Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial.

The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) is an international, multicenter, stepped-wedge (4 phases/3 steps) cluster randomized trial involving 110 hospitals in mainly low- and middle-income countries during 2017-2022. The aim is to determine the effectiveness of a goal-directed care bundle of intensive blood pressure (BP) lowering, glycemic control, antipyrexia, and anticoagulation reversal treatment versus usual standard of care, in patients with acute intracerebral hemorrhage (ICH). After a "usual care" period, hospitals were randomly allocated to implementing care-bundle protocols for control targets (systolic BP <140 mm Hg; glucose 6.1-7.8/7.8-10.0 mmol/L according to diabetes mellitus status; temperature ≤37.5°C; normalization of anticoagulation). A sample size of 8,360 patients (mean 19 per phase per site) provides 90% power (α = 0.05) for a 5.6% absolute improvement in the primary outcome of scores on the modified Rankin scale at 6 months, analyzed by ordinal logistic regression. A detailed statistical analysis plan (SAP) was developed to prespecify the method of analysis for all outcomes and key variables collected in the trial. The primary analysis will use ordinal logistic regression adjusted for the stepped-wedge design. The SAP also includes planned sensitivity analyses, including covariate adjustments, missing data imputations, and subgroup analysis. This SAP allows transparent, verifiable, and prespecified analyses in consideration of the challenges in conducting the study during the COVID pandemic. It also avoids analysis bias arising from prior knowledge of the findings in determining the benefits and harms of a care bundle in acute ICH.

Comorbidity of purulent meningitis with COVID‐19: A case report

To date, only a few cases of intracranial infection related to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) were reported. Here we describe a case of coronavirus disease 2019 (COVID‐19) that was comorbid with purulent meningitis. A 62‐year‐old male patient was diagnosed with moderate COVID‐19 and had no fever or cough after treatment. However, he suffered from a head injury and experienced headache and fever immediately after the accident. Computed tomography (CT) of the brain showed bilateral frontal lobe contusion, subdural hematoma, and subarachnoid hemorrhage. In the following days, the patient suffered from recurrent fever, although chest CT did not show evidence of worsening of infection. Several lumbar punctures were made, confirming increased cerebrospinal fluid (CSF) pressure and karyocyte count. SARS‐CoV‐2 nucleic acid was not detected in CSF but revealed the presence of Escherichia coli. Thus, the patient was diagnosed with purulent meningitis, presumably caused by brain trauma or the immunologic dysfunction caused by COVID‐19, which was supported by the significant reduction of all kinds of immune cells. Since immunologic dysfunction is commonly presented in COVID‐19 patients, comorbidity with meningitis should be considered when a COVID‐19 patient presents with headache and fever. Lumbar punctures and CSF cultures may help in the diagnosis.

Antiepileptogenesis after stroke-trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate.

There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization ("failure rate"). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10-item version; National Institutes of Health Stroke Scale); post-stroke depression (Patient Health Questionnaire-9; PHQ-9); and overall survival. Safety assessments include the evaluation of treatment-emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ-9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID-19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol.

[Thrombosis with Thrombocytopenia Syndrome after ChAdOx1 nCoV-19 vaccination].

A 48-year-old Japanese man who had no previous medical history received his first dose of the ChAdOx1 nCoV-19 vaccine. Ten days after the vaccine administration, he developed a headache. Laboratory results indicated throm-bocytopenia and DIC. A head CT revealed microbleeding in the left parietal lobe. Contrast-enhanced CT showed thrombus in the left transverse sinus and left sigmoid sinus. A brain MRI demonstrated venous hemorrhagic infarction and subarachnoid hemorrhages in the left parietal lobe, and whole-body enhanced CT also revealed portal vein embolism and renal infarction. He was diagnosed with thrombosis with thrombocytopenia syndrome, and was treated according to the guideline. He has been recovering with the treatments. This is the first reported case of TTS associated with the ChAdOx1 nCoV-19 vaccine in Japan.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

SARS-CoV-2 infection might be a predictor of mortality in intracerebral hemorrhage.

BACKGROUND: SARS-CoV-2 infection may be associated with uncommon complications such as intracerebral hemorrhage (ICH), with a high mortality rate. We compared a series of hospitalized ICH cases infected with SARS-CoV-2 with a non-SARS-CoV-2 infected control group and evaluated if the SARS-CoV-2 infection is a predictor of mortality in ICH patients. METHODS: In a multinational retrospective study, 63 cases of ICH in SARS-CoV-2 infected patients admitted to 13 tertiary centers from the beginning of the pandemic were collected. We compared the clinical and radiological characteristics and in-hospital mortality of these patients with a control group of non-SARS-CoV-2 infected ICH patients of a previous cohort from the country where the majority of cases were recruited. RESULTS: Among 63 ICH patients with SARS-CoV-2 infection, 23 (36.5%) were women. Compared to the non-SARS-CoV-2 infected control group, in SARS-CoV-2 infected patients, ICH occurred at a younger age (61.4 ± 18.1 years versus 66.8 ± 16.2 years, P = 0.044). These patients had higher median ICH scores ([3 (IQR 2-4)] versus [2 (IQR 1-3)], P = 0.025), a more frequent history of diabetes (34% versus 16%, P = 0.007), and lower platelet counts (177.8 ± 77.8 × 109/L versus 240.5 ± 79.3 × 109/L, P < 0.001). The in-hospital mortality was not significantly different between cases and controls (65% versus 62%, P = 0.658) in univariate analysis; however, SARS-CoV-2 infection was significantly associated with in-hospital mortality (aOR = 4.3, 95% CI: 1.28-14.52) in multivariable analysis adjusting for potential confounders. CONCLUSION: Infection with SARS-CoV-2 may be associated with increased odds of in-hospital mortality in ICH patients.

Cerebral venous sinus thrombosis following intracerebral hemorrhage after COVID-19 AstraZeneca vaccination: A case report.

The patient was a 55-year-old female patient who presented with sudden onset of left hemiplegia, facial hemiparesis, and hypoesthesia. She has received her first dose of the AstraZeneca COVID-19 vaccine. This case indicates that vaccination may raise the hypercoagulable state even in a condition of post-ICH and anticoagulant prophylaxis.

The Outcomes of COVID-19 Patients with Spontaneous Intracerebral Hemorrhage Comorbidity and the Efficacy of Enoxaparin in Decreasing the Mortality Rate in Them: Single Egyptian Center Report.

Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study.

Risk Stratification Models for Stroke in Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To derive models that identify patients with COVID-19 at high risk for stroke. MATERIALS AND METHODS: We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates. RESULTS: Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69. CONCLUSIONS: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Stroke Treatment in the Era of COVID-19: a Review.

Purpose of Review: To describe a comprehensive review of the epidemiology, pathophysiology, and treatment of stroke in the era of COVID-19. Recent Findings: COVID-19 is associated with myriad neurological disorders, including cerebrovascular disease. While ischemic stroke is the most common, COVID-19 is associated with an increased risk of intracranial hemorrhage, arterial dissection, posterior reversible encephalopathy syndrome, and cerebral venous sinus thrombosis. In this review, we discuss the epidemiology, pathophysiology, and treatment of stroke due to COVID-19. In addition, we describe how COVID-19 has changed the landscape of stroke systems of care and the effect this has had on patients with cerebrovascular disease. Summary: While COVID-19 is associated with a heightened risk of stroke, the pandemic has led to advances in stroke systems of care that may reduce the long-term burden of stroke.

Endovascular Treatment of Intracranial Vein and Venous Sinus Thrombosis-A Systematic Review.

BACKGROUND: Cerebral venous sinus or vein thromboses (SVT) are treated with heparin followed by oral anticoagulation. Even after receiving the best medical treatment, numerous patients experience neurological deterioration, intracerebral hemorrhage or brain edema. Debate regarding whether endovascular treatment (EVT) is beneficial in such severe cases remains ongoing. This systematic review summarizes the current evidence supporting the use of EVT for SVT on the basis of case presentations, with a focus on patient selection, treatment strategies and the effects of the COVID-19 pandemic. METHODS: This systemic literature review included randomized controlled trials (RCTs) and retrospective observational data analyzing five or more patients. Follow-up information (modified Rankin scale (mRS)) was required to be provided (individual patient data). RESULTS: 21 records (n = 405 patients; 1 RCT, 20 observational studies) were identified. EVT was found to be feasible and safe in a highly selected patient cohort but was not associated with an increase in good functional outcomes (mRS 0-2) in RCT data. In observational data, good functional outcomes were frequently observed despite an anticipated poor prognosis. CONCLUSION: The current evidence does not support the routine incorporation of EVT in SVT treatment. However, in a patient cohort prone to poor prognosis, EVT might be a reasonable therapeutic option. Further studies determining the patients at risk, choice of methods and devices, and timing of treatment initiation are warranted.

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.

Severe Intractable Headache as a Presentation of COVID-19 in a 23-Year-Old.

Severe acute respiratory syndrome coronavirus type 2 is a novel betacoronavirus with a new genome sequence that causes coronavirus disease 2019 (COVID-19), which primarily affects the lungs, thus causing pneumonia which can progress to severe acute respiratory distress syndrome. New emerging cases of extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiac, renal, and/or central nervous system involvement. Although an ischemic stroke converting to a hemorrhagic stroke is more commonly seen, spontaneous intracranial hemorrhage (ICH) in hospitalized COVID-19 patients is on the rise. This case report describes a 23-year-old female who tested positive (via a polymerase chain reaction test) for COVID-19 and presented with new onset of severe intractable headache. The investigation suggested COVID-19 as the most probable cause of this patients' spontaneous ICH. This case emphasizes the importance of adding COVID-19 to the differential diagnosis of hemorrhagic cerebrovascular accidents in patients with a spontaneous ICH of unclear etiology and, in the process, performing COVID testing.

Relationship between Social Distancing and Admissions for Cerebrovascular Accidents at a Tertiary Medical Center during the COVID-19 Pandemic: A Retrospective, Community-Based Study.

We evaluated the trend of admission of patients with acute cerebrovascular accidents (CVAs) during social distancing measures implemented during the coronavirus disease 2019 (COVID-19) era. The data of patients admitted with transient ischemic attack, ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) to the emergency department of the Hanyang University Seoul Hospital were retrospectively analyzed. The data were compared between the pre-COVID-19 and COVID-19 periods. Poisson regression analysis was performed to evaluate changes in admission rates as a function of the year, social distancing level, and the interaction between the year and social distancing level. The number of admissions for CVAs dropped from 674 in the pre-COVID-19 period to 582 in the COVID-19 period. The decline in the number of admissions for ICH during social distancing measures was statistically significant, while the declines in SAH and ischemic stroke admissions were not. When the social distancing level was raised, admissions for CVAs dropped by 19.8%. The correlation between social distancing and decreased admissions for CVAs is a paradoxical relationship that may be of interest to the field of public health.

A Longitudinal Research on the Distribution and Prognosis of Intracerebral Hemorrhage During the COVID-19 Pandemic.

Purpose: Globally, intracerebral hemorrhage (ICH) is a common cerebrovascular disease. At the beginning of 2020, due to the coronavirus disease 2019 (COVID-19) pandemic, the allocation of medical resources and the patient treatment and referrals were affected to varying degrees. We aimed to determine the characteristics and prognoses and associated factors of patients with ICH. Patients and Methods: The baseline demographic characteristics and ICH outcomes were compared between patients diagnosed with ICH between January and June 2020 (the 2020 group) and between January and June 2019 (the 2019 group). COVID-19 positive patients were excluded from the study. A 30-day data from patients in the 2019 and 2020 groups were analyzed to create survival curves for these patients. We also used regression models to identify the significant determinants of poor outcomes [modified Rankin score (mRS): 3-6] and death. Results: The number of patients diagnosed with ICH was slightly lower in the 2020 group (n = 707) than in the 2019 group (n = 719). During the lockdown period (February 2020), the admission rates for ICH decreased greatly by 35.1%. The distribution of the patients' domicile (P = 0.002) and the mRS (P < 0.001) differed significantly between the years. The survival curve revealed that the highest risk of death was in the acute stage (especially in the first 5 days) of ICH. At 30 days, mortality was 19.8% in February 2019 and 29.4% in February 2020 (P = 0.119). Multivariate analysis revealed age, baseline mRS, postoperative complications, massive brainstem hemorrhage, and creatinine as factors significantly associated with poor outcomes and death following ICH. Neurosurgery and massive supratentorial hemorrhage were only correlated with the risk of death. Conclusion: During the lockdown period, the COVID-19 pandemic caused a decrease in the admission rates and severe conditions at admission due to strict traffic constraints for infection control. This led to high mortality and disability in patients with ICH. It is necessary to ensure an effective green channel and allocate adequate medical resources for patients to receive timely treatment and neurosurgery.

Neurological Presentations of COVID-19

The plethora of neurological manifestations encountered in severe COVID-19 has been observed since the early days of the pandemic. The understanding that this is a novel condition, the magnitude of symptoms and signs of which is still being unraveled, cannot be overemphasized. This chapter offers a prelude to the rest of the book in which each category of neurological disorders will be discussed individually. © 2021 Elsevier Inc. All rights reserved.

COVID-19 and Cerebrovascular Diseases

SARS-CoV-2 infects endothelial cells, induces a hypercoagulable state, and, in extreme cases, can provoke a “cytokine storm.” These etiopathological mechanisms, in addition to the hemodynamic and respiratory compromises characterizing severe COVID-19, can culminate in the emergence of various acute stroke phenotypes, such as arterial and venous thromboses, and hemorrhages. COVID-19-associated strokes have been encountered in younger patients with no cerebrovascular risk factors but the disease is also found to target older patients with comorbidities who are more likely to contract the more severe forms of the disease. Anticoagulation, antiplatelets, statins, thrombolysis and endovascular thrombectomy remain the cornerstone therapies for patients with ischemic strokes and COVID-19. An important aspect of secondary stroke prevention is blood pressure management recommendations which are currently being revisited as renin-angiotensin-aldosterone antagonists were initially thought to be detrimental to infected patients due to the interaction of the virions with ACE2 receptors. We also focus our attention on the reshaping of all aspects of stroke care during the pandemic, from the prehospital stage to telehealth. © 2021 Elsevier Inc. All rights reserved.

Association of blood eicosapentaenoic acid levels with intracerebral hemorrhage during the COVID-19 pandemic: preliminary experience from a single-center in Japan.

BACKGROUND: The COVID-19 pandemic has forced lockdowns and declarations of states of emergency, resulting in marked changes to daily life such as dietary habits in many countries. Though serum omega-3 polyunsaturated fatty acids levels have been shown to be useful markers for recurrent vascular events or worse prognosis in cardiovascular diseases and ischemic stroke, the relationship between serum omega-3 PUFA levels and the occurrence of intracerebral hemorrhage has essentially been unknown. We explored the association of serum omega-3 polyunsaturated fatty acids with intracerebral hemorrhage during the COVID-19 pandemic. METHODS: Participants comprised patients admitted to Juntendo University Hospital (Tokyo, Japan) with intracerebral hemorrhage between January 1, 2016 and April 30, 2020. Clinical characteristics including serum omega-3 polyunsaturated fatty acid levels were compared between patients developing intracerebral hemorrhage during the period from January 1, 2016 to February 29, 2020, and the subsequent COVID-19 pandemic period (March 1 to April 30, 2020). Clinical characteristics independently related to intracerebral hemorrhage during the COVID-19 pandemic were analyzed by comparing these two cohorts of intracerebral hemorrhage patients in different periods. RESULTS: A total of 103 patients (age, 67.0 ± 13.9 years; 67 males) with intracerebral hemorrhage were enrolled. Intracerebral hemorrhage developed in 91 patients before and 12 patients during the COVID-19 pandemic. Monthly averages of intracerebral hemorrhage patients admitted to our hospital during and before the COVID-19 pandemic were 6 and 1.82, respectively. Serum eicosapentaenoic acid levels were significantly lower in intracerebral hemorrhage patients during the COVID-19 pandemic than before (31.87 ± 12.93 µg/ml vs. 63.74 ± 43.29 µg/ml, p = 0.007). Multiple logistic regression analysis showed that, compared to before the COVID-19 pandemic, dyslipidemia (odds ratio 0.163, 95% confidence interval 0.031-0.852; p = 0.032) and eicosapentaenoic acid levels (odds ratio 0.947, 95% confidence interval 0.901-0.994; p = 0.029) were associated with intracerebral hemorrhage during the COVID-19 pandemic. CONCLUSIONS: From our preliminary results, low eicosapentaenoic acid levels were linked with intracerebral hemorrhage during the COVID-19 pandemic. Low levels of eicosapentaenoic acid might be an endogenous surrogate marker for intracerebral hemorrhage during the COVID-19 pandemic.

Pathomechanisms and Treatment Implications for Stroke in COVID-19: A Review of the Literature.

Stroke in patients with COVID-19 has received increasing attention throughout the global COVID-19 pandemic, perhaps due to the substantial disability and mortality that can result when the two conditions co-occur. We reviewed the existing literature and found that the proposed pathomechanism underlying COVID-19-associated ischemic stroke is broadly divided into the following three categories: vasculitis, endothelialitis, and endothelial dysfunction; hypercoagulable state; and cardioembolism secondary to cardiac dysfunction. There has been substantial debate as to whether there is a causal link between stroke and COVID-19. However, the distinct phenotype of COVID-19-associated strokes, with multivessel territory infarcts, higher proportion of large vessel occlusions, and cryptogenic stroke mechanism, that emerged in pooled analytic comparisons with non-COVID-19 strokes is compelling. Further, in this article, we review the various treatment approaches that have emerged as they relate to the proposed pathomechanisms. Finally, we briefly cover the logistical challenges, such as delays in treatment, faced by providers and health systems; the innovative approaches utilized, including the role of tele-stroke; and the future directions in COVID-19-associated stroke research and healthcare delivery.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.