Coronavirus disease 2019 , caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.

S pontaneous intracerebral hemorrhage (ICH) accounts for 10% to 30% of all strokes and is characterized by high rates of mortality and disability. The inflammatory response contributes to the ICH-induced secondary brain injury although the mechanisms are unknown. 1 The aim of this study was to evaluate the relationships between the total and differential leukocyte counts and the neutrophil-to-lymphocyte ratio (NLR) at admission with the 3-month outcome in ICH patients. Methods Participants and Study OutcomeWe retrospectively identified consecutive patients hospitalized at the Stroke Unit of the Marche Polytechnic University, Ancona, Italy from January 2008 to September 2015 for stroke syndrome caused by acute spontaneous ICH who underwent admission routine blood sampling and cranial computed tomographic neuroimaging within 24 hours from symptom onset. Demographics, medical history, admission/discharge National Institutes of Health Stroke Scale 2 scores, baseline ICH topography and volume, 3 admission blood pressure and 24-hour blood pressure variability by means the coefficient of variation 4 were considered. Total white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and erythrocyte sedimentation rate were collected from admission blood work. The outcome measure was the 3-month functional status: poor outcome was the occurrence of death or major disability (modified Rankin Scale score, ≥3). 5 Statistical AnalysisValues are presented as mean±SD, median (interquartile range) or number (%) of subjects. Comparisons were made through the Student t test, Mann-Whitney U test or χ 2 test. Spearman correlation was used to correlate continuous variables. The associations between the WBC, ANC, ALC, NLR, and the study end point were determined using the logistic regression; the variables with P<0.05 from comparison of baseline characteristics and selected variables (age, sex, initial National Institutes of Health Stroke Scale score, baseline volume, location, and intraventricular extension of ICH) 6 were forced into the multivariate analysis. The analysis was performed after categorization of the WBC, ANC, and ALC values into higher and lower groups with respect to the normal reference ranges. 7 The receiver operating characteristic analysis evaluated the ability of the WBC, ANC, ALC, and NLR to predict the outcome. Results were significant for P<0.05 (2 sided). Analysis was performed using STATA/IC 13.1 (StataCorp LP, TX). Standard Protocol ApprovalsThe local ethical committee approved this study. The board allowed the study to be conducted without patients' consent because of the retrospective nature of the study. ResultsA total of 177 patients were recruited, whose 94 (53.1%) had a modified Rankin Scale score of ≥3 at 3 months (Table 1). The poor outcome patients had higher WBC, ANC, and NLR and lower ALC (Table I in the online-only Data Supplement); no difference was found in the admission erythrocyte sedimentation rate values (28±2 versus 26±2 mm/h for good and poor outcome, respec...

Background Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability. Objective The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques. Methods Randomized, placebo-controlled, single-or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs). Results Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54,; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I 2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59,; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/ day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. Conclusions Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure ...

Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 10 to 30% of all acute cerebrovascular events, and it is the type of stroke associated with the highest rates of mortality and residual disability. The inflammatory response is early triggered by hematoma components and can enhance the damage within the hemorrhagic brain. Assessment of peripheral biomarkers of inflammation could contribute to increase knowledge about some of the mechanisms involved in the ICH-induced injury and yield information on the disease course. The neutrophil-to-lymphocyte ratio (NLR) integrates information on both the innate and adaptive compartments of the immunity and represents a reliable measure of the inflammatory burden. The aim of the current review is to highlight the available evidence about the relationships between the NLR and clinical outcome in patients with acute ICH and provide critical insights into the underlying pathophysiology. Since no therapy targeting ICH-induced primary injury has yielded conclusive benefits and ICH treatment remains mainly supportive within a framework of general critical care management, these findings could also contribute to identify new potential targets for neuroprotection and develop novel therapeutic strategies.

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