Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19 : Results of a retrospective multicenter neuroimaging-based study from three central European countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. MATERIALS AND METHODS: Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. RESULTS: 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. DISCUSSION: AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.

Tectal Hemorrhage in the Setting of COVID-19 Infection.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has emerging evidence of a relationship to intracranial hemorrhage. The hemorrhages described to date often affect patients on anticoagulation, of advanced age, of nonwhite race, and requiring mechanical ventilation. Unusual or rare hemorrhage patterns have not as yet been described in the literature as being associated with COVID-19. CASE REPORT: A 36-year-old Hispanic male with no significant past medical history presented with isolated tectal intraparenchymal hemorrhage with intraventricular hemorrhage in the setting of no identifiable risk factors other than COVID-19. His management required temporizing with external ventricular drainage and subsequent endoscopic third ventriculostomy for ongoing obstruction of the cerebral aqueduct following the hemorrhage. He was discharged and did clinically well. To our knowledge, this is the first report of an intraparenchymal hematoma of the brain isolated to the midbrain tectum with only COVID-19 as a risk factor. CONCLUSION: COVID-19 may predispose patients to rare types of intraparenchymal hematomas which remain amenable to standard management algorithms.

Fatal Staphylococcus Aureus Endocarditis Misdiagnosed as Multisystem Inflammatory Syndrome in Children.

We present a case of a 10-year-old male with Staphylococcus aureus mitral endocarditis who was initially misdiagnosed with multisystem inflammatory syndrome associated with coronavirus disease 2019, with eventual fatal outcome due to brain hemorrhage after cardiac intervention. Our case differs from recent studies, in which microbleeds did not increase the risk of hemorrhagic stroke or global mortality risk.

Rare case of COVID-19 vaccine-associated intracranial haemorrhage with venous sinus thrombosis.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a relatively novel term which describes patients who have developed a low platelet count and prothrombotic tendencies secondary to receiving a vaccine. The concept has been derived from the well-established phenomenon of heparin-induced thrombocytopenia, and several cases of VITT have now been reported in patients who have received the AstraZeneca (ChAdOx1 nCov-19) vaccine. Unfortunately, some of these patients have gone on to develop intracranial venous sinus thrombosis. We present a case of VITT-associated sinus thrombosis secondary to the AstraZeneca (ChAdOx1 nCov-19) vaccine, which was complicated by a large intracerebral haemorrhage.

Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature.

BACKGROUND: SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood-brain barrier may then contribute to the occurrence of a brain haemorrhage. METHODS: We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19. RESULTS: We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES. CONCLUSIONS: Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood-brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis.

Intracranial Hemorrhage in COVID-19 Patients.

OBJECTIVE: To describe the clinical, laboratory, temporal, radiographic, and outcome features of acute Intracranial Hemorrhage (ICH) in COVID-19 patients. METHODS: Retrospective, observational, consecutive case series of patients admitted with ICH to Maimonides Medical Center from March 1 through July 31, 2020, who had confirmed or highly suspected COVID-19. Demographic, clinical, laboratory, imaging, and outcome data were analyzed. ICH rates among all strokes were compared to the same time period in 2019 in two-week time intervals. Correlation of systolic blood pressure variability (SBPV) and neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes were performed. RESULTS: Of 324 patients who presented with stroke, 65 (20%) were diagnosed with non-traumatic ICH: 8 had confirmed and 3 had highly suspected COVID-19. Nine (82%) had at least one associated risk factor for ICH. Three ICHs occurred during inpatient anticoagulation. More than half (6) suffered either deep or cerebellar hemorrhages; only 2 were lobar hemorrhages. Two of 8 patients with severe pneumonia survived. During the NYC COVID-19 peak period in April, ICH comprised the highest percentage of all strokes (40%), and then steadily decreased week-after-week (p = 0.02). SBPV and NLR were moderately and weakly positively correlated to discharge modified Rankin Scale, respectively. CONCLUSIONS: COVID-19 associated ICH is often associated with at least one known ICH risk factor and severe pneumonia. There was a suggestive relative surge in ICH among all stroke types during the first peak of the NYC pandemic. It is important to be vigilant of ICH as a possible and important manifestation of COVID-19.

Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series.

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

COVID-19-related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India.

BACKGROUND: COVID-19-related strokes are increasingly being diagnosed across the world. Knowledge about the clinical profile, imaging findings, and outcomes is still evolving. Here we describe the characteristics of a cohort of 62 COVID-19-related stroke patients from 13 hospitals, from Bangalore city, south India. OBJECTIVE: To describe the clinical profile, neuroimaging findings, interventions, and outcomes in COVID-19-related stroke patients. METHODS: This is a multicenter retrospective study of all COVID-19-related stroke patients from 13 hospitals from south India; 1st June 2020-31st August 2020. The demographic, clinical, laboratory, and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT-PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. RESULTS: During the three-month period, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes, while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males. Twenty-six percent (16/62) of patients did not have any conventional risk factors for stroke. Diabetes mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline National Institutes of Health Stroke Scale score was 12.7 ± 6.44. Stroke severity was moderate (National Institutes of Health Stroke Scale 5-15) in 27 (61.3%) patients, moderate to severe (National Institutes of Health Stroke Scale 16-20) in 13 (20.9%) patients and severe (National Institutes of Health Stroke Scale 21-42) in 11 (17.7%) patients. According to TOAST classification, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion, and 5% had cardioembolic strokes. Three (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/kg and 3 (5%) underwent mechanical thrombectomy, two endovascular and one surgical. Duration of hospital stay was 16.16 ± 6.39 days; 21% (13/62) died in hospital, while 37 (59.7%) had a modified Rankin score of 3-5 at discharge. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality. A comparison to 111 historical controls during the non-COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality, and higher morbidity in COVID-19-related stroke patients. CONCLUSION: COVID-19-related strokes are increasingly being recognized in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of COVID-19-related strokes. COVID-19-related strokes were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality.

Cerebral Herniation Secondary to Stroke-Associated Hemorrhagic Transformation, Fulminant Cerebral Edema in Setting of COVID-19 Associated ARDS and Active Malignancy.

SARS-CoV-2 infection has been associated with ischemic stroke as well as systemic complications such as acute respiratory failure; cytotoxic edema is a well-known sequelae of acute ischemic stroke and can be worsened by the presence of hypercarbia induced by respiratory failure. We present the case of a very rapid neurologic and radiographic decline of a patient with an acute ischemic stroke who developed rapid fulminant cerebral edema leading to herniation in the setting of hypercarbic respiratory failure attributed to SARS-CoV-2 infection. Given the elevated incidence of cerebrovascular complications in patients with COVID-19, it is imperative for clinicians to be aware of the risk of rapidly progressive cerebral edema in patients who develop COVID-19 associated acute respiratory distress syndrome.

Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage.

We document the neuropathologic findings of a 73-year old man who died from acute cerebellar hemorrhage in the context of relatively mild SARS-CoV2 infection. The patient developed sudden onset of headache, nausea, and vomiting, immediately followed by loss of consciousness on the day of admission. Emergency medical services found him severely hypoxemic at home, and the patient suffered a cardiac arrest during transport to the emergency department. The emergency team achieved return of spontaneous circulation after over 17 min of resuscitation. A chest radiograph revealed hazy bilateral opacities; and real-time-PCR for SARS-CoV-2 on the nasopharyngeal swab was positive. Computed tomography of the head showed a large right cerebellar hemorrhage, with tonsillar herniation and intraventricular hemorrhage. One day after presentation, he was transitioned to comfort care and died shortly after palliative extubation. Autopsy performed 3 h after death showed cerebellar hemorrhage and acute infarcts in the dorsal pons and medulla. Remarkably, there were microglial nodules and neuronophagia bilaterally in the inferior olives and multifocally in the cerebellar dentate nuclei. This constellation of findings has not been reported thus far in the context of SARS-CoV-2 infection.

Acute Hemorrhage After Intracerebral Biopsy in COVID-19 Patients: Report of 3 Cases.

BACKGROUND: When Belgium's coronavirus disease 2019 (COVID-19) outbreak began in March 2020, our neurosurgical department followed the protocol of most surgical departments in the world and postponed elective surgery. However, patients with tumor-like brain lesions requiring urgent surgery still received treatment as usual, in order to ensure ongoing neurooncologic care. From a series of 31 patients admitted for brain surgery, 3 were confirmed as infected by the novel severe acute respiratory syndrome coronavirus 2. CASE DESCRIPTION: We present the clinical outcomes of these 3 COVID-19 patients, who underwent an intracerebral biopsy in our department during April 2020. All suffered from a diffuse intraparenchymal hemorrhage postoperatively. Unfortunately, we were not able to identify a clear etiology of these postoperative complications. It could be hypothesized that an active COVID-19 infection status may be related to a higher bleeding risk. The remaining 28 neurooncologic non-COVID-19 patients underwent uneventful surgery during the same period. CONCLUSIONS: This case series reports the previously unreported and unexpected outcomes of COVID-19 patients suffering from acute hemorrhage after intracerebral biopsy procedures. Although no direct relation can yet be established, we recommend the neurosurgical community be cautious in such cases.

Atypical Deep Cerebral Vein Thrombosis with Hemorrhagic Venous Infarction in a Patient Positive for COVID-19.

There is growing evidence that Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has a neurotropic and neuroinvasive potential. In particular, neurologic complications associated with the infection by SARS-CoV-2 include strokes that may result from a dysregulated inflammatory response to the infection. We report an atypical deep cerebral vein thrombosis complicated with hemorrhagic venous infarction in a patient positive for SARS-CoV-2 with no risk factors for thrombosis.

Hemorrhagic stroke in setting of severe COVID-19 infection requiring Extracorporeal Membrane Oxygenation (ECMO).

OBJECTIVE: To highlight the increased risk of hemorrhagic stroke secondary to postulated COVID-19 mediated vasculopathy with concomitant ECMO related bleeding complications. BACKGROUND: COVID-19 has shown to be a systemic illness, not localized to the respiratory tract and lung parenchyma. Stroke is a common neurological complication. In particular, critically ill patients on ECMO are likely at higher risk of developing hemorrhagic stroke. CASE PRESENTATION: 38-year-old man presented with fever, cough, and shortness of breath. Due to severe respiratory failure, he required ECMO support. Subsequently, he was found to have left temporal intraparenchymal hemorrhage. Overall, his clinical course improved, and he was discharged with minimal neurological deficits. CONCLUSION: Although intracranial hemorrhage is a known complication of ECMO, patients with COVID-19 infection may be at a higher risk of cerebrovascular complications due to vasculopathy.

COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia.

OBJECTIVE: To describe a novel case of coronavirus disease 2019 (COVID-19)-associated acute necrotizing encephalopathy (ANE) in a patient with aplastic anemia where there was early brain stem-predominant involvement. METHODS: Evaluation of cause, clinical symptoms, and treatment response. RESULTS: A 59-year-old woman with a background of transfusion-dependent aplastic anemia presented with seizures and reduced level of consciousness 10 days after the onset of subjective fever, cough, and headache. Nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) was positive, and CT during admission demonstrated diffuse swelling of the brain stem. She required intubation and mechanical ventilation for airway protection, given her reduced level of consciousness. The patient's condition deteriorated, and MRI on day 6 demonstrated worsening brain stem swelling with symmetrical hemorrhagic lesions in the brain stem, amygdalae, putamina, and thalamic nuclei. Appearances were consistent with hemorrhagic ANE with early brain stem involvement. The patient showed no response to steroid therapy and died on the eighth day of admission. CONCLUSIONS: COVID-19 may be associated with an acute severe encephalopathy and, in this case, was considered most likely to represent an immune-mediated phenomenon. As the pandemic continues, we anticipate that the spectrum of neurologic presentation will broaden. It will be important to delineate the full clinical range of emergent COVID-19-related neurologic disease.