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Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case-control population-based cohort. Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3-9 months) phases post-infection. The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15-2.37); dementia, 1.30 (1.11-1.52); seizures, 1.91 (1.26-2.87); encephalopathy, 1.82 (1.02-3.23); and stroke, 1.74 (1.05-2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10-3.64); dementia, 1.36 (1.07-1.73); seizure, 1.77 (1.22-2.56); and brain fog, 1.96 (1.20-3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07-6.15) and coma (1.87, 1.22-2.87) also became significantly increased. Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19.
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http://dx.doi.org/10.1093/brain/awae117 | DOI Listing |
Clin Genet
September 2025
Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
LONP1 encodes a mitochondrial protease essential for protein quality control and metabolism. Variants in LONP1 are associated with a diverse and expanding spectrum of disorders, including Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS), congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD), with some individuals exhibiting features of mitochondrial encephalopathy. We report 16 novel LONP1 variants identified in 16 individuals (11 with NDD, 5 with CDH), further expanding the clinical spectrum.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
View Article and Find Full Text PDFNat Rev Neurol
September 2025
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Health disparities are preventable differences in health between different populations, and they are endemic throughout medicine owing to social, economic and environmental disadvantages. Neurology is no exception, and health disparities for systematically marginalized groups are present in the prevention, diagnosis, treatment and outcomes of all neurological disorders. The aetiology of these disparities is complex and multifactorial, reflecting the interplay of structural, institutional and individual-level factors.
View Article and Find Full Text PDFNat Aging
September 2025
Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging, possibly due to prolonged exposure to amyloid beta.
View Article and Find Full Text PDFNature
September 2025
Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth through paracrine mechanisms and by electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the central nervous system, innervation of tumours such as prostate, head and neck, breast, pancreatic, and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression.
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