Neuropathology最新文献

{"title":"Bridging minds: Participant perspectives on postmortem brain research and engagement.","authors":"Yusuke Inoue, Maki Obata, Maho Morishima, Shigeo Murayama, Yuko Saito","doi":"10.1111/neup.13030","DOIUrl":"https://doi.org/10.1111/neup.13030","url":null,"abstract":"<p><p>Postmortem research participation remains underrepresented in research ethics discussions. Herein, we examined the associated perspectives of individuals preregistered with the Brain Bank for Aging Research at the Tokyo Metropolitan Institute of Gerontology. We conducted a postal survey targeting 88 preregistrants, yielding 52 responses (response rate: 59.1%, average respondent age: 79.5 years, range: 49-97). The questionnaire gathered information on the reasons for agreeing to participate, helpful information provided during the explanation, and expectations regarding future information. The stated reasons for participating included a desire to contribute to science, gratitude for medical care received, memories of relatives' past donations, and inspiration from staff enthusiasm and materials. Beneficial information was given in brochures, coordinator explanations, and lectures; however, guidance for family members regarding postmortem procedures and updates on recent activities and research outcomes were highlighted as areas requiring future improvement. Willingness to participate in brain banks was influenced by altruistic factors, personal medical experiences, and the influence of statements from close contacts. Registrants maintained their interest after registration and prepare for future arrangements. Family cooperation was identified as a critical factor influencing the fulfillment of participant intentions, emphasizing the need for accessible and low-burden family guidance. Registrants generally seek information to help family members and associates avoid difficulties related to their participation. Brain banks should continue conducting such surveys for registrants and reflect the findings in their information dissemination and educational programs. This approach will help improve the understanding and support for brain bank participation, ultimately contributing to the advancement of medical research and ethics in postmortem studies.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autopsy case of coexisting spinal and bulbar muscular atrophy and multiple system atrophy.","authors":"Motoki Miura, Hiroshi Shintaku, Yoshiyuki Numasawa, Kokoro Ozaki, Tadashi Kanouchi, Kinya Ishikawa, Takanori Yokota","doi":"10.1111/neup.13031","DOIUrl":"https://doi.org/10.1111/neup.13031","url":null,"abstract":"<p><p>Here, we report an autopsy case of concurrent spinal and bulbar muscular atrophy (SBMA) and multiple system atrophy (MSA). A 55-year-old man presented with weakness, atrophy, and fasciculation of the tongue and the proximal parts of all limbs. The patient gradually developed severe orthostatic hypotension, urinary retention, and cerebellar ataxia; however, no parkinsonism was observed. The patient succumbed to sudden death during sleep. The autopsy revealed widespread and abundant α-synuclein-positive glial cytoplasmic inclusions in the central nervous system, indicative of MSA. Neuronal loss was also observed in the substantia nigra and locus coeruleus. Consequently, the patient was diagnosed with MSA. Additionally, immunostaining for the monoclonal 1C2 antibody revealed positive neurons in the medulla oblongata and spinal cord, supporting the additional diagnosis of SBMA. Genetic analysis revealed an expansion of 41 CAG repeats in the androgen receptor (AR) gene (normal range: 12-38), confirming the diagnosis of SBMA. Altogether, concurrent SBMA and MSA were diagnosed based on the autopsy findings, making this the first reported case of such coexistence in the Japanese and English literature.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of late-life blood pressure with CERAD, Braak, and Thal: Findings from the National Alzheimer's coordinating center neuropathology dataset.","authors":"Mo-Kyung Sin, N Maritza Dowling, Jeffrey M Roseman, Ali Ahmed, Edward Zamrini","doi":"10.1111/neup.13029","DOIUrl":"10.1111/neup.13029","url":null,"abstract":"<p><p>Mid-life high blood pressure (BP) is a risk factor for Alzheimer's disease (AD). CERAD amyloid β (Aβ) plaques, Braak tau neurofibrillary tangles, and Thal Aβ plaque location are major scoring systems for quantifying neuropathological features of AD. We examined the association of late-life systolic BP (SBP) with CERAD, Braak, and Thal in the National Alzheimer's Coordinating Center (NACC) Neuropathology Dataset. Of 1978 participants with data on CERAD, 762 had scores 0-1 (none to sparse) and 1216 had 2-3 (moderate to frequent). Of 1947 with data on Braak, 411 had stages 0-II (normal to mild) and 1536 had III-VI (moderately to very severe). Of 2132 with data on Thal, 438 had phases 0-I, 428 II-III, and 1266 IV-V. Using the mean of the last four SBP before death, SBP was categorized into <120 (references), 120-139, and ≥140 mmHg. Age-sex-adjusted ORs (95% CIs) associated with SBP ≥140 mmHg for CERAD 2-3 and Braak III-VI were 1.37 (1.03, 1.83, P = 0.03) and 1.26 (0.89, 1.78, P = 0.20), respectively. Similar association was observed for Thal II-III and IV-V. These associations essentially remained unchanged after additional adjustment for APOE and Lewy Body pathology. These findings suggest that higher late-life SBP is associated with markers of presence and severity of neuropathological features of AD. Further studies with larger sample sizes are necessary to confirm the findings.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autopsy report of a long-survival case of familial amyotrophic lateral sclerosis with SOD1 G93S gene mutation: Lack of SOD1-positive inclusion in the remaining neurons.","authors":"Asuka Funai, Kentaro Hayashi, Akihiro Kawata, Yuki Nakayama, Chiharu Matsuda, Michiko Haraguchi, Kazushi Takahashi, Takashi Komori","doi":"10.1111/neup.13004","DOIUrl":"10.1111/neup.13004","url":null,"abstract":"<p><p>We describe the case of a 70-year-old Japanese man with familial amyotrophic lateral sclerosis (fALS) associated with a p.Gly93Ser mutation in the copper/zinc superoxide dismutase (SOD1) gene. This mutation is one of the relatively rare SOD1 mutations, with only one previous autopsy report, and is known for its longer disease duration. As previously reported, the patient had weakness in the lower limbs at age 33, followed by dysphagia, dysesthesia in the lower limbs, and autonomic dysfunction. He required mechanical ventilation at age 44 and died of acute pancreatitis at age 70. Neuropathologically, multisystem degeneration was observed beyond lesions typical of familial ALS with posterior column involvement. In addition, there was no SOD1-positive inclusion in the remaining motor neurons. The absence of SOD1-positive inclusion is a rare feature observed predominantly in long survival cases with SOD1 gene mutations. We hypothesize that the considerably lower amount of abnormal SOD1 protein in the motor neuron cells might explain our patient's extraordinarily long clinical course.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"60-65"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALK-positive histiocytosis: Report of a rare case with exclusive involvement of the central nervous system in an adult woman.","authors":"Yuting Luo, Pingling Wang, Qinru Zhan, Jiao Luo, Baohong Luo","doi":"10.1111/neup.13002","DOIUrl":"10.1111/neup.13002","url":null,"abstract":"<p><p>ALK-positive histiocytosis is a rare histiocytic disease characterized by ALK positivity. It was first described in 2008 as a systemic disease in infants. The disease often shows positivity for CD68 and CD163 on immunohistochemistry, and genomic analysis frequently reveals KIF5B::ALK fusions. ALK-positive histiocytosis typically follows an indolent course and has a promising prognosis, with conventional treatments usually being effective. Here, we report a rare case of ALK-positive histiocytosis with exclusive involvement of the central nervous system in a 33-year-old Asian adult woman. Although cranial MRI suggested a meningioma, immunohistochemical workup showed that the ALK-positive tumor cells expressed macrophage/histiocyte markers such as CD163 and CD68. Additionally, second-generation sequencing revealed a KIF5B::ALK fusion. Our case highlights the importance of the differential diagnosis in adult central nervous system tumors, emphasizing the combination of morphology, immunophenotype, and molecular approach with ALK status evaluation to confirm a diagnosis of ALK-positive histiocytosis. This case also expands the clinicopathologic spectrum of ALK-positive histiocytosis.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"55-59"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and genotyping spectrum of two Iranian cases with RBCK1-associated polyglucosan body myopathy.","authors":"Marzieh Babaee, Yalda Nilipour, Sahar Alijanpour, Aida Ghasemi, Mohammad Mehdi Taghdiri, Payam Sarraf, Mohammad Miryounesi, Mahtab Ramezani","doi":"10.1111/neup.12993","DOIUrl":"10.1111/neup.12993","url":null,"abstract":"<p><p>Glycogen storage diseases (GSDs) are a group of metabolic disorders affecting glycogen metabolism, with polyglucosan body myopathy type 1 (PGBM1) being a rare variant linked to RBCK1 gene mutations. Understanding the clinical diversity of PGBM1 aids in better characterization of the disease. Two unrelated Iranian families with individuals exhibiting progressive muscle weakness underwent clinical evaluations, genetic analysis using whole exome sequencing (WES), and histopathological examinations of muscle biopsies. In one case, a novel homozygous RBCK1 variant was identified, presenting with isolated myopathy without cardiac or immune involvement. Conversely, the second case harbored a known homozygous RBCK1 variant, displaying a broader phenotype encompassing myopathy, cardiomyopathy, inflammation, and immunodeficiency. Histopathological analyses confirmed characteristic skeletal muscle abnormalities consistent with PGBM1. Our study contributes to the expanding understanding of RBCK1-related diseases, illustrating the spectrum of phenotypic variability associated with distinct RBCK1 variants. These findings underscore the importance of genotype-phenotype correlations in elucidating disease mechanisms and guiding clinical management. Furthermore, the utility of next-generation sequencing techniques in diagnosing complex neurogenetic disorders is emphasized, facilitating precise diagnosis and enabling tailored genetic counseling for affected individuals and their families.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"48-54"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autopsy case of type A FTLD-TDP with a GRN mutation presenting with the logopenic variant of primary progressive aphasia at onset and with corticobasal syndrome subsequently.","authors":"Takafumi Tomenaga, Shinobu Minatani, Hiroto Namba, Akitoshi Takeda, Takahito Yoshizaki, Joji Kawabe, Nazere Keyoumu, Hiroyuki Morino, Makoto Higuchi, Tomoyasu Matsubara, Hiroyuki Hatsuta, Masato Hasegawa, Shigeo Murayama, Yoshiaki Itoh","doi":"10.1111/neup.12980","DOIUrl":"10.1111/neup.12980","url":null,"abstract":"<p><p>A 68-year-old woman presented with difficulty finding words and writing characters. Neurological examination led to clinical diagnosis at onset of the logopenic variant of primary progressive aphasia accompanied with ideomotor apraxia, visuospatial agnosia on the right, and Gerstmann syndrome. Bradykinesia and rigidity on the right with shuffling gait developed after one year. Treatment with L-dopa had no effect. The patient was diagnosed with corticobasal syndrome (CBS). Brain magnetic resonance imaging revealed diffuse cortical atrophy dominantly on the left, especially in the temporal, parietal, and occipital lobes. Positron emission tomography did not reveal any significant accumulation of amyloid β or tau protein. She died five years later. Neuropathological examination revealed diffuse cortical atrophy with severe neuronal loss and fibrous gliosis in the cortex. Neuronal cytoplasmic inclusions, short dystrophic neurites, and, most notably, neuronal intranuclear inclusions, all immunoreactive for phosphorylated TDP-43, were observed. Western blotting revealed a full length and fragments of phosphorylated TDP-43 at 45 and 23 kDa, respectively, confirming the pathological diagnosis of type A FTLD-TDP. Whole exome sequencing revealed a pathogenic mutation in GRN (c.87dupC). FTLD-TDP should be included in the differential diagnosis of CBS.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"38-47"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurolymphomatosis mimicking a Guillain-Barré syndrome triggered by COVID-19 vaccination.","authors":"Daniele Colombo, Laura Falasca, Francesca Monardo, Mario D'Ambrosio, Arianna Di Napoli, Antonio Salerno, Franca Del Nonno, Giovanna Comanducci","doi":"10.1111/neup.13003","DOIUrl":"10.1111/neup.13003","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is an acute disorder of the peripheral nervous system, causing flaccid paralysis, areflexia, and variable sensory involvement. Proximal as well distal muscles of the limbs can be involved, and in most severe and advanced cases progresses to respiratory failure and death. GBS is considered an autoimmune disease, and at the basis of the attack at the peripheral nervous system different mechanisms have been recognized, in particular viral infections or other immune stimulations. Cranial nerve involvement in patients with diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma are rare conditions that could present with similar clinical features. Here we present a case of a 36-year-old man hospitalized for acute polyradiculoneuritis of the cranial nerves and lumbar roots that arose a 14 days after severe acute respiratory syndrome COVID-19 2 (Sars-CoV-2) vaccination. Most of the main criteria for the diagnosis of GBS were met, including clinical and electrophysiological criteria. Albuminocytologic dissociation and high protein level in cerebrospinal fluid were also found. Therefore, the patient was treated with a cycle of intravenous immunoglobulin (IVIG) with notable improvement of symptoms and gradual recovery of motility. A five months later, following SARS-CoV-2 infection, the patient presented with worsening of neurological symptoms and was readmitted to the hospital. He underwent instrumental tests again and was treated with repeated cycles of IVIG and then with a cycle of plasmapheresis without any improvement. In the following 10 days he developed very serious conditions; he was transferred to intensive care unit and deceased after 6 days. The cause of the neurological syndrome was determined only after autoptic analysis, which revealed the presence of primary peripheral nervous system (PNS) DLBCL. The reported case highlights that GBS-like presentation always requires a careful differential diagnosis, and physicians should also consider the possibility of an occult cancer.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"76-82"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.","authors":"Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis","doi":"10.1111/neup.12979","DOIUrl":"10.1111/neup.12979","url":null,"abstract":"<p><p>Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MB_SHH, 13.0% MB_WNT, 7.3% MB_Grp3, and 13.0% MB_Grp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MB_SHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MB_SHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"30-37"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.","authors":"Erika Seki, Xiaoli Guo, Kazuhiko Namekata, Takashi Komori, Hiroyuki Hayashi, Nobutaka Arai, Takayuki Harada","doi":"10.1111/neup.12978","DOIUrl":"10.1111/neup.12978","url":null,"abstract":"<p><p>Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"20-29"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}