Background Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease‐2019 (COVID‐19). Methods We searched MEDLINE, EMBASE and Cochrane CENTRAL databases to identify cases of COVID‐19‐associated CVT. The search period spanned January 1^st to December 1^st 2020 and the review protocol (PROSPERO‐CRD42020214327) followed PRISMA guidelines. Identified studies were evaluated for bias using the Newcastle‐Ottawa scale (NOS). Proportion meta‐analysis was performed to estimate the frequency of CVT among hospitalized COVID‐19 patients. Results We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37% and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS‐CoV‐2 infection were present in 31%. In‐hospital mortality was 40%. Using data from 34331 patients, the estimated frequency of CVT among hospitalized for SARS‐CoV‐2 infection was 0.08% (95%CI=0.01‐0.5). In an in‐patient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID‐19 (cohort of 406 patients, 95%CI=1.47‐11.39). Conclusion CVT in the context of SARS‐CoV‐2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, since the diagnosis of this potentially life‐threatening condition in COVID‐19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID‐19 associated CVT.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

Background and purpose: We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID‐19 to identify cases with severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 infection or immune‐mediated reaction in the nervous system.Methods: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID‐19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work‐up were extracted. Biases were assessed with the Newcastle–Ottawa scale.Results: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID‐19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain‐Barré syndrome/Miller‐Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS‐CoV‐2 polymerase chain reaction was negligible. Two had a positive SARS‐CoV‐2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards.Conclusions: This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID‐19 beyond immune‐mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS‐CoV‐2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.

The development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT). We performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH. We identified 187 patients with a median age of 74 years (interquartile range [IQR] 60–81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13–22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00–1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89. NLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system which is associated with numerous comorbidities. These include cardiovascular disease, psychiatric and neurologic disturbances, restless leg syndrome, migraine, cancer, autoimmune diseases, and metabolic disorders. Comorbid disease is an important consideration for clinicians treating patients with MS; early presentation of comorbidities can obscure or delay MS diagnosis, as well as significantly impacting the disease course. Improved understanding of comorbidities and their emergence in MS populations is important for improving the quality of life and optimizing treatment for patients. Therefore, we evaluated published studies reporting epidemiologic data on comorbidities and their associated impact on disease progression in patients with MS (PwMS). The prevalence of neurologic, cardiovascular, metabolic, and autoimmune comorbidities was elevated in PwMS in general, and furthermore, this adversely affected a broad range of outcomes. Compared with PwMS, cancer rates in people without MS or the general population were lower, which should prompt further studies into the mechanisms of both diseases. Studies were under-represented in many regions owing to the latitudinal gradient of MS and possible underfunding of studies.

Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. Systematic literature review from January 2000 to July 2018. We identified 38 patients (median age 45 years, range 1–73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.