Spreading pattern of phosphorylated tau-positive granular glial pathology in the cerebral white matter of patients with multiple system atrophy.

Multiple system atrophy (MSA) is a major neurodegenerative disorder characterized by phosphorylated α-synuclein-positive oligodendroglial cytoplasmic inclusions. The presence of phosphorylated τ-positive granular glia (pTGrG) in the cerebral white matter and putamen has recently been reported, and it has been suggested that pTGrG pathology may be a common pathological feature of MSA. However, its spreading pattern and relationship with clinical features remain unclear.

cIMPACT-NOW update 11: Proposal on adaptation of diagnostic criteria for IDH- and H3-wildtype diffuse high-grade gliomas and for posterior fossa ependymal tumors.

The Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (cIMPACT-NOW) updates provide guidelines for the diagnosis of central nervous system (CNS) tumors and suggestions for future World Health Organization (WHO) classification. Following publication of the fifth edition WHO Classification of CNS Tumors (WHO CNS5) in 2021, the cIMPACT-NOW working group "Clarification" reviewed WHO CNS5 and prioritized two topics for further elucidation: (a) distinction of Glioblastoma, IDH-wildtype from Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype and (b) clarification of subgroups of posterior fossa (PF) ependymal tumors. Recommendations regarding the IDH- and H3-wildtype diffuse high-grade gliomas include: (1) use caution assigning CNS WHO grade 4 (diagnosis of Glioblastoma, IDH-wildtype) to a "TERT promoter only", histologically low-grade, IDH-wildtype tumor; (2) EGFR gene amplification and +7/-10 chromosome copy number alterations should not be used as solitary defining features for diagnosing high-grade gliomas as Glioblastoma, IDH-wildtype in patients <40 years of age; (3) Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype should be considered in the differential diagnosis in adults, especially those <40 years of age; (4) PDGFRA alteration, EGFR alteration, or MYCN amplification count as key molecular features of Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype only in patients <25 years.

Association between autologous formalin-fixed tumor vaccine (AFTV) therapy, molecular pathological markers, and survival outcomes in glioblastoma.

Glioblastoma (GBM) is a primary brain tumor, characterized by rapid progression, high recurrence rates, and resistance to standard therapies. Current treatment modalities provide limited survival benefits, highlighting the need for novel therapeutic strategies. This retrospective study evaluated the efficacy of autologous formalin-fixed tumor vaccine (AFTV) in 375 patients with newly diagnosed GBM.

Myositis associated with antimitochondrial autoantibodies presenting with early respiratory failure.

Myositis associated with antimitochondrial M2 antibodies (AMA) is a distinct subtype of inflammatory myopathy characterized by axial muscle weakness and, occasionally, respiratory failure. This report highlights two cases involving patients presenting with severe respiratory failure while ambulant. Patient 1: An 82-year-old man was referred to our hospital for respiratory failure and truncal muscle weakness.

A randomized, placebo-controlled phase III trial of an autologous, formalin-fixed tumor vaccine for newly diagnosed glioblastoma: trial protocol.

Unlabelled: This multi-institutional, double-blind, randomized, placebo-controlled phase III trial was designed to evaluate the efficacy and safety of Cellm-001, an autologous formalin-fixed brain tumor immunostimulant, for newly diagnosed glioblastoma with gross total resection to prolong overall survival (OS) and prevent recurrence after surgery. One hundred twelve patients are to be randomized 1:1 to either Cellm-001 with standard chemoradiotherapy (CRT) or saline solution with standard CRT. Randomization is based on the following stratified randomization criteria: age, Karnofsky Performance Status, and the presence or absence of photodynamic therapy (PDT).

Glioma Image-Level and Slide-Level Gene Predictor (GLISP) for Molecular Diagnosis and Predicting Genetic Events of Adult Diffuse Glioma.

The latest World Health Organization (WHO) classification of central nervous system tumors (WHO2021/5th) has incorporated molecular information into the diagnosis of each brain tumor type including diffuse glioma. Therefore, an artificial intelligence (AI) framework for learning histological patterns and predicting important genetic events would be useful for future studies and applications. Using the concept of multiple-instance learning, we developed an AI framework named GLioma Image-level and Slide-level gene Predictor (GLISP) to predict nine genetic abnormalities in hematoxylin and eosin sections: , , mutations, promoter mutations, homozygous deletion (CHD), amplification (amp), 7 gain/10 loss (7+/10-), 1p/19q co-deletion, and promoter methylation.

Resource availability for CNS tumor diagnostics in the Asian Oceanian region: A survey by the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR).

The shift toward a histo-molecular approach in World Health Organization classification of central nervous system tumors (WHO CNS5) emphasizes the critical role of molecular testing, such as next-generation sequencing (NGS) and DNA methylation profiling, for accurate diagnosis. However, implementing these advanced techniques is particularly challenging in resource-constrained countries. To address this, the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR) was initiated to help pathologists in resource-limited regions to implement WHO CNS5 diagnoses using simpler diagnostic tools, mainly immunohistochemistry.

MYB::QKI fusion-positive diffuse glioma of the cerebellum: A case report.

Angiocentric glioma (AG) is a supratentorial diffuse low-grade glioma characterized by the MYB::QKI fusion gene, showing angiocentric growth of monomorphous spindle cells with astrocytic and ependymal immunophenotypes. We describe a rare case of MYB::QKI fusion-positive diffuse cerebellar glioma in a 54-year-old male. The patient initially presented with a T2/FLAIR hyperintense lesion in the left cerebellar hemisphere and slowly progressive neurological symptoms.

Image-based Re-evaluation of the JCOG0911 Study Focusing on Tumor Volume and Survival, Disease Progression Diagnosis, and Radiomic Prognostication for Newly Diagnosed Glioblastoma.

Purpose: To re-evaluate images recovered from JCOG0911, a randomized phase 2 trial for newly diagnosed glioblastoma (nGBM) conducted by the Japan Clinical Oncology Group (JCOG) Brain Tumor Study Group.

Methods: The correlation between tumor volumes and survival was evaluated, followed by progression-free survival (PFS) analysis by independent central review based on Response Assessment in Neuro-Oncology (RANO) criteria using MRI recovered from 118 nGBM patients enrolled in the JCOG0911 trial. A radiomic analysis was also performed to identify radiomic features predictive of nGBM prognosis.

Calcified Hofmann's ligaments as the cause of spinal cerebrospinal fluid leaks associated with spinal ventral dural tears.

Objective: Patients with spinal CSF leaks often have ventral dural abnormalities (type 1 CSF leaks); however, the pathological mechanism for developing dural abnormalities is unknown. The authors investigated whether calcified dural ligaments contribute to the development of ventral dural tears, which cause spinal CSF leaks.

Methods: Consecutive patients diagnosed with type 1 CSF leaks who had spiculated spinal lesions between 2010 and 2024 were included.

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.

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.

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries.

Prevalence, Radiological, and Pathological Findings of Ossification and Calcification of the Lumbar Spinal Ligamentum Flavum: A Comparative Study with Thoracic Lesions.

This study aimed to determine the prevalence of lumbar ligamentum flavum lesions and identify correlations between radiological and pathological findings. We conducted an observational cross-sectional study of 349 patients (lumbar: n = 296, thoracic: n = 39, lumbar and thoracic: n = 14, mean age: 69 ± 12 years, male: 74%) who underwent posterior surgery for thoracolumbar spinal canal stenosis between January 2008 and April 2023 at our hospital.Computed tomography (CT) revealed that the prevalence of ligamentum flavum lesions defined as a high-density area with a CT value of 200 Hounsfield Unit or higher in the lumbar and thoracic spine was 47% (147/310) and 85% (45/53), respectively.

Glioneuronal and neuronal tumors: A perspective.

Glioneuronal and neuronal tumors (GNTs) are slow-growing, lower-grade neuroepithelial tumors characterized by mature neuronal differentiation and, less consistently, glial differentiation. Their identification has traditionally relied on histological proof of neuronal differentiation, reflecting the well-differentiated nature of GNTs. However, after discovering genetic alterations in GNTs, particularly those in the MAP-kinase pathway, it became evident that histological diagnoses do not always correlate with genetic alterations and vice versa.

Adverse childhood experiences exacerbate peripheral symptoms of autism spectrum disorder in adults.

Aim: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD).

ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

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.