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Subdural hematomas (SDHs) are collections of blood between the dura mater and leptomeninges, typically due to shearing of bridging veins as a result of trauma. (1) SDHs can occur in [...], Context.--Spontaneous (nontraumatic) subdural hematomas have been reported yet have not been well studied. Objective.--To identify the neuropathologic features of acute spontaneous SDHs (ASSDHs) and their associated medical conditions. Design.--A retrospective study of 235 autopsy cases of SDH was conducted. Review of demographics, underlying medical conditions, and coagulation profile as well as gross and histopathologic examination of the brain and other organs were performed. Results.--Among the 32 cases of ASSDH, 5 cases (15.6%) had severe hemorrhage and 4 (12.5%) demonstrated brain herniation. Twenty-two cases (68.8%) had concurrent but nonconnecting subarachnoid hemorrhage or intraparenchymal hemorrhage. The most common underlying medical condition was thrombocytopenia (n = 21; 65.6%), followed by immunosuppression (n = 15; 46.9), bloodstream infections or sepsis (n = 12; 37.5%), hypertension (n = 13; 40.6%), and coronary artery disease (n = 12; 37.5%). Many patients with thrombocytopenia or immunosuppression had underlying malignancies, with leukemia being the most common type (n = 11; 34.4%). The use of circulatory devices or hemodialysis was noted in a significant portion of ASSDH cases. In terms of coagulation factors, most of our ASSDH patients had normal prothrombin time and activated partial thromboplastin time, but abnormal platelet count and D-dimer levels. Conclusions.--ASSDHs can be severe and are often associated with subarachnoid hemorrhage and/or intra-parenchymal hemorrhage. The causes of ASSDH are limited to certain underlying medical conditions that ultimately lead to bleeding tendency. Autopsies are helpful in determining the etiology. Given their association with abnormal platelet count, correcting platelet deficiencies is a potential preventive measure for ASSDHs. doi: 10.5858/arpa.2024-0003OA

Anaplastic astrocytomas are aggressive glial cancers that present poor prognosis and high recurrence. Heterozygous IDH1 R132H mutations are common in adolescent and young adult anaplastic astrocytomas. In a majority of cases, the IDH1 R132H mutation is unique to the tumor, although rare cases of anaplastic astrocytoma have been described in patients with mosaic IDH1 mutations (Ollier disease or Maffucci syndrome). Here, we present two siblings with IDH1 R132H mutant high grade astrocytomas diagnosed at 14 and 26 years of age. Analysis of IDHR132H mutations in the siblings tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDHR132H. Whole exome sequencing of the tumor tissue did not reveal any other common mutations between the two siblings. This study demonstrates the first example of IDH1 R132H mosaicism, acquired during early development, that provides an alternative mechanism of cancer predisposition.

For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management. Molecular-targeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown.

Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia. [ABSTRACT FROM AUTHOR]

Objective: The detection of neoplastic cells in cerebral spinal fluid (CSF) is pivotal for the management of patients with central nervous system (CNS) tumours. This article delves into the CSF cytological characteristics of common CNS neoplasms, aligning with the 2021 World Health Organization (WHO) classification of CNS tumours. Methods: A retrospective review of CSF specimens positive for primary CNS neoplasms was performed at three tertiary medical centres. Only cases that had histopathologic confirmation and/or molecular workup were included. Results: Common primary CNS neoplasms seen in CSF cytology specimens include medulloblastoma, (non‐WNT/non‐SHH as well as SHH‐activated and TP53 mutant), pineoblastoma, atypical teratoid/rhabdoid tumour (AT/RT), IDH‐wildtype glioblastoma, and primary diffuse large B‐cell lymphoma of the CNS. Ependymomas and germinomas can also have CSF involvement but are less common. Although the typical histologic architecture of these tumours may not be preserved in the CSF, unique cytomorphologic features such as nuclear moulding, nuclear pleomorphism, rhabdoid cells, prominent nucleoli and rosette formation can still be appreciated. Conclusion: Adopting the updated terminology and correlating cytologic observations with molecular findings will streamline the diagnostic process, reducing the complexities and ambiguities pathologists often encounter when analysing CSF specimens for potential primary CNS neoplasms. [ABSTRACT FROM AUTHOR]

This research models and forecasts bounded ordinal time series data that can appear in various contexts, such as air quality index (AQI) levels, economic situations, and credit ratings. This class of time series data is characterized by being bounded and exhibiting a concentration of large probabilities on a few categories, such as states 0 and 1. We propose using Bayesian methods for modeling and forecasting in zero-one-inflated bounded Poisson autoregressive (ZOBPAR) models, which are specifically designed to capture the dynamic changes in such ordinal time series data. We innovatively extend models to incorporate exogenous variables, marking a new direction in Bayesian inferences and forecasting. Simulation studies demonstrate that the proposed methods accurately estimate all unknown parameters, and the posterior means of parameter estimates are robustly close to the actual values as the sample size increases. In the empirical study we investigate three datasets of daily AQI levels from three stations in Taiwan and consider five competing models for the real examples. The results exhibit that the proposed method reasonably predicts the AQI levels in the testing period, especially for the Miaoli station. [ABSTRACT FROM AUTHOR]