关键词： biomarker   GFAP   Wilson disease  

摘要： Background Wilson disease is a rare, disabling, neurological genetic disease. Biomarkers of brain damage are less well developed. Objective The aim of this study was to evaluate the utility of plasma glial fibrillary acidic protein as a biomarker for neurological involvement in patients with Wilson disease. Methods This prospective cross-observational study compared plasma glial fibrillary acidic protein concentration among different subtypes of patients with Wilson disease and healthy control subjects. Plasma glial fibrillary acidic protein levels were measured in 94 patients and 25 healthy control subjects. Patients were divided into two subtypes: patients with neurological manifestations (n = 74) or hepatic manifestations (n = 20). Results Median levels of plasma glial fibrillary acidic protein were significantly elevated in patients with neurological manifestations (143.87 pg/mL) compared with those with hepatic manifestations (107.50 pg/mL) and healthy control subjects (86.85 pg/mL). Receiver operating characteristic curve revealed that a plasma glial fibrillary acidic protein cutoff value of 128.8 pg/mL provides sufficient sensitivity (80.0%) and specificity (63.5%) to differentiate patients with neurological manifestations from those with hepatic manifestations. Conclusions Plasma glial fibrillary acidic protein may serve as a biomarker for distinguishing different subtypes of Wilson disease. (c) 2021 International Parkinson and Movement Disorder Society

摘要： There is an accumulating volume of research into neurological manifestations of coronavirus disease 2019 (COVID-19). However, inconsistent study designs, inadequate controls, poorly validated tests, and differing settings, interventions, and cultural norms weaken study quality and comparability, hence the understanding of the spectrum, burden, and pathophysiology of these complications. Therefore, a global COVID-19 Neuro Research Coalition, together with the World Health Organization, has reviewed reports of COVID-19 neurological complications and harmonized clinical measures for future research. This will facilitate well-designed studies using precise, consistent case definitions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurological complications, with standardized forms for pooled data analyses that nonspecialists can use, including those in low-income settings. ANN NEUROL 2021

关键词： Neurodevelopmental disorders   Neurological disorders  

摘要： HEAT repeats are 37-47 amino acid flexible tandem repeat structural motifs occurring in a wide variety of eukaryotic proteins with diverse functions. Due to their ability to undergo elastic conformational changes, they often serve as scaffolds at sites of protein interactions. Here, we describe four affected children from two families presenting with pontocerebellar hypoplasia manifest clinically with neonatal seizures, severe intellectual disability, and motor delay. Whole exome sequencing identified biallelic variants at predicted splice sites in intron 31 of HEATR5B, encoding the HEAT repeat-containing protein 5B segregating in a recessive fashion. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. HEATR5B is expressed during brain development in human, and we failed to recover live-born homozygous Heatr5b knockout mice. Taken together, our results implicate loss of HEATR5B in pontocerebellar hypoplasia.

关键词： COVID-19   SARS-CoV-2 infection   Drug repurposing   Minocycline   Doxycycline   Neuroinflammation  

摘要： The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not fully understood. However, previous evidence about systemic viral infections pointed to an ongoing neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells from the periphery. Microglia cells mediate the overproduction of inflammatory cytokines, free radicals, and damage signals, culminating with neurotoxic consequences. Semi-synthetic second-generation tetracyclines, including minocycline (MINO) and doxycycline (DOXY), are safe bacteriostatic agents that have remarkable neuroprotective and anti-inflammatory properties. Promising results have been obtained in clinical trials using tetracyclines for major psychiatric disorders, such as schizophrenia and major depression. Tetracyclines can inhibit microglial reactivity and neuroinflammation by inhibiting nuclear factor kappa B (NF-kB) signaling, cyclooxygenase 2, and matrix metalloproteinases (MMPs). This drug class also has a broad profile of activity against bacteria associated with community-based pneumonia, including atypical agents. COVID-19 patients are susceptible to secondary bacterial infections, especially those on invasive ventilation. Therefore, we suggest tetracyclines' repurposing as a potential treatment for COVID-19 neuropsychiatric manifestations. These drugs can represent a valuable multi-modal treatment for COVID-19-associated neuroinflammatory alterations based on their broad antimicrobial profile and neuroinflammation control.

关键词： central nervous system   epilepsy   electroencephalogram   multisystem inflammatory syndrome   neurological involvement  

摘要： Children with COVID-19 tend to show milder symptoms than adults during the pandemic, but growing evidence of neurological involvement has emerged. Some studies have reported neurological symptoms in children with COVID-19, which include multisystem inflammatory syndrome, a disease that shares some, but not all, of the characteristics of Kawasaki disease. This review presents, and discusses, the evidence to date. Our initial findings suggest that neurological manifestations can be considered to be the direct result of central nervous system viral invasion or post-infection immuno-mediated disease.

关键词： cancer   GRP78   GRP78 autoantibodies   GRP78 signaling   heat shock protein   neurological disorders  

摘要： The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellular stress, GRP78 escapes from the ER and moves to the plasma membrane where it (a) functions as a receptor for many ligands, and (b) behaves as an autoantigen for autoantibodies that contribute to human disease and cancer. Cell surface GRP78 (csGRP78) associates with the major histocompatibility complex class I (MHC-I), and is the port of entry for several viruses, including the predictive binding of the novel SARS-CoV-2. Furthermore, csGRP78 is found in association with partners as diverse as the teratocarcinoma-derived growth factor 1 (Cripto), the melanocortin-4 receptor (MC4R) and the DnaJ-like protein MTJ-1. CsGRP78 also serves as a receptor for a large variety of ligands including activated alpha(2)-macroglobulin (alpha M-2*), plasminogen kringle 5 (K5), microplasminogen, the voltage-dependent anion channel (VDAC), tissue factor (TF), and the prostate apoptosis response-4 protein (Par-4). In this review, we discuss the mechanisms involved in the translocation of GRP78 from the ER to the cell surface, and the role of secreted GRP78 and its autoantibodies in cancer and neurological disorders.

关键词： History of neurology   COVID-19   Patient care  

摘要： This narrative account uses a moment of patient care to connect multiple influences on my training as a resident during the COVID-19 pandemic. Seemingly unrelated, my newly found interest in the history of neurology, my patient, and the new dynamics of hospital care have made me become a better physician through this reflective piece. (C) 2021 Elsevier B.V. All rights reserved.

关键词： Neurological soft signs   Treatment resistance   First-episode schizophrenia   Longitudinal   Clozapine  

摘要： Schizophrenia patients exhibit subtle and non-localizing neurological abnormalities, known as neurological soft signs (NSS). Life-span evidence suggests that NSS vary along the course of schizophrenia. An association between NSS and treatment response has been proposed, suggesting that NSS reflect the underlying neuropathology development in schizophrenia. However, few studies have investigated the relationship between NSS and treatment resistance in first-episode schizophrenia patients. We conducted a longitudinal study on 52 firstepisode schizophrenia patients, who were assessed at baseline, the sixth month, and the fifth year using the abridged version of the Cambridge Neurological Inventory. The trajectories of NSS between 29 treatmentresponsive patients (with full symptomatic remission) and 23 treatment-resistant patients (who received clozapine) were compared using mixed model ANOVA. We also controlled for the effect of age and estimated IQ, using a mixed ANCOVA model. Although the two schizophrenia groups had comparable NSS at the baseline, their trajectories of NSS differed significantly. Compared with their treatment-responsive counterparts, treatmentresistant schizophrenia patients had worsening of NSS over time. Our findings support the potential utility of NSS in identifying treatment resistance in first-episode schizophrenia. Progressive worsening of NSS in treatment-resistant schizophrenia patients may reflect the development of underlying neuropathology. Further studies using large samples of treatment-resistant schizophrenia patients are needed.

关键词： Brain-specific biomarkers   Glial fibrillary acidic protein   Microtubule-associated protein tau   Neuron-specific enolase   S100B protein   Subarachnoid hemorrhage  

摘要： Background Subarachnoid bleeding is associated with brain injuries and ranges from almost negligible to acute and life threatening. The main objectives were to study changes in brain-specific biomarker levels in patients after an aneurysmal subarachnoid hemorrhage (aSAH) in relation to early clinical findings, severity scores, and intensive care unit (ICU) outcome. Analysis was done to identify specific biomarkers as predictors of a bad outcome in the acute treatment phase. Methods Analysis was performed for the proteins of neurofilament, neuron-specific enolase (NSE), microtubule-associated protein tau (MAPT), and for the proteins of glial cells, S100B, and glial fibrillary acidic protein (GFAP). Outcomes were assessed at discharge from the ICU and analyzed based on the grade in the Glasgow Outcome Scale (GOS). Patients were classified into two groups: with a good outcome (Group 1: GOS IV-V,n = 24) and with a bad outcome (Group 2: GOS I-III,n = 31). Blood samples were taken upon admission to the ICU and afterward daily for up to 6 days. Results In Group 1, the level of S100B (1.0, 0.9, 0.7, 2.0, 1.0, 0.3 ng/mL) and NSE (1.5, 2.0, 1.6, 1.2, 16.6, 2.2 ng/mL) was significantly lower than in Group 2 (S100B: 4.7, 4.8, 4.4, 4.5, 6.6, 6.8 ng/mL;NSE: 4.0, 4.1, 4.3, 3.8, 4.4, 2.5 1.1 ng/mL) on day 1-6, respectively. MAPT was significantly lower only on the first and second day (83.2 +/- 25.1, 132.7 +/- 88.1 pg/mL in Group 1 vs. 625.0 +/- 250.7, 616.4 +/- 391.6 pg/mL in Group 2). GFAP was elevated in both groups from day 1 to 6. In the ROC analysis, S100B showed the highest ability to predict bad ICU outcome of the four biomarkers measured on admission [area under the curve (AUC) 0.81;95% CI 0.67-0.94,p < 0.001]. NSE and MAPT also had significant predictive value (AUC 0.71;95% CI 0.54-0.87,p = 0.01;AUC 0.74;95% CI 0.55-0.92,p = 0.01, respectively). A strong negative correlation between the GOS and S100B and the GOS and NSE was recorded on days 1-5, and between the GOS and MA

关键词： Ischemic stroke   Cardiac biomarker   Stroke-heart-syndrome   Cardiac troponin   Brain–heart interaction   Myocardial injury   Myocardial infarction  

摘要： The original article can be found online.