Neuropathology and applied neurobiology
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Neuropathol. Appl. Neurobiol. · Feb 2021
Case ReportsNeuropathological Findings in Two Patients with Fatal COVID-19.
To describe the neuropathological findings in two cases of fatal Coronavirus Disease 2019 (COVID-19) with neurological decline. ⋯ Our case series adds calcifying cerebral cortical infarction with associated megakaryocytes and brainstem encephalitis to the spectrum of neuropathological findings that may contribute to the neurological decompensation seen in some COVID-19 patients. Viral RNA was not detected in post-mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para-infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered.
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Neuropathol. Appl. Neurobiol. · Apr 2019
Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. ⋯ Altogether, these findings suggest that elevated serum NfL levels in ALS are driven by UMN degeneration and the disease progression rate and are independently associated with survival at time of diagnosis.
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Neuropathol. Appl. Neurobiol. · Oct 2018
Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. ⋯ Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1β reflect early changes in the skeletal muscle and may contribute to the denervation process.
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Gliomas are the most frequent intrinsic tumours of the central nervous system and encompass two principle subgroups: diffuse gliomas and gliomas showing a more circumscribed growth pattern ('nondiffuse gliomas'). In the revised fourth edition of the WHO Classification of CNS tumours published in 2016, classification of especially diffuse gliomas has fundamentally changed: for the first time, a large subset of these tumours is now defined based on presence/absence of IDH mutation and 1p/19q codeletion. ⋯ The most important changes in the very diverse group of 'nondiffuse' gliomas and neuronal-glial tumours are the introduction of anaplastic pleomorphic xanthoastrocytoma, of diffuse leptomeningeal glioneuronal tumour and of RELA fusion-positive ependymoma as entities. In the last part of this review, after very briefly touching upon classification of neuronal, choroid plexus and pineal region tumours, some practical implications and challenges associated with the WHO 2016 Classification of gliomas are discussed.
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Neuropathol. Appl. Neurobiol. · Jun 2016
Motor neurone disease/amyotrophic lateral sclerosis associated with intermediate-length CAG repeat expansions in Ataxin-2 does not have 1C2-positive polyglutamine inclusions.
Intermediate-length cytosine-adenine-guanine repeat expansions in the ATXN2 gene (which encodes for Ataxin-2 protein) have been linked to increased risk for motor neurone disease/amyotrophic lateral sclerosis (ALS). We screened DNA from cases for which we had post-mortem brain tissue to enable characterization of the neuropathology associated with this mutation. ⋯ Intermediate expansions of the CAG repeat in ATXN2 are associated with ALS. They are mostly associated with TDP-43 proteinopathy, but not with 1C2-positive polyglutamine inclusions. In the nervous system, Ataxin-2 protein expression is predominantly seen in large neurones. There is no consistent histopathological hallmark that is unique to ATXN2-ALS.