Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.1080/10428194.2023.2199895

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.0395-22

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

DOI： 10.1002/mds.29186

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mds.29186

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

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. Case presentation: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

DOI： 10.3390/jcm11195548

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

We report two patients with autosomal dominant neuronal intranuclear inclusion disease (NIID) harboring the biallelic GGC repeat expansion in NOTCH2NLC to uncover the impact of repeat expansion zygosity on the clinical phenotype. The zygosity of the entire NOTCH2NLC GGC repeat expansion and DNA methylation were comprehensively evaluated using fluorescent amplicon length PCR (AL-PCR), Southern blotting and targeted long-read sequencing, and detailed genetic/epigenetic and clinical features were described. In AL-PCR, we could not recognize the wild-type allele in both patients. Targeted long-read sequencing revealed that one patient harbored a homozygous repeat expansion. The other patient harbored compound heterozygous repeat expansions. The GGC repeats and the nearest CpG island were hypomethylated in all expanded alleles in both patients. Both patients harboring the biallelic GGC repeat expansion showed a typical dementia-dominant NIID phenotype. In conclusion, the biallelic GGC repeat expansion in two typical NIID patients indicated that NOTCH2NLC-related diseases could be completely dominant.

DOI： 10.1016/j.ygeno.2022.110469

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

BACKGROUND: We recently developed a positron emission tomography (PET) probe, [¹⁸ F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed. OBJECTIVE: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities. METHODS: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross-validation linear classification analysis with a one-versus-the-rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve. We defined PSP- and AD-tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others. RESULTS: The discriminatory ability of PSP- and AD-tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSP-tau scores correlated with the PSP rating scale in patients with PSP, and AD-tau scores correlated with Mini-Mental State Examination scores in healthy control-AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP- and AD-tau scores, respectively. CONCLUSIONS: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

DOI： 10.1002/mds.29173

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mds.29173

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

DOI： 10.1111/neup.12811

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/neup.12811

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

Abstract

Myotonic dystrophy type 1 is a multisystem genetic disorder involving the muscle, heart and CNS. It is caused by toxic RNA transcription from expanded CTG repeats in the 3′-untranslated region of DMPK, leading to dysregulated splicing of various genes and multisystemic symptoms. Although aberrant splicing of several genes has been identified as the cause of some muscular symptoms, the pathogenesis of CNS symptoms prevalent in patients with myotonic dystrophy type 1 remains unelucidated, possibly due to a limitation in studying a diverse mixture of different cell types, including neuronal cells and glial cells. Previous studies revealed neuronal loss in the cortex, myelin loss in the white matter and the presence of axonal neuropathy in patients with myotonic dystrophy type 1. To elucidate the CNS pathogenesis, we investigated cell type-specific abnormalities in cortical neurons, white matter glial cells and spinal motor neurons via laser-capture microdissection. We observed that the CTG repeat instability and cytosine–phosphate–guanine (CpG) methylation status varied among the CNS cell lineages; cortical neurons had more unstable and longer repeats with higher CpG methylation than white matter glial cells, and spinal motor neurons had more stable repeats with lower methylation status. We also identified splicing abnormalities in each CNS cell lineage, such as DLGAP1 in white matter glial cells and CAMKK2 in spinal motor neurons. Furthermore, we demonstrated that aberrant splicing of CAMKK2 is associated with abnormal neurite morphology in myotonic dystrophy type 1 motor neurons. Our laser-capture microdissection-based study revealed cell type-dependent genetic, epigenetic and splicing abnormalities in myotonic dystrophy type 1 CNS, indicating the significant potential of cell type-specific analysis in elucidating the CNS pathogenesis.

DOI： 10.1093/braincomms/fcac154

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Other Link： https://academic.oup.com/braincomms/article-pdf/4/3/fcac154/44180640/fcac154.pdf

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

DOI： 10.1111/nan.12805

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

We report two patients with meningoencephalomyelitis without evidence of extra central nervous system (CNS) involvement. Brain MRI showed linear perivascular radial gadolinium enhancement patterns and spinal cord MRI showed longitudinal extensive T2-hyperintensity lesions. Pathological findings from brain biopsies were angiocentric T-cell predominant lymphoid infiltrates that lacked Epstein-Barr virus-positive atypical B cells. The patients were initially suspected to have isolated CNS-lymphomatoid granulomatosis (LYG). Thereafter, glial fibrillary acidic protein (GFAP)-immunoglobulin G were detected in their cerebrospinal fluid. This finding suggested autoimmune GFAP astrocytopathy. We speculate there is a link between isolated CNS-LYG and autoimmune GFAP astrocytopathy.

DOI： 10.1016/j.jneuroim.2021.577748

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Authorship：Corresponding author   Language：English  

DOI： 10.1136/jnnp-2021-326257

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

Progressive supranuclear palsy (PSP) presents with a wide variety of signs/symptoms, making early initial diagnosis difficult. We investigated the clinical and neuropathological features of five patients with autopsy-proven PSP of short duration, ranging from 11 to 41 months (average, 26.2 months) due to unexpected death, focusing particularly on the distribution and severity of neuronal loss as well as neuronal and glial tau pathology in the affected brain. Clinical features were studied retrospectively through careful review of the medical records, and neuropathological examinations were carried out, along with tau immunohistochemistry using a monoclonal antibody AT8. These patients were diagnosed as having probable PSP (n = 4) and suggestive PSP (n = 1), respectively. In all cases, neuronal loss was evident in the substantia nigra, subthalamic nucleus, globus pallidus, and locus ceruleus. AT8-identified tau lesions, that is, pretangles/neurofibrillary tangles (PTs/NFTs), tufted astrocytes (TAs), and coiled bodies/neuropil threads (CBs/NTs), were distributed widely in the brain regions, especially in patients with longer disease duration. All cases showed variation in the regional tau burden among PTs/NFTs, TAs, and CBs/NTs. There was also a tendency for tau deposition to be more predominant in neuronal cells in the brainstem and cerebellum and in glial cells in the cerebral cortex and subcortical gray matter. These findings suggest that in PSP, the initial signs/symptoms are associated with degeneration and subsequent death of neurons with pathological tau deposition, and that the tau deposition in neuronal cells is independent of that in glial cells.

DOI： 10.1111/neup.12707

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

Correspondence: Hiroshi Shimizu

DOI： 10.1186/s40478-020-00945-2

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Other Link： https://link.springer.com/article/10.1186/s40478-020-00945-2/fulltext.html

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

Correspondence: Hiroshi Shimizu

DOI： 10.1002/ana.25652

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ana.25652

Authorship：Lead author  

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Language：English  

Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. A 15-month-old male infant presented with left-sided ptosis. Initially, the family denied any family history of inherited diseases, but later disclosed a family history of agammaglobulinemia previously diagnosed in two family members. In the early 1980s, one of the elder brothers of the index patient's mother who had been treated with intramuscular immunoglobulin [or later intravenous immunoglobulin (IVIG)] for agammaglobulinemia deceased at 10 years of age after showing progressive neurological deterioration during the last several years of his life. The index patient was diagnosed with XLA caused by Bruton tyrosine kinase deficiency (654delG; Val219Leufs*9), and chronic meningoencephalitis with an unknown infectious etiology. Magnetic resonance imaging of the brain demonstrated inflammatory changes in the basal ganglia, hypothalamus, midbrain, and pons, with multiple nodular lesions with ring enhancement, which showed impressive amelioration after the initiation of IVIG replacement therapy. Pleocytosis, which was characterized by an increase in CD4-positive and CD8-positive T cells expressing an activation marker and an elevation in inflammatory cytokines in the cerebrospinal fluid, was identified. No microorganism was identified as a cause of CNS complications. He thereafter developed brain infarction at 19 months of age and fatal status epilepticus at 5 years of age, despite regular IVIG with high trough levels and regular intraventricular immunoglobulin administration. The etiology of this rare CNS complication in XLA is currently unknown. Previous studies have suggested a possible association of IVIG, which was clearly denied in our index case because of the demonstration of his neurological disorder at presentation. In the future, extensive and unbiased molecular methods to detect causative microorganisms, as well as to investigate the possible role of autoimmunity are needed to clarify the etiology of CNS complications.

DOI： 10.3389/fped.2020.00579

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

Abstract

Fatal familial insomnia is a genetic prion disease, which is associated with the aspartic acid to asparagine substitution at codon 178 of the prion protein gene. Although the hallmark pathological feature is thalamic and olivary degeneration, there is a patient with an atypical fatal familial insomnia without the hallmark feature. The cause of the pathological variability is unclear. We analysed a Japanese fatal familial insomnia kindred and compared one atypical clinicopathological fatal familial insomnia phenotype case and typical fatal familial insomnia phenotype cases with transmission studies using multiple lines of knock-in mice and with protein misfolding cyclic amplification. We also analysed the transmissibility and the amplification properties of sporadic fatal insomnia. Transmission studies revealed that the typical fatal familial insomnia with thalamic and olivary degeneration showed successful transmission only using knock-in mice expressing human–mouse chimeric prion protein gene. The atypical fatal familial insomnia with spongiform changes showed successful transmission only using knock-in mice expressing bank vole prion protein gene. Two sporadic fatal insomnia cases with thalamic and olivary degeneration showed the same transmissibility as the typical fatal familial insomnia phenotype. Interestingly, one sporadic fatal insomnia case with thalamic/olivary degeneration and spongiform changes showed transmissibility of both the typical and atypical fatal familial insomnia phenotypes. Protein misfolding cyclic amplification could amplify both typical fatal familial insomnia cases and sporadic fatal insomnia cases but not the atypical fatal familial insomnia phenotype or other sporadic Creutzfeldt–Jakob disease subtypes. In addition to clinical findings and neuropathological features, the transmission properties and the amplification properties were different between the typical and atypical fatal familial insomnia phenotypes. It is suggested that two distinct prions were associated with the diversity in the fatal familial insomnia phenotype, and these two prions could also be detected in sporadic fatal insomnia.

DOI： 10.1093/braincomms/fcz045

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Other Link： http://academic.oup.com/braincomms/article-pdf/1/1/fcz045/33639239/fcz045.pdf

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

DOI： 10.1016/j.autneu.2019.102583

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.1080/13506129.2019.1632829

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

DOI： 10.1016/j.legalmed.2019.04.005

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

DOI： 10.1093/jnen/nly082

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

DOI： 10.1111/epi.13700

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

We previously reported familial amyotrophic lateral sclerosis (FALS) of 11years duration in a 57-year-old woman, who received artificial ventilation for 5years prior to death and exhibited widespread multisystem degeneration and neurofilamentous aggregates, so-called conglomerate inclusions (CIs). In the present study, we re-evaluated this autopsied patient (proband) with further immunohistochemical observation as well as mutational analysis of the superoxide dismutase 1 (SOD1) gene. A review of the clinical features of the proband's family revealed five affected members (including the proband) over two successive generations who showed marked variability in clinical presentation, such as the age at onset. The proband was found to harbor a heterozygous missense mutation in exon 4 (I104F) of the SOD1 gene. In the brain and spinal cord, SOD1-positive neuronal cytoplasmic inclusions (NCIs) were found to be more widely distributed than CIs, the latter being weakly positive for SOD1. No Lewy body-like hyaline inclusions were found. This is considered to be the first description of an autopsy case of FALS with an I104F SOD1 gene mutation, suggesting that combination of marked intra-familial clinical variability and multisystem degeneration with occurrence of CIs and SOD1-positive NCIs is a characteristic feature of FALS with this SOD1 gene mutation.

DOI： 10.1111/neup.12324

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

DOI： 10.1186/s40478-016-0335-2

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

DOI： 10.1016/j.ajhg.2016.08.005

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

DOI： 10.1007/s00401-016-1588-3

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Other Link： http://link.springer.com/article/10.1007/s00401-016-1588-3/fulltext.html

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

DOI： 10.1111/bpa.12262

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

DOI： 10.1007/s00401-013-1150-5

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Other Link： http://link.springer.com/article/10.1007/s00401-013-1150-5/fulltext.html

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

DOI： 10.1111/neup.12005

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/neup.12005

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

DOI： 10.1007/s00701-011-1250-8

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Other Link： http://link.springer.com/article/10.1007/s00701-011-1250-8/fulltext.html

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Hiroshi Shimizu, Mitsunori Yamada, Yasuko Toyoshima, Takeshi Ikeuchi, Osamu Onodera, Hitoshi Takahashi

DOI： 10.1007/s00401-010-0699-5

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Other Link： http://link.springer.com/article/10.1007/s00401-010-0699-5/fulltext.html

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

DOI： 10.1111/j.1440-1789.2009.01019.x

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CiNii Article

CiNii Books

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Correspondence: Hiroshi Shimizu
Hiroshi Shimizu, Akiyoshi Kakita, Hitoshi Takahashi

DOI： 10.1007/s00401-007-0321-7

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Other Link： http://link.springer.com/article/10.1007/s00401-007-0321-7/fulltext.html

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Total pages：358   Responsible for pages：300-307   Language：Japanese Book type：Scholarly book

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Total pages：435   Responsible for pages：374-378   Language：Japanese Book type：Textbook, survey, introduction

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Responsible for pages：332  

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Responsible for pages：334  

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Presentation type：Symposium, workshop panel (public)  

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