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Neurologic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can present with fever, headache, and meningism.

This cohort study examines the association of intracerebral hemorrhage and secondary injury with disability-adjusted life years., Key Points Question What is the burden of intracerebral hemorrhage and secondary injury? Findings In this cohort study of 1322 patients with intracerebral hemorrhage, the condition was associated with 9.46 disability-adjusted life-years, while perihemorrhagic edema and intraventricular hemorrhage were associated with increased disability compared with hematoma expansion in the overall cohort. Meaning These findings suggest that intracerebral hemorrhage is associated with a high burden of disability, and these findings may guide public health strategies., Importance Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. Objective To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. Design, Setting, and Participants This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation–associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. Exposures ICH occurrence and secondary injury. Main Outcomes and Measures DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). Results Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (< 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; >30 mL ICH: 12.42 [8.47] DALYs; P

ObjectiveThis study determined the effect of amantadine treatment on consciousness in patients with non-traumatic brain injury.MethodsWe pooled individual patient data of five single-centre observational studies to determine the effect of amantadine treatment among patients with ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, community-acquired bacterial meningitis and status epilepticus, admitted between January 2012 and December 2015 and ventilated ≥7 days. Patient selection and multivariable regression modelling were used to adjust for differences in intergroup comparison and for parameters associated with consciousness. Improvement of consciousness 5 days after treatment initiation was defined as primary outcome. Secondary outcomes included Glasgow Coma Scale (GCS) at day 5 and GCS at day 10, rate of ICU delirium, epileptic seizures and all-cause mortality at 90 days.ResultsOverall, 84 of 294 (28.6%) eligible patients received amantadine. Amantadine treatment was associated with improvement of consciousness at day 5 (amantadine: 86.9% vs control: 54.0%; absolute difference: 32.9 (20.0–44.2); adjusted OR (aOR): 5.71 (2.50–13.05), pConclusionsAmantadine treatment is associated with improved consciousness among patients with different types of non-traumatic brain injury in this observational cohort analysis. Epileptic seizures should be considered as potential side effects and randomised controlled trials are needed to confirm these findings.

Background and Purpose: The impact of statins on hematoma characteristics, perihemorrhagic edema (PHE), cardiovascular events, seizures, and functional recovery in patients with intracerebral hemorrhage (ICH) is insufficiently studied. Methods: Patients with ICH of the prospective UKER-ICH (Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage) study (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03183167) were analyzed by multivariable regression modeling and propensity score matching, and PHE volumes were volumetrically assessed. Outcomes comprised hematoma characteristics, the impact of continuation, discontinuation, and initiation of statins on peak PHE extent, and the influence of statin treatment on the occurrence of seizures, cardiovascular adverse events, and functional recovery after ICH. Results: A total of 1275 patients with ICH with information on statin treatment were analyzed. Statin treatment on hospital admission (21.7%) was associated with higher rates of lobar versus nonlobar ICH (odds ratio, 1.57 [1.03–2.40]; P =0.038). Initiation of statins after ICH was associated with increased peak PHE (β=0.12, SE=0.06, P =0.008), whereas continuation versus discontinuation of prior statin treatment was not significantly associated with edema formation ( P >0.10). There were no significant differences in the incidence of remote symptomatic seizures according to statin exposure during follow-up (statins: 11.5% versus no statins: 7.8%, subdistribution hazard ratio: 1.15 [0.80–1.66]; P =0.512). Patients on statins revealed less cardiovascular adverse events and more frequently functional recovery after 12 months (functional recovery: 57.7% versus 45.0%, odds ratio 1.67 [1.09–2.56]; P =0.019). Conclusions: Among statin users, lobar ICH occurs more frequently as compared with nonstatin users. While continuation of prior statin treatment appears to be safe regarding PHE formation, the initiation of statins during the first days after ICH may increase PHE extent. However, statins should be initiated thereafter (eg, at hospital discharge) to prevent cardiovascular events and potentially improve functional recovery.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal motoneuron disorder in children with unknown etiology. The disease is caused by mutations in the IGHMBP2 gene, encoding a Super Family 1 (SF1)-type RNA/DNA helicase. IGHMBP2 is a cytosolic protein that binds to ribosomes and polysomes, suggesting a role in mRNA metabolism. Here we performed morphological and functional analyses of isolated immunoglobulin μ-binding protein 2 (Ighmbp2)-deficient motoneurons to address the question whether the SMARD1 phenotype results from de-regulation of protein biosynthesis. Ighmbp2-deficient motoneurons exhibited only moderate morphological aberrations such as a slight increase of axonal branches. Consistent with the rather mild phenotypic aberrations, RNA sequencing of Ighmbp2-deficient motoneurons revealed only minor transcriptome alterations compared to controls. Likewise, we did not detect any global changes in protein synthesis using pulsed SILAC (Stable Isotope Labeling by Amino acids in Cell culture), FUNCAT (FlUorescent Non-Canonical Amino acid Tagging) and SUnSET (SUrface SEnsing of Translation) approaches. However, we observed reduced β-actin protein levels at the growth cone of Ighmbp2-deficient motoneurons which was accompanied by reduced level of IMP1/ZBP1, a known interactor of β-actin mRNA. Fluorescence Recovery after Photobleaching (FRAP) studies revealed translational down-regulation of an eGFP-myr-β-actin 3'UTR mRNA in growth cones. Local translational regulation of β-actin mRNA was dependent on the 3' UTR but independent of direct Ighmbp2-binding to β-actin mRNA. Taken together, our data indicate that Ighmbp2 deficiency results in local but modest disruption of protein biosynthesis which might partially contribute to the motoneuron defects seen in SMARD1.

BACKGROUND Based on prospective vein bypass trials for lower leg ischemia, objective performance goals (OPG) were established by the Society for Vascular Surgery (SVS) and are used as a benchmark tool for open and endovascular treatments. This study aims to analyze OPG of all patients with critical limb ischemia (CLI) treated by open revascularization techniques at a tertiary care facility in routine practice. METHODS From January 2005 to March 2013, 315 patients (mean age 72 years) with CLI were retrospectively included in this study. Inclusion criteria were patients with Fontaine stage III and IV, realized revascularization with open surgical procedures (bypass grafting or endarterectomy), or hybrid method (open + endovascular). Exclusion criteria were primary major amputations, patients with revascularization treatments of the index leg within the last 3 months, and missing aftercare. Primary end point was "amputation-free survival" (AFS), and secondary end point was "freedom from major adverse limb event + perioperative death (30 days)" (MALE + POD) according to the SVS. The technical end point was primary patency. Mean follow-up was 34 months. The following variables were studied: clinical stage (Fontaine), previous interventions, bypass material used, and site of the distal anastomosis. The statistical evaluation and preparation was carried out using the Kaplan-Meier estimator and the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. A P value ≤0.05 was considered to be statistically significant. RESULTS A total of 128 patients (31%) fulfilling the adjusted SVS OPG criteria showed significantly better results for AFS, MALE + POD, and primary patency (P = 0.013, P = 0.015, P = 0.002, respectively). Regarding the AFS (1 year: 74%), multivariate analysis displayed significant worse results for patients with end-stage renal disease (hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.83-4.60, P