Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Neurologic complications of cardiac arrest.

Cardiac arrest is a catastrophic event with high morbidity and mortality. Despite advances over time in cardiac arrest management and postresuscitation care, the neurologic consequences of cardiac arrest are frequently devastating to patients and their families. Targeted temperature management is an intervention aimed at limiting postanoxic injury and improving neurologic outcomes following cardiac arrest. Recovery of neurologic function governs long-term outcome after cardiac arrest and prognosticating on the potential for recovery is a heavy burden for physicians. An early and accurate estimate of the potential for recovery can establish realistic expectations and avoid futile care in those destined for a poor outcome. This chapter reviews the epidemiology, pathophysiology, therapeutic interventions, prognostication, and neurologic sequelae of cardiac arrest.

Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series.

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Leucine-Rich Glioma Inactivated-1 and Voltage-Gated Potassium Channel Autoimmune Encephalitis Associated with Ischemic Stroke: A Case Report.

Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage-gated potassium channel (VGKC) antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypotheses linking these two disease processes are proposed.

Neurologic Complications in the Intensive Care Unit.

Complications involving the central and peripheral nervous system are frequently encountered in critically ill patients. All components of the neuraxis can be involved including the brain, spinal cord, peripheral nerves, neuromuscular junction, and muscles. Neurologic complications adversely impact outcome and length of stay. These complications can be related to underlying critical illness, pre-existing comorbid conditions, and commonly used and life-saving procedures and medications. Familiarity with the myriad neurologic complications that occur in the intensive care unit can facilitate their timely recognition and treatment. Additionally, awareness of treatment-related neurologic complications may inform decision-making, mitigate risk, and improve outcomes.

Frequency of Direct Funduscopy Upon Initial Encounters for Patients with Headaches, Altered Mental Status, and Visual Changes: A Pilot Study.

OBJECTIVE: To determine the performance of direct funduscopy (DF) as part of the initial clinical assessment among different faculty physicians and residents from internal medicine, emergency medicine, and neurology (N). METHODS: Retrospective study of 163 randomly reviewed charts of patients (>18 years) presenting either to the ED, inpatient units, or outpatient clinics from January 2001 to July 2013, with corresponding ICD-9 codes for headaches, altered mental status, and visual changes. RESULTS: Although the Neurology Service was the one who performed most DF upon initial evaluation, DF is infrequently done throughout services independent of inpatient or outpatient location. Two thirds of the patients (66%) presenting with visual symptoms had evaluation done by Ophthalmology, which in some instances contributed to the final diagnosis. CONCLUSION: A more robust teaching of DF should be included among the basic clinical competencies during Medical School and Neurology Residency training.

Cervicocerebral artery dissection.

PURPOSE OF REVIEW: The purpose of this article is to review the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnostic methods and current treatment options for cervicocerebral artery dissection (CCD). RECENT FINDINGS: CCD incidence has increased over time largely because of improvements in and increasing availability of noninvasive imaging. CCD can be detected on computed tomography angiography, MRI, magnetic resonance angiography, carotid duplex ultrasonography and conventional catheter-based digital subtraction angiography. Additionally, ischemic stroke treatment with intravenous tissue plasminogen-activator for patients with suspected CCD appears to be well tolerated and effective. Moreover, a randomized clinical trial has shown antiplatelet agents to be as effective as anticoagulants at preventing recurrent ischemia. Surgical and endovascular techniques can be considered particularly for patients presenting with intracranial arterial dissection causing subarachnoid hemorrhage, developing recurrent ischemia due to hemodynamic impairment and whose dissecting aneurysms cause brainstem compression. SUMMARY: CCD is an important and one of the most common causes of ischemic stroke in young patients without traditional vascular risk factors. Cases can occur shortly after trauma. However, spontaneous CCD is common and is associated with many genetic, acquired and anatomical risk factors. CCD should be detected early to avoid complications and prevent long-term disability.

Early administration of therapeutic anticoagulation following intravenous thrombolysis for acute cardiogenic embolic stroke caused by left ventricular thrombus: case report and topic review.

Cardiogenic cerebral embolism represents 20% of all acute ischemic strokes (AISs) with one-third of these being caused by left ventricular thrombus (LVT). LVT is not a contraindication for treatment with intravenous recombinant tissue plasminogen activator (IV rtPA) for AIS. However, the subsequent treatment of a potentially unstable LVT is contraindicated for 24 h following the use of IV rtPA according to current guidelines. We present a 66-year-old man with AIS treated with IV rtPA. Echocardiogram shortly after treatment demonstrated both a large apical and septal thrombus in the left ventricle and at 12 h post IV rtPA infusion, therapeutic anticoagulation with heparin was started without complication. In practice, the action of IV rtPA outlasts its apparent half-life because of thrombin-binding and the prolonged effects and longer half-life of its product, plasmin; however, the pharmacokinetics do not warrant prolonged avoidance of therapeutic anticoagulation when clinically indicated. Our case demonstrates that anticoagulation for potentially unstable LVT can be safely initiated at 12 h following IV rtPA treatment for AIS.

Wall shear stress in major cerebral arteries as a function of age and gender--a study of 301 healthy volunteers.

BACKGROUND: The hemodynamic force of wall shear stress (WSS) has demonstrated a critical role in atherogenesis. PURPOSE: To study the effect of age and gender on mean WSS (MWSS) values in major cerebral arteries. METHOD: Thirteen cerebral arterial location sites in 301 healthy (157 M, 144 F; mean 47 ± 15 years; range 18-84 years old) were studied. Quantitative magnetic resonance angiography was used to obtain volume flow and diameter, and subsequently to calculate MWSS via the Hagen-Poiseuille equation. RESULTS: MWSS decreased significantly with age in all vessels, declining from 9.5 to 5.7 dynes/cm(2) in the neck vessels and from 22.9 to 16.2 dynes/cm2 in the intracranial vessels. MWSS is significantly higher in females than in males in all six neck vessels. The most significant drop in MWSS occurred between the age groups 48-57 and 58-67 (P < .05 for 12 vessels). CONCLUSION: The overall decline in MWSS observed with age may be due to a decrease in flow. However, the marked drop in MWSS between the 48-57 and 58-67 age groups corresponded with an increase in diameter and systolic blood pressure rather than a significant drop in flow.

Neurology of rheumatologic disorders.

Rheumatologic diseases encompass autoimmune and inflammatory disorders of the joints and soft tissues that often involve multiple organ systems, including the central and peripheral nervous systems. Common features include constitutional symptoms, arthralgia and arthritis, myalgia, and sicca symptoms. Neurological manifestations may present in patients with preexisting rheumatologic diagnoses, occur concurrently with systemic signs and symptoms, or precede systemic manifestations by months to years. Rheumatic disorders presenting as neurological syndromes may pose diagnostic challenges. Advances in immunosuppressive treatment of rheumatologic disease have expanded the treatment armamentarium. However, serious neurotoxic effects have been reported with both old and newer agents. Familiarity with neurological manifestations of rheumatologic diseases, diagnosis, and potential nervous system consequences of treatment is important for rapid diagnosis and appropriate intervention. This article briefly reviews the diverse neurological manifestations and key clinical features of rheumatic disorders and the potential neurological complications of agents commonly used for treatment.

Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management.

Posterior circulation strokes represent approximately 20% of all ischemic strokes (1, 2). In contrast to the anterior circulation, several differences in presenting symptoms, clinical evaluation, diagnostic testing, and management strategy exist presenting a challenge to the treating physician. This review will discuss the anatomical, etiological, and clinical classification of PC strokes, identify diagnostic pitfalls, and overview current therapeutic regimens.

Reversible cerebral vasoconstriction syndrome with multivessel cervical artery dissections and a double aortic arch.

Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with exposure to vasoactive substances and few reports with cervical arterial dissections (CADs). We evaluated a 32-year-old woman with history of depression, migraines without aura, and cannabis use who presented with a thunderclap headache unresponsive to triptans. She was found to have bilateral occipital infarcts, bilateral extracranial vertebral artery dissections, bilateral internal carotid artery dissecting aneurysms, and extensive distal multifocal segmental narrowing of the anterior and posterior intracranial circulation with a "sausage on a string-like appearance" suggestive of RCVS. Subsequently, she was found to have a distal thrombus of the basilar artery, was anticoagulated, and discharged home with no residual deficits. We highlight the potential association of CADs and RCVS. The association of RCVS and a double aortic arch has not been previously reported.

Platelet antiaggregants in stroke prevention.

Antiplatelet agents are one of the main interventions for recurrent ischemic stroke prevention. Their time of use, dosage, and combination of therapy have different effects in terms of stroke risk reduction and adverse effects. This review provides an evidence-based update of the latest on antiplatelet therapy for stroke prevention.

Telemedicine in stroke care and rehabilitation.

Telemedicine allows prompt assessment of acute stroke patients. This new technology has increased the administration of intravenous recombinant tissue plasminogen activator (rtPA) to eligible patients. In addition, telemedicine is being utilized in the rehabilitation of patients with cerebrovascular disease. This article will review the use of telemedicine in patients with acute ischemic stroke and its implementation in telerehabilitation to patients with residual neurologic deficits.

Prevention of venous thromboembolism in patients with hemorrhagic stroke.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are part of the spectrum of venous thromboembolism (VTE). It is one of the most frequent medical complications in stroke patients. The risk of VTE is even higher after hemorrhagic stroke. This article reviews various screening methods, diagnostic techniques, and pharmacologic as well as nonpharmacologic means of preventing VTE after hemorrhagic stroke.

Vascular risk factors and cardiovascular outcomes in the Alzheimer's disease neuroimaging initiative.

BACKGROUND: Vascular disease and medical factors are associated with cognitive decline and cardiovascular events. We examined the association between vascular risk factors and events in the Alzheimer's Disease Neuroimaging Initiative cohort. METHODS: The association between vascular risk factors and cardiovascular events in a cohort of 810 participants, including 400 with mild cognitive impairment, 184 with Alzheimer's, and 226 controls was investigated using a longitudinal hazard model. RESULTS: There were 31 events including 11 strokes, 7 myocardial infarctions, 5 revascularizations, and 8 deaths during an average follow-up of 31 months. Longitudinal cardiovascular event rates were low and similar between diagnostic groups. CONCLUSIONS: All baseline vascular risk factors that were expected to be associated with longitudinal cardiovascular events were, or were trending toward, associating with cardiovascular events except atrial fibrillation, depression, and apolipoprotein E genotype. Despite differences in baseline vascular risk factors, longitudinal cardiovascular event rates were similar between diagnostic groups.

Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke study (VERiTAS): rationale and design.

BACKGROUND: Over one-third of ischaemic strokes occur in the posterior circulation, and a leading cause is atherosclerotic vertebrobasilar disease. Symptomatic vertebrobasilar disease carries a high annual recurrent stroke risk, averaging 10-15% per year. Endovascular angioplasty and stenting are increasingly used but carry risks, and the benefit remains unproven. Determining stroke predictors in this population is critical to identifying high-risk patients for future trials of intervention. Preliminary studies indicate that stroke risk in vertebrobasilar disease is strongly related to haemodynamic compromise, which can be measured noninvasively using quantitative magnetic resonance angiography. METHODS/STUDY DESIGN: The Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke (VERiTAS) study, a prospective multicentre NIH-funded observational study of symptomatic vertebrobasilar stenosis (≥50%) or occlusion, is designed to test the hypothesis that patients demonstrating compromised blood flow as assessed by quantitative magnetic resonance angiography are at higher stroke risk. The study will recruit 80 patients at six sites in North America over 4-years. Upon enrollment, subjects will undergo haemodynamic assessment with blinded quantitative magnetic resonance angiography to assess large vessel flow in the vertebrobasilar territory, and be prospectively designated as compromised or normal flow. Patients will be re-imaged with quantitative magnetic resonance angiography at 6-, 12-, and 24-months, and followed for 12-24-months for the primary end-point of stroke in the vertebrobasilar territory. CONCLUSION: The VERiTAS study is the first prospective study of haemodynamics and stroke risk in the posterior circulation. The results may impact the selection criteria for interventional candidates and also define a low-risk population in whom the risks of invasive interventions would be unnecessary.