Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

Optimization of resources and modifications in acute ischemic stroke care in response to the global COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has presented unprecedented challenges to healthcare organizations worldwide. A steadily rising number of patients requiring intensive care, a large proportion from racial and ethnic minorities, demands creative solutions to provide high-quality care while ensuring healthcare worker safety in the face of limited resources. Boston Medical Center has been particularly affected due to the underserved patient population we care for and the increased risk of ischemic stroke in patients with COVID-19 infection. METHODS: We present protocol modifications developed to manage patients with acute ischemic stroke in a safe and effective manner while prioritizing judicious use of personal protective equipment and intensive care unit resources. CONCLUSION: We feel this information will benefit other organizations facing similar obstacles in caring for the most vulnerable patient populations during this ongoing public health crisis.

Infectious Etiologies of Stroke.

Central nervous system (CNS) infections are a frequently underappreciated potential etiology of cerebrovascular disease. Highlighted in this review are a selection of infectious agents that lead to cerebrovascular complications through various mechanisms including multifocal vasculopathy, focal infiltrative vasculitis and vasospasm, and direct vessel wall invasion and thrombus formation. Diagnosis of stroke due to underlying CNS infection requires a high index of clinical suspicion and careful consideration of neuroimaging, serum, and cerebrospinal fluid studies in addition to a detailed history and neurologic examination. Prompt and targeted treatment is essential in these conditions, which frequently herald a poor prognosis. Specifically, cerebrovascular complications associated with varicella zoster virus, syphilis, tuberculosis, aspergillosis, and acute bacterial meningitis are addressed here in detail.

Imaging of Central Nervous System Ischemia.

OBJECTIVE: This article describes imaging modalities used in the evaluation of patients presenting with symptoms of acute ischemic stroke. LATEST DEVELOPMENTS: The year 2015 marked the beginning of a new era in acute stroke care with the widespread adoption of mechanical thrombectomy. Subsequent randomized controlled trials in 2017 and 2018 brought the stroke community even further into this new territory with the expansion of the eligibility window for thrombectomy using imaging-based patient selection, which led to an increase in the use of perfusion imaging. Now, after several years of routine use, the debate is ongoing as to when this additional imaging is truly required and when it results in unnecessary delays in time-sensitive stroke care. At this time, more than ever, a robust understanding of neuroimaging techniques, applications, and interpretation is essential for the practicing neurologist. ESSENTIAL POINTS: CT-based imaging is the first step in most centers for the evaluation of patients presenting with symptoms of acute stroke because of its wide availability, speed, and safety. Noncontrast head CT alone is sufficient for IV thrombolysis decision making. CT angiography is very sensitive for the detection of large-vessel occlusion and can be used reliably to make this determination. Advanced imaging including multiphase CT angiography, CT perfusion, MRI, and MR perfusion can provide additional information useful for therapeutic decision making in specific clinical scenarios. In all cases, it is essential that neuroimaging be performed and interpreted rapidly to allow for timely reperfusion therapy.

Perceived Interpersonal Racism and Incident Stroke Among US Black Women.

Importance: Black individuals in the US experience stroke and stroke-related mortality at younger ages and more frequently than other racial groups. Studies examining the prospective association of interpersonal racism with stroke are lacking. Objective: To examine the association of perceived interpersonal racism with incident stroke among US Black women. Design, Setting, and Participants: The Black Women's Health Study, a prospective cohort study of 59 000 Black women from across the US, assessed the longitudinal association between perceived interpersonal racism and stroke incidence. Stroke-free participants were followed up from 1997 until onset of stroke, death, loss to follow-up, or the end of the study period (December 31, 2019). Cox models were used to estimate hazard ratios (HRs) and 95% CIs, adjusting for major confounders, including education, neighborhood socioeconomic environment, and cardiometabolic factors. Data analysis was performed from March 2021 until December 2022. Exposure: On a questionnaire completed in 1997, participants reported experiences of racism in everyday life and when dealing with situations that involved employment, housing, and interactions with police. Main Outcomes and Measures: Strokes were identified through self-report on biennial questionnaires, medical records adjudication, and linkage with the National Death Index. Results: In 1997, 48 375 Black women (mean [SD] age, 41 [10] years) provided information on perceived interpersonal racism and were free of cardiovascular disease and cancer. During the 22 years of follow-up, 1664 incident stroke cases were identified; among them, 550 were definite cases confirmed by neurologist review and/or National Death Index linkage. Multivariable HRs for reported experiences of racism in all 3 domains of employment, housing, and interactions with police vs no such experiences were 1.38 (95% CI, 1.14-1.67), a 38% increase, for all incident cases and 1.37 (95% CI, 1.00-1.88) for definite cases. For comparisons of women in the highest quartile of everyday interpersonal racism score vs women in the lowest quartile, multivariable HRs were 1.14 (95% CI, 0.97-1.35) for analyses that included all incident stroke and 1.09 (95% CI, 0.83-1.45) for analyses that included definite cases only. Conclusions and Relevance: In this study, Black women who reported experiences of interpersonal racism in situations involving employment, housing, and interactions with police appeared to have an increased risk of stroke, even after accounting for demographic and vascular risk factors, suggesting that the high burden of racism experienced by Black US women may contribute to racial disparities in stroke incidence.

Hypertensive Disorders of Pregnancy and Risk of Stroke in U.S. Black Women.

BACKGROUND: Black women have a disproportionately higher burden of both preeclamptic pregnancy and stroke compared with White women, but virtually all existing evidence on this possible association has been generated from women of European ancestry. METHODS: In the Black Women's Health Study, a prospective cohort of U.S. Black women who enrolled in 1995, 42,924 participants were parous and free of cardiovascular disease at baseline. Biennial questionnaires included questions on preeclampsia, gestational hypertension, and stroke. We sought the medical records for participants who reported a stroke, and we reviewed them blinded to reproductive history. Cox proportional-hazards models, with control for potential confounders, were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: Over a median of 22 years of follow-up, there were 1555 incident strokes, including 310 among 4938 women with a history of hypertensive disorders of pregnancy (HDOP). The multivariable hazard ratio for stroke for women with any HDOP compared with those who had never experienced HDOP was 1.66 (95% CI, 1.46 to 1.89). Comparable hazard ratios were 1.53 (95% CI, 1.29 to 1.82) for preeclampsia and 1.81 (95% CI, 1.53 to 2.13) for gestational hypertension only. Associations were similar among women under age 55 years and those aged 55 years and older. CONCLUSIONS: In this prospective study of Black women, a history of HDOP was associated with an estimated 66% increased long-term risk of stroke. This association may contribute to the disproportionately higher stroke incidence in Black women given the higher prevalence of HDOP in this population. (Funded by the U.S. National Institutes of Health.)

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.

Endovascular thrombectomy time metrics in the era of COVID-19: observations from the Society of Vascular and Interventional Neurology Multicenter Collaboration.

BACKGROUND: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown. METHODS: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment. RESULTS: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (ßadj=-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (ßadj=-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (ßadj=-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (ßadj=-2.15, 95% CI -4.2to - -0.1, P=0.05). CONCLUSIONS: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era.

Neurologic Emergencies during the Coronavirus Disease 2019 Pandemic.

Although minor neurologic complications of coronavirus disease 2019 are common, life-threatening neurologic emergencies are rare. Acute ischemic stroke, intracerebral hemorrhage, venous sinus thrombosis, seizures, and posterior reversible encephalopathy syndrome have been described. Hospitals have seen significant changes in the volume of patients presenting with neurologic emergencies. We review what has thus far been published about the intersection of coronavirus disease 2019 and neurologic emergencies with particular attention to cerebrovascular disease and seizure. Considerations in managing the acute presentations of these conditions in the context of the pandemic can serve as a model for management of other neurologic emergencies.

Acute occlusion of the fetal posterior cerebral artery: diagnosis and management paradigms.

BACKGROUND AND PURPOSE: The diagnosis and management of acute fetal posterior cerebral artery occlusion are challenging. While endovascular treatment is established for anterior circulation large vessel occlusion stroke, little is known about the course of acute fetal posterior cerebral artery occlusions. We report the clinical course, radiological findings and management considerations of acute fetal posterior cerebral artery occlusion stroke. METHODS: We performed a retrospective review of consecutive patients presenting with acute large vessel occlusion who underwent cerebral angiogram and/or mechanical thrombectomy between January 2015 and January 2021. Patients diagnosed with fetal posterior cerebral artery occlusion were included. Demographic data, clinical presentation, imaging findings and management strategies were reviewed. RESULTS: Between January 2015 and January 2021, three patients with fetal posterior cerebral artery occlusion were identified from 400 patients who underwent angiogram and/or mechanical thrombectomy for acute stroke (0.75%). The first patient presented with concomitant fetal posterior cerebral artery and middle cerebral artery occlusions. Thrombectomy was performed with recanalisation of the fetal posterior cerebral artery but the patient died from malignant oedema. The second patient presented with isolated fetal posterior cerebral artery occlusion. No endovascular intervention was performed and the patient was disabled from malignant posterior cerebral artery infarct. The third patient presented with carotid occlusion and was found to have fetal posterior cerebral artery occlusion after internal carotid artery recanalisation. No further intervention was performed. The patient was left with residual contralateral homonymous hemianopia and mild left sided weakness. CONCLUSION: Fetal posterior cerebral artery occlusion is a rare, but potentially disabling, cause of ischaemic stroke. Endovascular treatment is feasible. Further investigation is needed to compare the efficacy of medical versus endovascular management strategies.

Perihematomal edema surrounding spontaneous intracerebral hemorrhage by CT: Ellipsoidal versus morphometric volumetry.

Perihematomal edema (PHE) surrounding intracerebral hemorrhage (ICH) may contribute to disease-associated morbidity. Before quantifying PHE's effects on morbidity, a fast, accurate, and reproducible method for measuring PHE volume is needed. The aim of this study is to demonstrate the use of a semiautomated dual clustering segmentation algorithm to generate PHE volumetrics on noncontrast computed tomography (CT) of the head and compare this technique to physicians' manual calculations.This is a single-center, retrospective imaging study that included head CTs performed from January 2008 to December 2014 on 154 patients with ICH. Subjects ≥ 18 years old who were admitted to the hospital with spontaneous ICH were included. Included subjects had head CTs performed upon admission and within 6 to 24 hours. Two neurologists, 2 neuroradiologists, and a computer program all calculated hemorrhage and PHE volumes. Inter-rater correlation was evaluated using 2 statistical methods: intraclass correlations (ICCs) and limits of agreement (LOA). Additionally, correlation between volumes was separately evaluated using Pearson correlation coefficient.There was an excellent correlation between measurements performed by neurologists and neuroradiologists using ABC/2 for ICH (0.93) and PHE (0.78). There was a good correlation between measurements performed by neurologists using ABC/2 and the volume measurements generated by the algorithm for ICH (0.69) and PHE (0.70). There was a fair correlation between measurements performed by neuroradiologists using ABC/2 and volume measurements generated by the algorithm for ICH (0.47) and good correlation for PHE (0.73).Although the ABC/2 method for measuring PHE is quick and practical, algorithms that do not assume ellipsoidal shape may be more accurate.

Direct Visualization of Arterial Emboli in Moyamoya Syndrome.

BACKGROUND: Hemodynamic insufficiency is often considered the cause of ischemic stroke in patients with moyamoya syndrome. While high-intensity transient signals (HITS) on transcranial Doppler (TCD) have been reported in this population, the relationship between these signals and ischemic symptoms is not clearly established. Accordingly, current treatment is directed at improving perfusion. CLINICAL PRESENTATION: We present two patients with symptoms of cerebral ischemia and angiographic findings of moyamoya syndrome. In each case, ischemia may have been caused by either hypoperfusion or embolization. Patient A presented with multifocal right middle cerebral artery (MCA) territory infarctions and angiographic findings consistent with moyamoya disease. She underwent right superficial temporal artery-MCA bypass. Intra-operatively, embolic material was observed and recorded traveling through the recipient MCA branch artery on two occasions. Postoperative TCD demonstrated HITS that resolved with uptitration of antiplatelet therapy. Patient B presented with multifocal, embolic-appearing left MCA infarctions, and unilateral angiographic moyamoya syndrome. She was found to have HITS in the left MCA, which eventually resolved with a combination of antiplatelets and anticoagulation. CONCLUSION: Hemodynamic compromise may not be the only cause of brain infarction in patients with moyamoya syndrome. Observations from these two patients provide both direct visualization and TCD evidence of embolization as a potential etiology for brain ischemia. Future investigations into the role of antithrombotic agents should be considered.