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Shoji Tsuji

Publications and source records attributed to Shoji Tsuji.

At least 19 recordsLinked to original sources
PubMed2026

Reversible exacerbation of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PTEN hamartoma tumor syndrome and young-onset Parkinson's disease.

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS), caused by germline loss-of-function variants in PTEN, typically manifests as macrocephaly, neurodevelopmental disorders, and cancer susceptibility. Parkinson's disease has not been recognized as part of its known neurological spectrum. METHODS: We describe the clinical course of a patient with a germline PTEN nonsense variant (p.Arg130Ter) who developed young-onset Parkinson's disease before being diagnosed with bilateral breast cancer. RESULTS: The patient developed asymmetric, levodopa-responsive parkinsonism at 35 years of age, with reduced bilateral striatal dopamine transporter uptake. During two cycles of epirubicin-cyclophosphamide chemotherapy, her previously well-controlled parkinsonism showed reproducible and severe exacerbations. Symptoms began several days after chemotherapy, reached their maximum severity approximately one week after treatment, and resolved completely within approximately two weeks without modification of her antiparkinsonian medications. No dehydration, electrolyte disturbance, infection, or exposure to dopamine-receptor antagonists was identified. The chemotherapy regimen was discontinued after the second episode because of the reproducible temporal association. CONCLUSIONS: This case demonstrates reproducible, fully reversible exacerbations of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PHTS and young-onset Parkinson's disease. These episodes may reflect transient vulnerability of dopaminergic neurons to chemotherapy-related systemic stress, although the causal role of PTEN haploinsufficiency remains uncertain.

Humans↗
PubMed2026

Detection rate of pathogenic variants by postmortem genetic testing for sudden cardiac death among children and young adults: systematic review and meta-analysis.

PURPOSE: Postmortem genetic testing (PMGT) can clarify the causes of sudden cardiac death (SCD) in children and young adults and provide preventive care for relatives. We systematically reviewed studies to estimate the detection rate of pathogenic variants identified by PMGT in SCD cases aged 1-50 years and examined factors influencing detection rates. METHODS: Ovid MEDLINE and Ovid Embase were searched for observational studies on PMGT in cases of SCD, records in duplicate were screened, and study- and variant-level data were extracted. Risk of bias was assessed using the Joanna Briggs Institute checklist. The pooled detection rates were estimated using random-effects meta-analysis, and heterogeneity was explored based on subgroup and meta-regression analyses. RESULTS: Sixty-six studies (4,452 cases from 23 countries) were included. The pooled detection rate was 19% (95% confidence interval, 15% to 24%). Among the detected pathogenic variants, 76% were found in genes included on the ACMG Secondary Findings list. Higher detection rates were associated with earlier publication years, lower mean age, and lower risk of bias. Substantial between-study heterogeneity persisted (I2 = 91%) despite the subgroup and meta-regression analyses. CONCLUSION: PMGT can be used to identify pathogenic variants in young SCD cases, however, there is considerable heterogeneity in study conditions.

Forensic genetics↗
PubMed2025

Vanishing White Matter Disease With EIF2B2 c.254 >A Variant: Mild Clinical and MRI Findings.

OBJECTIVES: Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges. METHODS: We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant. RESULTS: A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance. DISCUSSION: This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings.

Journal Article↗
PubMed2025

Neurology pioneers in Japan.

The pioneers of neurology in Japan were professors Hiroshi Kawahara and Kinnosuke Miura. Kawahara published the first description of progressive bulbar palsy and wrote the first neurology textbook in Japan. Miura, on the other hand, published studies about amyotrophic lateral sclerosis, in addition to participating in the founding of the Japanese Society of Neurology. The influence of European neurology, particularly French and German, in the figures of Professor Jean-Martin Charcot and Professor Erwin Bälz, was fundamental in the consolidation of neurology in Japan.

Japan↗
PubMed2006

Neuronal atrophy and synaptic alteration in a mouse model of dentatorubral-pallidoluysian atrophy.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a hereditary spinocerebellar degeneration caused by expansion of a CAG repeat in the disease protein. Despite the restricted and stable brain lesions, DRPLA patients show a variety of clinical symptoms and the brain exhibits generalized atrophy. In previous studies of DRPLA, we proposed that intranuclear diffuse accumulation of the mutant protein is a significant pathological feature of neurons, and that the variable prevalence of this pathology may be relevant to the variation of symptoms observed in patients with different repeat sizes. In this study, to elucidate the pathogenesis of the brain atrophy in DRPLA, we conducted morphological and statistical analyses of neurons affected by the polyglutamine pathology in DRPLA transgenic (Tg) mice with 129 polyglutamine stretches. Golgi-impregnated pyramidal neurons in cerebral cortical layer V of 15-week-old Tg mice showed significant atrophy of the perikarya and dendrites. Dendritic spines were decreased in number and size, and showed a change in morphology resulting in dominance of stubby spines. Interestingly, dendritic arborization was preserved. Electron microscopy revealed that axons in the pyramis and corpus callosum were also atrophic. The number of axonal microtubules was preserved; however, the inter-microtubule spacing was significantly decreased. In the neuropil of cerebral cortical layers II and III, atrophy of the pre-synaptic areas and lengths of the post-synaptic density was detected, but synaptic vesicle diameter was preserved. These results suggest that neuronal atrophy is an essential feature of the cell pathology in DRPLA and that this is closely related to polyglutamine pathogenesis and development of the clinical phenotype.

Animals↗
PubMed2006

Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis.

OBJECTIVE: To elucidate the long-term therapeutic efficacy and safety of low-dose FK506 (tacrolimus) in patients with myasthenia gravis (MG). PATIENTS AND METHODS: We treated nine patients with MG (all women: age range: 35-83 years (mean: 51.1 years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients) with FK506 for more than 24 months (observation period: 24-46 months). All the patients had undergone extended thymectomy before FK506 treatment; two patients (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We evaluated total Quantitative MG (Q-MG) score, anti-acetylcholine receptor (AChR) antibody titer in the blood, interleukin 2 (IL-2) production in peripheral blood mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and adverse effects of FK506. RESULTS: A reduction in steroid dosage of 50% without worsening of the symptoms was observed 1 year after FK506 administration in three out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0-39 points) at 6 months and 1 year after FK506 administration improved by 3 points or more in six (66.7%) and seven (77.8%) out of nine patients, respectively. The efficacy of FK506 was maintained for more than 2 years. Although adverse effects were observed in three patients (33.3%), these were not serious. CONCLUSIONS: Our study indicates that low-dose FK506 treatment may be efficacious not only in controlling intractable myasthenic symptoms, but also in reducing steroid dosage, and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a maximum of 3 years.

Adult↗
PubMed2006

Polymyositis associated with focal mesangial proliferative glomerulonephritis with depositions of immune complexes.

A 58-year-old man concurrently developed polymyositis (PM), interstitial lung disease, and nephrotic-range proteinuria. Renal biopsy revealed focal mesangial proliferative glomerulonephritis (mesPGN) with depositions of immunoglobulin and complements. A combination therapy of corticosteroid, intravenous immunoglobulin, and cyclosporine was found very effective for the patient. Glomerulonephritis associated with PM/dermatomyositis (DM) is rare. In our review of related literature, mesPGN was exclusively observed in polymyositis while membranous nephropathy in DM. The mechanism underlying the association between myositis and glomerulonephritis remains to be elucidated.

Glomerulonephritis↗
PubMed2006

Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease.

Decreased cardiac uptake in (123)I-metaiodobenzylguanidine (MIBG) scintigraphy has been adopted as one of the most reliable diagnostic tests for Parkinson disease (PD) in Japan. To investigate the morphological basis for this finding, we performed a detailed neuropathological study of the cardiac sympathetic nervous system of a 71-year-old autopsy-proven PD patient, who presented with a marked decrease in cardiac uptake of MIBG, just 1 year prior to death. We carefully examined the intermediolateral column at several levels of the thoracic spinal cord, the sympathetic trunk and ganglia, and the nerve plexus of the anterior wall of the left ventricle and compared the findings with those of five age-matched controls. We found that the cardiac plexus was more heavily involved than the sympathetic ganglia in this patient with PD. Our study may provide further evidence that the markedly decreased cardiac uptake of MIBG observed in PD cases represents preferential involvement of the cardiac sympathetic nerve plexus in this disorder.

3-Iodobenzylguanidine↗
PubMed2006

A positron emission tomography study on the role of nigral lesions in parkinsonism in patients with amyotrophic lateral sclerosis.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) sometimes exhibit parkinsonism, but the lesion responsible for parkinsonism has not been extensively studied. OBJECTIVE: To test whether nigrostriatal system dysfunction is responsible for parkinsonism in ALS. DESIGN: From the 182 ALS patients who were admitted to our neurology ward during the past 10 years, we extracted all the patients who satisfied the criteria of both parkinsonism and ALS. SETTING: The University of Tokyo Hospital. METHODS: We conducted [(18)F]L-dopa and [(11)C]N-methylspiperone positron emission tomography and technetium Tc 99m hexamethylpropyleneamine oxime single-photon emission computed tomography studies on 5 patients with ALS manifesting overt parkinsonism. RESULTS: Two male and 3 female patients (average age, 63.2 +/- 5.8 years) had ALS for an average of 28.6 +/- 21.5 months and had parkinsonism for an average of 15.2 +/- 11.4 months. Features of their parkinsonism were characterized by outstanding bradykinesia without resting tremor or dementia. The results of positron emission tomography studies indicated normal nigrostriatal function, but those of single-photon emission computed tomography demonstrated decreased blood flow in the frontotemporal cortices. CONCLUSION: It is likely that parkinsonism in ALS is due to cortical lesions rather than nigrostriatal dysfunction and that both symptoms are the clinical manifestation of frontotemporal dementia with motor neuron diseases, including classic ALS.

Aged↗
PubMed2006

Polyglutamine disease: recent advances in the neuropathology of dentatorubral-pallidoluysian atrophy.

Polyglutamine diseases are hereditary neurodegenerative disorders that are caused by the expansion of a CAG repeat in the causative genes. They comprise at least nine disorders, including DRPLA, HD, and Machado-Joseph disease. Initially, the discovery of neuronal intranuclear inclusions (NIIs) in human brains and in a murine model of HD provided a plausible hypothesis that the expression of expanded polyglutamine stretches leads to NII formation, resulting in neuronal cell death in selective brain regions characteristic to each disease. Recent studies, however, suggest that nuclear dysfunction, especially transcriptional abnormalities caused by the diffuse intranuclear accumulation of mutant proteins, plays a pivotal role in the development and progression of clinical symptoms. Polyglutamine diseases have a similarity with neuronal storage disease, and this pathological process might become a target for the establishment of an effective therapy for these diseases.

Animals↗
PubMed2006

[A case of small cell carcinoma of the lung associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome].

A 51-year-old male who showed severe ataxia, dysarthria, bilateral blepharoptosis, diplopia and nystagmus with the subacute onset was reported. The chest roentgenogram and CT scan revealed mass lesions at the hilus of the left lung. The tumor markers, NSE and ProGRP, were elevated; 12.8 ng/ml (< or = 10) and 140.7 pg/ml (< or = 46), respectively. The biopsy was performed surgically and the small cell carcinoma of the lung was confirmed pathologically. His cerebellar symptoms were considered to be caused by the paraneoplastc cerebellar degeneration. However, the blepharoptosis was peculiar. The electrophysiological studies were carried out The muscle strength test of the right APB muscle was 5. But the supramaximum stimulation of the right median nerve evoked only 2.0 mV of CMAP of the right APB muscle. The repetitive stimulation tests of the same nerve showed that 3 Hz stimulation resulted in 42% waning but 20 Hz stimulation evoked no waxing. The post-exercise test of the right APB muscle showed 73% increase of the CMAP. These findings indicated that he also suffered from Lambert-Eaton myasthenic syndrome. The titer of the antibody against the P/Q type voltage-gated calcium channel (VGCC) was remarkably elevated, 1,920 pM. None of the following antibodies were detected ; they included antibodies against acetylcholine receptor, Hu, Yo, Ri, Ma-2, CRMP-5, amphiphysin and glutamic acid dehydrogenase. The small cell carcinoma was treated with the combination of irinotecan hydrochloride and cisplatin, leading to the reduction of the mass lesions and the tumor markers. His cerebellar symptoms improved slightly but his blepharoptosis was unchanged. The titer of antibody against the P/Q type VGCC reduced remarkably to 451.8 pM. We reviewed reported cases associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and discussed the relation between the paraneoplastic syndromes and autoantibodies.

Carcinoma, Small Cell↗
PubMed2006

[Oral cyclophosphamide therapy for multifocal fibrosclerosis with hypertrophic intracranial pachymeningitis].

A 54-year-old man was admitted to our hospital because of a headache, dry cough, low grade fever and hearing loss sustained for 6 months. Physical and neurological examinations revealed bilateral conjunctival hyperemia, fine crackles in the lower lungs, cutaneous scars, horizontal gaze evoked nystagmus, bilateral moderate sensorineural deafness and mild hyperreflexia. Hypertrophic intracranial pachymeningitis (HIP) accompanied by episcleritis, pulmonary fibrosis, subcutaneous fibrosis of the trunk and upper limbs, bilateral chronic otitis media and sinusitis of the paranasal cavities were observed. Histopathological investigation of biopsied tissues from the dura matter, lung, skin and nasal mucosa showed marked fibrosis with lymphocyte and plasma cell infiltrations. The diagnosis of multifocal fibrosclerosis (MF) was made; this is a rare syndrome of unknown etiology characterized by fibrosis involving multiple organ systems. Although steroid pulse therapy and cyclophosphamide (CP) pulse therapy was not effective in his illnesses, the combination therapy of corticosteroid and oral CP was dramatically effective. We concluded that HIP can be a manifestation of MF, and additional oral CP should be considered as a treatment for steroid-resistant MF with HIP.

Administration, Oral↗
PubMed2006

[An autopsied case of a woman with rheumatoid arthritis attacked by multiple cerebral emboli].

A 45-year-old woman, who had had rheumatoid arthritis for 12 years, had three attacks of cerebral embolism over two months and died after the final attack. Intensive clinical laboratory investigations did not disclose any specific origins of emboli, but an autopsy revealed a nodule at the base of the aortic valve which was pathologically proved to be a rheumatoid nodule. The thrombi were present from the distal part of left internal carotid artery up to the proximal part of the left middle cerebral artery. They were rich in fiber, but poorly organized endothelial cell, raising the possibility that they originated from other parts and have recently reached there. On the top of the rheumatoid nodule, a thrombus was present. It was easily ablated and a small amount of fibrin stuck the nodule. Based on these results, we concluded that cerebral emboli were originally generated at the top of a rheumatoid nodule in the heart. In patients with RA, rheumatoid nodules are rarely seen in the heart. If present, they usually cause cardiac failure or atrioventricular block, and seldom result in cerebral infarction. This is the first case in which an autopsy proved rheumatoid nodule in the heart which had caused multiple cerebral emboli. We should consider the possibility of rheumatoid nodules in the heart as an origin of cerebral emboli in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2005

Novel splice variants of human ADAR2 mRNA: skipping of the exon encoding the dsRNA-binding domains, and multiple C-terminal splice sites.

We report here two previously unknown alternative splice sites in the mRNA of human adenosine deaminase acting on RNA type 2 (ADAR2), an RNA editing enzyme. One splices out the whole of exon 2, which encodes two double-stranded RNA-binding domains (dsRBDs), resulting in a frameshift that introduces a stop codon in the downstream exon. This variant accounts for between 13% and 20% of the total ADAR2 mRNA in each developmental stage and brain region examined, even though its translated product is not expressed at levels that are detectable by Western blot analysis. The other new splice site is located in exon 9, 83 nucleotides downstream of the stop codon for the long C-terminus, resulting in a new 3' untranslated region (UTR) that is about 80 bp longer than the previously reported short C-terminus. The variant produced by this splice site has a stop codon at the same site as that in ADAR2 mRNA containing canonical exons 9 and 10, and is predicted to be translated as an enzymatically active ADAR2 protein. With these two additional splice sites, a total of 48 mRNA variants are theoretically possible, because each splicing event occurs independently. Among them, variants containing the long C-terminus are translated in human brains in situ, implying that alternative splicing in the 3' UTR of ADAR2 might regulate translational efficiency and mRNA stability in vivo.

3' Untranslated Regions↗
PubMed2005

Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.

Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). We quantified the RNA editing efficiency of the GluR2 Q/R site in single motor neurons of rats transgenic for mutant human Cu/Zn-superoxide dismutase (SOD1) as well as patients with spinal and bulbar muscular atrophy (SBMA), and found that GluR2 mRNA was completely edited in all the motor neurons examined. It seems likely that the death cascade is different among the dying motor neurons in sporadic ALS, familial ALS with mutant SOD1 and SBMA.

Aged↗
PubMed2005

Interference with activity-dependent transcriptional activation of BDNF gene depending upon the expanded polyglutamines in neurons.

Expanded polyglutamines (polyQ) have been demonstrated to impair the CREB-dependent transcription in established cell lines. Since activity-dependent transcription in neurons, which plays an important role in forming neuronal plasticity, is largely controlled by CREB, it is important to study whether polyQ interferes with the activity-dependent transcriptional activation of genes in neurons. In cultured rat cortical neurons, over-expression of truncated dentatorubral-pallidoluysian atrophy proteins containing expanded polyQ, which form aggregation bodies in nucleus, reduced the calcium (Ca(2+)) signal-mediated transcriptional activation of brain-derived neurotrophic factor, c-fos, and pituitary adenylate cyclase-activating polypeptide gene promoters in a dose-dependent manner. The interference with the transcriptional activation was dependent upon the presence of polyQ, the strength of which was increased as the length of polyQ stretches was expanded. Thus, polyQ interferes with the activity-dependent transcription in a polyQ-length-dependent manner, which may correspond to the severity of polyglutamine diseases.

Animals↗