Diagnostic and Therapeutic Challenges of Concurrent Intracranial Hemorrhage and Cerebral Venous Thrombosis in a Patient With Acute Lymphoblastic Leukemia: A Case Report and Literature Review.

Cerebral venous sinus thrombosis (CVST) is a cerebrovascular condition due to the thrombosis of cerebral venous sinuses, leading to intracranial hemorrhage, increased intracranial pressure, focal deficit, seizure, toxic edema, encephalopathy, and death. The diagnosis and therapeutic approach of CVST remain challenging because of its highly nonspecific clinical presentation including headaches, seizures, focal neurologic deficits, and altered mental status, etc. Anticoagulation is the mainstay of CVST treatment and should be started as soon as the diagnosis is confirmed. Here, we present the case of a 34-year-old male construction worker who presented to the emergency department with a complaint of right chest wall pain and swelling. He was admitted to the hospital following a diagnosis of anterior chest wall abscess and mediastinitis. During hospitalization, his complete blood count revealed pancytopenia with blast cells, and bone marrow biopsy revealed 78.5% lymphoid blasts by aspirate differential count and hypercellular marrow (100%) with decreased hematopoiesis. He developed concurrent CVST and intracranial hemorrhage while receiving CALGB10403 (vincristine, daunorubicin, pegaspargase, prednisone) with intrathecal cytarabine induction chemotherapy for acute lymphoblastic leukemia (ALL). The patient failed two standard chemotherapy for ALL and achieved remission while on third-line chemotherapy with an anti-CD19 monoclonal antibody, blinatumomab. Although this patient had an MRI scan of the brain with multiple follow-up non-contrast CT scans, it was CT angiography that revealed CVST. This showed the diagnostic challenge in CVST, with CT and MRI venography having excellent sensitivity in diagnosing CVST. Risk factors for CVST in our patient were ALL and its intensive induction chemotherapy with pegaspargase.

SARS-CoV-2 vaccination induced cerebral venous sinus thrombosis: Do megakaryocytes, platelets and lipid mediators make up the orchestra?

The COVID-19 vaccines comprised of adenoviral vectors encoding the Spike (S) glycoprotein of SARS-CoV-2 are highly effective but associated with rare thrombotic complications. The adenovirus vector infects epithelial cells expressing the coxsackievirus and adenovirus receptor (CAR). The S glycoprotein expressed locally stimulates neutralizing antibody and cellular immune responses. These vaccines have been associated with thromboembolic events including cerebral venous sinus thrombosis (CVST). S glycoprotein stimulates the expression of cyclooxygenase-2 (COX-2) and leads to massive generation of thromboxane A2 in COVID-19. Megakaryocytes express CAR and we postulate that S glycoprotein stimulated generation of thromboxane A2 leads to megakaryocyte activation, biogenesis of activated platelets and thereby increased thrombogenicity. Cerebral vein sinuses express podoplanin, a natural ligand for CLEC2 receptors on platelets. Platelets traversing through the cerebral vein sinuses could be further activated by thromboxane A2-dependent podoplanin-CLEC2 signaling, leading to CVST. A prothrombotic hormonal milieu, and increased generation of thromboxane A2 and platelet activation in healthy females compared to males is consistent with increased risk for CVST observed in women. We propose that antiplatelet agents targeting thromboxane A2 receptor signaling such as low-dose aspirin merit consideration for chemoprophylaxis when administering the adenovirus based COVID-19 vaccines to young adults at risk of thrombosis provided there are no contraindications.

A Case of Bilateral Cerebral Venous Sinus Thrombosis: More Than Meets the Eye.

Cerebral venous sinus thrombosis (CVST) is a rare etiology of stroke that results from inherited and/or acquired conditions, which can present in a variety of symptoms. CVST in the setting of the 2019 coronavirus disease (COVID-19) has rarely been observed. Herein, we present the case of a 32-year-old female with a recent history of COVID-19 subsequently found to have CVST involving bilateral transverse sinuses. Further workup demonstrated several hypercoagulable conditions, which were likely exacerbated by the viral infection. This case demonstrates an atypical outcome for young, COVID-19-positive patients, which emphasizes the importance of diligence when examining symptomatic patients with a history of COVID-19 infection. The patient was treated with apixaban therapy with radiographic resolution of bilateral CVST and improved vision.

A Case of Vaccine-Induced Thrombocytopenic Thrombosis Manifesting as Cerebral Venous Thrombosis and Intracerebral Bleed.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but detrimental syndrome that has been most commonly reported after the administration of vaccination for the prevention of viral infections. VITT often presents with thrombosis at unusual sites such as cerebral venous sinuses, portal, splanchnic or hepatic veins, in association with thrombocytopenia and elevated anti-platelet factor 4 (aPF-4) antibodies. We describe the case of a young male patient who developed thrombocytopenia, cerebral sinus venous thrombosis, and intracerebral bleed 12 days after receiving the Ad26.COV2.S (Janssen/Johnson&Johnson) COVID-19 vaccine.

Cerebral venous sinus thrombosis (CVST), an unusual presentation of COVID-19: A case report from Bangladesh

Newly recognized pandemic infectious disease COVID-19 (Corona-virus disease) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This viral infection causes hypercoagulability and inflammation leading to increased incidence of both arterial and venous thrombotic events (VTEs). Therefore, patients infected with this novel virus seem to be at higher risk of thrombotic events (TEs) resulting in thromboembolic diseases, especially stroke and pulmonary embolism, or even cerebral venous sinus thrombosis (CVST). We report a case of 42-year-old female, presented with features of venous thrombotic events (extensive dural venous sinus thrombosis) and was subsequently found to have COVID-19 positive by reverse transcriptase-polymerase chain reaction (RT-PCR) test. The case report indicates CVST might be an unusual manifestation of COVID-19. Cerebral venous sinus thrombosis even presents as an initial symptom of COVID-19 without significant respiratory symptoms. Early diagnosis and treatment with thrombolytic agent in case of SARS-CoV-2 infection result in reduced morbidity and mortality. We recommend further studies to establish SARS-CoV-2 virus (the COVID-19 disease) as a known risk factor for CVST. © 2020 The author (s).

Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19.

Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the case of a 59-year-old man who presented with headache, hypertension and a single episode of fever with no other symptoms. He subsequently developed unilateral weakness. Computer tomography identified a cerebral venous sinus thrombosis (CVST). A subsequent test for COVID-19 was positive. This is the first report of CVST as a presenting symptom of COVID-19 infection. LEARNING POINTS: Thrombotic events may be the initial presenting symptom of COVID-19.These thrombotic events include stroke, venous thromboembolism, pulmonary embolism and cardiac complications.Clinicians should carefully consider the risk of thrombosis in patients positive for COVID-19, including prophylaxis and treatment beyond discharge.

Immune Thrombocytopenia and Cerebral Venous Sinus Thrombosis Following COVID-19 Vaccination: A Case Report.

Mass vaccination against coronavirus disease 2019 (COVID-19) has been safe and effective. The ongoing emergence of vaccine-induced complications has challenged the public trust in vaccination programs and, though uncommon, can lead to significant morbidity and mortality. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and fatal complication of the COVID-19 vaccine. We present a rare case of VITT in a young female who presented with worsening headache, body rash with deteriorating neurological deficit after 12 days of the second dose of the ChAdOx1 COVID-19 vaccine. Initial blood tests showed thrombocytopenia with deranged clotting time and D-dimer levels. Her computed tomography venogram showed thrombosis in the left transverse sinus, and she was diagnosed with a provisional diagnosis of VITT. She initially managed with dexamethasone, intravenous immunoglobulins, and apixaban to reverse the autoimmune process. Our case highlights the clinical course, diagnosis, and management of VITT, which will assist physicians in the timely recognition and adequate management of VITT.

Surgical Thrombectomy for Extensive Cerebral Venous Sinus Thrombosis after COVID-19 Vaccination : A Novel Surgical Technique and Literature Review.

Surgical treatment of refractory and extensive cerebral venous sinus thrombosis (CVST) has limited applications. Here, we describe an open, direct sinus thrombectomy in the early phase of extensive CVST. A 49-year-old man with extensive CVST that occurred after the coronavirus disease 2019 (COVID-19) vaccination and affected the drainage of the Labbé vein presented with clinical deterioration and left temporal hemorrhagic infarction. Since the patient had extensive CVST, we determined that systemic anticoagulation and endovascular treatment were not suitable treatment options. Therefore, we decided on an emergency surgical treatment and performed direct surgical thrombectomy. We followed extended suboccipital approach and made multiple incisions on the sinuses, exposing the posterior superior sagittal sinus to the transverse sigmoid junction. Consequently, the clinical condition of the patient dramatically improved, resulting in a favorable outcome with a modified Rankin Scale score of 0. Performing emergency open surgical thrombectomy was a technically feasible treatment option that recanalized obstructed sinuses. Importantly, the patient recovered with a good clinical outcome. Early maximal surgical thrombectomy is an effective and lifesaving method to treat extensive CVST with hemorrhagic infarction.

Extensive Cerebral Venous Sinus Thrombosis Post COVID-19 Vaccination.

Extensive cerebral sinus thrombosis following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is rare. We report the case of a 42-year-old man who presented with a severe generalized headache that was not relieved by analgesics for nine days. It started four days after he received the third dose of BNT162b2 (BioNTech/Pfizer). He also complained of numbness at the back of the neck, vomiting, mild blurring of vision, and diplopia. The visual acuity (VA) in the right eye was 6/9 (improved to 6/7.5 with a pinhole) and 6/6 in the left eye. He was not able to abduct both eyes and noticed a double image at lateral gaze. Fundoscopy showed swollen optic discs with the presence of disc hemorrhages. A computed tomography venogram (CTV) of the brain showed loss of normal signal void with filling defects in the superior sagittal sinus, straight sinus, bilateral transverse sinuses, bilateral sigmoid sinuses, and bilateral internal jugular veins. The nasopharyngeal swab sample was negative for SARS-CoV-2. His platelet was normal (271x109/L) and his coagulation profile was normal. Workup for connective tissue disease was negative. He was diagnosed with extensive cerebral vascular thrombosis post-vaccination. He received a one-week course of subcutaneous clexane, followed by oral anticoagulant treatment. After treatment, his headache was relieved, and the diplopia subsided. The venous thrombosis was partially resolved. Both the swollen optic discs improved, and his VA improved to 6/6 in both eyes.

Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.

Neurological autoimmune diseases following vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A follow-up study.

BACKGROUND AND PURPOSE: Population-based studies suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger neurological autoimmunity including immune-mediated thrombotic thrombocytopenia. Long-term characterization of cases is warranted to facilitate patient care and inform vaccine-hesitant individuals. METHODS: In this single-center prospective case study with a median follow-up of 387 days long-term clinical, laboratory and imaging characteristics of patients with neurological autoimmunity diagnosed in temporal association (≤6 weeks) with SARS-CoV-2 vaccinations are reported. RESULTS: Follow-up data were available for 20 cases (central nervous system demyelinating diseases n = 8, inflammatory peripheral neuropathies n = 4, vaccine-induced immune thrombotic thrombocytopenia n = 3, myositis n = 2, myasthenia n = 1, limbic encephalitis n = 1, giant cell arteritis n = 1). Following therapy, the overall disability level improved (median modified Rankin Scale at diagnosis 3 vs. 1 at follow-up). The condition of two patients worsened despite immunosuppressants possibly related to their autoimmune diagnoses (limbic encephalitis n = 1, giant cell arteritis n = 1). At 12 months' follow-up, 12 patients achieved complete clinical remissions with partial responses in five and stable disease in one case. Correspondingly, autoimmune antibodies were non-detectable or titers had significantly lowered in all, and repeat imaging revealed radiological responses in most cases. Under vigilant monitoring 15 patients from our cohort underwent additional SARS-CoV-2 vaccinations (BNT162b2 n = 12, mRNA-1273 n = 3). Most patients (n = 11) received different vaccines than prior to diagnosis of neurological autoimmunity. Except for one short-lasting relapse, which responded well to steroids, re-vaccinations were well tolerated. CONCLUSIONS: In this study long-term characteristics of neurological autoimmunity encountered after SARS-CoV-2 vaccinations are defined. Outcome was favorable in most cases. Re-vaccinations were well tolerated and should be considered on an individual risk/benefit analysis.

[Cerebral venous sinus thrombosis presenting transient ischemic attack after recovery from COVID-19 with Graves' disease and IgG4-related ophthalmic disease: a case report].

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

Stroke treatment during the COVID-19 pandemic.

Studies have reported that COVID-19 is associated not only with pneumonia but also with cerebrovascular disease. Consequently, medical personnel involved in treating stroke in the emergency medicine setting have been placed in a situation that requires them to provide treatment while always remaining mindful of the possibility of COVID-19. Here, we describe the current state of stroke treatment during the COVID-19 pandemic. Four patients with stroke and concomitant COVID-19 were treated at our facility. We treated 3 patients with cerebral infarction and 1 patient with cerebral venous sinus thrombosis. All 3 patients with cerebral infarction had a poor outcome. This was attributed in part to the poor general condition of the patients due to concomitant COVID-19, as well as to the severity of the major artery occlusion and cerebral infarction. One patient with cerebral venous sinus thrombosis had a good outcome. Anticoagulant therapy was administered at our hospital and resulted in a stable clinical course. Our hospital has worked to establish an examination and treatment system that enables mechanical thrombectomy to be performed even during the COVID-19 pandemic. We devised a protocol showing the steps to be taken from initial treatment to admission to the cerebral angiography room. Our hospital was able to continue accepting requests for emergency admission thanks to the examination and treatment system we established. Up-to-date information should continue to be collected to create examination and treatment systems.

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.

Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.

To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.

Vaccine-induced immune thrombotic thrombocytopenia and patients with cancer.

Vaccines to combat SARS-CoV-2 infection and the COVID-19 pandemic were quickly developed due to significant and combined efforts by the scientific community, government agencies, and private sector pharmaceutical and biotechnology companies. Following vaccine development, which took less than a year to accomplish, randomized placebo controlled clinical trials enrolled almost 100,000 people, demonstrating efficacy and no major safety signals. Vaccination programs were started, but shortly thereafter a small number of patients with a constellation of findings including thrombosis in unusual locations, thrombocytopenia, elevated D-dimer and often low fibrinogen led another intense and concentrated scientific effort to understand this syndrome. It was recognized that this occurred within a short time following administration of adenoviral vector SARS-CoV-2 vaccines. Critical to the rapid understanding of this syndrome was prompt communication among clinicians and scientists and exchange of knowledge. Now known as vaccine-induced immune thrombotic thrombocytopenia syndrome (VITT), progress has been made in understanding the pathophysiology of the syndrome, with the development of diagnostic criteria, and most importantly therapeutic strategies needed to effectively treat this rare complication of adenoviral vector vaccination. This review will focus on the current understanding of the pathophysiology of VITT, the findings that affected patients present with, and the rational for therapies, including for patients with cancer, as prompt recognition, diagnosis, and treatment of this syndrome has resulted in a dramatic decrease in associated mortality.

Cerebral Venous Sinus Thrombosis Following COVID-19 and Otogenic Infection: A Diagnostic and Therapeutic Dilemma Followed by mRNA COVID-19 Vaccination.

IntroductionCerebral venous sinus thrombosis (CVST) is a rare neurovascular emergency that has been observed following COVID-19 infection, as well as following the use of non-mRNA COVID-19 vaccines. Case PresentationThe authors report a case of CVST in a 67-year-old woman, unvaccinated for COVID-19, who presented with acute otitis externa. It remains unclear whether the CVST was a following COVID-19 infection complication, otogenic CVST, or a combination of both. ConclusionThis case demonstrates the diagnostic and therapeutic dilemmas in managing this patient's challenging anticoagulation and antibiotic duration, as well as subsequent COVID-19 vaccination recommendations.

Ad26.COV2.S Vaccine-Induced Thrombocytopenia Leading to Dural Sinus Thrombosis and Intracranial Hemorrhage Requiring Hemicraniectomy: A Case Report and Systematic Review.

The coronavirus disease 2019 (COVID-19) pandemic has claimed nearly 5.5 million lives worldwide. Adenovirus-based vaccines are safe and effective, but they are rarely associated with vaccine-induced thrombosis and thrombocytopenia (VITT) as well as cerebral venous sinus thrombosis (CVST). We conducted a systematic literature search of intracerebral hemorrhage (ICH) secondary to CVST associated with VITT from the Ad26.COV2.S vaccine, and we present the first case of this pathology in the reviewed literature of a patient who required neurosurgical decompression. The systematic literature review was completed on December 19, 2021, by searching PubMed and Ovid for articles with primary data on CVST associated with VITT following the Ad26.COV2.S vaccine. We also specifically searched for cases that required neurosurgical intervention. Articles were independently screened by two authors, and both secondary and tertiary searches were done as well. Descriptive statistics were collected and presented in table form. Nine studies were identified that met inclusion criteria. There were no cases identified of patients who underwent neurosurgical decompression after developing this pathology. We thus present the first case in the reviewed literature of a patient who developed ICH after receiving the Ad26.COV2.S vaccine and underwent decompressive hemicraniectomy. Despite severe thrombocytopenia and prolonged intensive care, the patient was discharged to neurorehabilitation. There is a much greater risk of CVST and ICH during COVID-19 infections than from the vaccines. However, as booster vaccines are approved and widely distributed, it is critical to make prompt, accurate diagnoses of this vaccine-related complication and consider neurosurgical decompression.