Project description:ObjectiveCoronavirus Disease 2019 (COVID-19) initially thought to be confined to the respiratory system only, is now known to be a multisystem disease. It is critical to be aware of and timely recognize neurological and neuroradiological manifestations affecting patients with COVID-19, to minimize morbidity and mortality of affected patients.MethodsWe performed a retrospective chart review of patients admitted to our Level 1 trauma and stroke center during the peak of the COVID-19 outbreak in New York from March 1st to May 30, 2020, with a positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) who presented mainly with neurological findings and had acute radiological brain changes on Computed Tomography (CT) scan. Patients with known chronic neurological disease processes were excluded from the study. We obtained and reviewed demographics, complete blood count, metabolic panel, D-dimer, inflammatory markers such as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), imaging, and patient's hospital course. We reviewed the current literature on neuroimaging, pathophysiology, and their clinical correlations on COVID-19. This case series study was approved by our institutional review board.ResultA total of 16 patients were selected for our case series. The most common neuroimaging features on CT, were territorial to multifocal ischemic infarcts, followed by a combination of ischemia and acute white matter encephalopathic changes, followed by temporal lobe predominant focal or more generalized encephalopathy with both confluent and non-confluent patterns, isolated cortical or more extensive intracranial hemorrhages and some combination of ischemia or hemorrhage and white matter changes. All our patients had severe acute respiratory distress syndrome (ARDS), most of them had elevated inflammatory markers, and D dimer.ConclusionCOVID-19 infection is a multi-organ disease, which can manifest as rapidly progressive neurological disease beyond the more common pulmonary presentation. Early recognition of various neurological findings and neuroimaging patterns in these patients will enable timely diagnosis and rapid treatment to reduce morbidity and mortality. Our retrospective study is limited due to small non-representative sample size, strict selection criteria likely underestimating the true extent of neurological manifestations of COVID-19, mono-modality imaging technique limited to predominantly CT scans and lack of CSF analysis in all except one patient. Multi-institutional, multi-modality, largescale studies are needed with radio-pathological correlation to better understand the complete spectrum of neurologic presentations in COVID-19 patients and study the causal relationship between SARS-CoV-2 and CNS disease process.

Project description:Neurodegenerative diseases of the central nervous system are characterised by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity and inflammation are observed in most, if not all, neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data for Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, Parkinson’s disease and schizophrenia using an extensive cohort of well characterised post-mortem CNS tissues. The analysis of whole genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease specific changes, but more importantly to uncover potential common molecular pathogenic mechanisms that could be targeted for therapeutic gain. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all 6 diseases using our primary method of analysis. However, 61 dysregulated genes were shared when comparing five and four diseases. Our analysis indicates firstly the involvement of common neuronal homeostatic, survival and synaptic plasticity pathways. Secondly, we report changes to immunoregulatory and immunomodulatory pathways in all diseases. Our secondary method of analysis confirmed significant up-regulation of a number of genes in diseases presenting degeneration and showed that somatostatin was downregulated in all 6 diseases. The latter is supportive of a general role for neuroinflammation in the pathogenesis and/or response to neurodegeneration. Unravelling the detailed nature of the molecular changes regulating inflammation in the CNS is key to the development of novel therapeutic approaches for these chronic conditions. A total of 113 cases were selected retrospectively on the basis of a confirmed clinical and neuropathological diagnosis and snap-frozen brain blocks were provided by various tissue banks within the BrainNet Europe network. Total RNA was extracted from dissected snap-frozen tissue (< 100 mg) by the individual laboratories according to a BNE optimised common protocol using the RNeasy(r) tissue lipid mini kit (Qiagen Ltd, Crawley, UK) according to the manufacturer's instructions, and was stored at -80C until further use. Gene expression analysis was performed on the RNA samples using the Illumina whole genome HumanRef8 v2 BeadChip (Illumina, London, UK). All the labelling and hybridisation of the samples was carried out in a single experiment by the Imperial College group to reduce the technical variability. RNA samples were prepared for array analysis using the Illumina TotalPrep(tm)-96 RNA Amplification Kit (Ambion/Applied Biosystems, Warrington, UK). Finally, the BeadChips we re scanned using the Illumina BeadArray Reader. The data was extracted using BeadStudio 3.2 (Illumina). Data normalisation and gene differential expression analyses were conducted using the Rosetta error models available in the Rosetta Resolver(r) system (Rosetta Biosoftware, Seattle, Wa, USA). Two samples presented very low signal expression most likely due to hybridization problems and did not pass the quality control test. They are not represented here. One of the 2 samples was a replicate, therefore there was loss of only 1 case bringing the grand total of cases used to 112 (total of samples of 118 including 6 replicates).

Project description:Neurodegenerative diseases of the central nervous system are characterised by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity and inflammation are observed in most, if not all, neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data for Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, Parkinson’s disease and schizophrenia using an extensive cohort of well characterised post-mortem CNS tissues. The analysis of whole genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease specific changes, but more importantly to uncover potential common molecular pathogenic mechanisms that could be targeted for therapeutic gain. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all 6 diseases using our primary method of analysis. However, 61 dysregulated genes were shared when comparing five and four diseases. Our analysis indicates firstly the involvement of common neuronal homeostatic, survival and synaptic plasticity pathways. Secondly, we report changes to immunoregulatory and immunomodulatory pathways in all diseases. Our secondary method of analysis confirmed significant up-regulation of a number of genes in diseases presenting degeneration and showed that somatostatin was downregulated in all 6 diseases. The latter is supportive of a general role for neuroinflammation in the pathogenesis and/or response to neurodegeneration. Unravelling the detailed nature of the molecular changes regulating inflammation in the CNS is key to the development of novel therapeutic approaches for these chronic conditions.

Dataset Information

Neuroimaging Advances in Neurologic and Neurodegenerative Diseases.

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Neuroimaging Advances in Neurologic and Neurodegenerative Diseases.

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