Biomarkers for CNS injury in CSF are elevated in COVID-19 and associated with neurological symptoms and disease severity

BACKGROUND: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19) and biomarkers of CNS injury are reported to be increased in plasma but not extensively studied in CSF. This study examines CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain protein (NfL) glial fibrillary acidic protein (GFAp) and total tau) was performed and related to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL, GFAp and total-tau protein were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL correlated with disease severity, time in intensive care and level of consciousness. NfL in CSF was higher in patients with central neurological symptoms. CONCLUSION: Although limited by small sample size, our data suggest that levels of NfL, GFAp and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF work-up where pathological findings are scarce. NfL in particular, is associated with central neurological symptoms and disease severity

The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care

Background and purpose: A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. Material and methods: Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. Results and conclusions: The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers

Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms

Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables

Deep brain stimulation of the anterior nucleus of the thalamus in drug-resistant epilepsy in the MORE multicenter patient registry

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background and objectives: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. Methods: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. Results: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p 10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. Discussion: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. Classification of evidence: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy.The MORE registry was sponsored and funded by Medtronic, plc.info:eu-repo/semantics/publishedVersio

Rehabilitation needs for older adults with stroke living at home: perceptions of four populations

<p>Abstract</p> <p>Background</p> <p>Many people who have suffered a stroke require rehabilitation to help them resume their previous activities and roles in their own environment, but only some of them receive inpatient or even outpatient rehabilitation services. Partial and unmet rehabilitation needs may ultimately lead to a loss of functional autonomy, which increases utilization of health services, number of hospitalizations and early institutionalization, leading to a significant psychological and financial burden on the patients, their families and the health care system. The aim of this study was to explore partially met and unmet rehabilitation needs of older adults who had suffered a stroke and who live in the community. The emphasis was put on needs that act as obstacles to social participation in terms of personal factors, environmental factors and life habits, from the point of view of four target populations.</p> <p>Methods</p> <p>Using the focus group technique, we met four types of experts living in three geographic areas of the province of Québec (Canada): older people with stroke, caregivers, health professionals and health care managers, for a total of 12 groups and 72 participants. The audio recordings of the meetings were transcribed and NVivo software was used to manage the data. The process of reducing, categorizing and analyzing the data was conducted using themes from the Disability Creation Process model.</p> <p>Results</p> <p>Rehabilitation needs persist for nine capabilities (e.g. related to behaviour or motor activities), nine factors related to the environment (e.g. type of teaching, adaptation and rehabilitation) and 11 life habits (e.g. nutrition, interpersonal relationships). The caregivers and health professionals identified more unmet needs and insisted on an individualized rehabilitation. Older people with stroke and the health care managers had a more global view of rehabilitation needs and emphasized the availability of resources.</p> <p>Conclusion</p> <p>Better knowledge of partially met or unmet rehabilitation needs expressed by the different types of people involved should lead to increased attention being paid to education for caregivers, orientation of caregivers towards resources in the community, and follow-up of patients' needs in terms of adjustment and rehabilitation, whether for improving their skills or for carrying out their activities of daily living.</p

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Permethrin-impregnated curtains in malaria control

The impact of permethrin-impregnated curtains on the incidence of malaria episodes, parasitaemia and splenomegaly was assessed during a 22 month period in 2 groups of children aged 0.5-6 years. One group lived in houses where permethrin-impregnated curtains had been installed, the other group lived in houses without curtains. A significant reduction of incidence of malaria episodes, mean parasite density, parasite prevalence and splenomegaly was consistently observed in the intervention group towards the end of the period of moderate transmission, whereas no clear-cut impact could be demonstrated during the high transmission period. The influence of malaria pressure and community utilization on the protective efficiency of curtains is discussed. Because of their acceptability and the ease of reimpregnation, curtains proved to be a suitable technique for integration into primary health care

PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy

Objectives– This study compares positron emission tomography (PET) using 11C-deuterium-deprenyl (DED) with PET using 18F-fluorodeoxyglucose(18F-FDG) for examining epileptogenic regions in patients with focal epilepsy. Material and methods– Twenty-three patients undergoing evaluation for epilepsy surgery were subjected to PET with DED. Fourteen patients had mesial temporal lobe epilepsy (TLE) and 9 patients had seizures of neocortical origin. In addition, 6 healthy control subjects were examined. Pixel-by-pixel analysis was used to generate graphical images of tracer distribution volume (intercept) and the accumulation rate (slope). Asymmetries with respect to relative intercept and slope were compared in patients with temporal lobe epilepsy (TLE), in patients with extra-temporal lobe epilepsy (exTLE), and in the control subjects. The results were compared with 18F-FDG-PET. Results– Among the patients with TLE, significant differences between the epileptogenic and the contralateral lobe were found with DED intercept and FDG-uptake. No significant differences were found with DED slope. The exTLE and the control groups showed no significant differences between sides or lobes. Conclusions– This study indicates that PET with 11C-deuterium-deprenyl is a useful method for identifying TLE and is equivalent to PET with 18F-FDG in this sense. The method has little localizing value in seizures originating from neocortical structures