-associated peripheral neuropathy defined by impaired binding with TUBB3.

encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant in p.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts.

Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric disorder that involves an inflammatory response thought to be characterized by microglial activation. The inflammasome complex may play critical roles in the pathomechanism of neuroinflammation but how this relates to SCZ remains unclear. In this study, we performed an immunohistochemical (IHC) analysis to compare the expression of inflammasome proteins in brain tissue from donors with SCZ (n = 16) and non-psychiatric donors (NP; n = 13) isolated from the superior frontal cortex (SFC), superior temporal cortex, and anterior cingulate cortex brain regions.

Association of region-specific hippocampal reduction of neurogranin with inflammasome proteins in brains of Alzheimer's disease.

Introduction: Neurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology.

Methods: We investigated the protein expression, morphological differences of Ng, and correlated Ng to hyperphosphorylated tau in the brains of 17 AD cases and 17 age- and sex-matched controls.

Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells.

Neurofibromatosis Type 2 (NF2) is a tumor predisposition syndrome caused by germline inactivating mutations in the NF2 gene encoding the merlin tumor suppressor. Patients develop multiple benign tumor types in the nervous system including bilateral vestibular schwannomas (VS). Standard treatments include surgery and radiation therapy, which may lead to loss of hearing, impaired facial nerve function, and other complications.

Identification of inflammasome signaling proteins in neurons and microglia in early and intermediate stages of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive function. Inflammasome activation has been suggested to play a critical role in the neuroinflammatory response in AD progression, but the cell-type expression of inflammasome proteins in the brain has not been fully characterized. In this study, we used samples from the hippocampus formation, the subiculum, and the entorhinal cortex brain from 17 donors with low-level AD pathology and 17 intermediate AD donors to assess the expression of inflammasome proteins.

A Case of Glioblastoma, Isocitrate Dehydrogenase Wild Type, With Widely Disseminated Osseous Metastasis.

Glioblastoma, isocitrate dehydrogenase (IDH) wild type, is an aggressive primary brain malignancy with a poor prognosis, despite treatment including surgery, chemotherapy, and radiation therapy. Few patients with glioblastoma develop metastasis outside the neuroaxis, likely due to disease progression in the brain prior to extraneural dissemination. The driving mutations of tumors in patients with extraneural metastases are not well described.

Assessing fetal human neural stem cells tumorigenicity potential in athymic rats with penetrating traumatic brain injury (pTBI).

Traumatic brain injuries (TBI) often produce disability in survivors due to unresolved inflammation and progressive neurodegeneration. The central nervous system in mammals is incapable of self-repair. Two decades of preclinical studies and clinical trials have provided insights into TBI pathophysiology that could be utilized to develop clinically relevant therapy.

Effect of AR42 in Primary Vestibular Schwannoma Cells and a Xenograft Model of Vestibular Schwannoma.

Hypothesis: AR42, a histone deacetylase (HDAC) inhibitor, reduces viability of primary vestibular schwannoma (VS) cells and delays tumor progression and hearing loss (HL) in a xenograft model of VS.

Background: The impact of HDAC expression on AR42 response in primary VS cells is unknown, as well as the effects of AR42 on VS-associated HL and imbalance.

Methods: Primary human VS cells (n = 7) were treated with AR42 (0-3.

Acute Ascending Necrotizing Myelitis After COVID-19 Infection: A Clinicopathologic Report.

Objectives: Neurologic manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, COVID-19) infection are common and varied. The objective of this report was to describe clinicopathologic findings of rare acute ascending necrotizing myelitis (ANM) and briefly summarize similar COVID-19-associated longitudinally extended transverse myelitis cases.

Methods: We described the clinical presentation, disease course, diagnostic workup, therapeutic measures, and pathologic findings of ANM associated with COVID-19 infection.

Recurrent adult pilocytic astrocytoma presenting with intraventricular and leptomeningeal spread.

Background: Infratentorial pilocytic astrocytomas are uncommon tumors in adulthood but are thought to be prognostically similar to their pediatric counterparts with excellent overall survival following gross total resection. However, given the relative rarity of these tumors, no management guidelines exist for recurrent adult pilocytic astrocytomas (APAs). This lack of consensus is especially problematic for inoperable recurrences or those with aggressive features concerning for malignant transformation.

Defining the Extracellular Matrix of Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy, and surgical resection; nevertheless, little to no improvement in long term survival has been achieved in decades-underlining the need for target discovery and new therapeutic approaches to targeting tumor cells or the tumor microenvironment. To evaluate cross-species sarcoma extracellular matrix production, we have used murine models which feature knowledge of the myogenic cell-of-origin.

Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Gliomas.

Background: Intraoperative pathologic diagnosis traditionally involves frozen section histopathology, which may be labor and time intensive. Indeed, a technique that streamlines the acquisition and evaluation of intraoperative histologic data may expedite surgical decision-making and shorten operative time. Stimulated Raman histology (SRH) is an emerging technology that allows for more rapid acquisition and interpretation of intraoperative histopathologic data.

Rapid Intraoperative Diagnosis of Meningiomas using Stimulated Raman Histology.

Background: Frozen section is a time- and labor-intensive method for intraoperative pathologic diagnosis. As a result, there exists a need to expedite and streamline the acquisition and interpretation of diagnostic histologic data to inform surgical decision making. Stimulated Raman histology (SRH) is an emerging technology that may serve to expedite the acquisition and interpretation of histologic data in the operating room.

Complete Regression of a Solitary Cholangiocarcinoma Brain Metastasis Following Laser Interstitial Thermal Therapy.

Background: To our knowledge, we report the first case of a cholangiocarcinoma brain metastasis successfully treated with magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy.

Case Description: In 2017, a 71-year-old man was diagnosed with unresectable intrahepatic cholangiocarcinoma. In August 2018, a brain MRI scan was performed after a transient episode of altered mental status and revealed a subcentimeter enhancing lesion in the deep white matter of the right cerebellum.

Rare Tumor-to-Tumor Metastases Involving Lung Adenocarcinoma to Petroclival Meningiomas.

Background: Lung carcinoma metastasizing to a skull base meningioma remains an extremely rare phenomenon, with only 3 studies reported. Furthermore, no documented cases have been reported in the petroclival region. Thus, we have presented the first 2 cases of tumor-to-tumor metastasis (TTM) in which a petroclival lesion, initially thought to be purely meningioma, was also found to contain metastatic lung adenocarcinoma.

Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, -mutant glioblastoma: a case report from a Phase I study.

Glioblastoma is the most common and aggressive primary brain tumor. Despite standard multimodality therapy, median overall survival remains poor with a 5-year survival rate of approximately 5% in most studies (range 4.7-13.

Stimulated Raman histology for rapid and accurate intraoperative diagnosis of CNS tumors: prospective blinded study.

Objective: In some centers where brain tumor surgery is performed, the opportunity for expert intraoperative neuropathology consultation is lacking. Consequently, surgeons may not have access to the highest quality diagnostic histological data to inform surgical decision-making. Stimulated Raman histology (SRH) is a novel technology that allows for rapid acquisition of diagnostic histological images at the bedside.

Brain microvascular pathology in Susac syndrome: an electron microscopic study of five cases.

Susac syndrome is a rare, immune-mediated disease characterized by encephalopathy, branch retinal artery occlusion, and hearing loss. Herein, we describe the electron microscopic findings of three brain biopsies and two brain autopsies performed on five patients whose working clinical diagnosis was Susac syndrome. In all five cases, the key findings were basement membrane thickening and collagen deposition in the perivascular space involving small vessels and leading to thickening of vessel walls, narrowing, and vascular occlusion.

Granulomatous amoebic encephalitis caused by in a patient with AIDS: a challenging diagnosis.

Introduction: spp. is a ubiquitous free-living amoeba that causes human infections affecting predominantly the cornea and central nervous system. The diagnosis and treatment of encephalitis is very challenging.

A case of recurrent epilepsy-associated rosette-forming glioneuronal tumor with anaplastic transformation in the absence of therapy.

Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment.

Enhancing nodular lesions in Chiari II malformations in the setting of persistent hindbrain herniation: case report and literature review.

Background: Chiari II malformation includes concomitant cerebellar tonsillar herniation, hydrocephalus, and myelomeningocele. Rarely, pediatric patients with persistent hindbrain herniation develop a new enhancing nodule at the cervicomedullary junction as adults. These new lesions may be suspicious for neoplastic growth, but it remains unclear if neurosurgical intervention is necessary.

Exogenous expression of the glycosyltransferase LARGE1 restores α-dystroglycan matriglycan and laminin binding in rhabdomyosarcoma.

Background: α-Dystroglycan is the highly glycosylated component of the dystrophin-glycoprotein complex (DGC) that binds with high-affinity to extracellular matrix (ECM) proteins containing laminin-G-like (LG) domains via a unique heteropolysaccharide [-GlcA-beta1,3-Xyl-alpha1,3-] called matriglycan. Changes in expression of components of the DGC or in the O-glycosylation of α-dystroglycan result in muscular dystrophy but are also observed in certain cancers. In mice, the loss of either of two DGC proteins, dystrophin or α-sarcoglycan, is associated with a high incidence of rhabdomyosarcoma (RMS).