Search

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, it became evident that the SARS-CoV-2 virus infects multiple organs including the brain. Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes. Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood, several theories have been suggested including direct and indirect pathways induced by the virus. One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route. Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells. Nevertheless, the indirect mechanisms, including blood-clotting abnormalities and prolonged activation of the immune system, can result in further tissue and organ damages seen during the course of the disease. This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.

Introduction SARS‐CoV‐2 infection may be associated with uncommon complications such as intracerebral hemorrhage (ICH), with a high mortality rate. We compared a series of hospitalized ICH cases infected with SARS‐CoV‐2 with a non‐SARS‐CoV‐2 infected control group and evaluated if the SARS‐CoV‐2 infection is a predictor of mortality in ICH patients. Methods In a multinational retrospective study, 63 cases of ICH in SARS‐CoV‐2 infected patients admitted to 13 tertiary centers from the beginning of the pandemic were collected. We compared the clinical and radiological characteristics and in‐hospital mortality of these patients with a control group of non‐SARS‐CoV‐2 infected ICH patients of a previous cohort from the country where the majority of cases were recruited. Results Among 63 ICH patients with SARS‐CoV‐2 infection, 23 (36.5%) were women. Compared to the non‐SARS‐CoV‐2 infected control group, in SARS‐CoV‐2 infected patients, ICH occurred at a younger age (61.4± 18.1 years versus 66.8± 16.2 years, P = 0.044). These patients had higher median ICH scores ([3 (IQR 2–4)] versus [2 (IQR 1–3)], P = 0.025), a more frequent history of diabetes (34% versus 16%, P = 0.007), and lower platelet counts (177.8± 77.8 × 109/L versus 240.5± 79.3 × 109/L, P< 0.001). The in‐hospital mortality was not significantly different between cases and controls (65% versus 62%, P = 0.658) in univariate analysis; however, SARS‐CoV‐2 infection was significantly associated with in‐hospital mortality (aOR = 4.3, 95% CI: 1.28‐14.52) in multivariable analysis adjusting for potential confounders. Conclusions Infection with SARS‐CoV‐2 may be associated with increased odds of in‐hospital mortality in ICH patients.

Abstract Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients’ comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method.

Background: The history of intracranial hemorrhage (ICrH) is considered a contraindication for intravenous thrombolysis (IVT) among patients with acute ischemic stroke (AIS). Objective: This study aimed at comparing the safety of IVT among patients with and without a history of ICrH. Methods: We performed a systematic review of the literature. Data regarding all AIS patients with prior ICrH who received IVT were retrieved. Meta-analysis was performed to compare the rate of symptomatic hemorrhagic transformation (sHT), death within 90 days, and favorable and unfavorable 90-day functional outcomes based on modified Rankin Scale (mRS) among stroke patients with and without prior ICrH. Results: Out of 13,032 reviewed records, 7 studies were included in the systematic review and meta-analysis. Quantitative synthesis of data regarding the rate of sHT (5068 patients) revealed no significant difference between the two groups [odds ratio, OR: 1.55 (0.77, 3.12); p = 0.22]. However, a significantly higher risk of death within 90 days [OR: 3.91 (2.16, 7.08); p < 0.00001] and a significantly higher 90-day poor functional outcomes (mRS, 4–6) [OR: 1.57 (1.07, 2.30); p = 0.02] were observed among patients with prior ICrH. Likewise, the percentage of 90-day good functional outcomes (mRS, 0–1) was lower in the prior ICrH group [OR: 0.54 (0.35, 0.84); p = 0.06]. Subgroup analyses in patients with a history of ICrH (based on both patients’ medical history and imaging confirmation) revealed no significant between-group differences in rates of sHT. Also, sensitivity analysis consisting of only studies using standard-dose IVT showed no difference in sHT rates and 90-day outcomes between the two groups. There was no evidence of heterogeneity ( I 2 >50%) among included studies. Conclusion: The results of this study indicated that prior history of ICrH does not increase the risk of sHT post-IVT, but it is associated with a higher risk of death and poor functional outcomes in 90 days.

Background: The current guideline recommends using an intravenous tissue-type plasminogen activator (IV tPA) prior to mechanical thrombectomy (MT) in eligible acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). Some recent studies found no significant differences in the long-term functional outcomes between bridging therapy (BT, i.e., IV tPA prior to MT) and direct MT (dMT). Methods: We conducted a systematic review and meta-analysis to compare the safety and functional outcomes between BT and dMT in AIS patients with ELVO who were eligible for IV tPA administration. Based on the ELVO location, patients were categorized as the anterior group (occlusion of the anterior circulation), or the combined group (occlusion of the anterior and/or posterior circulation). A subgroup analysis was performed based on the study type, i.e., RCT and non-RCT. Results: Thirteen studies (3985 patients) matched the eligibility criteria. Comparing the BT and dMT groups, no significant differences in terms of mortality and good functional outcome were observed at 90 days. Symptomatic intracranial hemorrhagic (sICH) events were more frequent in BT patients in the combined group (OR = 0.73, p = 0.02); this result remained significant only in the non-RCT subgroup (OR = 0.67, p = 0.03). The RCT subgroup had a significantly higher rate of successful revascularization in BT patients (OR = 0.73, p = 0.02). Conclusions: Our meta-analysis uncovered no significant differences in functional outcome and mortality rate at 90 days between dMT and BT in patients with AIS who had ELVO. Although BT performed better in terms of successful recanalization rate, there is a risk of increased sICH rate in this group.

Background: Ischemic and hemorrhagic stroke are associated with a high rate of long-term disability and death. Recent investigations focus efforts to better understand how alterations in gut microbiota composition influence clinical outcomes. A key metabolite, trimethylamine N-oxide (TMAO), is linked to multiple inflammatory, vascular, and oxidative pathways. The current biochemical underpinnings of microbial effects on stroke remain largely understudied. The goal of our study is to explore the current literature to explain the interactions between the human gut microbiome and stroke progression, recovery, and outcome. We also provide a descriptive review of TMAO.Methods: A systematic literature search of published articles between January 1, 1990, and March 22, 2020, was performed on the PubMed database to identify studies addressing the role of the microbiome and TMAO in the pathogenesis and recovery of acute stroke. Our initial investigation focused on human subject studies and was further expanded to include animal studies. Relevant articles were included, regardless of study design. The analysis included reviewers classifying and presenting selected articles by study design and sample size in a chart format.Results: A total of 222 titles and abstracts were screened. A review of the 68 original human subject articles resulted in the inclusion of 24 studies in this review. To provide further insight into TMAO as a key player, an additional 40 articles were also reviewed and included. Our findings highlighted that alterations in richness and abundance of gut microbes and increased plasma TMAO play an important role in vascular events and outcomes. Our analysis revealed that restoration of a healthy gut, through targeted TMAO-reducing therapies, could provide alternative secondary prevention for at-risk patients.Discussion: Biochemical interactions between the gut microbiome and inflammation, resulting in metabolic derangements, can affect stroke progression and outcomes. Clinical evidence supports the importance of TMAO in modulating underlying stroke risk factors. Lack of standardization and distinct differences in sample sizes among studies are major limitations.

Failed Back Surgery Syndrome (FBSS) is persistent pain and disability following lumbar laminectomy which is associated with decreased quality of life and disability and has been reported in up to 40% of the patients undergoing lumbar laminectomy. Several approaches have been introduced to reduce the rate of the FBSS. Among these, applying anti-adhesive barrier gels have been studied with interest with controversial results. The aim of the current study was to determine the effects of anti-adhesive barrier gels on functional outcome and recurrence of patients undergoing lumbar disc surgery. We searched databases including EMBASE, PUBMED, Web of Science, Scopus, Cochrane Library, and scholar databases until November 2019. To assess the heterogeneity across included studies was used Cochran's Q and I-square (I2) statistics. Standardized mean difference (SMD) and 95% CI between were used to estimate pooled effect sizes. Out of 4507, 10 clinical trials found to be appropriate for current meta-analysis. The pooled results of included clinical trials indicated that adhesion barrier gel significantly decreased leg pain (LP) (SMD = −0.31; 95% CI, −0.60, −0.03; P = 0.032; I2: 59.2%) among patients with lumbar disc herniation surgery. Back pain (BP) (SMD = −0.03; 95% CI, −0.23, 0.16; P = 0.734; I2: 40.2%), and Oswestry disability index (ODI) (SMD = −0.11; 95% CI, −0.27, 0.05; P = 0.178; I2: 0.0%), were not significantly affected following adhesion barrier gel application. Application of adhesion barrier gel in single level lumbar disc surgery is associated with deceased leg pain. However, its application does not affect the low back pain, disability and gate. Further, larger randomized clinical trials are required.

Since the early days of the pandemic, there have been several reports of cerebrovascular complications during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Numerous studies proposed a role for SARS-CoV-2 in igniting stroke. In this review, we focused on the pathoetiology of stroke among the infected patients. We pictured the results of the SARS-CoV-2 invasion to the central nervous system (CNS) via neuronal and hematogenous routes, in addition to viral infection in peripheral tissues with extensive crosstalk with the CNS. SARS-CoV-2 infection results in pro-inflammatory cytokine and chemokine release and activation of the immune system, COVID-19-associated coagulopathy, endotheliitis and vasculitis, hypoxia, imbalance in the renin-angiotensin system, and cardiovascular complications that all may lead to the incidence of stroke. Critically ill patients, those with pre-existing comorbidities and patients taking certain medications, such as drugs with elevated risk for arrhythmia or thrombophilia, are more susceptible to a stroke after SARS-CoV-2 infection. By providing a pictorial narrative review, we illustrated these associations in detail to broaden the scope of our understanding of stroke in SARS-CoV-2-infected patients. We also discussed the role of antiplatelets and anticoagulants for stroke prevention and the need for a personalized approach among patients with SARS-CoV-2 infection.

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.

Background: Several studies suggest women may be disproportionately affected by poorer stroke outcomes than men. This study aims to investigate whether women have a higher risk of all-cause mortality and recurrence after an ischemic stroke than men in a rural population in central Pennsylvania, United States. Methods: We analyzed consecutive ischemic stroke patients captured in the Geisinger NeuroScience Ischemic Stroke research database from 2004 to 2019. Kaplan–Meier (KM) estimator curves stratified by gender and age were used to plot survival probabilities and Cox Proportional Hazards Ratios were used to analyze outcomes of all-cause mortality and the composite outcome of ischemic stroke recurrence or death. Fine–Gray Competing Risk models were used for the outcome of recurrent ischemic stroke, with death as the competing risk. Two models were generated; Model 1 was adjusted by data-driven associated health factors, and Model 2 was adjusted by traditional vascular risk factors. Results: Among 8900 adult ischemic stroke patients [median age of 71.6 (interquartile range: 61.1–81.2) years and 48% women], women had a higher crude all-cause mortality. The KM curves demonstrated a 63.3% survival in women compared with a 65.7% survival in men ( p = 0.003) at 5 years; however, the survival difference was not present after controlling for covariates, including age, atrial fibrillation or flutter, myocardial infarction, diabetes mellitus, dyslipidemia, heart failure, chronic lung diseases, rheumatic disease, chronic kidney disease, neoplasm, peripheral vascular disease, past ischemic stroke, past hemorrhagic stroke, and depression. There was no adjusted or unadjusted sex difference in terms of recurrent ischemic stroke or composite outcome. Conclusion: Sex was not an independent risk factor for all-cause mortality and ischemic stroke recurrence in the rural population in central Pennsylvania.

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke—123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1–3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4–4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None.

Objective. Myelomeningocele may be isolated but more frequently is associated with other anomalies. Congenital heart disease occurs with different incidence rate in myelomeningocele which is observed more frequently with skeletal malformations. Methods. This study was undertaken in the Children’s Hospital Medical Center between 2010 to 2012 to evaluate 75 myelomeningocele patients for cardiac anomalies, with electrocardiography and echocardiography in addition to clinical examination of the cardiopulmonary system. Demographic information, myelomeningocele location and characteristics, orthopedic deformities, neurological deficits and radiographic findings were studied besides cardiologic assessments. Results. The ages of the patients ranged from 1 day to 4 years. The myelomeningocele locations were lumbosacral, lumbar and sacral area in most cases. Physical examination of the heart was abnormal in 6 children, but echocardiography revealed cardiac anomalies in only two children. Both children were female patients with severe scoliosis, multiple rib deficiencies and associated vertebral anomalies. Conclusion. Congenital heart defects are not very common in MMC patients. Female patients with suspicious clinical examinations for cardiac anomalies and associated rib and vertebral anomalies are advised to be investigated by echocardiography to rule out associated cardiac anomalies.