Stroke as a Neurological Complication of COVID-19: A Systematic Review and Meta-Analysis of Incidence,Outcomes and Predictors

IntroductionCOVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis. The consequences of this include renal dysfunction, hepatitis and stroke. In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19.MethodsWe conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19.Results326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included. The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4–76.4 years). The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%). The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%). These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts.ConclusionAlthough stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality. In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.     

Stroke Associated with COVID-19 Vaccines

ObjectivesDevelopment of safe and effective vaccines against coronavirus disease 2019 (COVID-19) remains the cornerstone of controlling this pandemic. However, there are increasing reports of various types of stroke including ischemic stroke, and hemorrhagic stroke, as well as cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination. This paper aims to review reports of stroke associated with COVID-19 vaccines and provide a coherent clinical picture of this condition.Materials and methodsA literature review was performed with a focus on data from recent studies.ResultsMost of such patients are women under 60 years of age and who had received ChAdOx1 nCoV-19 vaccine. Most studies reported CVST with or without secondary ischemic or hemorrhagic stroke, and some with Vaccine-induced Thrombotic Thrombocytopenia (VITT). The most common clinical symptom of CVST seen after COVID-19 vaccination was headache. The clinical course of CVST after COVID-19 vaccination may be more severe than CVST not associated with COVID vaccination. Management of CVST following COVID-19 vaccination is challenging and may differ from the standard treatment of CVST. Low molecular weight heparin is commonly used in the treatment of CVST; however, it may worsen outcomes in CVST associated with VITT. Furthermore, administration of intravenous immunoglobulin and high-dose glucocorticoids have been recommended with various success rates.ConclusionThese contradictory observations are a source of confusion in clinical decision-making and warrant further study and development of clinical guidelines. Clinicians should be aware of clinical presentation, diagnosis, and management of stroke associated with COVID-19 vaccination.     

COVID-19 Impact on Stroke Presentations

BackgroundAs Covid-19 evolved into a world-wide pandemic, hospitals reported marked declines in strokes, only to be followed by reports of increased numbers of young people presenting with large-vessel occlusions. We reviewed our patient data-base to determine if similar or other novel trends were present.ResultsOur Thrombectomy Stroke Center experienced marked declines in ED visits from 2,349 in early March to 1,178 in late April, stroke alerts dropped from 34 to 14 during the same period. Average monthly stroke admissions dropped from 34 in 2019 to 23 in 2020. Nonetheless, in March, we had 12 patients eligible for tPA, which is twice the typical caseload and was unexpected given the low overall stroke presentations. Although the neurointervention caseload was low, the patients were significantly younger. Of the acute intervention patients in March, 5 of the 12 patients were ≤ 60 years old, and two were in their 30’s. These trends are similar to those reported elsewhere but were highly unusual for our center as our catchment area is predominantly Caucasian with 34 % of the population > 65 years of age.ConclusionsEven in low risk centers Covid-19 will likely impart unique stroke presentations. It will be imperative to determine the mechanisms responsible for these changes so we can institute effective strategies for optimal stroke prevention as well as maintain timely acute interventions.     

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

BackgroundThere is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19.MethodsThis 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.ResultsA 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).ConclusionIV-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.     

Hypercoagulability of COVID-19 and Neurological Complications: A Review

The SARS-CoV-2 virus, which causes Coronavirus disease 2019 (COVID-19), has resulted in millions of worldwide deaths. When the SARS-CoV-2 virus emerged from Wuhan, China in December 2019, reports of patients with COVID-19 revealed that hospitalized patients had acute changes in mental status, cognition, and encephalopathy. Neurologic complications can be a consequence from overall severity of the systemic infection, direct viral invasion of the SARS-CoV-2 virus in the central nervous system, and possible immune mediated mechanisms. We will examine the landscape regarding this topic in this review in addition to current understandings of COVID-19 and hemostasis, treatment, and prevention, as well as vaccination.     

Quality of Care and Outcomes for Patients with Acute Ischemic Stroke and Transient Ischemic Attack During the COVID-19 Pandemic

Background and PurposeHospitalizations for acute ischemic stroke (AIS) and transient ischemic attack (TIA) decreased during the COVID-19 pandemic. We compared the quality of care and outcomes for patients with AIS/TIA before vs. during the COVID-19 pandemic across the United States Department of Veterans Affairs healthcare system.MethodsThis retrospective cohort study compared AIS/TIA care quality before (March–September 2019) vs. during (March-September 2020) the pandemic. Electronic health record data were used to identify patient characteristics, quality of care and outcomes. The without-fail rate was a composite measure summarizing whether an individual patient received all of the seven processes for which they were eligible. Mixed effects logistic regression modeling was used to assess differences between the two periods.ResultsA decrease in presentations occurred during the pandemic (N = 4360 vs. N = 5636 patients; p = 0.003) and was greater for patients with TIA (-30.4%) than for AIS (-18.7%). The without-fail rate improved during the pandemic (56.2 vs. before 50.1%). The use of high/moderate potency statins increased among AIS patients (OR 1.26 [1.06–1.48]) and remained unchanged among those with TIA (OR 1.04 [0.83,1.29]). Blood pressure measurement within 90-days of discharge was less frequent during the pandemic (57.8 vs. 89.2%, p < 0.001). Hypertension control decreased among patients with AIS (OR 0.73 [0.60–0.90]) and TIA (OR 0.72 [0.54-0.96]). The average systolic and diastolic blood pressure was 1.9/1.4 mmHg higher during the pandemic than before (p < 0.001). Compared to before, during the pandemic fewer AIS patients had a primary care visit (52.5% vs. 79.8%; p = 0.0001) or a neurology visit (27.9 vs. 41.1%; p = 0.085). Both 30- and 90-day unadjusted all-cause mortality rates were higher in 2020 (3.6% and 6.7%) vs. 2019 (2.9, 5.4%; p = 0.041 and p = 0.006); but these differences were not statistically significant after risk adjustment.ConclusionsOverall quality of care for patients with AIS/TIA did not decline during the COVID-19 pandemic.     

Spectrum of Neurological Complications Following COVID-19 Vaccination in India

Background and PurposeAccording to WHO statistics, approximately 6.9 billion people worldwide had been vaccinated against SARS-CoV-2 as at October 27, 2021, including around 1.0 billion people in India. Most Indian recipients received the Covishield (ChAdOx1-S/nCoV-19) vaccine, followed by the Covaxin (an inactivated SARS-CoV-2 antigen) vaccine. This study was conducted to characterize the neurological phenotypic spectrum of patients with adverse events following immunization with any of the available COVID-19 vaccines in India (Covishield or Covaxin) during the study period and their temporal relationship with vaccination.MethodsThis ambispective multicenter hospital-based cohort study covered the period from March to October 2021. The study included all cases suspected of having neurological complications following COVID-19 vaccination.ResultsWe report a spectrum of serious postvaccination neurological complications comprising primary central nervous system demyelination (4 cases), cerebral venous thrombosis (3 cases), Guillain-Barre syndrome (2 cases), vaccine-induced prothrombotic immune thrombocytopenia syndrome (2 cases), cranial nerve palsies (2 cases), primary cerebral hemorrhage (1 case), vestibular neuronitis (1 case), chronic inflammatory demyelinating polyneuropathy (1 case), generalized myasthenia (1 case), and seizures (1 case).ConclusionsAlthough the benefits of vaccination far outweigh its risks, clinicians must be aware of possible serious adverse events associated with COVID-19 vaccinations.     

COVID-19 presenting as stroke

ObjectiveAcute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations. Here we present a series of four patients with COVID-19 that presented with acute stroke.MethodsWe searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection. All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study. Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained.ResultsWe identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course.ConclusionsTimely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient. Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection.     

Potential mechanisms of cerebrovascular diseases in COVID-19 patients

Journal of NeuroVirology - Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological...     

Successful Endovascular Therapy in COVID-19 Associated Pediatric Ischemic Stroke

Cerebrovascular diseases attributed to coronavirus disease 2019 (COVID-19) are uncommon but can result in devastating outcomes. Pediatric acute ischemic strokes are themselves rare and with very few large vessel occlusion related acute ischemic strokes attributed to COVID-19 described in the literature as of date. COVID-19 pandemic has contributed to acute stroke care delays across the world and with pediatric endovascular therapy still in its infancy, it poses a great challenge in facilitating good outcomes in children presenting with acute ischemic strokes in the setting of COVID-19. We present a pediatric patient who underwent endovascular therapy for an internal carotid artery occlusion related acute ischemic stroke in the setting of active COVID-19 and had an excellent outcome thanks to a streamlined stroke pathway involving the vascular neurology, neuro-interventional, neurocritical care, and anesthesiology teams.     

Acute Brain Diseases as Triggers for Stress Cardiomyopathy: Clinical Characteristics and Outcomes

Background

Patients with aneurysmal subarachnoid hemorrhage (SAH) often develop hydrocephalus requiring an external ventricular drain (EVD). The best available evidence suggests that a rapid EVD wean and intermittent CSF drainage is safe, reduces complications, and shortens ICU and hospital length of stay as compared to a gradual wean and continuous drainage. However, optimal EVD management remains controversial and the baseline practice among neurological ICUs is unclear. Therefore, we sought to determine current institutional practices of EVD management for patients with aneurysmal SAH.

Methods

An e-mail survey was sent to attending intensivists and neurosurgeons from 72 neurocritical care units that are registered with the Neurocritical Care Research Network or have been previously associated with the existing literature on the management of EVDs in critically ill patients. Only one response was counted per institution.

Results

There were 45 out of 72 institutional responses (63%). The majority of responding institutions (80%) had a single predominant EVD management approach. Of these, 78% favored a gradual EVD weaning strategy. For unsecured aneurysms, 81% kept the EVD continuously open and 19% used intermittent drainage. For secured aneurysms, 94% kept the EVD continuously open and 6% used intermittent drainage. Among continuously drained patients, the EVD was leveled at 18 (unsecured) and 11 cm H₂O (secured) (p < 0.0001). When accounting for whether the EVD strategy was to enhance or minimize CSF drainage, there was a significant difference in the management of unsecured versus secured aneurysms with 42% using an enhance drainage approach in unsecured patients and 92% using an enhance drainage approach in secured patients (p < 0.0001).

Conclusion

Most institutions utilize a single predominant EVD management approach, with a consensus toward a continuously open EVD to enhance CSF drainage in secured aneurysm patients coupled with a gradual weaning strategy. This finding is surprising given that the best available evidence suggests that the opposite approach is safe and can reduce ICU and hospital length of stay. We recommend a critical reassessment of the approach to the management of EVDs. Given the potential impact on patient outcomes and length of stay, more research needs to be done to reach a threshold for practice change, ideally via multicenter and randomized trials.

     

Clinical Characteristics of Stroke with COVID-19: A Systematic Review and Meta-Analysis

BackgroundThe coronavirus disease 2019 (COVID-19) potentially increases the risk of thromboembolism and stroke. Numerous case reports and retrospective cohort studies have been published with mixed characteristics of COVID-19 patients with stroke regarding age, comorbidities, treatment, and outcome. We aimed to depict the frequency and clinical characteristics of COVID-19 patients with stroke.MethodsPubMed and EMBASE were searched on June 10, 2020, to investigate COVID-19 and stroke through retrospective cross-sectional studies, case series/reports according to PRISMA guidelines. Study-specific estimates were combined using one-group meta-analysis in a random-effects model.Results10 retrospective cohort studies and 16 case series/reports were identified including 183 patients with COVID-19 and stroke. The frequency of detected stroke in hospitalized COVID-19 patients was 1.1% ([95% confidential interval (CI)]: [0.6-1.6], I² = 62.9%). Mean age was 66.6 ([58.4-74.9], I² = 95.1%), 65.6% was male (61/93 patients). Mean days from symptom onset of COVID-19 to stroke was 8.0 ([4.1-11.9], p< 0.001, I² = 93.1%). D-dimer was 3.3 μg/mL ([1.7-4.9], I² = 86.3%), and cryptogenic stroke was most common as etiology at 50.7% ([31.0-70.4] I² = 64.1%, 39/71patients). Case fatality rate was 44.2% ([27.9-60.5], I² = 66.7%, 40/100 patients).ConclusionsThis systematic review assessed the frequency and clinical characteristics of stroke in COVID-19 patients. The frequency of detected stroke in hospitalized COVID-19 patients was 1.1% and associated with older age and stroke risk factors. Frequent cryptogenic stroke and elevated d-dimer level support increased risk of thromboembolism in COVID-19 associated with high mortality. Further study is needed to elucidate the pathophysiology and prognosis of stroke in COVID-19 to achieve most effective care for this population.     

新型冠状病毒肺炎疫情时期急性缺血性卒中的急诊取栓治疗

目的 探讨总结新型冠状病毒（coronavirus disease-19,COVI D-19）肺炎疫情时期急性缺血性卒中（acute ischemic stroke,AIS）的急诊取栓治疗经验。方法 回顾性分析2020年1月20日-3月20日疫情期间,首都医科大学附属北京天坛医院神经介入中心进行急诊取栓治疗的AIS病例资料,包括患者的一般资料、NIHSS评分、ASPECTS评分（DWI）、病变部位、手术策略、恢复情况,以及COVID-19筛查、预防标准与流程。并与2019年1月20日-3月20日同期取栓病例进行对照分析。结果 共纳入33例颅内大血管闭塞致AIS进行急诊取栓的患者,其中2020年18例,2019年15例。2020年疫情期间与2019年同期相比,入院到手术开始时间稍长[4.0（2.9～4.1）h vs 3.0（2.0～4.0）h,P =0.103],更少采用全身麻醉（55.6% vs 100.0%,P =0.003）,更倾向采取直接导管抽吸取栓（27.8%vs 13.3%,P =0.32）。出院时死亡率低于2019年同期取栓患者（0 vs 20.0%,P =0.050）。2020年疫情期间纳入的患者及参与救治的医护人员无COVID-19可疑病例,无COVI D-19疑似或确诊病例。结论 COVID-19疫情期间,入院到手术开始时间受到疫情筛查的影响而有所延长,取栓策略倾向于采取局部麻醉、抽吸取栓策略,作为疫情期间的特殊考虑是合理的。     

Stroke Mechanism in COVID-19 Infection: A Prospective Case-Control Study

BackgroundThe characteristics and pathophysiological mechanisms involved in acute ischemic stroke in patients with COVID-19 infection have not been fully clarified. We prospectively studied the phenotypic and etiological features of acute stroke occurring in COVID-19 infection.Patients & methodsWithin nine months starting from April-2020, the presence of COVID-19 infection was determined by thoracic CT and SARS-CoV-2 PCR in all acute stroke cases managed in a single tertiary center. Consecutive and prospective data on vascular risk factors/comorbidities, in-hospital quality metrics, discharge outcomes, etiological subclassification and blood markers of thrombosis / inflammation were compared in 44 COVID-19 positive cases (37 acute ischemic stroke, 5 TIA, 2 intracerebral hematoma) and 509 COVID-19 negative patients (355 ischemic, 105 TIA, 44 hematoma and 5 stroke mimic).ResultsCOVID-19 positive patients had more severe strokes, delayed hospital admission, longer hospital stay, higher mortality rates, but had similar vascular risk factors/comorbidities frequency, thrombolysis/thrombectomy utilization rates, metrics, and stroke etiological subtype. They had significantly higher CRP, fibrinogen, ferritin, leukocyte count and lower lymphocyte count. No difference was detected in aPTT, INR, D-dimer, platelet, hemoglobin, homocysteine levels and ANA, anti-dsDNA antibody and ENA panel positivity rates. Anti-phospholipid antibodies have been studied in 70% of COVID-19 positive and all cryptogenic patients, but were never found positive. Tests for coagulation factor levels and hereditary thrombophilia did not show major thrombophilia in any of the stroke patients with COVID-19.ConclusionWe documented that there is no significant difference in etiological spectrum in acute stroke patients with COVID-19 infection. In addition, cryptogenic stroke and antiphospholipid antibody positivity rates did not increase.     

The Effects of COVID-19 on Patients with Acute Ischemic and Hemorrhagic Stroke

ObjectiveThe objective of this study was to evaluate how COVID-19 affects patients with acute ischemic or hemorrhagic stroke outcome.Materials and methodsThis retrospective study was performed on adult patients (> 18 years old) with stroke (ischemic or hemorrhagic) who were admitted to hospital with or without COVID-19. The primary outcome was stroke-related disability, which was measured by mRS at baseline and discharge. Hospital duration, intensive care unit (ICU) admission, and mortality were considered the secondary outcomes.ResultsFrom February 2019 until August 2020, we recruited and analyzed 151 patients, 42 of whom had COVID-19 based on RT-PCR tests or lung CT scan findings. COVID-19 positive patients had higher baseline and final mRS scores than the control group (4.46 ± 0.67 vs 4.79 ± 0.61, P: 0.001, 3.83 ± 1.22 vs 4.46 ± 0.67, P: 0.001). Moreover, stroke patients with COVID-19 experienced a more severe disease and required a higher rate of ICU admission (17 vs 0, P:0.001) and longer hospitalization compared to those without COVID-19 (8.50 ± 7.86 vs 7.5 ± 11.20, P: 0.021). Also, mortality was higher in the COVID-19 group (19 vs 13, P:0.001). There was not any significant differences between the two groups in terms of the involvement of cerebral arteries and type of stroke. Male sex, COVID-19, and ICU admission were the main independent risk factors for death.ConclusionThe results of the study showed stroke patients (ischemic or hemorrhagic) with COVID-19 can have more disabilities and incur more hospital complications and mortality than non-COVID-19 patients.     

卒中后抑郁脑网络的研究进展

卒中后抑郁(post-stroke depression,PSD)是卒中后最常见的精神并发症,有近三分之一的卒中幸存者会罹患PSD。目前越来越多的证据支持脑网络的异常改变是导致PSD的神经生理病理基础。卒中局部病变不仅导致特定局部脑网络(情感网络、默认网络、突显网络、记忆控制网络等)发生重构,而且还可引发全脑脑网络拓扑结构的重塑。部分卒中患者在脑网络重塑过程中,情感相关的网络发生了特征性重构,最终导致脑功能的失常出现了临床抑郁症状,导致PSD的发生。本文就PSD的脑网络研究的最新进展进行综述,以探讨PSD的发病机制。     

Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19

Background/Purpose: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19.Methods: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA.Results: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3–26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0–25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml).Conclusions: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results.