COVID-19 and Cerebrovascular Disease.

COVID-19 has been associated with numerous neurological complications, with acute cerebrovascular disease being one of the most devastating complications. Ischemic stroke is the most common cerebrovascular complication of COVID-19, affecting between 1 and 6% of all patients. Underlying mechanisms for COVID-related ischemic strokes are thought to be due to vasculopathy, endotheliopathy, direct invasion of the arterial wall, and platelet activation. Other COVID-19-associated cerebrovascular complications include hemorrhagic stroke, cerebral microbleeds, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, and subarachnoid hemorrhage. This article discusses the incidence of these cerebrovascular complications, risk factors, management strategies, prognosis and future research directions, as well as considerations in pregnancy-related cerebrovascular events in the setting of COVID-19.

Coronavirus disease 2019 infection and cerebrovascular diseases: an update on the pathophysiology and management.

PURPOSE OF REVIEW: COVID-19 is an ongoing global pandemic since it was first discovered in 2020. Cerebral vascular disease and stroke are among the most common and devastating neurological manifestations of COVID-19. This review offers an up-to-date information on the possible underlying mechanism of COVID-19-related stroke, its diagnosis, and management. RECENT FINDINGS: The thromboembolism associated with COVID-19 infection is likely related to the cytokine storm with innate immune activation, pulmonary disease leading to hypoxia-induced ischemia, thrombotic microangiopathy, endothelial damage and multifactorial activation of the coagulation cascade. Currently, there is no clear guidelines on the use of antithrombotics for the prevention and treatment of this phenomenon. SUMMARY: COVID-19 infection can directly cause a stroke or facilitate the formation of thromboembolism in the presence of other medical conditions. Physicians treating patients with COVID-19 should stay vigilant about the signs and symptoms of stroke, detect and treat early.

Reversible Cerebral Vasoconstriction Syndrome and Multisystem Inflammatory Syndrome in Children With COVID-19.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) involves multiple organs and shows increased inflammatory markers. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, several studies have reported the association between severe COVID-19 and MIS-C. Reversible cerebral vasoconstriction syndrome (RCVS) presents with thunderclap headaches and multifocal reversible vasoconstriction on imaging. RCVS is very rare in children. This article reports two cases of pediatric COVID-19 with severe MIS-C and clinical and imaging features indicative of RCVS. METHODS: Clinical, laboratory, and imaging data of the patients were reviewed. The diagnosis of RCVS was confirmed based on clinical symptomatology and brain magnetic resonance imaging findings. RESULTS: Two pediatric patients with clinical findings compatible with severe MIS-C and hemodynamic compromise presented to the hospital. During their hospitalization course, they developed thunderclap headaches and neurological deficits. Both were receiving vasoactive agents, intravenous immunoglobulin, and immunosuppressants. Imaging studies showed marked multifocal cerebral vasoconstriction in both cases and infarcts in one. The course and management of the patients will be presented. After controlling inflammation and elimination of triggers, both patients were ultimately symptom free upon discharge. Cerebral vasoconstriction had completely resolved on follow-up imaging. CONCLUSIONS: Although a variety of symptoms including headaches may be seen in pediatric COVID-19 patients with MIS-C, RCVS should be considered as a differential diagnosis in cases of thunderclap headache accompanied by neurological signs in these patients. Imaging findings and follow-up are also key in establishing the diagnosis.

The impact of the COVID-19 pandemic on cerebrovascular disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a systemic disease that affects nearly all organ systems through infection and subsequent dysregulation of the vascular endothelium. One of the most striking phenomena has been a coronavirus disease 2019 (COVID-19)-associated coagulopathy. Given these findings, questions naturally emerged about the prothrombotic impact of COVID-19 on cerebrovascular disease and whether ischemic stroke is a clinical feature specific to COVID-19 pathophysiology. Early reports from China and several sites in the northeastern United States seemed to confirm these suspicions. Since these initial reports, many cohort studies worldwide observed decreased rates of stroke since the start of the pandemic, raising concerns for a broader impact of the pandemic on stroke treatment. In this review, we provide a comprehensive assessment of how the pandemic has affected stroke presentation, epidemiology, treatment, and outcomes to better understand the impact of COVID-19 on cerebrovascular disease. Much evidence suggests that this decline in stroke admissions stems from the global response to the virus, which has made it more difficult for patients to get to the hospital once symptoms start. However, there does not appear to be a demonstrable impact on quality metrics once patients arrive at the hospital. Despite initial concerns, there is insufficient evidence to ascribe a causal relationship specific to the pathogenicity of SARS-CoV-2 on the cerebral vasculature. Nevertheless, when patients infected with SARS-CoV-2 present with stroke, their presentation is likely to be more severe, and they have a markedly higher rate of in-hospital mortality than patients with either acute ischemic stroke or COVID-19 alone.

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.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study.

BACKGROUND: While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE: To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS: A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS: Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION: LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.

Hospital admissions of acute cerebrovascular diseases during and after the first wave of the COVID-19 pandemic: a state-wide experience from Austria.

We investigated hospital admission rates for the entire spectrum of acute cerebrovascular diseases and of recanalization treatments for ischaemic stroke (IS) in the Austrian federal state of Styria during and also after the first coronavirus disease 2019 (COVID-19) wave. We retrospectively identified all patients with transient ischaemic attack (TIA), IS and non-traumatic intracranial haemorrhage (ICH; including intracerebral, subdural and subarachnoid bleeding types) admitted to one of the 11 public hospitals in Styria (covering > 95% of inhospital cerebrovascular events in this region). Information was extracted from the electronic medical documentation network connecting all public Styrian hospitals. We analysed two periods of interest: (1) three peak months of the first COVID-19 wave (March-May 2020), and (2) three recovery months thereafter (June-August 2020), compared to respective periods 4 years prior (2016-2019) using Poisson regression. In the three peak months of the first COVID-19 wave, there was an overall decline in hospital admissions for acute cerebrovascular diseases (RR = 0.83, 95% CI 0.78-0.89, p < 0.001), which was significant for TIA (RR = 0.61, 95% CI 0.52-0.72, p < 0.001) and ICH (0.78, 95% CI 0.67-0.91, p = 0.02), but not for IS (RR = 0.93, 95% CI 0.85-1, p = 0.08). Thrombolysis and thrombectomy numbers were not different compared to respective months 4 years prior. In the recovery period after the first COVID-19 wave, TIA (RR = 0.82, 95% CI 0.71-0.96, p = 0.011) and ICH (RR = 0.86, 95% CI 0.74-0.99, p = 0.045) hospitalizations remained lower, while the frequency of IS and recanalization treatments was unchanged. In this state-wide analysis covering all types of acute cerebrovascular diseases, hospital admissions for TIA and ICH were reduced during and also after the first wave of the COVID-19 pandemic, but hospitalizations and recanalization treatments for IS were not affected in these two periods.

COVID-19 Respiratory Illness and Subsequent Cerebrovascular Events, the Initial Iranian Experience.

OBJECTIVES: COVID-19 disproportionately affects older adults and individuals with cardiovascular co-morbidities. This report presents fifteen patients who had COVID-19 respiratory illness followed by cerebrovascular events. MATERIALS AND METHODS: A call by the Iranian Neurological Association gathered cases across the country who developed neurological symptoms attributed to hemorrhagic or ischemic stroke after a definite or probable Covid-19 respiratory illness. Definite cases were those with a typical respiratory illness, positive nasopharyngeal Covid-19 PCR test, and chest CT consistent with Covid-19 infection. Probable cases were defined by a typical respiratory illness, history of contacts with a Covid-19 case, and chest CT characteristic for Covid-19 infection. RESULTS: Fifteen patients (12 men and 3 women) with an age range of 38 to 93 years old (median: 65 years old) were included. Fourteen patients had a first-ever acute ischemic stroke and one patient had a subarachnoid hemorrhage. Eleven patients (73%) had previous cardiovascular comorbidities. The median time between respiratory symptoms and neurological symptoms was seven days (range 1-16 days). Stroke severity in two patients was mild (NIHSS ≤ 6), in six patients moderate (NIHSS: 7-12), and in seven patients severe (NIHSS ≥13). One patient received intravenous tissue plasminogen activator ( IV-tPA) with improved neurological symptoms. Six out of 15 patients (40%) died. All but one of those who survived had significant disability assessed by a modified ranking scale >2. The majority of patients in this case series had vascular risk factors and their stroke was associated with severe disability and death. CONCLUSION: This report highlights the need for further investigation of the links between Covid-19 and cerebrovascular events.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

The Association of Cerebrovascular Disease with Adverse Outcomes in COVID-19 Patients: A Meta-Analysis Based on Adjusted Effect Estimates.

OBJECTIVE: The aim of this study was to address the association between cerebrovascular disease and adverse outcomes in coronavirus disease 2019 (COVID-19) patients by using a quantitative meta-analysis based on adjusted effect estimates. METHOD: A systematic search was performed in PubMed, Web of Science, and EMBASE up to August 10th, 2020. The adjusted effect estimates were extracted and pooled to evaluate the risk of the unfavorable outcomes in COVID-19 patients with cerebrovascular disease. Subgroup analysis and meta-regression were also carried out. RESULTS: There were 12 studies with 10,304 patients included in our meta-analysis. A significant trend was observed when evaluating the association between cerebrovascular disease and adverse outcomes (pooled effect = 2.05, 95% confidence interval (CI): 1.34-3.16). In addition, the pooled effects showed that patients with a history of cerebrovascular disease had more likelihood to progress fatal outcomes than patients without a history of cerebrovascular disease (pooled effect = 1.78, 95% CI: 1.04-3.07). CONCLUSION: This study for the first time indicated that cerebrovascular disease was an independent risk factor for predicting the adverse outcomes, particularly fatal outcomes, in COVID-19 patients on the basis of adjusted effect estimates. Well-designed studies with larger sample size are needed for further verification.

Neurological Complications Among Native Americans with COVID-19: Our Experience at a Tertiary Care Academic Hospital in the U.S.

OBJECTIVE: To study the central nervous system (CNS) complications in patients with COVID-19 infection especially among Native American population in the current pandemic of severe acute respiratory syndrome virus (COVID-19). METHODS: Patients with confirmed COVID-19 infection at University of New Mexico hospital (UNMH) were screened for development of neurological complications during Feb 01 to April 29, 2020 via retrospective chart review. RESULTS: Total of 90 hospitalized patients were screened. Out of seven patients, majority were Native Americans females, and developed neurological complications including subarachnoid hemorrhage (SAH), Intraparenchymal hemorrhage (IPH), Ischemic stroke (IS) and seizure. All 7 patients required Intensive care unit (ICU) level of care. Patients who developed CNS complications other than seizure were females in the younger age group (4 patients, 38-58 years) with poor outcome. Out of 7, three developed subarachnoid hemorrhage, two developed ischemic infarction, and four developed seizure. Two patients with hemorrhagic complication expired during the course of hospitalization. All three patients with seizure were discharged to home. CONCLUSION: Patients with serious CNS complications secondary to COVID-19 infection were observed to be Native Americans. Patients who developed hemorrhagic or ischemic events were observed to have poor outcomes as compared to patients who developed seizures.

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.

Temporal trends in the presentation of cardiovascular and cerebrovascular emergencies during the COVID-19 pandemic in Germany: an analysis of health insurance claims.

AIMS: The first reports of declining hospital admissions for major cardiovascular emergencies during the COVID-19 pandemic attracted public attention. However, systematic evidence on this subject is sparse. We aimed to investigate the rate of emergent hospital admissions, subsequent invasive treatments and comorbidities during the COVID-19 pandemic in Germany. METHODS AND RESULTS: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalized for acute myocardial infarction, acute limb ischemia, aortic rupture, stroke or transient ischemic attack (TIA) between January 1, 2019, and May 31, 2020, were included. Admission rates per 100,000 insured, invasive treatments and comorbidities were compared from January-May 2019 (pre-COVID) to January-May 2020 (COVID). A total of 115,720 hospitalizations were included in the current analysis (51.3% females, mean age 72.9 years). Monthly admission rates declined from 78.6/100,000 insured (pre-COVID) to 70.6/100,000 (COVID). The lowest admission rate was observed in April 2020 (61.6/100,000). Administration rates for ST-segment elevation myocardial infarction (7.3-6.6), non-ST-segment elevation myocardial infarction (16.8-14.6), acute limb ischemia (5.1-4.6), stroke (35.0-32.5) and TIA (13.7-11.9) decreased from pre-COVID to COVID. Baseline comorbidities and the percentage of these patients treated with interventional or open-surgical procedures remained similar over time across all entities. In-hospital mortality in hospitalizations for stroke increased from pre-COVID to COVID (8.5-9.8%). CONCLUSIONS: Admission rates for cardiovascular and cerebrovascular emergencies declined during the pandemic in Germany, while patients' comorbidities and treatment allocations remained unchanged. Further investigation is warranted to identify underlying reasons and potential implications on patients' outcomes.

Decline of emergency admissions for cardiovascular and cerebrovascular events after the outbreak of COVID-19.

BACKGROUND: The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2. METHODS: We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1-9, 2020) and after (calendar weeks 10-16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year. RESULTS: In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ - 71% (p = 0.007) for unstable angina, Δ - 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ - 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1-9 to 62 patients in calendar weeks 10-16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ - 32% (p = 0.18), ischemic stroke: Δ - 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1-9 (213 patients) and weeks 10-16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020. CONCLUSIONS: The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.

Coronavirus 2019 (COVID-19)-Associated Encephalopathies and Cerebrovascular Disease: The New Orleans Experience.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has had a dramatic impact on health care systems and a variable disease course. Emerging evidence demonstrates that severe acute respiratory syndrome coronavirus 2 is associated with central nervous system disease. We describe central nervous system manifestations in critical patients with COVID-19 at our tertiary center. METHODS: We conducted a single-center retrospective analysis of all actively critical patients with COVID-19 admitted to our tertiary care academic center in New Orleans, Louisiana, on April 22, 2020, with new onset of neurologic disease. Patients were grouped into 1 of 3 categories according to imaging and clinical features; encephalopathy, acute necrotizing encephalopathy, and vasculopathy. RESULTS: A total of 27 of 76 (35.5%) critical patients with COVID-19 met inclusion criteria. Twenty patients (74%) were designated with COVID-19-associated encephalopathy, 2 (7%) with COVID-19-associated acute necrotizing encephalopathy, and 5 (19%) with COVID-19-associated vasculopathy. Sixty-three percent of neurologic findings were demonstrated on computed tomography, 30% on magnetic resonance imaging, and 44% on electroencephalography. Findings most often included ischemic strokes, diffuse hypoattenuation, subcortical parenchymal hemorrhages, and focal hypodensities within deep structures. Magnetic resonance imaging findings included diffuse involvement of deep white matter, the corpus callosum, and the basal ganglia. For patients with large-territory ischemic stroke, all but one displayed irregular proximal focal stenosis of the supraclinoid internal carotid artery. CONCLUSIONS: Analysis of active critical COVID-19 admissions at our revealed a high percentage of patients with new neurologic disease. Although variable, presentations followed 1 of 3 broad categories. A better understanding of the neurologic sequalae and radiographic findings will help clinicians mitigate the impact of this disease.