The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Largevessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke. ABBREVIATIONS: CCA ¼ common carotid artery; COVID-19 ¼ coronavirus disease 2019; LVO ¼ large-vessel occlusion; SARS CoV-2 ¼ Severe Acute Respiratory Syndrome coronavirus-2 C oronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by infection with the Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). 1,2 There are now multiple reports of COVID-19 affecting the central nervous system, ranging from meningitis/encephalitis to stroke. [3][4][5] In a single-center study of 214 hospitalized patients with COVID-19 from Wuhan, China, where the infection first occurred, up to 36.4% of patients had neurologic manifestation, including acute cerebrovascular disease with severe and nonsevere infection in 5.7% and 0.8% of these patients, respectively. 3 In addition, there are also reports of ischemic stroke being caused by large-vessel occlusion (LVO) in patients with COVID-19 without significant pre-existing cardiovascular risk factors. 6 While the reasons for ischemic stroke in COVID-19 are unclear, hypotheses of an inflammatory cytokine storm-triggered hypercoagulable state, endothelial damage, and arrythmias have been postulated. 7,8 However, as it stands, the mechanisms, phenotype, and optimal management of ischemic stroke associated with COVID-19 still remain uncertain.There is an urgent need to identify associations and predictors of severity, morbidity, and mortality in patients with ischemic stroke and COVID-19, especially in the LVO subgroup, given that it is most disabling.

Highlights When comparing stroke admissions from March 1 st -May 10 th in 2019 and 2020 at a single comprehensive stroke center in Middle East, there was a 41.9% increase in stroke admissions in 2020. A higher rate of large vessel occlusion (LVO) and significant delay in initiation of mechanical thrombectomy after hospital arrival was observed in 2020. Among all COVID-19 admissions in 2020, 5.24% patients suffered stroke including 3.21% with ischemic and 2% with hemorrhagic stroke. Patients with COVID-19 and ischemic stroke were significantly younger, predominantly male, had fewer vascular risk factors, had more severe clinical presentation, and higher rate of LVO ccompared to ischemic stroke patients without COVID-19 For hemorrhagic stroke, COVID-19 patients did not differ from non-COVID-19 patients.

Super-refractory status epilepticus (SRSE) is a devastating neurological condition with limited treatment options. We conducted an extensive literature search to identify and summarize the therapeutic options for SRSE. The search mainly resulted in case reports of various pharmacologic and non-pharmacologic treatments. The success rate of each of the following agents, ketamine, inhaled anesthetics, intravenous immunoglobulin G (IVIG), IV steroids, ketogenic diet, hypothermia, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and vagal nerve stimulation (VNS), are discussed in greater detail. The choice of appropriate treatment options for a given patient is based on clinical presentation. This review focuses on evidence-based, pharmacotherapeutic strategies for patients in SRSE.

Objective: To determine whether the extent of leukoaraiosis, a composite marker of baseline brain integrity, differed between patients with TIA with diffusion-weighted imaging (DWI) evidence of infarction (transient symptoms with infarction [TSI]) and patients with ischemic stroke.Methods: Leukoaraiosis volume on MRI was quantified in a consecutive series of 153 TSI and 354 ischemic stroke patients with comparable infarct volumes on DWI. We explored the relationship between leukoaraiosis volume and clinical phenotype (TIA or ischemic stroke) using a logistic regression model. Results:Patients with TSI tended to be younger (median age 66 vs 69 years, p ϭ 0.062) and had smaller median normalized leukoaraiosis volume (1.2 mL, interquartile range [IQR] 0.2-4.7 mL vs 3.5 mL, IQR 1.2-8.6 mL, p Ͻ 0.001). In multivariable analysis controlling for age, stroke risk factors, etiologic stroke mechanism, infarct volume, and infarct location, increasing leukoaraiosis volume remained associated with ischemic stroke (odds ratio 1.05 per mL, 95% confidence interval 1.02-1.09, p ϭ 0.004), along with infarct volume and infarct location. Conclusion:The probability of ischemic stroke rather than TSI increases with increasing leukoaraiosis volume, independent of infarct size and location. Our findings support the concept that the integrity of white matter tracts connecting different parts of the brain could contribute to whether or not patients develop TSI or ischemic stroke in an event of brain infarction. Neurology Approximately one-third of traditionally defined TIAs present with imaging evidence consistent with acute infarction (now termed transient symptoms with infarction [TSI]).1 Rapid and complete clinical recovery in TSI suggests that the brain has the ability to quickly compensate for the neurologic dysfunction caused by underlying infarcts. One of the most characteristic features of TSI-related infarcts is that they are invariably very small 2 ; 96% of all infarcts in TSI are smaller than 1 mL. While small infarcts are frequent in TSI, they are not specific; such small infarcts also occur in patients with clinical deficits lasting for more than 24 hours (traditionally defined ischemic stroke).2 Furthermore, small infarcts in TSI do not occur solely in so-called silent brain regions but can also involve the same brain structures that are often infarcted in ischemic stroke.2 Hence, it is not known how neurologic symptoms rapidly recover in some patients, but do not in others, despite the evidence of cerebral infarction of similar size and in similar location.Functional recovery after brain injury is a complex process which involves recruitment and reorganization of structures that are functionally similar but anatomically distinct from those that are infarcted. [3][4][5] Prior observations suggest that the integrity of the white matter as quanti-*These authors contributed equally to this work.From the A.A.

We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890  nmol/min and 123  nmol and increased significantly to 1943  nmol/min (P < 0.01) and 301  nmol (P < 0.01) 30  min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.