The application of perfusion fixation in brain banking settings is hampered by numerous practical obstacles, such as the organ's substantial mass, pre-existing vascular deterioration and patency problems, and the divergence in investigator objectives which sometimes require targeted brain freezing. Hence, there is a substantial need to create a malleable and scalable perfusion fixation technique within brain banking procedures. Our ex situ perfusion fixation protocol development approach is detailed in this technical report. Our journey of implementing this procedure was marked by challenges and insightful lessons, which we now discuss. RNA in situ hybridization, when combined with routine morphological staining, indicates that the perfused brains exhibit a well-maintained tissue cytoarchitecture and intact biomolecular signal. Yet, the improvement in histology quality, when contrasted with immersion fixation, through this procedure remains uncertain. Furthermore, ex vivo magnetic resonance imaging (MRI) data indicate that the perfusion fixation protocol might produce imaging anomalies, such as air bubbles within the vascular system. The implications of this study are discussed by proposing further research avenues into the effectiveness of perfusion fixation as a rigorous and repeatable substitute for immersion fixation in the preparation of postmortem human brains.
Hematopoietic malignancies, often refractory to conventional treatments, find a promising avenue in chimeric antigen receptor (CAR) T-cell therapy. Neurotoxicity, a prominent adverse event, is frequently observed. Nonetheless, the precise mechanisms of physiopathology are currently obscure, and neurological examination findings are infrequent. Between the years 2017 and 2022, a post-mortem examination of six patient brains, recipients of CAR T-cell therapy, was completed. Polymerase chain reaction (PCR) was invariably used on paraffin blocks for the purpose of identifying CAR T cells. Two patients tragically passed away due to the progression of hematologic conditions, the others dying from various factors, including cytokine release syndrome, lung infections, encephalomyelitis, and acute liver failure. From the six presented neurological symptoms, two cases exhibited distinct neurological presentations; one with progressing extracranial malignancy, and the second with encephalomyelitis. Severe perivascular and interstitial lymphocytic infiltration, largely CD8+, was a key finding in the neuropathology of the latter sample. Concurrently, a diffuse interstitial histiocytic infiltration impacted the spinal cord, midbrain, and hippocampus, along with extensive gliosis in the basal ganglia, hippocampus, and brainstem. Neurotropic viral presence was absent in microbiological assessments, and CAR T-cell detection by PCR proved negative. Neurological indicators absent in another case revealed cortical and subcortical gliosis as a consequence of acute hypoxic-ischemic damage. In just four instances, a mild, patchy gliosis and microglial activation were the only observed abnormalities, and polymerase chain reaction (PCR) revealed CAR T-cell presence in only one of these cases. Our analysis of fatalities following CAR T-cell treatment in this cohort principally showed nonspecific or limited neuropathological changes. The autopsy, rather than solely focusing on CAR T-cell toxicity, could unveil other pathological contributing factors to the neurological symptoms.
Pigment other than melanin, neuromelanin, lipofuscin, or a combination is uncommonly observed within ependymomas. A pigmented ependymoma is described in the fourth ventricle of an adult patient in this case report, accompanied by an analysis of 16 further instances of this tumor type, gleaned from published medical literature. With hearing loss, headaches, and nausea, a 46-year-old woman appeared at the clinic. A 25-centimeter contrast-enhancing cystic mass within the fourth ventricle was discovered via magnetic resonance imaging and subsequently excised. The operative procedure revealed a cystic, grey-brown tumor that was tightly bound to the brainstem. The routine histology showed a tumor with the characteristic features of true rosettes, perivascular pseudorosettes, and ependymal canals, strongly suggesting an ependymoma. Furthermore, the presence of chronic inflammation and a significant number of distended, pigmented tumor cells resembling macrophages was observed in both frozen and permanent tissue specimens. learn more Glial tumor cells, as indicated by the pigmented cells' GFAP positivity and CD163 negativity, were present. The pigment demonstrated negative staining with Fontana-Masson, but displayed positive staining with Periodic-acid Schiff, and exhibited autofluorescence, which are all hallmarks of lipofuscin. A low value was shown by the proliferation indices, alongside a partial loss of H3K27me3. Histone H3, tri-methylated at lysine 27, undergoes the epigenetic modification H3K27me3, altering the DNA packaging structure. The methylation classification proved consistent with a posterior fossa group B ependymoma (EPN PFB) diagnosis. The patient's postoperative follow-up appointment, three months after the procedure, revealed no recurrence and excellent clinical well-being. Examining the 17 cases, including the present one, our study shows that pigmented ependymomas are the most frequent type in middle-aged patients, with a median age of 42 years, and usually have a favorable outcome. Nevertheless, a different patient, which also displayed secondary leptomeningeal melanin accumulations, experienced a fatal outcome. While a vast 588% of occurrences are in the 4th ventricle, the spinal cord (176%) and supratentorial (176%) locations are less prevalent. upper extremity infections Given the presentation's age and generally good prognosis, a question arises: could most other posterior fossa pigmented ependymomas similarly be classified within the EPN PFB group? More research is needed to answer this query.
This update presents a selection of papers focusing on vascular disease issues that have gained prominence during the last year. Concerning the genesis of vascular malformations, the inaugural two papers explore brain arteriovenous malformations in the first paper, and cerebral cavernous malformations in the second. Significant brain damage, in the form of intracerebral hemorrhage (if ruptured) or other neurological complications like seizures, can stem from these disorders. Papers 3-6 provide insights into the developing understanding of how the brain and immune system interact following a cerebral injury, including a stroke. The first observation reveals T cell participation in the recovery of white matter from ischemic damage; this effect is mediated by microglia, demonstrating the significant communication between the innate and adaptive immune systems. Subsequent papers delve into the role of B cells, a previously less explored area in the study of brain trauma. The contribution of B cells residing in the meninges and skull bone marrow, which have prior antigen experience, rather than blood-borne B cells, to neuroinflammation represents an exciting new area of study. Future research will certainly delve into the potential contribution of antibody-secreting B cells to the pathology of vascular dementia. In a similar vein, investigators in paper six found that myeloid cells found within the CNS originate in tissues on the periphery of the brain. These cells possess unique transcriptional marks that differentiate them from their blood-originated counterparts and probably promote the movement of myeloid cells from nearby bone marrow environments into the brain. Investigating microglia's contributions to amyloid deposition and spreading, the primary innate immune cells of the brain, is followed by a review of the proposed clearance of perivascular A from cerebral vessels in those with cerebral amyloid angiopathy. The final two papers center on the contribution of senescent endothelial cells and pericytes. The utilization of an accelerated aging model (Hutchinson-Gilford progeria syndrome; HGPS) demonstrates the potential application of a telomere shortening reduction strategy for decelerating the aging process. The concluding paper reveals how capillary pericytes affect basal cerebral blood flow resistance and the gradual modulation of cerebral blood flow within the brain. It is quite interesting that a considerable amount of the studies showcased therapeutic strategies that may be utilized in clinical settings.
The Department of Neuropathology, at NIMHANS, Bangalore, India, organized the virtual 5th Asian Oceanian Congress of Neuropathology and the 5th Annual Conference of the Neuropathology Society of India (AOCN-NPSICON), spanning September 24th to 26th, 2021. From 20 countries in Asia and Oceania, a total of 361 attendees, including India, participated. Attendees of the event included a significant number of pathologists, clinicians, and neuroscientists from across Asia and Oceania, together with guest speakers from the USA, Germany, and Canada. The program’s content encompassed neurooncology, neuromuscular disorders, epilepsy, and neurodegenerative disorders, with the upcoming WHO 2021 classification of CNS tumors as a central theme. The 78 distinguished international and national faculty’s expertise was shared in keynote addresses and symposia. Radioimmunoassay (RIA) Furthermore, case-study-based learning modules were available, alongside opportunities for paper presentations and poster sessions specifically designed for junior faculty and postgraduate students. These included several awards for young researchers, top papers, and top posters. A standout moment at the conference was a singular debate about Methylation-based classification of CNS tumors, a defining issue of the decade, and a subsequent panel discussion dedicated to COVID-19. The participants found the academic content to be highly commendable.
Confocal laser endomicroscopy (CLE) is a novel, non-invasive in vivo imaging method with substantial potential in the fields of neurosurgery and neuropathology.