Stroke is a leading cause of long-term disability and death in the United States. Currently, tissue plasminogen activator (tPA), is the only Food and Drug Administration-approved treatment for acute ischemic stroke. However, the use of tPA is restricted to a small subset of acute stroke patients due to its limited 3-h therapeutic time window. Given the limited therapeutic options at present and the multi-factorial progression of ischemic stroke, emphasis has been placed on the discovery and use of combination therapies aimed at various molecular targets contributing to ischemic cell death. Protein kinase C (PKC) and Akt (protein kinase B) are serine/threonine kinases that play a critical role in mediating ischemic-reperfusion injury and cellular growth and survival, respectively. The present review will examine the role of PKC and Akt in the cellular response to ischemic-reperfusion injury.

No abstract

BackgroundTo analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome.MethodsMulticentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications.ResultsA total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome.ConclusionThere may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.

Each year, more than 790 000 people in the United States suffer from a stroke. Although progress has been made in diagnosis and treatment of ischemic stroke (IS), new therapeutic interventions to protect the brain during an ischemic insult is highly needed. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally. Growing evidence suggests that miRNAs have a profound impact on ischemic stroke progression and are potential targets of novel treatments. Notably, inflammatory pathways play an important role in the pathogenesis of ischemic stroke and its pathophysiologic progression. Experimental and clinical studies have illustrated that inflammatory molecular events collaboratively contribute to neuronal and glial cell survival, edema formation and regression, and vascular integrity. In the present review, we examine recent discoveries regarding miRNAs and their roles in post-ischemic stroke neuropathogenesis.

Background Acute ischemic stroke (AIS) in the context of COVID‐19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS‐CoV‐2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID‐19 who were diagnosed with AIS, the median age was 63 years (range, 27–94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, ( P =0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P =0.047). After multivariable adjustment for possible confounders, a 1‐year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90–0.99; P =0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02–1.10; P =0.007). Conclusions AIS in the context of COVID‐19 affects young patients at much greater rates than pre‐pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

Spontaneous intracranial hypotension (SIH) associated with cerebrospinal fluid leak classically presents with postural headache. It is most commonly caused by the spontaneous dehiscence of a meningeal diverticulum or as a consequence of dural tears. The association between connective tissue disease and SIH is well known. However, the occurrence of SIH associated with systemic lupus erythematosus has rarely been reported. We present a 53 years old female with a history of systemic lupus erythematosus who was diagnosed with SIH. The patient was worked up with Magnetic resonance imaging and Computed tomographic myelography, and successfully treated with a nontargeted epidural blood patch. Furthermore, we review the current literature and focus on the various imaging techniques that can be used in the workup of a cerebrospinal fluid leak.

No abstract

Introduction: Underlying biological, genetic, or epigenetic characteristics may predispose to health differences and outcomes with COVID-19 associated stroke. Social determinants of health, access and geographical differences pertaining both to population density and other location-based factors may also be important. Methods: We report 69 cases of acute stroke in patients positive for SARS-CoV-2, in a dichotomized analysis of ischemic stroke outcomes between patients of African American background versus all other backgrounds. All patients presented to 14 major hospitals in the United States and Canada, from March 14-April 14, 2020. All patients had nasopharyngeal swab samples that were positive for SARS-CoV-2 on qualitative RT-PCR assays. Results: We found no significant difference in age (64.4 versus 62.9 years) or the proportion of females (51.9% versus 38.1%) (table 1). Diabetes mellitus was present significantly less in African American cases versus others (37% vs. 66.7%). The African American cohort had a similar mean NIHSS score of 16.3 compared with 14.9 in other races (p=0.63). The door-to-CT time was also similar (23 versus 19 minutes). The proportion of patients presenting with a large vessel occlusion was not significantly different (40.7% versus 47%). We noted 14.8% of African American cases received intravenous tPA compared to 31% in other races but was not significantly different. The proportion of thrombectomy cases mirrored this (14.8% versus 31%). Regarding stroke functional outcomes, there was no difference between African Americans and other races with respect to discharge mRS or proportion of favorable outcome (mRS 0-2). Symptomatic intracranial hemorrhage (sICH) was significantly higher for African Americans (11.1% versus 3%, p<0.001). Mortality was significantly higher in African Americans compared to other races (51.9% vs. 28.6%, p=0.03). Discussion: The reasons for increased mortality in African Americans with COVID-19-associated stroke are unknown. The finding in this study that mortality rate of COVID-19 positive stroke patients is greater than that previously reported in either COVID-19 respiratory infection alone or acute ischemic stroke alone, suggests an interaction that also warrants further study.