Cognitive and neuropsychological trajectories in patients with mixed neurodegenerative pathologies.

Introduction: The presence and interaction of multiple comorbid neuropathologies are a major contributor to the worldwide dementia burden.

Methods: We analyzed 1183 subjects from the National Alzheimer's Coordinating Center dataset with various combinations of isolated and mixed neurodegenerative pathologies and conducted mixed-effects multiple linear regression modeling to comprehensively compare the neurocognitive and neuropsychological trajectories between groups over time.

Results: In combination with Alzheimer's disease neuropathologic change, various combinations of limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy, Lewy body dementia, and cerebrovascular disease further impair global cognition and specific neurocognitive domains; however, they do not appear to extensively affect the rate of decline with time across these domains, suggesting an additive but not synergistic effect.

Antemortem radiologic and histopathologic presentation of Marchiafava-Bignami disease.

Marchiafava-Bignami disease (MBD) is a rare disorder, characterized by demyelination and cystic necrosis of the corpus callosum; it is typically seen in the setting of chronic alcoholism but may also occur with severe malnutrition. Clinical features include altered mental status, loss of consciousness, dysarthria, spasticity, ataxia, and seizures. To our knowledge, only 1 case of MBD with antemortem histology has been reported in the literature.

Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors.

Unlabelled: DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing.

Towards a single-assay approach: a combined DNA/RNA sequencing panel eliminates diagnostic redundancy and detects clinically-relevant fusions in neuropathology.

Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and fluorescence in-situ hybridization. Here, we demonstrate that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to fluorescence in-situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q.