[The neurology of COVID-19]. / La neurología de COVID-19.

The clinical manifestations of COVID-19 are reminiscent of those of acute respiratory distress syndrome induced by cytokine release syndrome and secondary hemophagocytic lymphohistiocytosis that is observed in patients with other coronaviruses such as SARS-CoV and MERS-CoV. Neurologists face the challenge of assessing patients with pre-existing neurological diseases who have contracted SARS-CoV-2, patients with COVID-19 who present neurological emergencies, and patients who are carriers of the virus and have developed secondary neurological complications, either during the course of the disease or after it. Some authors and recent literature reports suggest that the presence of neurological manifestations in patients who are carriers of SARS-CoV-2 may be associated with a greater severity of the disease.

Las manifestaciones clínicas de COVID-19 recuerdan las del síndrome de insuficiencia respiratoria aguda inducido por el síndrome de liberación de citocinas y la linfohistiocitosis hemofagocitica observada en pacientes con otros coronavirus como SARS-CoV y MERS-CoV. Los neurólogos tienen el reto de evaluar pacientes con enfermedades neurológicas preexistentes que contraen SARS-CoV-2, pacientes con COVID-19 que presentan emergencias neurológicas y pacientes portadores del virus que desarrollan complicaciones neurológicas secundarias, durante el curso de la enfermedad o posterior a la misma. Algunos autores y reportes en la literatura recientes sugieren que las manifestaciones neurológicas en pacientes portadores de SARS-CoV-2 pueden asociarse con mayor gravedad de la enfermedad.

[Ethiopathogenetic features and course of ischemic stroke associated with COVID-19]. / Etiopatogeneticheskie osobennosti i techenie ishemicheskogo insul'ta, assotsiirovannogo s COVID-19.

OBJECTIVE: To analyze etiopathogenetic factors and course of ischemic stroke associated with new coronavirus infection (COVID-19). MATERIAL AND METHODS: A retrospective clinical study of 173 patients with ischemic stroke and COVID-19 (main group) and 86 patients with ischemic stroke without COVID-19 (comparison group) was carried out. There were no statistically significant differences in age and gender. All patients underwent standard clinical-instrumental, laboratory and neuroimaging assessments. RESULTS: Compared with the comparison group, patients with COVID-19 were less likely to have cardiovascular risk factors, the difference being statistically significant. Stroke in the main group was more severe than in the comparison group. According to the TOAST classification, an unknown stroke subtype significantly predominated in the main group. Laboratory data in the main group indicated the significance of an increase in renal-hepatic markers (creatinine, aspartate aminotransferase) and systemic inflammatory response syndrome (C-reactive protein). CONCLUSION: The development of cardiovascular diseases in patients with COVID-19 is an important negative prognostic factor that requires further study to determine the optimal management strategy.

Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

Implications of COVID-19 to Stroke Medicine: An Epidemiological and Pathophysiological Perspective.

The neurological complications of Coronavirus 2019 (COVID-19) including stroke have been documented in the recent literature. COVID-19-related inflammation is suggested to contribute to both a hypercoagulable state and haemorrhagic transformation, including in younger individuals. COVID-19 is associated with a heightened risk of ischaemic stroke. Haemorrhagic stroke in COVID-19 patients is associated with increased morbidity and mortality. Cerebral venous sinus thrombosis (CVST) accounts for <1% of stroke cases in the general population but has come to heightened public attention due to the increased risk associated with adenoviral COVID-19 vaccines. However, recent evidence suggests the prevalence of stroke is less in vaccinated individuals than in unvaccinated COVID-19 patients. This review evaluates the current evidence of COVID-19-related ischaemic and haemorrhagic stroke, with a focus on current epidemiology and inflammatory-linked pathophysiology in the field of vascular neurology and stroke medicine.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke.

Inflammation and immune mechanisms are crucially involved in the pathophysiology of the development, acute damage cascades, and chronic course after ischemic stroke. Atherosclerosis is an inflammatory disease, and, in addition to classical risk factors, maladaptive immune mechanisms lead to an increased risk of stroke. Accordingly, individuals with signs of inflammation or corresponding biomarkers have an increased risk of stroke. Anti-inflammatory drugs, such as IL (interleukin)-1ß blockers, methotrexate, or colchicine, represent attractive treatment strategies to prevent vascular events and stroke. Lately, the COVID-19 pandemic shows a clear association between SARS-CoV2 infections and increased risk of cerebrovascular events. Furthermore, mechanisms of both innate and adaptive immune systems influence cerebral damage cascades after ischemic stroke. Neutrophils, monocytes, and microglia, as well as T and B lymphocytes each play complex interdependent roles that synergize to remove dead tissue but also can cause bystander injury to intact brain cells and generate maladaptive chronic inflammation. Chronic systemic inflammation and comorbid infections may unfavorably influence both outcome after stroke and recurrence risk for further stroke. In addition, stroke triggers specific immune depression, which in turn can promote infections. Recent research is now increasingly addressing the question of the extent to which immune mechanisms may influence long-term outcome after stroke and, in particular, cause specific complications such as poststroke dementia or even poststroke depression.

COVID-19-associated ischaemic stroke due to underlying carotid artery thrombosis in a healthy young woman.

SARS-CoV-2 has proven its versatility in host presentations; one such presentation is a hypercoagulable state causing large-vessel thrombosis. We report a case on a previously asymptomatic COVID-19-positive patient presenting with an acute ischaemic stroke and an incidental left internal carotid artery thrombus. The patient's medical, social and family history and hypercoagulability screening excluded any other explanation for the left carotid thrombus or stroke, except for testing positive for the COVID-19. This case explores the known hypercoagulable state associated with COVID-19 and the effect of the virus on the host's immune response. It also questions whether administration of recombinant tissue plasminogen activator (t-PA), according to the American Heart Association guidelines, following a negative head CT for haemorrhagic stroke is safe without prior extended imaging in this patient population. We recommend, in addition to obtaining a non-contrast CT scan of the brain, a CT angiogram or carotid duplex of the neck be obtained routinely in patients with COVID-19 exhibiting stroke symptoms before t-PA administration as the effects may be detrimental. This recommendation will likely prevent fragmentation and embolisation of an undetected carotid thrombus.

Acute Ischemic Stroke Associated with COVID-19.

During the prevailing coronavirus disease 2019 (COVID-19) pandemic, the disease has started manifesting with some neurological symptoms. There have been reports on acute ischemic stroke, cerebral venous thrombosis, and intracerebral hemorrhage associated with COVID-19. The plausible mechanism that causes these ischemic processes is called "sepsis-induced coagulopathy." A 40-year male patient, who was hospitalised due to COVID-19 pneumonia, developed sudden-onset motor aphasia and right-sided hemiplegia. He was then placed in, with the diagnosis of acute ischemia, most probably associated with COVID-19, considering that the patient's medical history was not remarkable for a relevant etiology, and all tests for the etiology of ischemic stroke showed normal findings. The patient was placed on therapy with acetyl salicylic acid, 300 mg/day. It is presumed that ischemic events occur by an increase in coagulopathy secondary to inflammation. COVID-19 causes ischemic processes by inducing endothelial dysfunction and arterial or venous thrombosis. Key Words: COVID-19, Stroke, Coagulopathy, Ischemia; SARS-CoV-2.

Increased Incidence of In-Hospital Ischemic Stroke During SARS-CoV-2 Outbreak: A Single-Center Study.

BACKGROUND: Meta-analyses of observational studies report a 1.1-1.7% pooled risk of stroke among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalization, but consultations for stroke and reperfusion procedures have decreased during the outbreak that occurred during the first half of the year 2020. It is still unclear whether a true increase in the risk of stroke exists among patients with coronavirus disease 2019 (COVID-19). In-hospital ischemic stroke (IHIS) complicated the 0.04-0.06% of all admissions in the pre-COVID-19 era, but its incidence has not been assessed among inpatients with COVID-19. We aimed to compare IHIS incidence among patients with SARS-CoV-2 infection with that of inpatients with non-COVID-19 illnesses from the same outbreak period and from previous periods. METHODS: This historical cohort study belongs to the COVID-19@Vallecas cohort. The incidence of IHIS was estimated for patients with SARS-CoV-2 hospitalized during March-April 2020 [COVID-19 cohort (CC)], for patients with non-COVID-19 medical illness hospitalized during the same outbreak period [2020 non-COVID-19 cohort (20NCC)], and for inpatients with non-COVID-19 illness admitted during March-April of the years 2016-2019 [historical non-COVID-19 cohort (HNCC)]. Unadjusted risk of IHIS was compared between the three cohorts, and adjusted incidence rate ratio (IRR) of IHIS between cohorts was obtained by means of Poisson regression. RESULTS: Overall, 8126 inpatients were included in this study. Patients in the CC were younger and more commonly men than those from the HNCC and 20NCC. Absolute risk of IHIS was 0.05% for HNCC, 0.23% for 20NCC, and 0.36% for CC, (p = 0.004 for HNCC vs. CC). Cumulative incidence for IHIS by day nine after admission, with death as a competing risk, was 0.09% for HNCC, 0.23% for 20NCC, and 0.50% for CC. In an adjusted Poisson regression model with sex, age, needing of intensive care unit admission, and cohort (HNCC as reference) as covariates, COVID-19 was an independent predictor for IHIS (IRR 6.76, 95% confidence interval 1.66-27.54, p = 0.01). A nonsignificant increase in the risk of IHIS was observed for the 20NCC (IRR 5.62, 95% confidence interval 0.93-33.9, p = 0.06). CONCLUSIONS: SARS-CoV-2 outbreak was associated with an increase in the incidence of IHIS when compared with inpatients from a historical cohort. Viral infection itself may be related to the increased risk of IHIS among patients with COVID-19, but in view of our results from the 20NCC, it is likely that other factors, such as hospital saturation and overwhelming of health systems, may have played a role in the increased frequency of IHIS.

Delayed Endovascular Thrombectomy for Ischemic Stroke in a Young Woman with No Known Risk Factors: A Case Report.

BACKGROUND National guidelines and consensus statements suggest a 24-hour window for endovascular recanalization in patients presenting with acute ischemic stroke due to large-vessel occlusion. However, the safety and efficacy of extending the window for intervention remains to be definitively established. CASE REPORT A healthy 26-year-old woman presented with headache, left-sided hemiplegia, and rightward gaze palsy 2 days after a minor trauma. Time last known well was approximately 50 hours prior to presentation. Computed tomography angiography revealed dissection of the distal right internal carotid artery and occlusion of the M1 segment of the right middle cerebral artery. Magnetic resonance imaging showed a small area of acute infarct in the right basal ganglia and right insular cortex, but suggested a large ischemic penumbra; this was confirmed with cerebral perfusion analysis. In light of the patient's young age and potential for penumbral salvage, mechanical thrombectomy of an M1 thrombus and stenting of an internal carotid artery dissection were performed nearly 60 hours after the onset of symptoms. The patient demonstrated marked clinical improvement over the following days and was discharged home in excellent condition one week after presentation. Based on our clinical experience and other emerging data, we propose that extension of the 24-hour window for endovascular intervention may improve functional outcomes among select individuals. CONCLUSIONS A 24-hour window for endovascular thrombectomy is appropriate for many patients presenting with acute ischemic stroke. However, in select individuals, extension of the window to 48 hours or beyond may improve functional outcomes.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Characteristics and Comparison of 32 COVID-19 and Non-COVID-19 Ischemic Strokes and Historical Stroke Patients.

OBJECTIVES: The presence of COVID-19 infection may increase the risk of thrombotic events including ischemic strokes. Whilst a number of recent reports suggest that COVID-19 associated stroke tends to be severe, there is limited data on the effects of COVID-19 in prospective registries. MATERIAL AND METHODS: To determine how COVID-19 infection may affect cerebrovascular disease, we evaluated the ischemic stroke sub-types, clinical course and outcomes prior to and during the pandemic in Qatar. The Hamad General Hospital (HGH) stroke database was interrogated for stroke admissions during the last 4 months of 2019 and January-May 2020. RESULTS: In Qatar the number of confirmed cases of COVID-19 increased from only 2 in February to 779 in March, 12,628 in April and 45,501 in May. Stroke admissions to HGH declined marginally from an average of 97/month for six pre-COVID months to 72/month in March-May. There were 32 strokes that were positive for COVID-19. When compared to non-COVID-19 stroke during the three months of the pandemic, COVID-19 patients were younger with significantly lower rates of hypertension, diabetes and dyslipidemia. COVID-19 positive patients had more cortical strokes (34.4% vs 5.6%; p = 0.001), severe disease (NIHSS >10: 34.4% vs 16.7%; p = 0.001) prolonged hospitalization and fewer with good recovery (mRS 0-2: 28.1% vs 51.9%; p = 0.001). CONCLUSIONS: When compared to six pre-COVID-19 months, the number of ischemic stroke admissions during the three months of the pandemic declined marginally. COVID-19 positive patients were more likely to have a large cortical stroke with severe symptoms and poor outcome.