Objective To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions. Methods We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes. Results Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco₂ (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury. Conclusion Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

Pathogenic variants in the NDUFV1 gene, which codes for complex I of the mitochondrial respiratory chain, have been associated with a variety of clinical phenotypes, including a progressive cavitating leukoencephalopathy. The neuropathology of NDUFV1-associated leukoencephalopathy is not well-described. We present a report of a 24-year-old female with two pathogenic variants in the NDUFV1 gene, together with antemortem skeletal muscle biopsy and postmortem neuropathologic examination. Autopsy neuropathology showed a cavitating leukoencephalopathy with extensive white matter involvement, regions of active demyelination, and sparing of the subcortical U-fibers. Muscle biopsy showed subtle but distinct histologic abnormalities by light microscopy, and ultrastructural analysis demonstrated mitochondrial abnormalities including abnormal subsarcolemmal mitochondrial accumulation, electron-dense inclusions, and enlarged mitochondria with abnormal cristae. Our report is the first comprehensive description of the neuropathology in a patient with compound heterozygous variants in the NDUFV1 gene and progressive cavitating leukoencephalopathy. This case is evidence of pathogenicity of one NDUFV1 variant (c.565 T > C, p.S189P), which has not been previously described as pathogenic. These findings, in combination with the ultrastructural abnormalities in the mitochondria by electron microscopy, support the mitochondrial nature of the pathology. Together, this case highlights the link between mitochondrial abnormalities and demyelinating processes in the central nervous system (CNS).

The use of social media platforms in pathology and medical laboratory science has increased in recent years, revolutionizing the way professionals in these fields interact, disseminate information, and collaborate. To gain an understanding of the current landscape regarding social media use in pathology and medical laboratory science, a novel systematic review was conducted. A search of PubMed, Medline, Embase, and Scopus was performed to identify articles evaluating social media use within pathology and medical laboratory science. Articles published in English within the previous 10 years were searched on December 22, 2022. Inclusion criteria were articles containing information regarding social media utility in pathology or laboratory medicine and related articles that mentioned specific hashtags for pathology. The review process involved analyzing the social media platforms referenced, hashtags mentioned, and the presence of international authors as key endpoints of interest. 802 publications were identified; 54 studies met inclusion criteria. Subspecialties represented were considered, but none were found to be statistically significant. X/Twitter (n = 42) was the most discussed social media platform. The top hashtags discussed were #pathJC (5.1%), #dermpathJC (4.2%), #USCAP2016 (3.4%), and #PathBoards (3.4%). Analysis of these articles provides insights into current trends, including the social media platforms referenced, hashtags used, and involvement of international authors. This review will contribute to a deeper understanding of the role and impact of social media in these fields, highlighting opportunities and challenges for future research and practice in pathology and lab medicine.

The classification, grading, and risk stratification of central nervous system (CNS) tumors have rapidly evolved with the advent of integrative advanced molecular testing. Here, we review the advances and challenges associated with DNA methylation-based classification of central nervous system (CNS) tumors. Specifically, we will review the brief background information about the role of epigenetic signatures, including DNA methylation status of CpG islands, in identifying the cell of origin, bioinformatic methods, and products of DNA methylation profiling, namely t-distributed stochastic neighbor embedding (t-SNE) plot vs. uniform manifold approximation and projection (UMAP), CNS tumor classifications, methylguanine methyltransferase (MGMT), and chromosomal copy number variations. We will follow with the diagnostic utility, accuracy, and impact on clinical outcomes. We will conclude the chapter by highlighting the limitations of DNA methylation, bioethical issues, and the future directions for this diagnostic tool.

Context.—: Although the basic principles of intraoperative diagnosis in surgical neuropathology have not changed in the last century, the last several decades have seen dramatic changes in tumor classification, terminology, molecular classification, and modalities used for intraoperative diagnosis. As many neuropathologic intraoperative diagnoses are performed by general surgical pathologists, awareness of these recent changes is important for the most accurate intraoperative diagnosis. Objective.—: To describe recent changes in the practice of intraoperative surgical neuropathology, with an emphasis on new entities, tumor classification, and anticipated ancillary tests, including molecular testing. Data Sources.—: The sources for this review include the fifth edition of the World Health Organization Classification of Tumours of the Central Nervous System, primary literature on intraoperative diagnosis and newly described tumor entities, and the authors' clinical experience. Conclusions.—: A significant majority of neuropathologic diagnoses require ancillary testing, including molecular analysis, for appropriate classification. Therefore, the primary goal for any neurosurgical intraoperative diagnosis is the identification of diagnostic tissue and the preservation of the appropriate tissue for molecular testing. The intraoperative pathologist should seek to place a tumor in the most accurate diagnostic category possible, but specific diagnosis at the time of an intraoperative diagnosis is often not possible. Many entities have seen adjustments to grading criteria, including the incorporation of molecular features into grading. Awareness of these changes can help to avoid overgrading or undergrading at the time of intraoperative evaluation.

BACKGROUND: Our objective was to investigate whether primary Sjögren’s syndrome (pSS) is associated with multiple system atrophy (MSA). METHODS: We performed a retrospective cohort study assessing (a) rates of MSA in a cohort of patients with pSS and (b) rates of pSS in a cohort of patients with MSA. These data were compared with rates in respective control groups. We additionally reviewed the neuropathologic findings in 2 patients with pSS, cerebellar degeneration, parkinsonism, and autonomic dysfunction. RESULTS: Our cohort of 308 patients with pSS had a greater incidence of MSA compared with 4 large population-based studies and had a significantly higher prevalence of at least probable MSA (1% vs. 0%, P = 0.02) compared with 776 patients in a control cohort of patients with other autoimmune disorders. Our cohort of 26 autopsy-proven patients with MSA had a significantly higher prevalence of pSS compared with a cohort of 115 patients with other autopsy-proven neurodegenerative disorders (8% vs. 0%, P = 0.03). The 2 patients we described with pSS and progressive neurodegenerative disease showed classic MSA pathology at autopsy. CONCLUSION: Our findings provide evidence for an association between MSA and pSS that is specific to both pSS, among autoimmune disorders, and MSA, among neurodegenerative disorders. The 2 cases we describe of autopsy-proven MSA support that MSA pathology can explain neurologic disease in a subset of patients with pSS. These findings together support the hypothesis that systemic autoimmune disease plays a role in neurodegeneration. FUNDING: The Michigan Brain Bank is supported in part through NIH grant P30AG053760.