Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.

Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.e., hypertension), and medical interventions during acute infection. We aimed to evaluate CSVD in acute and recovered COVID-19 patients and to differentiate COVID-19-related cerebrovascular pathology from the above-mentioned contributing factors by assessing the localization of microbleeds and ischemic lesions/infarctions in the cerebrum, cerebellum, and brainstem. A systematic search was performed in December 2022 on PubMed, Web of Science, and Embase using a pre-established search criterion related to history of, or active COVID-19 with CSVD pathology in adults. From a pool of 161 studies, 59 met eligibility criteria and were included. Microbleeds and ischemic lesions had a strong predilection for the corpus callosum and subcortical/deep white matter in COVID-19 patients, suggesting a distinct CSVD pathology. These findings have important implications for clinical practice and biomedical research as COVID-19 may independently, and through exacerbation of age-related mechanisms, contribute to increased incidence of CSVD.

Effect of COVID-19 pandemic on outcomes in intracerebral hemorrhage.

OBJECTIVES: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period. MATERIALS AND METHODS: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status. RESULTS: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups. CONCLUSIONS: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic.

Prevalence of acute neurological complications and pathological neuroimaging findings in critically ill COVID-19 patients with and without VV-ECMO treatment.

Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital's databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.

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.

Influence of COVID-19 disease on subarachnoid hemorrhage and intracerebral hemorrhage.

This study aims to make a comparative evaluation of the change in the incidence of intracranial hemorrhage [intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH)] cases that attended our hospital in the Covid-19 pandemic period with that of the same term one year ago. This study included 80 patients diagnosed with ICH and/or SAH in the period that started with the pandemic in 2020. It was determined that 51 patients had been diagnosed with ICH and/or SAH during the same period of 2019. A total of 131 ICH and SAH patients (2019; n=51, 39%; and 2020; n=80, 61 %) having an average age of 64.52±7.33 including 66 women (50.4 %) were included in the study in the nine -month follow-up periods covering the period of March-November of 2019 and 2020, respectively. It was determined that the number of patients diagnosed with ICH and SAH during the pandemic was higher than the number of those who attended our clinic in 2019 (80 vs 51) and that they were older (65.76±6.56 years vs 62.57±8.09 years) (p=0.014 and p=0.026, respectively). The incidence and distribution of ICH and SAH among the patients were similar (p >0.05). It was determined that in 1 patient, ICH and SAH co-existed. In the study, it was determined that among the patients treated for intracranial hemorrhage in 2020, 32.5 % were diagnosed with COVID-19 as validated by positive nasopharyngeal SARS-CoV-2 PCR. The evaluation of the patients in 2020 revealed that the average age and ICH and SAH incidence in COVID-19 (+) and COVID-19 (-) patients were similar. Although increased incidence of acute intracranial hemorrhage has been observed during COVID-19 pandemic a athophysiological correlation between the two clinical presentations could not be clearly demonstrated. When rapidly progressing neurological deterioration findings are present in COVID-19 patients, existence of intracranial hemorrhage should always be considered (Tab. 2, Ref. 21). Keywords: subarachnoid hemorrhage, intracerebral hemorrhage, COVID-19.

APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.

Delays in Intracerebral Hemorrhage Management Is Associated with Hematoma Expansion and Worse Outcomes: Changes in COVID-19 Era.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic disrupted the emergency medical care system worldwide. We analyzed the changes in the management of intracerebral hemorrhage (ICH) and compared the pre-COVID-19 and COVID-19 eras. MATERIALS AND METHODS: From March to October of the COVID-19 era (2020), 83 consecutive patients with ICH were admitted to four comprehensive stroke centers. We retrospectively reviewed the data of patients and compared the treatment workflow metrics, treatment modalities, and clinical outcomes with the patients admitted during the same period of pre-COVID-19 era (2017-2019). RESULTS: Three hundred thirty-eight patients (83 in COVID-19 era and 255 in pre-COVID-19 era) were included in this study. Symptom onset/detection-to-door time [COVID-19; 56.0 min (34.0-106.0), pre-COVID-19; 40.0 min (27.0-98.0), p=0.016] and median door to-intensive treatment time differed between the two groups [COVID-19; 349.0 min (177.0-560.0), pre-COVID-19; 184.0 min (134.0-271.0), p<0.001]. Hematoma expansion was detected more significantly in the COVID-19 era (39.8% vs. 22.1%, p=0.002). At 3-month follow-up, clinical outcomes of patients were worse in the COVID-19 era (Good modified Rankin Scale; 33.7% in COVID19, 46.7% in pre-COVID-19, p=0.039). CONCLUSION: During the COVID-19 era, delays in management of ICH was associated with hematoma expansion and worse outcomes.

COVID-19 Vaccine-Associated Cerebral Venous Thrombosis in Germany.

OBJECTIVE: We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. METHODS: A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. RESULTS: A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38-0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00-2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22-10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. INTERPRETATION: Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women. ANN NEUROL 2021;90:627-639.

Intracerebral Hemorrhage and Coronavirus Disease 2019 in a Cohort of 282,718 Hospitalized Patients.

BACKGROUND: To identify whether the risk of intracerebral hemorrhage is higher in patients with coronavirus disease 2019 (COVID-19), we compared the risk factors, comorbidities, and outcomes in patients intracerebral hemorrhage and COVID-19 and those without COVID-19. METHODS: We analyzed the data from the Cerner deidentified COVID-19 data set derived from 62 health care facilities. The data set included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated with suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: There were a total of 154 (0.2%) and 667 (0.3%) patients with intracerebral hemorrhage among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of intracerebral hemorrhage in patients with COVID-19 (odds ratio 0.5; 95% confidence interval 0.5-0.6; p < .0001) after adjustment for sex, age strata, race/ethnicity, hypertension, diabetes mellitus, nicotine dependence/tobacco use, hyperlipidemia, atrial fibrillation, congestive heart failure, long-term anticoagulant use, and alcohol abuse. The proportions of patients who developed pneumonia (58.4% versus 22.5%; p < .0001), acute kidney injury (48.7% versus 31.0%; p < .0001), acute myocardial infarction (11% versus 6.4%; p = .048), sepsis (41.6% versus 22.5%; p < .0001), and respiratory failure (61.7% versus 42.3%; p < .0001) were significantly higher among patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19. The in-hospital mortality among patients with intracerebral hemorrhage and COVID-19 was significantly higher compared with that among those without COVID-19 (40.3% versus 19.0%; p < .0001). CONCLUSIONS: Our analysis does not suggest that rates of intracerebral hemorrhage are higher in patients with COVID-19. The higher mortality in patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of comorbidities and adverse in-hospital events.

Intracerebral Hemorrhage in Patients With COVID-19: An Analysis From the COVID-19 Cardiovascular Disease Registry.

[Figure: see text].

Intracerebral hemorrhage in COVID-19: A narrative review.

Coronavirus Disease 19 (COVID-19) pandemic affects the worldwide healthcare system and our understanding of this disease grows rapidly. Although COVID-19 is a mainly respiratory disease, neurological manifestations are not uncommon. The aim of this review is to report on the etiology, clinical profile, location, and outcome of patients with intracerebral hemorrhage (ICH) and COVID-19. This review includes 36 studies examining ICH in the clinical presentation of COVID-19. Overall, 217 cases with intracranial hemorrhage, of which 188 ICHs, were reported. Generally, a low incidence of both primary and secondary ICH was found in 8 studies [106 (0.25%) out of 43,137 hospitalized patients with COVID-19]. Available data showed a median age of 58 years (range: 52-68) and male sex 64%, regarding 36 and 102 patients respectively. Furthermore, 75% of the patients were on prior anticoagulation treatment, 52% had a history of arterial hypertension, and 61% were admitted in intensive care unit. Location of ICH in deep structures/basal ganglia was ascertained in only 7 cases making arterial hypertension an improbable etiopathogenetic mechanism. Mortality was calculated at 52.7%. Disease related pathophysiologic mechanisms support the hypothesis that SARS-CoV2 can cause ICH, however typical ICH risk factors such as anticoagulation treatment, or admission to ICU should also be considered as probable causes. Physicians should strongly suspect the possibility of ICH in individuals with severe COVID-19 admitted to ICU and treated with anticoagulants. It is not clear whether ICH is related directly to COVID-19 or reflects expected comorbidity and/or complications observed in severely ill patients.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States.

OBJECTIVE: To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort. METHODS: We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes. RESULTS: There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge. CONCLUSIONS: Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.

Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

[Figure: see text].

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.

Coronavirus disease 2019 (COVID-19) can predispose young to Intracerebral hemorrhage: a retrospective observational study.

BACKGROUND: The respiratory system involvement is the most common presentation of Coronavirus disease 2019 (COVID-19). However, other organs including the central nervous system (CNS) could be affected by the virus. Strokes, seizures, change in mental status, and encephalitis have been reported as the neurological manifestation of the disease. We hypothesized that COVID-19 could predispose younger patients to spontaneous intracerebral hemorrhage (ICH). The present study aimed to investigate whether COVID-19 has any relationship with the occurrence of spontaneous ICH in young or not. METHODS: We retrospectively evaluated all the patients with spontaneous ICH who were referred to our center between 20 Feb and 1 Sep 2020. The demographic, clinical, radiological, and laboratory test data were evaluated. Patients were divided into two groups. The COVID-19 positive patients and COVID-19 negative ones. All the variables including age, sex, history of hypertension, diabetes mellitus, smoking, Glasgow Coma Scale (GCS), hematoma volume and location, the presence of intraventricular hemorrhage and hydrocephalus on admission, the length of hospital stay, the lab test results and the clinical outcome at last visit or discharge as Glasgow Outcome Scale (GOS) were compared between the two groups. RESULTS: There were 22 COVID-19 positive patients (20.8%) and 84 COVID-19 negative ones (79.2%). The mean age of the patients in the case group (54.27 ± 4.67) was significantly lower than that in the control group (69.88 ± 4.47) (p < 0.05). Meanwhile, our results showed a significant difference between the two groups based on the presence of chronic arterial hypertension (p < 0.05). There were no significant differences between the two groups based on gender, diabetes mellitus, smoking, Glasgow Coma Scale (GCS), hematoma volume, need for surgery, the presence of intraventricular hemorrhage and hydrocephalus on admission, White Blood Cell (WBC) count, platelet count, Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) (p > 0.05). CONCLUSIONS: Our results show that COVID positive patients with ICH are younger and with less predisposing factors than COVID negative subjects with ICH.

Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients.

BACKGROUND AND PURPOSE: Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts. We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke. METHODS: We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset. The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19. Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke. Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders. A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19. Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders. CONCLUSIONS: Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

Incidence of hemorrhagic cerebrovascular disease due to vascular malformations during the COVID-19 national quarantine in Italy.

BACKGROUND: hemorrhagic cerebrovascular disease due to vascular malformations represents an emergency for neurosurgery and neuro-interventional departments. During the COVID-19 pandemic, a dramatic reduction in the number of hospitalizations for acute myocardial infarction or stroke and a larger time interval from symptom onset to first medical contact have been reported. This study aims to verify the hypothesis that there would also have been a reduction of admissions for hemorrhagic cerebrovascular disease during the Italian lockdown. MATERIAL AND METHOD: s A multicenter, observational survey was conducted to collect data on hospital admissions for hemorrhagic cerebrovascular disease due to vascular malformations throughout two-months (March 15th to May 15th); the years 2020 (COVID-19 Italian lockdown), 2019 and 2018 were compared. Cases were identified by ICD-9 codes 430, 431, 432.1, 432.9, 747.81 of each hospital database. The statistical significance of the difference between the event rate of one year versus the others was evaluated using Poisson Means test, assuming a constant population. RESULTS: During the 2020 lockdown, the total number of admissions for hemorrhagic cerebrovascular disease was 92 compared with 116 in 2019 and 95 in 2018. This difference was not significant. GCS upon admission was 3-8 in 44 % of cases in 2020 (41 patients), 39.7 % in 2019 (46 patients) and 28 % in 2018 (27 patients). CONCLUSION: Reduction of admissions for hemorrhagic cerebrovascular disease due to vascular malformations during the COVID-19 lockdown was not confirmed. Nevertheless, some patients reached the emergency rooms only several days after symptoms onset, resulting in a worse clinical condition at admission.

Characteristics of intracerebral haemorrhage associated with COVID-19: a systematic review and pooled analysis of individual patient and aggregate data.

BACKGROUND AND PURPOSE: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. METHODS: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. RESULTS: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53-67) years and 64% (95% CI 54-73.7%) were male; 79% (95% CI 70.0-86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3-76.0%), and of multifocal ICH was 36% (95% CI 26.4-47.0%). 71% (95% CI 61.0-80.4%) of patients were treated with anticoagulation (58% (95% CI 48-67.8%) therapeutic). The median NIHSS was 28 (IQR 15-28); mortality was 54% (95% CI 43.7-64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22-0.58%). CONCLUSIONS: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.