Faculty Profiles - TAKASHIMA Hiroshi

Papers - TAKASHIMA Hiroshi

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Masayuki Wakita, Ran Takei, Fumio Miyashita, Yuki Hamada, Satoshi Ohyama, Hideki Matsuoka, Hiroshi Takashima . Carotid ultrasound features of anomalous left vertebral artery originating from the aortic arch proximal to the left subclavian artery . Neuroradiology Journal30 ( 2 ) 168 - 171 2017.4Reviewed International journal

Publisher：SAGE Publications Inc.

We present three cases of anomalous origin of the left vertebral artery (LVA) detected during the evaluation of stroke. The VA usually enters the transverse foramen of the sixth cervical vertebra (C6), but an anomalous LVA originating from the aorta frequently enters at a higher level. In our series, ultrasound of the LVA showed entry at C4 in two patients and at C5 in one patient. These findings suggested anomalous LVA origin, and three-dimensional computed tomography demonstrated the LVA arising from the aorta proximal to the left subclavian arteries. Carotid duplex ultrasound is useful for the diagnosis of this anomaly.

DOI： 10.1177/1971400916687585

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Hideaki Nishihara, Masatoshi Omoto, Masaki Takao, Yujiro Higuchi, Michiaki Koga, Motoharu Kawai, Hiroo Kawano, Eiji Ikeda, Hiroshi Takashima, Takashi Kanda . Autopsy case of the C12orf65 mutation in a patient with signs of mitochondrial dysfunction. . Neurology. Genetics3 ( 4 ) e171 2017Reviewed International journal

Language：English

OBJECTIVE: To describe the autopsy case of a patient with a homozygous 2-base deletion, c171_172delGA (p.N58fs), in the C12orf65 gene. METHODS: We described the clinical history, neuroimaging data, neuropathology, and genetic analysis of the patients with C12orf65 mutations. RESULTS: The patient was a Japanese woman with a history of delayed psychomotor development, primary amenorrhea, and gait disturbance in her 20s. She was hospitalized because of respiratory failure at the age of 60. Pectus excavatum, long fingers and toes, and pes cavus were revealed by physical examination. Her IQ score was 44. Neurologic examination revealed ophthalmoplegia, optic atrophy, dysphagia, distal dominant muscle weakness and atrophy, hyperreflexia at patellar tendon reflex, hyporeflexia at Achilles tendon reflex, and extensor plantar reflexes. At age 60, she died of pneumonia. Lactate levels were elevated in the patient's serum and CSF. T2-weighted brain MRI showed symmetrical hyperintense brainstem lesions. At autopsy, axial sections exposed symmetrical cyst formation with brownish lesions in the upper spinal cord, ventral medulla, pons, dorsal midbrain, and medial hypothalamus. Microscopic analysis of these areas demonstrated mild gliosis with rarefaction. Cell bodies in the choroid plexuses were eosinophilic and swollen. Electron microscopic examination revealed that these cells contained numerous abnormal mitochondria. Whole-exome sequencing revealed the 2-base deletion in C12orf65. CONCLUSIONS: We report an autopsy case of the C12orf65 mutation, and findings suggest that mitochondrial dysfunction may underlie the unique clinical presentations.

DOI： 10.1212/NXG.0000000000000171

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Takashima Hiroshi, Kuwabara Satoshi, Kuriyama Masaru, Iizuka Takahiro . Discussion on Clinical Diversity of Various Encephalitis/Encephalopathy . Nihon Naika Gakkai Zasshi106 ( 8 ) 1598 - 1610 2017International journal

Takashima Hiroshi . Diagnostic tips and treatment of autoimmune encephalopathy . Neurological Therapeutics34 ( 3 ) 160 - 162 2017Reviewed

Authorship：Lead author Language：Japanese Publisher：Japanese Society of Neurological Therapeutics

Autoimmune encephalopathies are clinically and immunologically heterogeneous disorders. Many different types of autoimmune encephalopathy have been discovered, and most common type may be Hashimoto encephalopathy in it. In clinical situations, we often recognize that patients with autoimmune encephalopathy are often misdiagnosed as exhibiting functional psychogenic movement, conversion, or somatoform disorders. We clinically analyzed 63 patients with autoimmune encephalopathy. Two–thirds of patients showed motor disturbance mostly with give–way weakness. About 70% of patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or fast neurologic pain. Most pain was distributed in manner that was not explainable anatomically. 27% of patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. We observed memory loss, PNES (psychogenic non–epileptic seizure), dissociative amnesia, hyperventilation, opsoclonus, epilepsy, or autonomic symptoms amongst our patients. Although give–way weakness, anatomically unexplainable pain, and strange involuntary movements were thought to be psychogenic, the presence of one of these three symptoms was indicative of autoimmune encephalopathy. As autoimmune encephalitis exhibits diffuse involvement with the whole brain, these symptoms were entirely understandable. Except for the presence of organic disease, most patients were classified into somatoform disorders or functional movement disorders. Without first excluding autoimmune encephalopathy, physicians should not diagnose somatoform disorders.

DOI： 10.15082/jsnt.34.3_160

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髙嶋博, 荒田仁, 東桂子, 松浦英治 . 子宮頸がんワクチンに関連した自己免疫脳症 . 神経治療学34 ( 6 ) S136 - S136 2017

Ikenoshita S., Nomura T., Shimazaki H., Uetani H., Nakahara K., Okazaki T., Imamura M., Mizutani H., Fudo A., Jo Y., Matsubara S., Higuchi Y., Hirai T., Takashima H., Ueda M. . Six novel SACS mutations expand the autosomal recessive spastic ataxia of Charlevoix–Saguenay spectrum . Orphanet Journal of Rare Diseases21 ( 1 ) 2026.12

Language：Japanese Publisher：Orphanet Journal of Rare Diseases

Background: The clinical spectrum of autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) in Asian populations remains incompletely defined. We aimed to characterize the clinical, radiological, and genetic features of Japanese patients with ARSACS and to expand the mutational and phenotypic spectrum of this disorder. Methods: We conducted a retrospective case series of patients diagnosed with ARSACS in our department between January 2016 and December 2023. Five patients from four families with biallelic SACS variants were identified. Results: Genetic analysis revealed seven pathogenic SACS variants, of which six were novel. Clinical heterogeneity was notable, with age at onset ranging from 1 to 27 years. Four patients showed classical ARSACS-related neuroimaging findings, whereas one patient presented with a Charcot–Marie–Tooth disease (CMT)-mimicking phenotype characterized by predominant peripheral neuropathy, mild cerebellar involvement, and absence of the classical pontocerebellar magnetic resonance imaging features. Conclusions: The recognition of CMT-mimicking presentations supports considering ARSACS in the differential diagnosis of hereditary peripheral neuropathies, particularly in patients with additional cerebellar, pyramidal, or supportive neuroimaging features.

DOI： 10.1186/s13023-026-04337-y

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Terahara M., Hobara T., Higuchi Y., Hirakata S., Noguchi Y., Nozuma S., Takashima H. . Isolated Paramedian Pontine Reticular Formation (PPRF) syndrome in AQP4 antibody–positive neuromyelitis optica spectrum disorder: a case report . BMC Neurology26 ( 1 ) 2026.12

Language：Japanese Publisher：BMC Neurology

Background: Paramedian pontine reticular formation (PPRF) syndrome is characterized by horizontal gaze palsy due to lesions in the PPRF or the abducens nucleus. It is relatively rare and is typically associated with medial longitudinal fasciculus (MLF) syndrome. Case presentation: A 53-year-old Japanese woman presented with right lateral gaze palsy and facial nerve palsy, with preserved convergence and left lateral gaze. Neurological evaluation confirmed PPRF syndrome and facial nerve palsy, with no involvement of the MLF. Brain MRI showed a lesion in the right dorsal pons, affecting the PPRF, abducens nucleus, and facial nerve. Serum testing revealed positive antinuclear and anti-AQP4 antibodies. The patient responded well to immunotherapy, with substantial clinical and radiological improvements. She was ultimately diagnosed with AQP4 antibody-positive NMOSD. Conclusion: This is the first documented case of isolated PPRF syndrome in AQP4 antibody–positive NMOSD. The findings expand the known phenotypic spectrum of NMOSD and highlight the importance of considering NMOSD, with targeted AQP4 antibody testing, in patients presenting with isolated PPRF syndrome.

DOI： 10.1186/s12883-026-04670-6

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Dozono M., Nozuma S., Yoshida T., Kodama D., Matsuzaki T., Matsuura E., Tanaka M., Takashima H., Kubota R. . HTLV-1-Infected CD4+ T Cells Drive Spontaneous Lymphoproliferation and Virus-Specific CD8+ Cytotoxic T Lymphocyte Expansion in HAM/TSP . Neurology R Neuroimmunology Neuroinflammation13 ( 4 ) e200581 2026.7

Language：Japanese Publisher：Neurology R Neuroimmunology Neuroinflammation

BACKGROUND AND OBJECTIVES: Spontaneous lymphoproliferation (SP) is an ex vivo phenomenon where lymphocytes proliferate without exogenous stimulation in peripheral blood mononuclear cells (PBMCs) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). SP is thought to reflect spinal cord pathology in HAM/TSP, but its cellular mechanisms remain unclear. METHODS: PBMCs from 30 patients with HAM/TSP, 12 asymptomatic HTLV-1 carriers, and 8 healthy controls (HCs) were labeled with a proliferation tracer and cultured for 6 days without exogenous stimulation. Flow cytometry was used to identify T-cell subsets, HTLV-1-infected cells, and HTLV-1-specific cytotoxic T lymphocytes (CTLs). Additional analyses included CTL antigen specificity, proviral load (PVL), phenotypic profiling (differentiation, activation, exhaustion markers), and cytokine/chemokine quantification in culture supernatants. RESULTS: CD8+ T cells exhibited greater proliferation than CD4+ T cells during SP. Among proliferating CD4+ T cells, 38.15% were CADM1+, 61.84% were Tax+, and PVL analysis indicated that nearly all proliferating CD4+ T cells were HTLV-1 infected. The frequency of HTLV-1 Tax 301-309-specific CTLs among CD8+ T cells increased from 3.81% to 17.67% during SP. After a subsequent resting phase, IFN-γ responses were detected in 37.38% of CD8+ T cells to a Tax peptide mixture and in 33.42% to an HTLV-1 bZIP factor peptide mixture, together accounting for over 70% of proliferating CD8+ T cells. Sorted CD4+ T cells proliferated independently, whereas sorted CD8+ T cells did not; however, coculture with CD4+ T cells restored CD8+ T-cell proliferation. Proliferating infected cells exhibited a Th1 phenotype, and most proliferating T cells coexpressed activation and exhaustion markers with memory phenotypes. IL-6 and IFN-γ levels were significantly elevated in culture supernatants from patients with HAM/TSP compared with HCs. IFN-γ levels in SP supernatants correlated with CSF PVL. SP responses in HTLV-1 carriers were attenuated, with reduced proliferation compared with patients with HAM/TSP. DISCUSSION: SP is driven by HTLV-1-infected CD4+ T cells, which are essential for sustaining HTLV-1-specific CD8+ CTL expansion. This phenomenon appears to recapitulate certain immunologic features of neuroinflammation in HAM/TSP. This ex vivo model may help evaluate therapies targeting HTLV-1-infected cells and immune-mediated pathology.

DOI： 10.1212/NXI.0000000000200581

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Higuchi Y., Yoshizaki K., Nakanishi K., Yuan J., Hobara T., Kojima F., Hiramatsu Y., Ando M., Yoshimura A., Nozuma S., Sakiyama Y., Hashiguchi A., Okamoto Y., Matsuura E., Yamasaki R., Hashida H., Hisano T., Okada J., Hara T., Sakakima H., Suda K., Yoshida H., Yamaguchi M., Mitsui J., Tsuji S., Takashima H. . Biallelic variants in FAT3 cause axonal neuropathy with multisystem neurodevelopmental features . Genetics in Medicine28 ( 6 ) 102570 2026.6

Language：Japanese Publisher：Genetics in Medicine

Purpose Despite advances in diagnostics, many inherited peripheral neuropathies remain genetically unexplained. We investigated whether biallelic variants in FAT3 ( FAT Atypical Cadherin 3 ) are implicated in inherited axonal neuropathies. Methods We identified biallelic FAT3 variants in three unrelated individuals among 3315 Japanese patients with inherited peripheral neuropathies. Variants were evaluated by segregation analysis, in silico modeling, and functional studies in Drosophila and mouse models. Results All patients exhibited progressive distal muscle weakness and cranial nerve involvement, including tongue atrophy, dysarthria, and facial weakness. Two required ventilatory support because of respiratory muscle paralysis. One patient additionally showed central hypomyelination, autonomic dysfunction, and developmental anomalies, such as congenital scoliosis and intestinal pseudo-obstruction. Identified variants were ultrarare, affected conserved residues, segregated with disease, and were predicted to impair domain stability. FAT3 knockdown in Drosophila resulted in rough eye phenotype, shortened lifespan, impaired motor function, and defective motor neuron branching. Fat3 knockout and knockin mice displayed perinatal lethality, sciatic nerve axonal degeneration, and central nervous system abnormalities despite preserved motor performance. Conclusion Our findings establish FAT3 as a novel gene for autosomal-recessive axonal neuropathies and support the concept of a FAT3 -related multisystem neurodevelopmental disorder characterized by motor neuron degeneration and systemic abnormalities.

DOI： 10.1016/j.gim.2026.102570

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Okada T, Miyashita F, Hiramine T, Tsuruzono N, Watanabe O, Takashima H . Cancer-Associated Stroke Complicated by Heparin-Induced Thrombocytopenia: A case report. . Internal medicine (Tokyo, Japan) 2026.5

Hamada Y., Matsuoka H., Sato T., Hamada K., Shimada T., Kawabata Y., Iwamoto K., Ikeda M., Takaguchi G., Higuchi Y., Takashima H. . Mid-term systolic BP variability beyond 24 h after successful recanalization predicts poor outcomes following ischemic stroke . Hypertension Research49 ( 5 ) 1610 - 1620 2026.5

Language：Japanese Publisher：Hypertension Research

Although intensive blood pressure (BP) lowering after mechanical thrombectomy (MT) may adversely affect outcomes, the prognostic significance of post-recanalization BP variability remains unclear. This study aimed to evaluate the association between systolic blood pressure (SBP) variability after successful recanalization and 90-day functional outcomes following MT. Among 342 consecutive patients who underwent MT between May 2014 and June 2025, 280 patients who achieved successful recanalization were included in this retrospective analysis. SBP was recorded from immediately after recanalization up to 72 h thereafter. BP variability indices, including variability independent of the mean (VIM), time rate, and coefficient of variation, were calculated. The primary outcome was defined as a modified Rankin Scale (mRS) score of 4–6 at 90 days. Associations between SBP variability and outcomes were assessed using multivariable logistic regression models. Of the 280 patients, 104 (37.1%) experienced poor functional outcomes. Higher SBP variability was significantly associated with unfavorable outcomes. In time-segmented analyses, only SBP variability during the 24–72-h period remained significantly associated with poor outcomes (aOR per 10-unit increase in VIM [VIM/10], 1.89; 95% CI, 1.20–3.06, p = 0.005). Sensitivity analyses excluding patients who received antihypertensive therapy during 24–72 h and those with symptomatic intracranial hemorrhage confirmed the robustness of the association between 24–72 h VIM and poor outcomes (aOR VIM/10, 1.94; 95% CI, 1.26–3.11, p = 0.003). In conclusion, these findings highlight the clinical importance of stabilizing BP beyond the first 24 h after recanalization.

DOI： 10.1038/s41440-026-02608-6

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Ando M., Okamoto Y., Higuchi Y., Yuan J.H., Yoshimura A., Yano C., Nagatomo R., Hobara T., Kojima F., Hiramatsu Y., Nozuma S., Sakiyama Y., Takashima H. . Arginine ameliorates motor and survival deficits in MFN2-Deficient Drosophila models . Neurotherapeutics23 ( 3 ) e00900 2026.4

Language：Japanese Publisher：Neurotherapeutics

Charcot-Marie-Tooth disease type 2 A (CMT2A) is an inherited axonal neuropathy linked to mutations in MFN2, a key regulator of mitochondrial dynamics. Currently, no effective drug therapies exist. l-arginine has shown promise in treating mitochondrial disorders, though its effect on MFN2-associated neuropathy remains uncertain. To investigate this, we used Drosophila models with the neuron-specific knockdown of Marf, the fly ortholog of MFN2, employing a temporally controlled GAL4/UAS system. Flies were administered different doses of l-arginine to examine its influence on motor ability and lifespan. To evaluate responses under mitochondrial stress, flies were also treated with rotenone, a mitochondrial complex I inhibitor. l-arginine markedly improved climbing performance under baseline conditions and extended lifespan under both baseline and stress conditions. However under rotenone-induced mitochondrial stress, high-dose l-arginine improved survival without a corresponding improvement in locomotor performance. These results support a neuroprotective role for l-arginine in MFN2-deficient Drosophila, possibly through effects on mitochondrial dynamics involving complex I. l-arginine may hold therapeutic promise for CMT2A, meriting further investigation in vertebrate models.

DOI： 10.1016/j.neurot.2026.e00900

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Sato Takeo, Tsuchimochi Yuka, Hamada Yuki, Kukihara Kaishi, Kawabata Yutaro, Iwamoto Kana, Takaguchi Go, Higuchi Yujiro, Matsuoka Hideki, Takashima Hiroshi . 【Current evidence and perspectives for hypertension management in Asia】Fibrosis-4 index and prognosis and hematoma volume: association with lobar and non-lobar intracerebral hemorrhage(タイトル和訳中) . Hypertension Research49 ( 3 ) 628 - 640 2026.3

Yoshida T, Nozuma S, Tanaka M, Dozono M, Kodama D, Matsuzaki T, Kondo T, Kubota R, Takashima H . Dimethyl fumarate as a promising therapeutic candidate for virus-associated myelopathy. . Brain : a journal of neurology 2026.2

Yuan J.H., Higuchi Y., Ando M., Yoshimura A., Nozuma S., Sakiyama Y., Kanda T., Nomoto M., Nakamura T., Nobuhara Y., Takashima H. . Functional and Epigenomic Consequences of DNMT1 Variants in Inherited Neurological Disorders . International Journal of Molecular Sciences27 ( 3 ) 2026.2

Language：Japanese Publisher：International Journal of Molecular Sciences

DNMT1 variants are linked to complex neurodegenerative syndromes, yet their variant-specific functional and epigenomic consequences remain poorly defined. DNMT1 variants were identified in eight patients using gene-panel or whole-exome sequencing. Functional effects were assessed by site-directed mutagenesis and transient expression in HEK293T cells. Genome-wide methylation profiling of peripheral blood leukocyte DNA was performed using Nanopore sequencing, enabling direct quantification of 5-methylcytosine (5mC). CpG island-level differential methylation and gene set enrichment analysis (GSEA) were conducted. Variants in the replication foci targeting sequence (RFTS) domain (p.Y511H, p.Y540C, p.H569R) exhibited reduced DNMT1 protein expression, decreased enzymatic activity, and cytosolic aggregation. Variants in the C-terminal catalytic domain (p.A1334V and p.P1546S) showed reduced protein expression with relatively mild enzymatic impairment. Patients carrying the p.Y511H variant demonstrated a significant reduction in global 5mC levels compared with controls. Principal component analysis revealed distinct methylomic profiles separating most patients from controls, with marked intra- and inter-familial heterogeneity. CpG island-level analysis identified a single significantly hypomethylated region in p.Y511H carriers, and GSEA revealed differential enrichment of multiple Gene Ontology biological pathways. This study defines domain-dependent functional effects of DNMT1 variants and provides the first nanopore-based methylome analysis, revealing variant-specific and heterogeneous epigenomic alterations.

DOI： 10.3390/ijms27031232

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Shiho Arishima, Masahiko Takahashi, Mika Dozono, Takashi Yoshida, Satoshi Nozuma, Hiroshi Takashima, Masahiro Fujii, Ryuji Kubota . Downregulation of the deubiquitinating enzyme USP10 correlates with neuronal apoptosis in HTLV-1-associated myelopathy. . Scientific reports16 ( 1 ) 6062 - 6062 2026.1International journal

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

UNLABELLED: Human T-cell leukemia virus type 1–associated myelopathy (HAM) is a chronic neuroinflammatory disease characterized by spinal cord neuronal loss. The mechanisms underlying this degeneration remain unclear. We investigated the role of ubiquitin-specific peptidase 10 (USP10), a regulator of oxidative stress and apoptosis, in HAM pathogenesis. Spinal cord tissues from eight HAM patients and two healthy controls (HCs) were analyzed by immunohistochemistry. We assessed USP10 expression, neuronal density (NeuN), apoptotic markers (TUNEL, active caspase-3), and p62, a stress-responsive regulator of autophagy and apoptosis. USP10 expression was markedly reduced in HAM neurons compared to HCs. This downregulation was associated with increased neuronal apoptosis and decreased NeuN-positive cell density, particularly among large neurons, and some surviving neurons showed diminished NeuN immunoreactivity. Reduced p62 expression was also observed in cases with low USP10 and high apoptotic activity. Notably, one HAM patient with preserved USP10 and p62 expression exhibited minimal neuronal loss and mild neurological symptoms. Although exploratory, this study supports an association between downregulation of USP10 and reduced p62 levels, and neuronal apoptosis and loss in HAM, and highlights USP10 as a potential regulator of neuronal survival, and a promising diagnostic or prognostic marker and a future therapeutic pathway in virus-induced neuroinflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37271-x.

DOI： 10.1038/s41598-026-37271-x

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Sato T., Tsuchimochi Y., Hamada Y., Kukihara K., Kawabata Y., Iwamoto K., Takaguchi G., Higuchi Y., Matsuoka H., Takashima H. . Severe cerebral small vessel disease burden is associated with intraventricular extension of intracerebral hemorrhage . Journal of the Neurological Sciences480 125680 2026.1

Language：Japanese Publisher：Journal of the Neurological Sciences

Objectives: Factors associated with intraventricular extension (IE) following intracerebral hemorrhage (ICH) are not fully clarified. We aimed to elucidate the correlation between IE and cerebral small vessel disease (SVD) in ICH. Materials & methods: Consecutive patients with acute ICH between July 2012 and November 2023 were screened. The inclusion criteria: 1) onset to door time within 7 days; 2) availability of SVD evaluation using total SVD score; and 3) availability of IE evaluation on admission and/or more than 24 h after admission. Total SVD score was calculated as the sum of the points for the following observations: old lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMBs), and enlarged perivascular spaces. Results: Of 608 ICH screened, 449 (234 [52 %] males, median age 75 years) were included. IE was observed in 151 (34 %). Total SVD score was independently associated with IE (prevalence ratio (PR) 1.188, 95 % confidence interval (CI) 1.063–1.329, p = 0.002). Further, a positive linear trend was observed between total SVD score and IE relative to a total SVD score of 0 (total SVD score 0: PR 1.000, total SVD score 1–2: PR 3.769, total SVD score 3–4: PR 4.109, p = 0.011 for trend). Among the items comprising the total SVD score, WMH (PR 1.406 95 % CI 1.041–1.899, p = 0.026) and CMBs (PR 1.800, 95 % CI 1.068–3.036, p = 0.027) were associated with IE. Conclusion: In acute ICH, higher total SVD score is associated with IE. In particular, WMH and CMBs might correlate with the occurrence of IE.

DOI： 10.1016/j.jns.2025.125680

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Nozuma S., Dozono M., Tanaka M., Kodama D., Yoshida T., Higuchi Y., Sakiyama Y., Matsuura E., Matsuzaki T., Takashima H., Kubota R. . HTLV-1-Specific CTL Accumulation in CSF Contributes to Neuroinflammation in HTLV-1-Associated Myelopathy . Neurology R Neuroimmunology Neuroinflammation13 ( 1 ) e200508 2026.1

Language：Japanese Publisher：Neurology R Neuroimmunology Neuroinflammation

BACKGROUND AND OBJECTIVES: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurologic disorder characterized by chronic inflammation in the CNS. HTLV-1-specific cytotoxic CD8+ T lymphocytes (CTLs) play a crucial role in the pathogenesis of HAM/TSP; however, the dynamics of CTLs in the CSF remain poorly understood. The aim of this study was to investigate the accumulation of HTLV-1-specific CTLs in the CSF of patients with HAM/TSP and to evaluate their association with neuroinflammation and neural damage. METHODS: The frequency of HTLV-1-specific CTLs was compared between paired peripheral blood (PB) and CSF from patients with HAM/TSP and asymptomatic HTLV-1 carriers (ACs) using MHC/antigen tetramers. In addition, cytokine levels and neurofilament light chain (NfL) concentration were analyzed in the CSF of patients with HAM/TSP and ACs. RESULTS: The frequency of HTLV-1-specific CTLs in PB was significantly higher in patients with HAM/TSP compared with ACs (median [interquartile range (IQR)] = 3.0 [0.9-8.3] % vs 0.3 [0.2-3.1] %, p < 0.01). Notably, this difference was even more pronounced in CSF, where patients with HAM/TSP exhibited a significantly elevated frequency compared with ACs (19.1 [7.9-33.4] % vs 6.1 [0.9-15.7] %, p < 0.01). Furthermore, the frequency of HTLV-1-specific CTLs in the CSF was considerably higher than in the PB of patients with HAM/TSP (p < 0.0001). The lack of accumulation of cytomegalovirus-specific CTLs indicates that HTLV-1-specific CTLs selectively accumulate in the CSF of patients with HAM/TSP. These accumulated HTLV-1-specific CTLs in the CSF significantly correlated with increased levels of cytokines in patients with HAM/TSP. In addition, CSF NfL levels were significantly higher in patients with HAM/TSP than in ACs (696 [534-1,407] vs 429 [373-717] pg/mL, p < 0.05) and showed a positive correlation with HTLV-1 proviral load. DISCUSSION: HTLV-1-specific CTLs selectively accumulate in the CSF of patients with HAM/TSP. Chronic inflammation, primarily driven by the interaction between proliferating HTLV-1-infected cells and accumulated HTLV-1-specific CTLs, may contribute to neural damage in patients with HAM/TSP.

DOI： 10.1212/NXI.0000000000200508

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Tsuchimoto K., Mori A., Tanaka M., Arishima S., Kodama D., Dozono M., Nozuma S., Takashima H., Kubota R. . CXCR3/CXCL10 Axis-Mediated T Cell Infiltration in the Lungs of Patients With HTLV-1-Associated Diseases: Implications for Subclinical Pulmonary Involvement . Journal of Medical Virology98 ( 1 ) e70804 2026.1

Language：Japanese Publisher：Journal of Medical Virology

HTLV-1 is a retrovirus associated with adult T cell leukemia/lymphoma (ATL) and inflammatory diseases, including HTLV-1-associated myelopathy (HAM) and HTLV-1-associated bronchopneumonopathy (HAB). Although pulmonary complications are common in HTLV-1-associated diseases, the underlying mechanisms remain unclear. We compared HTLV-1 proviral load (PVL) and chemokine receptor expression in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ACs) and patients with HAB, HAM, or ATL. T cell subsets were analyzed by flow cytometry, and the expression of CXCR3 and CXCL10 in lung tissue was assessed by immunohistochemistry. HTLV-1 proviral DNA was detectable in BAL cells not only from HAB and ATL cases with pulmonary involvement, but also from some ACs and HAM cases without clinical respiratory symptoms, suggesting subclinical pulmonary infiltration. BAL samples from HAB and ATL showed increased CD8 + T cell frequency. Both CD4+ and CD8 + T cells in BAL expressed higher CXCR3 than their PBMC counterparts, whereas CCR4 and CXCR5 were not elevated. CADM1 + CD4 + T cells in BAL also exhibited higher CXCR3 than in PBMCs, and CXCR3+ frequencies were similar between CADM1+ and CADM1- CD4 + T cells within BAL, indicating that enhanced CXCR3 expression was largely independent of infection status. Histology revealed CD3+ mononuclear cell infiltration in alveolar septa and peribronchiolar regions in HAB and HAM, consistent with T cell–mediated alveolitis and bronchiolitis, and CXCL10 expression was elevated in infiltrated lesions. Collectively, these findings implicate the CXCR3/CXCL10 axis as a common pathway for pulmonary T cell recruitment in HTLV-1-associated diseases.

DOI： 10.1002/jmv.70804

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Hamada Yuki, Yotsumoto Tetsu, Matsuoka Hideki, Mitsuhashi Hakuryu, Yoshidome Moe, Yamanaka Nao, Kawabata Yutaro, Iwamoto Kana, Ikeda Mei, Hamada Kyosuke, Sato Takeo, Higuchi Yujiro, Takashima Hiroshi . Factors Contributing to Residents’ Interest in Stroke Care: A Questionnaire Survey . Japanese Journal of Stroke48 ( 2 ) 63 - 70 2026

Language：Japanese Publisher：The Japan Stroke Society

Background and Purpose: Fostering young physicians who are interested in stroke care is an important challenge. This study aimed to identify factors that influence interest in stroke care among physicians who underwent initial clinical training at our institution. Methods: We conducted a questionnaire-based survey targeting physicians in their 1st to 7th postgraduate years who had trained at our hospital. The primary outcome was the change in interest in stroke care before and after the training in our department. We performed exploratory factor analysis (EFA) and conducted multivariate analysis based on the identified factors. Results: Responses were obtained from 58 out of 85 physicians (68.2%). In the multivariate analysis, only a specific factor—comprising participation in emergency department care, one-on-one lectures by individual physicians, scrub-in experiences, and hands-on procedures such as arterial puncture during cerebral angiography—was independently associated with an increased interest in stroke care (adjusted odds ratio: 7.6, 95% CI: 1.39–57.1, p=0.018). Conclusion: These findings suggest that providing hands-on practical experiences alongside building strong interpersonal relationships may be key to enhancing interest and aspiration toward stroke care among young physicians.

DOI： 10.3995/jstroke.11362

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