-photon emission computed tomography (DaTSPECT) demonstrated reduced putaminal tracer binding concordant with the size and location of the vascular lesion, the specific binding ratio was within the normal range. Five months after onset, the patient was free from parkinsonism without the use of any antiparkinsonian agents. When patients show bilateral parkinsonism, it is important to consider infarction of the lenticulostriate arteries. Additionally, DaTSPECT might be useful for predicting the prognosis of parkinsonism caused by infarction.

DOI： 10.1016/j.ensci.2020.100291

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Language：Japanese  

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

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

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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In 2008, we reported a clinically and genetically new type of autosomal dominant disorder of motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough. To identify the nucleotide variant causative of this disease, we reanalyzed the linkage of the original Japanese pedigree including seven newly ascertained subjects with updated information. We assigned the locus of the disease to 1p13.3-q23 (maximum logarithm-of-odds score = 2.71). Exome sequencing for five patients and one healthy relative from the pedigree revealed 2526 patient-specific single-nucleotide variants (SNVs). By rigorous filtering processes using public databases, our linkage results, and functional prediction, followed by Sanger sequencing of the pedigree and 520 healthy Japanese individuals, we identified an intronic SNV in IQGAP3, a gene known to be associated with neurite outgrowth. Upon pathological examination of the sural nerve, moderate, chronic, mainly axonal neuropathy was observed. By histochemical analyses, we observed a patient-specific increase of IQGAP3 expression in the sural nerve. We concluded that the variant of IQGAP3 is associated with the disease in our pedigree.

DOI： 10.1038/s10038-020-0761-7

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an autosomal dominant neurodegenerative disorder caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We, herein, report the first Japanese case of ALSP caused by a de novo p.Phe849del mutation in CSF1R: a 44-year-old man who presented callosal disconnection symptoms. Brain MRI revealed dilation of the lateral ventricles, periventricular white matter hyperintensities, and thinning of the corpus callosum with hyperintensities on T2-weighted and FLAIR images. Brain single photon emission computed tomography (SPECT) showed hypoperfusion in the anterior corpus callosum. White matter lesions in MRI and hypoperfusion in SPECT increased with age. A brain biopsy at 44 years revealed axonal spheroids. Callosal disconnection symptoms and hypoperfusion in the anterior corpus callosum may be important indicators of ALSP, especially when caused by a p.Phe849del CSF1R mutation.

DOI： 10.1111/ncn3.12367

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

Distal hereditary motor neuropathies (dHMNs) comprise a group of clinically and genetically heterogeneous inherited lower motor neuron syndromes mainly characterized by a distal-predominant pattern of progressive muscle atrophy, weakness and hyporeflexia, without sensory dysfunction. Although at least 21 causative genes for dHMN have been reported, mutational scanning of these genes often fails to identify the causative variants in dHMN cohorts, suggesting that additional causative genes remain to be identified. We studied a four-generation pedigree of a Japanese family with autosomal dominant dHMN to provide insight into the pathogenetic basis of the disease. Neurological examinations were performed on all six family members enrolled in this study. Whole-exome sequencing (WES) was used to identify the causative gene for dHMN. The clinical features of the patients included muscle weakness with distal extensor dominancy in the lower extremities, accompanied by facial and neck flexor muscle impairment, no sensory involvement, and areflexia. Nerve conduction studies demonstrated axonal changes mainly in the peroneal nerve. WES combined with rigorous filtering revealed three missense variants (NM_001083964: c.851G > A [p.Arg284His] in TDRKH, NM_002858: c.1654G > T [p.Gly552Cys] in ABCD3, NM_001005164: c.898A > T [p.Ile300Phe], in OR52E2). The variant in TDRKH is located in a conserved region of the tudor domain which is also present in the survival of motor neuron (SMN) protein, encoded by the SMN1 gene. Therefore, we concluded the variant in TDRKH is likely to be responsible for dHMN in our pedigree.

DOI： 10.1016/j.ejmg.2018.11.028

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We describe a 60-year-old woman with combined central and peripheral demyelination who presented with obstinate constipation, weakness in the lower limbs, and a bilateral sensory disturbance below her chest followed by girdle sensation in the right region of the abdomen, which was responsive to steroid therapy and plasmapheresis. Serum anti-lactosylceramide antibody was positive without anti-neurofascin 155 antibody or anti-galactocerebroside antibody positivity. Two months later, the patient had a first relapse that was responsive to steroid treatment. A nerve conduction study confirmed reversible conduction failure (RCF) in both episodes. Our case is unique in that she had an RCF episode as well as some similarities to encephalomyeloradiculoneuropathy.

DOI： 10.3389/fneur.2019.00600

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

There are no specific radiologic features in MOG-Ab (autoantibodies directed against myelin oligodendrocyte glycoprotein)-associated diseases. We present two MOG-Ab-positive patients with symmetrical lesions in the bilateral cingulate cortex of the frontal and parietal lobes. Those lesions showed hyperperfusion in acute phase and hypoperfusion in chronic phase on brain SPECT. In both patients, steroid therapy was effective in acute phase and for prevention of recurrence. High signal in the bilateral cingulate cortex on MR T2-weighted and FLAIR images might to be one of the unique findings considered MOG-Ab associated diseases.

DOI： 10.1016/j.msard.2019.01.035

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

Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1-3, 6-8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.

DOI： 10.1016/j.ejmg.2018.07.005

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

BACKGROUND AND OBJECTIVES: Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is an effective tool for distinguishing Parkinson's disease (PD) from other diseases accompanied by parkinsonism. Unlike other Parkinsonian diseases, in PD, MIBG accumulation in the heart tends to decrease. However, previous studies have reported that a decrease in MIBG accumulation also occurs in progressive supranuclear palsy (PSP). Thus, we analyzed the relationship between the degree of MIBG accumulation decrease, clinical symptoms, and brainstem atrophy in PSP. METHODS: We retrospectively collected data from patients who underwent MIBG myocardial scintigraphy and compared MIBG indices (heart to mediastinum [H/M] ratio, washout rate) between subjects with PSP and other diseases including PD. In addition, we evaluated the relationship between clinical characteristics, MIBG accumulation, and brainstem atrophy in patients with PSP. RESULTS: Patients with PSP had a significantly lower early H/M ratio compared with multiple system atrophy with predominant parkinsonism (MSA-P) patients, and a control group. In PSP patients there was a correlation between the decrease in delay H/M ratio, atrophy of the pons, and clinical severity as evaluated by Hoehn and Yahr score. CONCLUSION: Unlike in PD, PSP patients exhibited a mild decrease in MIBG accumulation in MIBG myocardial scintigraphy, which may be related to brainstem atrophy.

DOI： 10.1016/j.jns.2018.10.019

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Language：Japanese   Publisher：(一社)日本脳卒中学会  

脳底動脈の窓形成(fenestration)を有し、同部に脳梗塞を発症した1例を報告した。症例は高血圧症、糖尿病および脂質異常症で加療中の74歳男性である。呂律の回りにくさ、歩行時のふらつきを自覚し、発症1ヵ月後に当科入院した。MRIで右中小脳脚に亜急性期の梗塞像を認めた。脳底動脈近位側に窓形成があり、その右動脈幹および右前下小脳動脈がアテローム血栓性に閉塞していた。頭蓋内プラークイメージングが閉塞部の不安定プラークの評価に有用であり、診断の一助となった。同部におけるアテローム血栓性脳梗塞の発症には血行力学的な要因と脳卒中危険因子が相互的に関与する可能性が考えられ、今後さらなる症例の蓄積と検討が必要である。脳底動脈窓形成例においては将来的な脳梗塞発症の可能性も念頭において経過観察する必要がある。(著者抄録)

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DOI： 10.1016/j.ejmg.2017.07.006

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

Dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF) is an autosomal dominant hereditary form of Charcot-Marie-Tooth disease (CMT) caused by variations in the guanine nucleotide-binding protein, subunit beta-4 gene (GNB4). We examined two Japanese familial cases with CMT. Case 1 was a 49-year-old male whose chief complaint was slowly progressive gait disturbance and limb dysesthesia that appeared at the age of 47. On neurological examination, he showed hyporeflexia or areflexia, distal limb muscle weakness, and distal sensory impairment with lower dominancy. Nerve conduction studies demonstrated demyelinating sensorimotor neuropathy with reduced action potentials in the lower limbs. Case 2 was an 80-year-old man, Case 1's father, who reported difficulty in riding a bicycle at the age of 76. On neurological examination, he showed areflexia in the upper and lower limbs. Distal sensory impairment in the lower limbs was also observed. Nerve conduction studies revealed mainly axonal involvement. Exome sequencing identified a novel heterozygous nonsynonymous variant (NM_021629.3:c.659T &gt; C [p.Gln220Arg]) in GNB4 exon 8, which is known to be responsible for CMT. Sanger sequencing confirmed that both patients are heterozygous for the variation, which causes an amino acid substitution, Gln220Arg, in the highly conserved region of the WD40 domain of GNB4. The frequency of this variant in the Exome Aggregation Consortium Database was 0.000008247, and we confirmed its absence in 502 Japanese control subjects. We conclude that this novel GNB4 variant is causative for CMTDIF in these patients, who represent the first record of the disease in the Japanese population. (C) 2017 Published by Elsevier Masson SAS.

DOI： 10.1016/j.ejmg.2017.06.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Recent findings have indicated a close relationship between myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive hypertrophic pachymeningitis and the limited form of granulomatosis with polyangiitis (GPA). In Japan, MPO-ANCA-positive hypertrophic pachymeningitis predominantly occurs in elderly individuals. We herein describe the cases of two patients with MPO-ANCA-positive hypertrophic pachymeningitis associated with the limited form of GPA who were successfully treated with a combination of corticosteroids and methotrexate. Although methotrexate has been shown to be less effective than cyclophosphamide for inducing the remission of GPA in patients with organ-threatening diseases, its safety and efficacy may make it a useful alternative treatment modality for patients with the limited form of GPA who show meningeal involvement.

DOI： 10.2169/internalmedicine.56.7742

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

Spastic paraplegia (SPG) type 28 is an autosomal recessive SPG caused by mutations in the DDHD1 gene. We examined a Japanese 54-years-old male patient with autosomal recessive SPG. His parents were consanguineous. He needed a wheelchair for transfer due to spastic paraplegia. There was a history of operations for bilateral hallux valgus, thoracic ossification of the yellow ligament, bilateral carpal tunnel syndrome, bilateral ankle contracture, and lumbar spinal canal stenosis. He noticed gait disturbance at age 14. He used a cane for walking in his 40s. On neurological examination, he showed hyperreflexia, spasticity, and weakness in the lower extremities and bilateral Babinski reflexes. Urinary dysfunctions and impaired vibration sense in the lower limbs were observed. By exome sequencing analysis using Agilent SureSelect and Illumina MiSeq, we identified 17,248 homozygous nucleotide variants in the patient. Through the examination of 48 candidate genes known to be responsible for autosomal recessive SPG, we identified a novel homozygous 4-bp deletion, c.914_917delGTAA, p.Ser305Ilefs*2 in exon2 of the DDHD1 gene encoding phosphatidic acid-preferring phospholipase A(1) (PA-PLA(1)). The mutation is expected to cause a frameshift generating a premature stop codon 3-bp downstream from the deletion. In consequence, the DDHD domain that is known to be critical for PLA(1) activity is completely depleted in the mutated DDHD1 protein, predicted to be a functionally null mutation of the DDHD1 gene. By Sanger sequencing, we confirmed that both parents are heterozygous for the mutation. This variation was not detected in 474 Japanese control subjects as well as the data of the 1,000G Project. We conclude that the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population. (C) 2016 Elsevier Masson SAS. All rights reserved.

DOI： 10.1016/j.ejmg.2016.05.010

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DOI： 10.12771/emj.2016.39.3.93

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(有)科学評論社  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kurume University School of Medicine  

We describe two cases of typical essential tremor with aspartic acidemia and mildly increased concentrations of plasma glutamic acid. Although this is a preliminary report, we emphasize the possibility of using amino acids, including aspartic acid, as biomarkers for the detection of essential tremor.

DOI： 10.2739/kurumemedj.MS00015

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (similar to 40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.

DOI： 10.1093/hmg/ddv347

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

Persistent elevation of serum creatine kinase (CK) without any symptoms has been called idiopathic hyper CK-emia (IHCK). We examined a four-generation Japanese pedigree of familial IHCK. The multipoint linkage analysis of the pedigree showed seven clear peaks of logarithm of odds (LOD) scores (>1.4). By the exome sequencing followed by multiple filtering processes, we identified one novel heterozygous nonsynonymous single nucleotide variant (SNV), c.7034G>C, p.S2345T in the iyanodine receptor 1 gene, RYR1 cosegregated with IHCK in the pedigree. Mutation Taster predicted this substitution as "disease causing" (p = 0.999). The PolyPhen-2 and PANTHER subPSEC scores for the substitution are 0.911 (possibly damaging) and 3.56 (probably damaging), respectively. We confirmed the absence of the SNV in 511 healthy Japanese individuals excluding the possibility of a normal variant with a very low frequency. Immunohistochemistry and Western blotting of biopsy samples consistently showed the expression level of RYR1 reduced in the patient. In real-time RT-PCR, the mRNA expression level of RYR1 was also significantly reduced in the patient (p = 0.009). These results suggest that the novel nonsynonymous SNV contribute to the vulnerability of the RYR1 protein through the dominant negative effect. We conclude that the SNV in the RYR1 gene is one of the responsible genes of IHCK. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2015.06.035

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

Mutations in the anoctamin 5 gene cause either limb girdle muscular dystrophy or Miyoshi muscular dystrophy 3 in Caucasians. We herein describe a 49-year-old Japanese man with asymmetry of the leg circumference since childhood. Muscle involvement began at the calf muscles, and later spread to the thigh and paraspinal muscles on imaging and physical examination. His external genitalia were morphologically hypoplastic. Genetic analysis identified a novel homozygous mutation, c. 1178G>A (p. Trp393X), in the anoctamin 5 gene. This is the first Japanese case with Miyoshi muscular dystrophy 3 caused by an anoctamin 5 gene mutation (anoctaminopathy). The muscle impairment associated with Miyoshi muscular dystrophy 3 appears to spread from the distal to proximal lower extremities.

DOI： 10.1111/ncn3.175

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Language：Japanese   Publisher：日本神経感染症学会  

症例は76歳男性で、7年前に慢性C型肝炎と2型糖尿病を指摘された。右顔面の疼痛が出現し、2日後より顔面に皮疹が出現した。アシクロビル、PSLで加療したが、皮疹による眼瞼の腫脹の改善と共に複視の増悪を自覚した。複視の原因と考えられる右動眼神経麻痺及び滑車神経麻痺を認めた。発症34日目の頭部MRIで、右眼窩内の脂肪織や視神経鞘、眼窩先端部、海綿状静脈洞にかけて造影効果を伴う異常信号および右視床前方内側にもわずかに造影効果を伴う異常信号を認めた。視力および動眼神経麻痺が改善傾向にあることからステロイドによる加療は行わず、ビタミン製剤で加療した。73日目の頭部MRIにて眼窩内および視床前方の病変は改善傾向にあったが、新たに右後頭葉に異常信号を認めた。左手の自発痛を訴え、発症240日目に頭部MRIを行った。眼窩内および視床前方の病変は改善したが、その外側に小病変を呈した。抗血小板剤の内服を開始した。

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

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

PURPOSE: Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. METHODS: We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). RESULTS: In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. CONCLUSIONS: POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.

DOI： 10.1167/iovs.13-12779

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

Parkinson's disease (PD) reportedly includes altered connectivity of neural loops involving the basal ganglia and cerebellum, although little is known regarding any changes in the connectivity of motor loops. The goal of this study was to further understand the connectivity within the basal ganglia-thalamo-motor (BGTM) and cerebro-cerebellar (CC) loops in PD. Twelve PD patients and 12 age-matched control subjects performed a protocol involving self-initiated (SI) and externally-triggered (ET) finger movements, while being scanned with functional magnetic resonance imaging. Compared with the control subjects, the PD subjects showed hypo-activation in the bilateral putamen, right supplementary motor area and hyper-activation in the right premotor cortex. In the sensorimotor cortex and cerebellar hemisphere, PD subjects tended to show hyper-activation in a main effects analysis, but hypo-activation in a linear effects analysis. Analysis using structural equation modeling (SEM) revealed significant positive interactions within the right BGTM loop during the SI task and within the right (right cerebral hemisphere-left cerebellum) CC loop during the ET task. SEM also revealed task-related quantitative changes between the thalamus and the motor cortices in the control subjects. We found that the PD patients showed reduced connectivity in the right BGTM loop and inter-hemispheric connections in SEM, which is the first demonstration of this phenomenon. Interestingly, PD patients exhibited preserved connectivity within the right CC loop during the ET task. These results suggest disruption of cortico-striatal processing and preservation of relatively intact neural circuits that do not involve the basal ganglia in PD. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.03.027

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

症例は14歳、女性。主訴は日中の倦怠感、頭重感、神経学的に特記所見なし。終夜睡眠ポリグラフ検査(polysomnography:PSG)でapnea hypopnea index(AHI)が92.8(すべて中枢性)であり、重症の中枢性睡眠時無呼吸症候群であった。頭部MRI矢状断で小脳扁桃の大後頭孔への陥入を認め、Chiari I型奇形と診断、手術適応と判断し大後頭孔減圧術を施行した。3ヵ月後のPSGではAHIが24.2(central apnea 18.1、hypopnea 6.1)、10ヵ月後ではAHI 0.8(central apnea 0.5、hypopnea 0.3)と改善した。本症例のように、Chiari I型奇形が他神経症状を伴わずに睡眠時無呼吸で発症する例はまれであるが、Chiari奇形による睡眠時無呼吸は早期の手術が望ましい。したがって、症状が睡眠時無呼吸のみであってもChiari奇形を積極的に疑い、上部頸椎レベルを含む頭部MRI矢状断を行うことが重要である。(著者抄録)

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

Background: Anhedonia, a lowered ability to experience physical or social pleasure, has recently been recognized as a non-motor symptom of Parkinson's disease.
Objective: To identify the frequency of anhedonia and the factors influencing hedonic tone in Japanese patients with Parkinson's disease.
Patients and methods: We recruited 86 consecutive outpatients with a clinical diagnosis of PD attending two Japanese hospitals (one university hospital and one community hospital) in February 2010. We used the self-rating Snaith-Hamilton Pleasure Scale (SHAPS) translated into Japanese language from the original English version to assess and quantify hedonic tone as a subjectively experienced phenomenon. We studied the association of anhedonia with the variables age, age at onset, gender, disease duration, disease severity and antiparkinsonian drugs.
Results: Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was 72.01 +/- 9.07 (49-89) years, with mean age at onset of 64.93 +/- 11.42 (31-88) years. Mean disease duration was 7.20 +/- 5.54 (1-23) years. The mean Hoehn and Yahr scale was 2.76 +/- 0.78. The mean SHAPS score of the total sample was 1.19 +/- 1.86. The SNAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia. The mean SNAPS score was lower in patients taking pramipexole (0.58 +/- 0.97) than in patients not taking pramipexole (1.57 +/- 2.16). Multiple linear regression analysis identified pramipexole as a significant negative influencing factor on the SHAPS score, while disease severity and entacapone treatment were identified as positive influencing factors. The age, onset age, gender, disease duration, and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents and droxidopa did not significantly affect the SHAPS score.
Conclusion: Anhedonia is not rare non-motor symptom in Japanese patients with Parkinson's disease. This study suggests an anti-anhedonic property of pramipexole. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.clineuro.2011.11.008

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

Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant hereditary SPG caused by mutations in the SPAST gene. We studied the four-generation pedigree of a Japanese family with autosomal dominant hereditary SPG both clinically and genetically. Twelve available family members (ten affected; two unaffected) and two spouses were enrolled in the study. The clinical features were hyperreflexia in all four limbs, spasticity of the lower extremities, impaired vibration sense, mild cognitive impairment confirmed by the Wechsler Adult Intelligence Scale-Third Edition, and peripheral neuropathy confirmed by neurophysiological examinations. All four female patients experienced miscarriages. The cerebrospinal fluid tau levels were mildly increased in two of three patients examined. Linkage analyses revealed the highest logarithm of odds score of 2.64 at 2p23-p21 where the SPAST gene is located. Mutation scanning of the entire exonic regions of the SPAST gene by direct sequencing revealed no mutations. Exonic copy number analysis by real-time quantitative polymerase chain reaction revealed heterozygous deletion of exons 1 to 4 of the SPAST gene. Breakpoint analysis showed that the centromeric breakpoint was located within intron 4 of SPAST while the telomeric breakpoint was located within intron 3 of the neighboring DPY30 gene, causing a deletion of approximately 70 kb ranging from exons 1 to 3 of DPY30 to exons 1 to 4 of SPAST. To our knowledge, this is the first report of SPG4 associated with partial deletions of both the SPAST and DPY30 genes. The partial heterozygous deletion of DPY30 could modify the phenotypic expression of SPG4 patients with this pedigree.

DOI： 10.1007/s10048-010-0260-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ASEAN NEUROLOGICAL ASSOC  

We describe a 56-year-old man with relapsing sarcoidosis who presented with persistent hiccup responsive to steroid and clonazepam treatments. The patient also showed parkinsonism. The interval between the initial presentation and current symptoms was about 30 years. Brain MRI demonstrated foci of abnormal signal intensity in the cerebral white matter bilaterally, with decreased signal intensity on T1-weighted imaging and increased signal intensity on T2-weighted, diffusion-weighted, and FLAIR images. Gadolinium-enhanced MRI of the brain showed diffuse linear enhancement throughout the cerebral white matter with a configuration suggesting perivascular infiltration. Spinal MRI revealed spotty gadolinium-enhancing lesions from C2 to T3 segments. This case suggests that in some sarcoidosis patients intractable hiccup may be associated with high spinal cord lesions and parkinsonism with frontal white matter lesions.

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Language：Japanese   Publisher：(有)科学評論社  

43歳男性(理容師)。患者はハーフマラソン完走後に両眼上転・両上肢ふるえを自覚したが、30分程度の安静にて回復した。しかし翌日、歩きにくい、手がふるえてハサミが使えない、しゃべりにくいなどの症状が出現し、2ヵ月経過でも症状が改善しないため、著者らの施設へ受診となった。初診時、安静時・姿勢時・動作時振戦がみられ、WAIS-IIIではVIQ 77・PIQ 69・FIQ 70と知能低下が認められた。乳酸・ピルビン値は正常で、筋生検、頭部MRIでも異常は認められなかったが、遺伝子検査にてミトコンドリア12S rRNA遺伝子のA1555G変異が確認された。以上、これらの所見より、パーキンソニズム症状に対し塩酸アマンタジン、L-dopa、ユビデカレノン投与を開始したところ、症状は徐々に改善し、3ヵ月後には姿勢反射障害、振戦はほぼ消失した。だが、両上肢寡動と構音障害は残存した。

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

We describe a case of recurrent invasive thymoma associated with myasthenia gravis that responded to combined treatment with prednisolone and tacrolimus. The patient suffered from a myasthenic crisis and received methylprednisolone pulse therapy and partial thymomectomy. Low maintenance doses of prednisolone and tacrolimus shrank the size of the invasive thymoma and maintained the patient without any myasthenic symptoms. We stress the usefulness of combined treatment with tacrolimus and prednisolone for invasive thymoma, especially for unresectable tumors.

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

Mutations in the fused in sarcoma gene (FUS) were recently found in patients with familial amyotrophic lateral sclerosis (ALS). The present study aimed to clarify unique features of familial ALS caused by FUS mutation in the Japanese population. We carried out clinical, neuropathological, and genetic studies on a large Japanese pedigree with familial ALS. In six successive generations of this family, 16 individuals of both sexes were affected by progressive muscle atrophy and weakness, indicating an autosomal dominant trait. Neurological examination of six patients revealed an age at onset of 48.2 +/- A 8.1 years in fourth generation patients, while it was 31 and 20 years in fifth and sixth generation patients, respectively. Motor paralysis progressed rapidly in these patients, culminating in respiratory failure within 1 year. The missense mutation c.1561 C &gt; T (p.R521C) was found in exon 15 of FUS in the four patients examined. Neuropathological study of one autopsied case with the FUS mutation revealed multiple system degeneration in addition to upper and lower motor neuron involvement: the globus pallidus, thalamus, substantia nigra, cerebellum, inferior olivary nucleus, solitary nucleus, intermediolateral horn, Clarke&apos;s column, Onuf&apos;s nucleus, central tegmental tract, medial lemniscus, medial longitudinal fasciculus, superior cerebellar peduncle, posterior column, and spinocerebellar tract were all degenerated. Argyrophilic and basophilic neuronal or glial cytoplasmic inclusions immunoreactive for FUS, GRP78/BiP, p62, and ubiquitin were detected in affected lesions. The FUS R521C mutation in this Japanese family caused familial ALS with pathological features of multiple system degeneration and neuronal basophilic inclusions.

DOI： 10.1007/s00401-009-0621-1

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

We report here, for the first time, the case of a 41-year-old man with both Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) and myotonic dystrophy type 1. The patient noted dysarthria at 14 years of age and unsteady gait at 30 years of age. Similar sized expansions of the CAG trinucleotide repeats in one allele of the ataxin-3 (ATXN3) gene were found in both the patient and his father, although in the other allele the length of the CAG repeats was shorter in the father compared with the patient. In the dystrophia myotonica protein kinase (DMPK) gene the CTG repeats were much more expanded in the patient compared with his father. Thus it is possible that, in the farther, the short CTG repeat in the non-expanded ATXN3 allele delayed the onset of cerebellar symptoms, and/or that the expanded CMG repeat in the DMPK gene in the patient accelerated the pathogenesis of MJD/SCA3. (C) 2009 Published by Elsevier B.V.

DOI： 10.1016/j.clineuro.2009.07.016

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

We describe a 53-year-old man with herpes simplex Virus (HSV) brainstem encephalitis diagnosed based by positive HSV immunoglobulin M antibodies from cerebrospinal fluid. The MRI findings of this case had three unique features. First, the lesions were symmetrical. Second, the lesions may have been associated with reactivation of HSV infection in the region of the trigeminal nerve. Third, diffusion-weighted and apparent diffusion coefficient (ADC) imaging, conducted for the first time on an HSV brainstem encephalitis Case, Suggested that the lesions were associated with vasogenic edema. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2008.06.005

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

Two cases of spinocerebellar ataxia type 14 (SCA14) with a G128D mutation in the protein kinase C gamma gene (PRKCG) without a definite family history have been reported previously. Here, we describe the first familial cases of SCA14 with a G128D mutation in PRKCG. Among three family members, the chief complaints varied and included ataxic gait, cervical dystonia, and positional vertigo. Moreover, retinal degeneration and facial muscle weakness were observed, although these are not expected to be present in SCA14. Cerebral blood flow evaluation using single photon emission computed tomography (SPECT) also differed among family members. It is possible that patients with the G128D mutation suffering from SCA14 may sometimes be classified as unaffected due to the varying clinical signs among family members. (c) 2008 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.clineuro.2008.09.013

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：ELSEVIER SCI LTD  

DOI： 10.1016/j.jocn.2008.01.004

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

We Studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful Muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder.
We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) Score was over 1.0, no loci fulfilled the Criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary Motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of &lt;-3 on both 3p12-q13 and 3p22-p24. Mutation scanning of the entire coding regions of the MPZ and PMP22 genes revealed no mutations. We conclude that the disorder described here is a newly classified hereditary motor and sensory neuropathy with autosomal dominant inheritance. (c) 2008 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2008.06.027

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

We describe the first case of a patient with Japanese encephalitis suffering from central sleep apnea. The patient was a 58-year-old man who presented with high fever, semicomatose state, nuchal stiffness, and incontinence of feces. The patient had complication of severe pneumonia, and was ventilated with a respirator. After weaning from the respirator, desaturation of oxygen was observed during the night. Simplified polysomnography revealed a pure central apnea pattern. This case illustrates that Japanese encephalitis can result in central sleep apnea.

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Language：Japanese   Publisher：(一社)日本内科学会  

50歳男。両肩と両側下腿の疼痛の数ヵ月後に一過性の意識消失が出現、MRIにて右前頭葉病変を指摘されていた。当科受診時に意識消失強直性痙攣発作で緊急入院となった。両手掌と手背および両側下腿中央より末梢側に強い浸潤を触る小豆大の紅斑を認めた。また、深部腱反射は全般性亢進、両側Babinski反射は陽性であった。右前頭葉皮質下と両側基底核にT1強調画像で低信号、T2強調画像で高信号の異常信号域を認め、CTでは右側中肺野に小葉間隔壁と一部気管支血管束の肥厚を認めた。皮膚生検により、血管中心性に血管炎様の中〜大型リンパ球の浸潤を認めたため、lymphomaと診断した。MTX大量療法で改善傾向を認めた。1クール終了後の皮膚生検よりLYG GradeIIと診断し、3クール後左眼瞼下垂と複視を除いて提舌と構音は正常化、経口摂取、歩行も改善した。さらにCHOP療法を施行したが橋出血をきたし死亡した。

DOI： 10.2169/naika.97.417

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Other Link： https://jlc.jst.go.jp/DN/JALC/00309969350?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

We have previously mapped autosomal dominant spinocerebellar ataxia (SCA) 16 to 3p26, overlapping with the locus of SCA15. Recently, partial deletions of ITPR1 and the neighbouring SUMF1 in the SCA15 and two additional families were reported. In the present study we determined the copy number of these genes by real time quantitative polymerase chain reaction (PCR) and found a heterozygous deletion of exons 1-48 of ITPR1, but not SUMF1 in SCA16. Breakpoint analysis revealed that the size of the deletion is 313,318 bp and the telomeric breakpoint is located in the middle of their intergenic region. Our data provide evidence that haploinsufficiency of ITPR1 alone causes SCA16 and SCA15.

DOI： 10.1136/jmg.2007.053942

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

We describe a 45-year-old man with neurosarcoidosis complaining of bell-shaped tightening and pain with sensory disturbance of superficial and deep sensations. The patient showed subacute progressive sensory impairment in bilateral C7-Th12 dermatomes. Triceps and patellar tendon reflexes were decreased. Chest X-ray revealed bilateral hilar lymphadenopathy without pleural effusion. There was abnormal accumulation of gallium in the bilateral hilar lymph nodes, parotid glands, and lacrimal glands on scintigraphy. Examination of bronchoalveolar lavage fluid showed an elevated CD4/CD8 ratio. Transbronchial lung biopsy showed non-caseating granulomas with many epitheloid cells and occasional Langhans giant cells without any necrotic lesion. The tuberculin reaction was negative, and elevation of serum lysozyme and IgG level were seen. These findings fulfilled the clinical criteria for sarcoidosis. Spine MRI demonstrated no abnormality. Studies of short-latency somatosensory evoked potentials showed delayed N 13 latency and absent N 19 and N28 potentials bilaterally. A nerve conduction study revealed no abnormality. The patient's muscle strength was normal through the entire clinical course. Therefore, we consider that his sensory impairment was caused by peripheral neuropathy, especially in the dorsal root region. Neurosarcoidosis is important for differentiating bell-shaped sensory impairments of all modalities. (C) 2007 Published by Elsevier B.V.

DOI： 10.1016/j.clineuro.2007.06.003

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(有)科学評論社  

75歳、男。歩行障害、両下肢異常感覚、排尿困難を主訴とした。入院15ヵ月前から症状を自覚し、3ヵ月前から日によって変動する歩行障害が出現した。入院時、不安定歩行でトイレまで歩行不能、右腸腰筋軽度筋力低下、両側膝踵試験拙劣、両下肢遠位部優位の自覚的ピリピリ感・冷感・痛覚過敏および触覚・振動覚・位置覚は中等度低下、排尿困難、右膝蓋腱反射消失、両側アキレス腱反射低下を認めた。脊髄MRIのT2強調画像でTh7からconusにかけて髄内高信号域を認め、硬膜内髄外にflow void signと考えられる低信号域を認めた。造影MRIではdraining veinに相当すると考えられる脊髄周囲の増強効果をTh4〜馬尾周囲に認めた。脊椎血管造影では右第一腰髄神経根-髄質動脈を栄養動脈とした動静脈瘻を認め、拡張した髄質静脈への血液逆流を認めた。脊髄硬膜動静脈瘻血管塞栓術、高圧酸素療法を行い、症状の消失、改善を認めた。

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(有)科学評論社  

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

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To identify of the gene responsible for the onset of spinocerebellar ataxia type 16 (SCA16). Methods: We reanalyzed the linkage of the original Japanese pedigree using updated information, including three additional subjects. We then screened all exons located in the critical region. Results: We reassigned the locus of SCA16 to 3p26.2-pter (maximum logarithm-of-odds score = 5.177) and identified only one point mutation (4,256C -&gt; T) in the 3 ' untranslated region of the contactin 4 gene (CNTN4) on chromosome 3p26.2-26.3, which cosegregated with the disease. This mutation was not detected in 520 control subjects; moreover, we revised the phenotype of SCA16 from pure to complicated SCA. Conclusion: The contactin 4 gene (CNTN4) is associated with cerebellar degeneration in spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C -&gt; T to be a causative mutation.

DOI： 10.1212/01.wnl.0000238510.84932.82

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

A 62-year-old man who developed akinetic mutism with delayed white matter demyelination after hypoxia was treated with hyperbaric oxygen (HBO). HBO in the subacute period markedly improved the patient's activity in daily life, cognitive function and organization on EEG. H-1-MRS showed a recovery of aerobic metabolism of the neurons. However, dementia and cerebral atrophy slowly progressed despite HBO treatment. Thus, HBO had a beneficial effect on the activity of depressed neurons but did not improve the prognosis. (C) 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0303-8467(02)00019-7

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Authorship：Lead author   Language：Japanese   Publisher：(有)科学評論社  

62歳男.両側の顔面筋に高度な麻痺が出現し,味覚低下,唾液分泌低下を伴っていたが,涙液分泌低下はなかった.血液生化学検査等の検査所見や画像所見に異常を認めず,単純ヘルペスウイルス感染の可能性を考え,アシクロビル,プレドニゾロンを開始した.顔面神経麻痺の回復速度は極めて緩徐で,発症6週間後より外来で経過観察とした.各種血清抗体価の検索で血清Ehrlichia muris抗体価のみが80倍と陽性で,2ヵ月後には40倍となった.発症8ヵ月目に後遺症なく完全に回復した

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Authorship：Lead author   Language：Japanese   Publisher：(有)科学評論社  

34歳男.知能低下,Parkinson症候群,ジストニー肢位および錐体路徴候を認め,成人型Hallervorden-Spatz症候群と考えられた1例を報告した.MRIでは中等度の小脳萎縮を認めたが,淡蒼球のT2低信号化(虎の目徴候)は明らかではなかった.L-dopa剤投与により,無動症,自発語の改善を認めた.本例ではParkinson病類似の黒質病変の存在が推察された

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Authorship：Lead author   Language：Japanese   Publisher：(有)科学評論社  

35歳女.幼児期発症のcentronuclear myopathy(CN-M)の1例を報告した.一側眼瞼下垂が長期間持続しており,稀ではあるがCN-Mも一側眼瞼下垂の鑑別診断として考慮すべきである

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Language：Japanese   Publisher：(株)医学書院  

症例1:53歳女.亜急性な経過で感覚障害が主であり,前斜角筋リンパ節生検にてサルコイドーシスと診断した.症例2:63歳女.急性な経過で,運動障害,感覚障害が共に顕著であり当初ギラン・バレー症候群が疑われたが,ガリウムシンチによる両肺門,縦隔の異常集積,肺胞洗浄液のCD4/CD8比上昇,ツベルクリン反応陰性,血清リゾチーム高値より臨床診断群の診断基準を満たしサルコイドーシスと診断した.多発神経根障害による帯状絞扼感は,神経サルコイドーシスを想起すべき症状である

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PubMed

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Authorship：Lead author   Language：Japanese   Publisher：九州リウマチ学会  

50歳女,ステロイド治療に反応良好であったループス膀胱炎,ループス腹膜炎合併SLEを経験した.早期に治療開始できた例の予後は良く,SLEではこれらの合併症を念頭に置く必要がある

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：Japanese   Publisher：日本神経感染症学会  

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

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Language：Japanese   Publisher：別府大学短期大学部  

電位依存性カルシウムチャネル α１A サブユニット（CACNA1A ）遺伝子上にある DNAの三塩基配列 CAG リピートの異常伸長が脊髄小脳失調症６型（Spinocerebellar ataxia type ６： SCA６）の発症に関わることが知られている。SCA６の原因遺伝子であるCACNA1A 遺伝子上では CAG リピート数が健常者では４から１９, 罹患者では21から３３となる。また、SCA６は家族歴のある常染色体優性遺伝性の罹患者が多く、日本では優性遺伝性の脊髄小脳失調症の約３０％を占めている。本研究では孤発性（家族歴のない）SCA患者および両親の末梢血検体を使用し、遺伝学的解析による CAG リピート異常から遺伝性を検証した。結果として患者は CAG リピートの異常伸長（変異アレルでリピート数２３）が認められた。さらに遺伝学的解析により父親由来の正常アレルが伸長して罹患者の変異アレルになったのではないかと示唆された。これらのことから孤発性 SCA の症例でも遺伝学的解析により原因の究明ができる可能性が考えられる。

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

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DOI： 10.1016/j.ejmg.2017.07.006

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

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Language：English   Publisher：生命科学系学会合同年次大会運営事務局  

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Language：Japanese   Publisher：日本神経感染症学会  

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

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Language：Japanese   Publisher：別府大学短期大学部  

進行性ミオクローヌスてんかんの一病型であり、染色体２１q２２．３上にあるCSTB（CystatinB）遺伝子の異常リピートにより引き起こされるウンフェルリヒト・ルントボルク病（Unverricht-Lundborg disease: ULD）検体の遺伝子解析研究である。進行性ミオクローヌスてんかんの中でCSTB 遺伝子のリピート異常が原因の疾患はULD として知られている。ULD を調べるために放射性同位体（Radioisotope:RI）を使用したサザンブロッティングによる解析が行われる。そこで本研究では、簡便なポリメラーゼ連鎖反応（Polymerase chain reaction: PCR）を使用してCSTB 遺伝子の異常リピートの検出を試み、診断手法の確立およびULD の診断に寄与できないか検討した。PCR の結果、健常者と比較して患者では異常リピートと考えられるDNA 増幅を確認したがサンガーシークエンスによる配列確認により異常リピートではなく、別の配列の挿入が示唆される結論に至った。

CiNii Books

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：GENETICS SOC JAPAN  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：GENETICS SOC JAPAN  

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：English   Publisher：別府大学短期大学部  

本研究は、日本人の脊髄小脳失調症（Spinocerebellar ataxia： SCA）症例の遺伝解析研究である。本症例は臨床的にSCA タイプ５に矛盾せず、頭部ＭＲＩ画像では小脳萎縮が認められ、脳幹は保たれていた。遺伝学的解析により、SCA５の原因遺伝子であるβ-IIIスペクトリン遺伝子（SPTBN２ ）の新規非同義変異（c９２４G&gt;C，p．E３０８D）が認められた。１１番染色体に位置する本遺伝子は細胞骨格たんぱく質をコードしており、Ｅ３０８Ｄ変異はホットスポットに局在していた。日本人健常者５０７人を検討した結果、９人が同様の変異を有していた。したがって、SCA５の責任遺伝子内のミスセンス変異であるＥ３０８Ｄは責任変異ではない可能性が示唆された。

CiNii Books

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

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：GENETICS SOC JAPAN  

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

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

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Language：Japanese   Publisher：(一社)日本臨床内科医会  

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：Japanese   Publisher：(一社)日本臨床内科医会  

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

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

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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

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Language：Japanese   Publisher：(一社)日本臨床内科医会  

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

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

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

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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

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

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

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Language：Japanese   Publisher：日本神経感染症学会  

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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

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

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

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