The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin D-dimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.

Background and ObjectivesCOVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.MethodsThis was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).ResultsOf a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).DiscussionPatients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.

We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with neurological manifestations

Carotid artery stenting (CAS) for carotid stenosis (CS) is widely performed. Randomized trials may not be reflective of real-world outcomes. We used the 2012-19 ACS-NSQIP CAS Procedure Targeted Dataset to identify the incidence and risk factors associated with periprocedural 30-day adverse events (AE). AE were categorized as follows: vascular (embolization - proximal and distal thrombosis, myocardial infarction [MI], stroke, restenosis, and TIA) , stroke/TIA alone, major (organ-space surgical site infection [SSI]), pneumonia, intubation, pulmonary embolism, post-operative ventilator use, blood transfusion, deep venous thrombosis, sepsis), minor (urinary tract infections, acute renal failure, superficial SSI). Other outcome variables were readmissions, reoperations, mortality, and non-home discharges. Multivariate logistic regression analysis, using backward stepwise model with entry and removal probabilities of p=0.05 and p=0.1. 1552 patients (median age=70 IQR 62-76) were included. 64% were male. 49% of CAS procedures were in asymptomatic patients, whereas 24% were following stroke, 16% to TIA and 8% for amaurosis fugax. 2.1% were mild (<50%) carotid stenosis, 26.6% were moderate (50%-79%) stenosis and 65.6% were severe (80%-99%) stenosis, while 2.7% were complete occlusions. Perioperative mortality was 1.9% and 10.6% were non-home discharges. 6.2% experienced vascular AE; 2.8% patients had perioperative strokes, 0.9% had TIA, 2.3% had MI, 0.7% had thrombosis, 0.4% had proximal embolization, 0.5% were restenosis, and 0.6% had distal embolization. Risks for major AE were COPD (OR 2.37; p=0.004), BUN>21 (OR 1.68; p=0.043), hypoalbuminemia (OR 3.00; p=0.002), and operative time >77mins (OR 1.92; p=0.013). Pre-procedural aspirin lowered odds of experiencing major AE (OR 0.43; p=0.035). Risk factors of 30-day readmissions were contralateral severe (OR 2.73; p=0.002) or complete (OR 3.07; p=0.001) stenosis, COPD (OR 2.01; p=0.003) and congestive heart failure (OR 2.85; p=0.004). In conclusion, almost half of CAS procedures were performed in asymptomatic patients. Periprocedural complications were higher than those reported in randomized trials. Physicians should use the findings for risk stratification.

Background and Objectives COVID-19–related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19. Methods This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). Results Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16–2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20–2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23–1.99), 24-hour mortality (OR 2.47; 95% CI 1.58–3.86), and 3-month mortality (OR 1.88; 95% CI 1.52–2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26–1.60). Discussion Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non–COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis. Trial Registration Information The study was registered under ClinicalTrials.gov identifier NCT04895462.

We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with encephalopathy.

We report a patient with infectious complication of patent foramen ovale (PFO) closure device two years after implantation, leading to septic embolic stroke with hemorrhagic conversion. We also describe the challenges in management of the case, particularly in deciding the timing for safe anticoagulation for cardiac surgery.

Objective: To report two patients with Susac syndrome (SS) mimicking Multiple Sclerosis (MS). It’s important to diagnosed Susac syndrome (SS) as there are several differential diagnoses including MS, Acute Disseminated Encephalomyelitis, Systemic Lupus Erythematosus. Background: Case 1: A 27 year old woman presented with cognitive changes and hearing loss. MRI brain showed discrete snowball-like lesions in the corpus callosum. Ophthalmologic evaluation revealed bilateral retinal artery occlusions. Case 2: A 50 year old woman developed hearing loss, gait imbalance and progressive confusion over three weeks. MRI revealed multiple bilateral punctate lesions, some in the corpus callosum. Lumbar puncture (LP) revealed elevated protein. She was treated with intravenous methylprednisolone and intravenous immune globulin (IVIG) with clinical and radiographic improvement. Both patients remained clinically and radiographically stable on maintenance immunomodulating therapy (Mycophenolate and Azathioprine, respectively). Design/Methods: Information regarding patients obtained via retrospective review of electronic medical records. Results: Both patients had extensive evaluations including LP with elevated protein and negative MS markers. Serum studies included negative antinuclear antibody, anti-nuclear cytoplasmic antibody, extractable nuclear antigen panel, homocysteine, and anti-cardiolipin antibody. Fluorescein angiogram revealed multiple branch retinal artery occlusions, further supporting a diagnosis of SS. Conclusions: Susac syndrome is an immune-mediated vasculopathy involving small vessels in the brain, eye, and ear. Classic clinical triad consists of hearing loss, vision changes, and encephalopathy. Imaging findings in SS can be mistakenly identified as demyelinating lesions, and there are reports of patients with SS erroneously being treated for MS. Red flags raising concern for SS include hearing loss, branch retinal artery occlusions, and corpus callosum lesions. Early diagnosis of SS is important with excellent prognosis if treated aggressively at an early stage of the disease. Disclosure: Dr. Sriwastava has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Rajamani has nothing to disclose.

The brain and kidney both uniquely are highly susceptible to vascular injury from shared vascular risk factors. However these are not sufficient to explain the complete extent of cerebrovascular disease especially small vessel disease in its myriad presentations that patients with chronic kidney disease manifest. They both require a large amount of blood supply to function optimally. Shared anatomical and physiological factors such as the presence of strain vessels, the local vascular autoregulation that control blood supply possible, results in the vulnerability of these organs to the vascular risk factors. Because it is a bidirectional system where each affects the other, it is best considered as a cerebro-renal unit.

May 8, 2019April 9, 2019Free AccessRate of ischemic stroke and intracranial hemorrhage following left ventricular assist device placement: a systematic review (P4.3-054)Mohammed Alhaidar, saber Hamidreza, Ali Ebrahim, and Kumar RajamaniAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.P4.3-054 Letters to the Editor

A 66-year-old woman presented with a history of recurrent, transient neurologic symptoms including limb shaking, focal paresthesias, focal weakness, dysphasia, and unresponsiveness. The episodes showed no preference for time of day, lasted less than 6 minutes, and occurred less than monthly in small clusters, increasing in frequency slowly over 2 years. She lived independently, denied cognitive or other complaints, and had no history of smoking, hypertension, hyperlipidemia, coronary atherosclerosis or diabetes mellitus, or family history of stroke. Clinical examination was unremarkable. Cognition was grossly intact but not formally tested. Differential diagnosis included transient ischemic attacks (TIAs), seizures, and psychogenic nonepileptic seizures (PNESs). MRI of the brain was consistent with probable cerebral amyloid angiopathy (CAA) (figure) with cortical microbleeds and superficial siderosis.1,2 Two habitual transient focal neurologic episodes (TFNEs) were captured on video EEG (video 1).

May 9, 2019April 9, 2019Free AccessAcute anterior thalamic infarcts affecting Memory and Cognition- an important but less well known lacunar syndrome (P5.3-063)Deepmala Nandanwar and KUMAR RAJAMANIAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement) Letters to the Editor

Department of Neurology, Detroit Medical Center, Wayne State University, Detroit, MI The authors have no conflicts of interest to declare.

Asymmetries in grasp force matching extend beyond quantifying a single measure of maximum grip strength and advance our application of side-specific treatment interventions. A cross sectional study design investigated grasp-force matching performance in right-handed individuals with a stroke and age-matched healthy controls. A visual representation of the 20% Maximum Voluntary Contraction (MVC) was matched in three conditions in the absence of visual feedback with the same (Ipsilateral Remembered - IR) or opposite hand (Concurrent CC and Contralateral Remembered - CR). Greater overall relative error (RE) was found in contralateral compared to ipsilateral matching tasks. In the CR condition, post hoc analysis revealed significant differences between control and right hemisphere damage (RHD) group (95% CI [16.41-88.59]; p < 0.01) as well as left hemisphere damage (LHD) group and RHD (95% CI [23.4-95.09]; p < 0.01). Right hand matching relative error was 2.49 times larger in the RHD compared to the LHD group. Within the RHD group, matching errors were greater for the right than left hand in both contralateral conditions (95% CI [34,25-101.07]; p < 0.001). Individuals with RHD showed greater asymmetries in contralateral matching tasks compared to LHD and controls. More specifically, the RHD group had the greatest difficulty matching tasks with their right (non-paretic) than left (paretic) hand. In order to elucidate this asymmetry in the clinic the use of complementary grasp measures may be considered.

Atherosclerosis is a global disorder and accounts for almost half the annual mortality in the western world. It often remains clinically silent until it causes end organ damage resulting in stroke, ischemic heart disease, or peripheral vascular insufficiency of the extremities. The distribution of atherosclerosis in the vascular tree is fairly characteristic. The aorta is involved more extensively and earlier than other vessels and the abdominal aorta is more widely involved than the aortic arch or the thoracic aorta. The pulmonary arteries, the renal arteries, and the mesenteric arteries are the least susceptible. Lower limb vessels are more often affected than the upper limb vessels. Fatty streaks, which are the earliest lesion of atherosclerosis, can be seen in the aorta in infancy or early childhood. Epidemiological studies have shown a high degree of association between atherosclerosis and elevated lipids. The ratio of total cholesterol to high-density cholesterol is an important factor in predicting risk. Elevated low-density lipoprotein (LDL) induces endothelial injury, and increases the adhesion of monocytes to the endothelium. LDL is oxidatively modified by endothelial cells, macrophages, and smooth muscle cells. Oxidation of LDL leads to increased collagen production and progression of atherosclerosis.

Objective: To report a case of acute Ischemic Stroke treated with IV tPA after reversal of Heparin in an anticoagulated patient. Background: One of the main exclusion criteria for IV tPA has been prior administration of anticoagulants and PT > 15 seconds, INR > 1.7, or IV Heparin within 48 hours preceding the onset of stroke and an elevated aPTT . There is currently no evidence regarding safety and efficacy of acute thrombolysis with IV tPA after rapid Heparin reversal with Protamine in patients undergoing thrombolysis. Design/Methods: A 52 year old woman undergoing a diagnostic cardiac angiogram, was administered Heparin 5000 IU IV during the procedure who became unresponsive with right sided hemiparesis. Her last known well was 13 minutes prior to stroke alert. Her initial NIHSS score was 16 and CT Brain w/o contrast was negative for ICH. The initial aPTT was determined to be 51.4 seconds. Given the severity of the stroke and availability of time, decision was made to reverse the Heparin with IV Protamine. 25 mg and repeat aPTT obtained after 30 minutes was down to 25.0. IV tPA at 1 hour and 34 minutes from her LKW. Soon after tPA was given, symptoms started to improve and patient’s NIHSS dropped down to 4 by the end of infusion, which dropped further to 1 by the time of discharge. Brain MRI showed restricted diffusion in left thalamus with no hemorrhagic changes. Results: NA Conclusions: Anticoagulation with Heparin use within last 48 hours with abnormal aPTT before stroke is an absolute contraindication for IV tPA but there is no clear evidence regarding whether reversal of heparin will affect the long term outcome. To our knowledge, this is the first case of acute stroke with Heparin reversal followed by IV tPA. Disclosure: Dr. Almarhoon has nothing to disclose. Dr. Danoun has nothing to disclose. Dr. Rajamani has nothing to disclose.

BACKGROUND:Venous thrombosis affecting cerebral veins and sinuses (CVT) is an uncommon neurological condition. Traditionally patients are treated with intravenous heparin followed by an oral vitamin K antagonist like warfarin. Direct oral anticoagulants (DOACs) may offer advantages over warfarin. There is evidence to demonstrate the effectiveness of both dabigatran and rivaroxaban. No data, however, has been published describing the use of apixaban in patients with CVT.METHODS:Report of three cases of CVT and review literature on available treatment options; efficacy and safety of novel oral anticoagulants in patients with systemic thrombosis.RESULTS:All patients presented with typical features of CVT. After confirming the diagnosis, they were acutely treated with heparin and later discharged on apixaban. During follow up visits, they tolerated apixaban well and did not have any bleeding complications. Follow up scans showed resolution of the thrombus and recanalization.CONCLUSION:CVT is an uncommon neurological condition and is often complicated by associated intraparenchymal hemorrhage. Although not recommended in current guidelines, apixaban may be a safe and effective option for the treatment of CVT.