Stroke mechanisms in adult moyamoya disease: The association between infarction patterns and quantitative magnetic resonance angiography flow state.

INTRODUCTION: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. METHODS: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. RESULTS: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04). CONCLUSION: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.

Hypoperfusion Intensity Ratio is Associated with Stroke Mechanism in Patients Undergoing Mechanical Thrombectomy.

BACKGROUND: Hypoperfusion Intensity Ratio (HIR), defined as Tmax >10s/Tmax >6s on computed tomography perfusion (CTP), and stroke mechanisms have been independently correlated with angiographic collaterals and patient outcomes. Slowly developing atherosclerotic stenosis may foster collateral development, whereas cardioembolic occlusion may occur before collaterals mature. We hypothesized that favorable HIR is associated with large artery atherosclerosis (LAA) stroke mechanism and good clinical outcome. METHODS: Retrospective study of consecutive endovascularly-treated stroke patients with intracranial ICA or MCA M1/M2 occlusions, who underwent CTP before intervention, between January 2018 and August 2021. Patients were dichotomized into LAA+ or LAA- based on presence of LAA on angiography. HIR was dichotomized into favorable (HIR+) or unfavorable (HIR-) groups based on published thresholds. Good early outcome was defined as discharge mRS of 0-2. Bivariate and multivariable logistic regression were performed. RESULTS: 143 patients met inclusion. 21/143 were LAA+ (15%) and 65/143 (45%) were HIR+. HIR+ was significantly more frequent in LAA+ patients (67% vs. 42%, p= 0.035). Controlling for demographics, stroke severity, imaging findings, and medical comorbidities, LAA+ remained independently associated with HIR+ (OR 5.37 [95% CI 1.43 - 20.14]; p=0.013) as did smaller infarction core volume (<30 mL of CBF <30%: OR 7.92 [95% CI 2.27 - 27.64]; p = 0.001). HIR+ was not associated with good clinical outcome. CONCLUSIONS: Large artery atherosclerosis was independently associated with favorable HIR in patients undergoing mechanical thrombectomy. While favorable HIR was associated with smaller pre-treatment core infarcts, reflecting more robust collaterals, it was not associated with good clinical outcome.

Cerebrovascular Complications of COVID-19.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke. We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection. METHODS: Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020. Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior. RESULTS: Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women). Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%). Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%; P<0.001), mortality (29.1% versus 9.0%; P<0.001), and Black/multiracial race (58.1% versus 36.9%; P=0.001). COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2]; P<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality. CONCLUSIONS: COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

Cerebral venous thrombosis: A typical presentation of COVID-19 in the young.

OBJECTIVE: Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. BACKGROUND: SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. CASE DESCRIPTION: Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. CONCLUSION: Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.

Prevalence and Risk Factors for Paroxysmal Atrial Fibrillation and Flutter Detection after Cryptogenic Ischemic Stroke.

INTRODUCTION: Long-term cardiac monitoring with implantable loop recorders (ILRs) has revealed occult paroxysmal atrial fibrillation and flutter (PAF) in a substantial minority of cryptogenic ischemic stroke (CIS) patients. Herein, we aim to define the prevalence, clinical relevance, and risk factors for PAF detection following early poststroke ILR implantation. MATERIALS AND METHODS: A retrospective study of CIS patients (n = 100, mean age 65.8 years; 52.5% female) who underwent ILR insertion during, or soon after, index stroke admission. Patients were prospectively followed by the study cardiac electrophysiologist who confirmed the PAF diagnosis. Univariate and multivariate analyses compared clinical, laboratory, cardiac, and imaging variables between PAF patients and non-PAF patients. RESULTS: PAF was detected in 31 of 100 (31%) CIS patients, and anticoagulation was initiated in almost all (30 of 31, 96.8%). Factors associated with PAF detection include older age (mean [year] 72.9 versus 62.9; P = .003), white race (odds ratio [OR], 4.5; confidence interval [CI], 1.8-10.8; P = .001), prolonged PR interval (PR > 175 ms; OR, 3.3; CI, 1.2-9.4; P = .022), larger left atrial (LA) diameter (mean [cm] 3.7 versus 3.5; P = .044) and LA volume index (mean [cc/m2]; 30.6 versus 24.2; P = .014), and lower hemoglobin (Hb)A1c (mean [%] 6.0 versus 6.4; P = .036). Controlling for age, obesity (body mass index > 30 kg/m2; OR, 1.2; CI, 1.1-1.4; P = .033) was independently associated with PAF detection. DISCUSSION: PAF was detected with high prevalence following early postcryptogenic stroke ILR implantation and resulted in significant management changes. Older age, increased PR interval, LA enlargement, and lower HbA1c are significantly associated with PAF detection. Controlling for age, obesity is an independent risk factor. A larger prospective study is warranted to confirm these findings.

Improving Regional Stroke Systems of Care.

PURPOSE OF REVIEW: Acute ischemic stroke (AIS) care is rapidly evolving. This review discusses current diagnostic, therapeutic, and process models that can expedite stroke treatment to achieve best outcomes. RECENT FINDINGS: Use of stent retrievers after selection via advanced imaging is safe and effective, and is an important option for AIS patients with large vessel occlusion (LVO). Significant time delays occur before and during patient transfers, and upon comprehensive stroke center (CSC) arrival, and have deleterious effects on functional outcome. Removing obstacles, enhancing inter-facility communication, and creating acute stroke management processes and protocols are paramount strategies to enhance network efficiency. Inter-departmental CSC collaboration can significantly reduce door-to-treatment times. Streamlined stroke systems of care may result in higher treatment rates and better functional outcomes for AIS patients, simultaneously conserving healthcare dollars. Stroke systems of care should be structured regionally to minimize time to treatment. A proactive approach must be employed; a management plan incorporating stroke team prenotification and parallel processes between departments can save valuable time, maximize brain salvage, and reduce disability from stroke.

Improving Transfer Times for Acute Ischemic Stroke Patients to a Comprehensive Stroke Center.

BACKGROUND AND OBJECTIVE: The transfer of acute ischemic stroke (AIS) patients to a comprehensive stroke center (CSC) must be rapid. Delays pose an obstacle to time-sensitive stroke treatments and, therefore, increase the likelihood of exclusion from endovascular stroke therapy. This study aims to evaluate the impact of the Stroke Rescue Program, with its goal of minimizing interfacility transfer delays and increasing the number of transport times completed within 60 minutes. METHODS: The Stroke Rescue Program was initiated to facilitate the rapid transfer of AIS patients from regional primary stroke centers (PSCs) to the network's CSC. The transfer process was divided into 3 time elements: transport 1 time (initial phone call from the PSC until emergency medical service [EMS] arrival at the PSC), emergency department (ED) time (EMS PSC arrival to PSC departure), and transport 2 time (PSC departure to CSC arrival). The total transport time target was set at less than 60 minutes. Protocols and procedures were implemented with a focus on decreasing the ED time. RESULTS: Comparing baseline (preimplementation) quarter (n = 21) to postproject quarter (1 year later, n = 31), the percent transported within 60 minutes increased from 62% to 81%. A statistically significant improvement was seen for both median ED time (23 minutes versus 14 minutes; U = 171, P < .01) and median total transport time (56 minutes versus 44 minutes; U = 199, P < .05). CONCLUSION: Interfacility transfer protocols minimizing the time paramedics spend in a PSC ED can significantly reduce total transfer time to a comprehensive stroke center.

Use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients ≥90 Years of Age.

BACKGROUND AND PURPOSE: Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged ≥90 years. METHODS: We analyzed data from the Get With The Guidelines-Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged ≥90 and 3 younger age groups (18-64, 65-79, and 80-89 years). RESULTS: Among 35 708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were ≥90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged ≥90 years (67.4% versus 84.1% in 18-89-year olds; P<0.0001). Discharge outcomes among individuals aged ≥90 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged ≥90 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds. CONCLUSIONS: The use of intravenous tPA among those aged ≥90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower.

Recurrent Stroke due to Patent Foramen Ovale Closure Device Thrombus Eight Years after Implantation.

Patent foramen ovale (PFO) is a common heart defect and is found in about 25% of the general population. Although randomized trials have failed to show the superiority of percutaneous closure of PFO over medical management, the number of patients with closure device placement has grown over the years. Delayed complications from PFO closure are rare. We present a case of cardioembolic stroke secondary to a mobile thrombus on a PFO closure device 8 years after implantation.

Bilateral Vein of Trolard Thrombosis.

Isolated cortical vein thrombosis without dural sinus involvement is not common. The vein of Trolard is an important cortical vein as it drains eloquent cortex. We report 2 cases of bilateral vein of Trolard thrombosis; one with and the other without dural sinus involvement. To our knowledge, there have been no cases of bilateral vein of Trolard thrombosis reported in literature. The clinical presentation of cerebral venous thrombosis is variable; patients can present with isolated intracranial hypertension, focal neurological abnormalities, seizures, or encephalopathy.

Poor Hypertension Control and Longer Transport Times Are Associated with Worse Outcome in Drip-and-Ship Stroke Patients.

BACKGROUND: The "drip-and-ship" paradigm is an important treatment modality for acute ischemic stroke (AIS) patients who do not have immediate access to a comprehensive stroke center (CSC). Intravenous thrombolysis is initiated at a primary stroke center followed by expeditious transfer to a CSC. We sought to determine factors associated with poor outcomes in drip-and-ship AIS patients transferred to a CSC. METHODS: This study is a retrospective analysis of 130 consecutive drip-and-ship patients transferred by ambulance to a single CSC between July 2012 and June 2014. Multiple patient and transport factors were analyzed. Transport blood pressure (BP) control was considered inadequate if the systolic BP was greater than 180 mmHg and/or diastolic BP was greater than 105 mmHg upon CSC arrival. Poor patient outcome was defined as discharge to hospice or expiry, a discharge modified Rankin Scale (mRS) score higher than 2, or symptomatic intracerebral hemorrhage (ICH). RESULTS: There was a significant association between inadequate BP control upon CSC arrival and in-hospital mortality or discharge to hospice (P < .0007). Arrival BP was not associated with the risk of post-thrombolysis symptomatic ICH. Longer transport time was significantly associated with a poorer mRS score at discharge (P < .0174) and death (P < .0351). CONCLUSIONS: Post-thrombolysis BP guideline violations and longer transport times during drip-and-ship transfers were significantly associated with poor outcome. Guidelines for strict transport BP management and alternative modes of transfer for longer-distance transports may be warranted.

Thrombolysis for Ischemic Stroke during Pregnancy: A Case Report and Review of the Literature.

BACKGROUND AND PURPOSE: Our knowledge of the safety of thrombolytic therapy in pregnancy stems from individual case reports and series. We report the successful use of intravenous alteplase (tissue plasminogen activator; tPA) thrombolysis in a pregnant woman with acute cardioembolic stroke presumed to be paradoxical embolism through a patent foramen ovale. METHODS: A literature review found several case reports and case series of pregnant patients treated with either intravenous or intra-arterial tPA for acute ischemic stroke. RESULTS: A literature review yielded 10 cases of intravenous tPA administration and 5 cases of intra-arterial tPA. In total, there were 3 cases of asymptomatic intracerebral hemorrhage and 1 case of maternal and fetal death. CONCLUSIONS: Our patient improved clinically with no residual deficits. There was no evidence of placental or fetal injury following administration of tPA on follow-up obstetrical evaluations.

Catastrophic Intracranial Hemorrhages after IV tPA in a Patient with Insidious Onset of Fever and Back Pain.

Infective endocarditis is associated with unstable infective vegetations, which have a propensity to embolize and cause embolic events, such as stroke. Many cases present with an embolic event as the first sign of infective endocarditis. We present a patient who had a history of recent and persistent fever, an acute ischemic stroke treated with intravenous tissue plasminogen activator (IV tPA), and severe, multifocal intracerebral hemorrhage as a complication of tPA treatment. Suspected infective endocarditis in a stroke patient should most likely be considered a contraindication to IV tPA.

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.

BACKGROUND: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. METHODS: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. FINDINGS: Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. INTERPRETATION: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Ischemic and Hemorrhagic Strokes due to Eosinophilic Granulomatosis with Polyangiitis.

BACKGROUND: We report a case of ischemic and hemorrhagic strokes occurring almost simultaneously in a patient diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) previously known as Churg-Strauss vasculitis. To our knowledge, this is the first known case. METHODS: A 59-year-old man presented with a 2-month history of bilateral leg weakness, difficulty ambulating, and dyesthesias. While in the hospital, he developed acute right hand weakness, and magnetic resonance imaging of the brain revealed multiple, bilateral ischemic infarcts. After a few days, he acutely became unresponsive and was found to have a large left frontal hematoma and underwent emergent hematoma evacuation. His weakness was unexplained by the infarcts based on location and so a peripheral process was suspected. RESULTS: Nerve conduction studies showed severe axonal sensorimotor neuropathy. A sural nerve biopsy showed necrotizing vasculitis, consistent with EGPA. CONCLUSIONS: EGPA is the rarest of the antineutrophilic cytoplasmic antibody vasculitides. The peripheral nervous system is frequently involved, but the central nervous system can also be affected. The vasculitis damages the vessel walls, which leads either to stenosis or to dilatation, resulting in ischemic or bleeding consequences which can occur simultaneously, such as in this case. Caution should be exercised when prescribing antiplatelet therapy to such patients.

Stroke chameleons.

BACKGROUND: Many conditions called "stroke mimics" may resemble acute stroke. The converse of the "stroke mimic" is a presentation suggestive of another condition, which actually represents stroke. These would be "stroke chameleons." The recognition of a chameleon as stroke has implications for therapy and quality of care. METHODS: We performed a retrospective chart review, including all cases for 1 year in which patients had a stroke missed on hospital presentation. Initial erroneous diagnoses were compared for all patients correctly admitted with those diagnoses to determine positive predictive value (PPV) for each chameleon. RESULTS: Ninety-four cases were identified as chameleons where brain imaging revealed acute stroke. The common chameleons were initially diagnosed as altered mental status (AMS) (29, 31%), syncope (15, 16%), hypertensive emergency (12, 13%), systemic infection (10, 11%), and suspected acute coronary syndrome (ACS) (9, 10%). The total number of patients who were diagnosed with these conditions over the same year were AMS (393), syncope (326), hypertensive emergency (144), systemic infection (753), and suspected ACS (817) (total N = 2528). For each chameleon diagnosis, the PPV of each presentation for acute stroke was AMS (7%), syncope (4%), hypertensive emergency (8%), systemic infection (1%), and suspected ACS (1%). CONCLUSIONS: Stroke chameleons may result in patients not receiving appropriate care. The largest proportions of chameleons were AMS, syncope, hypertensive emergency, systemic infection, and suspected ACS. Patients diagnosed with hypertensive emergency or AMS had an 8% and 7% chance of having an acute stroke. Physicians should consider stroke in patients with these diagnoses with a lower threshold to obtain neuroimaging with subsequent appropriate management.

A bibliometric analysis of tenecteplase research utilizing a commonly used citation index.

BACKGROUND AND PURPOSE: Tenecteplase is increasingly being used as a first-line treatment for acute ischemic stroke after several randomized studies demonstrated its safety and efficacy, resulting in a massive increase in the number of published studies on this topic. Our aim was to investigate the most impactful authors and relevant journals that have been instrumental in validating this treatment, in hopes of identifying objective research trends that may assist scientists, health organizations, and funding agencies to collaborate and plan future avenues of research. METHODS: Using the search terms "Tenecteplase" and "Tenecteplase" AND "Stroke," 2683 and 1150 references were queried, respectively, using the abstract and citation database, Scopus. Scopus Citation Analysis was used to categorize the countries and authors who produced the most research. Metadata was retrieved and transferred to bibliographic visualization software, VOSviewer, for co-authorship and co-occurrence analyses to identify trends in tenecteplase research. RESULTS: Data visualization software identified three tenecteplase research clusters - myocardial infarction, pulmonary embolism, and acute ischemic stroke. Our bibliographic analysis graphically identified that ischemic stroke currently leads both myocardial infarction and pulmonary embolism in annual publications pertaining to tenecteplase therapy, and further pinpointed perfusion imaging and wake-up strokes as the most relevant areas of study. The United States led all countries in tenecteplase publications, including exclusively stroke studies. The European Heart Journal led all journals in overall publications, while Stroke led all journals in stroke-related studies. CONCLUSIONS: Through the use of bibliographic analysis and data visualization, we identified major articles and journals that reflected and shaped the current landscape of tenecteplase; recognized authors who engaged in tenecteplase research as it progressed from cardiopulmonary disease to stroke; and postulated future avenues of research.

An Unusual Presentation of Stroke and Reperfusion: A Case Report.

Intravenous tissue plasminogen activator (tPA) is a mainstay of therapy in acute ischemic stroke but transient neurologic changes related to reperfusion have not been well described. One of the authors (ISN) experienced a cardioembolic stroke due to apical hypertrophic cardiomyopathy with a left ventricular apical aneurysm. He received tPA and we describe his unusual cognitive symptoms during the infusion. The patient's presenting neurologic deficit improved with tPA, suggesting reperfusion. His subsequent restlessness, disorientation, and déjà vu lasted about 10 minutes and resolved spontaneously. Imaging studies confirmed an ischemic infarction in the left posterior cerebral artery (PCA) distribution. Cardiac events, including arrhythmias related to coronary reperfusion after myocardial infarction, are well described. Neurologic events due to reperfusion have not been previously described in patients with stroke. We describe a case of transient neurologic symptoms during revascularization of an embolic stroke.