Endovascular treatment for vaccine-induced cerebral venous sinus thrombosis and thrombocytopenia following ChAdOx1 nCoV-19 vaccination: a report of three cases.

BACKGROUND: Vaccine-induced thrombosis and thrombocytopenia (VITT) is a rare complication following ChAdOx1 nCoV-19 vaccination. Cerebral venous sinus thrombosis (CVST) is overrepresented in VITT and is often associated with multifocal venous thromboses, concomitant hemorrhage and poor outcomes. Hitherto, endovascular treatments have not been reviewed in VITT-related CVST. METHODS: Patient records from a tertiary neurosciences center were reviewed to identify patients who had endovascular treatment for CVST in VITT. RESULTS: Patient records from 1 January 2021 to 20 July 2021 identified three patients who underwent endovascular treatment for CVST in the context of VITT. All were female and the median age was 52 years. The location of the CVST was highly variable. Two-thirds of the patients had multifocal dural sinus thromboses (sigmoid, transverse, straight and superior sagittal) as well as internal jugular vein thromboses. Intracerebral hemorrhage occurred in all patients; subarachnoid blood was noted in two of them, and intraparenchymal hemorrhage occurred in all. There was one periprocedural parenchymal extravasation which abated on temporary cessation of anticoagulation. Outcome data revealed a 90-day modified Rankin Scale (mRS) score of 2 in all cases. CONCLUSIONS: We demonstrate that endovascular treatment for VITT-associated CVST is feasible and can be safe in cases that deteriorate despite medical therapy. Extensive clot burden, concomitant hemorrhage, rapid clinical progression and persistent rises in intracranial pressure should initiate multidisciplinary team discussion for endovascular treatment in appropriate cases.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Incidence of sinus thrombosis with thrombocytopenia-A nation-wide register study.

Safe vaccination is essential for mitigation of the COVID-19 pandemic. Two adenoviral vector vaccines, ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson&Johnson/Janssen) have shown to be effective and they are distributed globally, but reports on serious cerebral venous sinus thrombosis (CVST) associated with thrombocytopenia, have emerged. Our objective was to evaluate the background incidence of CVST with thrombocytopenia and to compare it to incidences following COVID-19 vaccines. We conducted a register-based nation-wide cohort study in Finland, including all 5.5 million individuals alive in Finland, 1 Jan 2020. COVID-19 vaccinations registered in the National Vaccination Register served as the exposure. We detected CVST admissions or hospital visits recorded in the hospital discharge register from Jan 1, 2020 through April 2, 2021. We confirmed the diagnosis of CVST and thrombocytopenia (platelet count <150,000 per cubic millimeter) using radiology reports and laboratory data. By Poisson regression, we compared the baseline incidences to the risks within four weeks after COVID-19 vaccinations. Out of the 167 CVST episodes identified in the registers, 117 were confirmed as CVST, 18 of which coincided with thrombocytopenia (baseline incidence 0.18 per 28 days per million persons). We found 2 episodes of CVST with thrombocytopenia within 28 days of the first ChAdOx1 nCov-19 vaccination (among 200,397 vaccinated, aged 16 or above). No cases were found following the first mRNA vaccine dose among 782,604 vaccinated. The background incidence of CVST combined with thrombocytopenia was minuscule compared to the incidence during the weeks following the ChAdOx1 nCov-19 vaccination. Accurate estimation of the baseline incidence is essential in the critical appraisal of the benefit-risk of any vaccination program.

Case Report: Papilledema Secondary to Cerebral Venous Sinus Thrombosis after Severe COVID-19 Infection.

SIGNIFICANCE: This case highlights ocular adverse effects of a rare, potentially life-threatening complication from coronavirus disease 2019 (COVID-19). Papilledema can occur because of increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 because of an induced hypercoagulable state. PURPOSE: This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19). CASE REPORT: A 29-year-old man hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anticoagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide, there was improvement in his optic nerve edema. CONCLUSIONS: Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vision loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.

Cerebral Venous Sinus Thrombosis After a Third Dose of mRNA COVID-19 Vaccine in an Adolescent: A case report (preprint)

Background: Several effective vaccines against Coronavirus disease 2019 (COVID-19) have been developed to control the spread of the disease. A few cases of thrombosis have been reported post-vaccination, especially among young adult women immunized with viral vector-based vaccines; although pediatric cases of cerebral venous sinus thrombosis (CVST) have been rarely reported after messenger ribonucleic acid (mRNA) vaccine administration. Case presentation: Here, we report a case of CVST in a 14-year-old girl immunized with the BNT16B2b2 vaccine. Other than this recent COVID-19 vaccination, there were no precipitant risk factors in her medical history. Laboratory work-up showed low levels of protein S activity. Further research revealed no pathological gene mutation. She was treated with anticoagulant therapy and discharged with mildly impaired coordination/movement of the fingers. Conclusion: CVST may occur following a mRNA COVID-19 vaccination, even among children. Further investigations are needed to establish whether thrombotic events are merely incidental or are a complication associated with mRNA-based vaccines.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Sagittal sinus thrombosis with subarachnoid haemorrhage in a patient with COVID-19 infection.

A man in his late 50s was admitted with a 10-day history of right frontotemporal headache, left arm and leg weakness, and a sudden decline in visual acuity in the right eye. The patient had recent exposure to COVID-19 infection and tested positive for the same on admission. A CT scan of the head done on arrival demonstrated a subarachnoid haemorrhage in the right central sulcus with an underlying superior sagittal sinus thrombosis. No other known risk factors for central venous sinus thrombosis could be identified. The patient had a normal level of consciousness on admission clinically; however, he was in severe pain. A collective decision was made to administer anticoagulants to the patient with heparin after carefully deliberating the risk-to-benefit ratio of a superior sagittal thrombus with an associated subarachnoid haemorrhage. Our patient recovered and was discharged after 2 weeks on warfarin. We present this case to highlight the potential risks of hypercoagulable and neurotropic complications of COVID-19 infections, with special emphasis on cerebral venous thrombosis.

A neonatal case of cerebral venous sinus thrombosis with intrauterine onset after COVID-19 infection during pregnancy: Cause or coincidence?

Coronavirus 19 disease (COVID-19) is known to predispose patients to increased thrombotic events and the risk is higher in pregnancy which is already a hypercoagulable state. Vertical transmission of the disease during pregnancy was neglected according to data early in the pandemic, however, despite conflicting results from different studies, there is an increasing suspicion of vertical transmission with the rise of new fetal and neonatal cases and perinatal transmission can be higher than expected. An early term neonate, with the history of maternal COVID-19 infection in the start of third trimester, was diagnosed as cerebral venous sinus thrombosis and chronic hemorrhagic ischemia, with intrauterine onset.

Encephalopathy as the Only Manifestation in Simultaneous Arterial Infarct and Cerebral Venous Sinus Thrombosis in Recent COVID-19 Infection.

BACKGROUND Emerging cases of SARS-CoV-2 infection associated with cerebral thromboembolism episodes manifesting as arterial strokes or cerebral venous thrombosis have been reported. However, the co-occurrence of arterial strokes and cerebral venous thrombosis is rare. CASE REPORT We report the case of a previously healthy young patient with recent SARS-CoV-2 infection, who presented with encephalopathy. His computed tomography venography and magnetic resonance imaging of the brain showed thrombosis of the vein of Galen and straight sinus, and arterial infarcts in both hemispheres. His inflammatory markers, D-dimer levels, and coagulation profile were normal. He was started on anticoagulation and recovered well. CONCLUSIONS Concurrent arterial and venous thrombosis can happen rarely in patients with SARS-CoV-2 infection, including patients who have recently recovered from COVID-19. Cerebral thromboembolism associated with SARS-CoV-2 can present with a variety of subtle clinical manifestations, including encephalopathy without focal neurological deficits. Inflammatory markers, D-dimer levels, and coagulation profiles can be normal, especially in patients with mild infection or who have recovered from the infection. Therefore, it is important to be vigilant and recognize this clinical entity so that the diagnosis can be made and treatment can be started promptly. However, larger and prospective studies are needed to determine the clinical outcomes, therapeutic benefits, and complications of concurrent arterial stroke and cerebral venous thrombosis associated with SARS-CoV-2 infection.

Late-post-COVID-19 cerebral venous sinus thrombosis and stroke: a case report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) disease increases risk of venous thromboembolisms (VTE), primarily deep vein thrombosis and pulmonary embolism. Only a few cases of cerebral venous sinus thrombosis (CVST) in association with a COVID-19 infection have been reported and are limited to acute COVID-19 disease. Hypercoagulable conditions persist in postacute COVID-19 disease, which carries an increased risk of VTE. CASE PRESENTATION: We report a case of CVST and stroke 56 days post-COVID-19 infection presenting with an atypical clinical picture. DISCUSSION: To the best of our knowledge, this is one of the first observations of CVST in the postacute phase of COVID-19 disease. Clinicians should be aware of this potential late complication and should consider appropriate diagnostic imaging techniques in patients with COVID-19-infection history.

Management of severe cerebral venous sinus thrombosis after post-vaccination breakthrough COVID-19 infection: a case report and review of the literature (preprint)

Introduction: Neurological manifestations related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may involve both peripheral and central nervous system, including acute ischemic stroke and cerebral venous sinus thrombosis (CVST).  Case Presentation: Hereby, we present an adult patient with post-vaccination breakthrough COVID-19 infection and CVST, treated with venous mechanical thrombectomy (MT). The patient manifested continuous tonic-clonic seizures, after an insidious presentation with headache and left-sided weakness. SARS-CoV-2 testing was positive, despite fully vaccination, using two approved mRNA platforms. Factor V Leiden polymorphism was detected. The patient was initially managed with anticoagulation, followed by MT with a positive response. We provided a comparison to similar cases of COVID-19 associated CVST undergoing mechanical thrombectomy.  Conclusions: High index of suspicion and prompt diagnosis are extremely important to ensure immediate hospitalization and therapy, since CVST associated with either vaccines or COVID-19 seems to evolve rapidly and with a high mortality rate. Even a breakthrough infection may present severe vascular complications. In addition, evaluation of acquired and hereditary thrombophilia may be beneficial in acute phase, also without a previous history of thrombosis. Clinicians should start early medical treatment, and additionally consider the endovascular approach as an optimistic choice in refractory CVST related to SARS-CoV-2 infection.

Moderna, Pfizer-BioNTech, and Johnson & Johnson/Janssen Post-Covid Vaccine Hematological Adverse Events Including Cerebral Venous Sinus Thrombosis (CVST), Thrombotic Thrombocytopenia (VITT), Blood Clots, Increased Vaginal/Menstrual Bleeding and/or Miscarriage, Stillbirth Delivery, or Premature Birth.

The Centers for Disease Control (CDC) indicated in 2021 that it would monitor for possible post-COVID-19 vaccination coagulopathy adverse events (AEs).

Cavernous sinus thrombosis linked to COVID-19 infection: a case report. (preprint)

Introduction: The severity of SARS-CoV-2 virus infection is mainly related to its respiratory complications. However, it can also lead to numerous and varied thromboembolic events. Symptoms may include headache, fever, and neurological disorders. Since 2020, the clinical presentation of COVID-19 infection have become increasingly varied, leading in some cases to complex symptom associations, including numerous neurological symptoms. SARS-CoV-2 may lead to neurotropism which could reach the central nervous system and all cranial nerves. Cavernous sinus thrombosis is a rare condition, occurring as a complication of an ear, nose, and throat (ENT) or facial infection.Case presentation: A 73-year-old man without personal or family history of thrombosis, was referred to the emergency room for a sudden appearance of diplopia and ptosis, 3 days after testing positive for COVID-19 infection. An initial head CT-scan found no signs of stroke. He underwent a cerebral MRI 7 days later, which revealed a thrombosis of his right cavernous sinus. A brain CT scan follow-up 7 days later showed regression of the thrombosis with complete recanalization of the cavernous sinus. This was accompanied by a complete regression of diplopia and fever. He was discharged from the hospital 10 days after hospital admission.Conclusions In this case report, we describe a rare event of cavernous thrombophlebitis following a COVID-19 infection.

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.

Cerebral venous sinus thrombosis following Russell's viper (Daboia russelii) envenomation: A case report and review of the literature.

Snakebite is a life-threatening and often-neglected public health hazard with high chronic disability and mortality, mainly faced by rural communities in the tropics/subtropics. Stroke and neuromuscular paralysis are the most severe neurological complications. However, cerebral venous sinus thrombosis has rarely been reported among cerebrovascular complications. We report a previously healthy middle-aged Indian woman who developed cerebral venous sinus thrombosis preceded by features of disseminated bleeding diathesis following Russell's viper bite. The cerebral venous sinus thrombosis was diagnosed by magnetic resonance imaging. The patient responded well to treatment with antivenom and subcutaneous enoxaparin and had no demonstrable neurological deficits at three months of follow-up.

SARS-CoV-2 vaccination associated venous sinus thrombosis in three patients.

INTRODUCTION: There is increasing evidence that vaccinations against the severe acquired respiratory syndrome coronavirus type-2 (SARS-CoV-2) virus can be followed by venous sinus thrombosis (VST). Here we report on three patients who developed VST shortly after SARS-CoV-2 vaccinations. CASE SERIES: An 80-year-old male, a 58-year-old male, and a 34-year-old female developed VST 14 to 24 days after the first dose of an mRNA-based SARS-CoV-2 vaccine. All three patients profited from analgesics, heparinisation, and oral anticoagulation, but made only an incomplete recovery at the time of discharge. Arguments for a causal relationship are: VST was time-linked to vaccination in the three patients; VST was previously reported after SARS-CoV-2 vaccination; SARS-CoV-2 infections can be complicated by VST; and SARS-CoV-2 can be associated with hypercoagulability. The fact that no hypercoagulability occurred in a pilot study after SARS-CoV-2 vaccination and that there has been no evidence of an increased prevalence/incidence of VST after vaccination since the introduction of the SARS-CoV-2 vaccination speak against a causal relationship. CONCLUSIONS: SARS-CoV-2 vaccinations can occasionally be followed by a VST. There are more arguments for than against a causal relationship.

High Incidence and Unique Features of Cerebral Venous Sinus Thrombosis in Hospitalized Patients With COVID-19 Infection.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) secondary to vaccine-induced thrombotic thrombocytopenia is an extremely rare side effect of adenovirus-based COVID-19 vaccines. CVST incidence associated with COVID-19 itself has not been widely reported. We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We analyzed de-identified electronic medical records of a retrospective cohort of patients admitted with COVID-19 to >200 hospitals between March 2020 and March 2021. We used International Classification of Diseases, Tenth Revision codes and natural language processing extracts to identify patients with a new CVST diagnosis during COVID-19 hospitalization. The primary outcome was CVST incidence in hospitalized, COVID-19-positive patients. Secondary outcomes included CVST incidence and mortality. Incidence rates were calculated using the DerSimonian-Laird estimator method. RESULTS: Ninety-one thousand seven hundred twenty-seven patients were evaluated; 22 had new CVST diagnoses by electronic medical record review. CVST incidence in the hospitalized COVID-19 cohort was 231 per 1 000 000 person-years (95% CI, 152.1-350.8). Females<50 had the highest incidence overall (males <50: 378.4 [142-1008.2]; females<50: 796.5 [428.6-1480.4]). In patients ≥50 years old, males had a higher estimated CVST incidence (males≥50: 130.5 [54.3-313.6]; females≥50: 88.8 [28.6-275.2]). Older patients (45.5% of patients ≥50 versus 0% of <50 years of age, P=0.012) and males (44.4% of males versus 7.7% of females, P=0.023) were more likely to die in hospital. CONCLUSIONS: CVST incidence in COVID-19-positive hospitalized patients is high. Advanced age and male gender were associated with likelihood of death in hospital; further studies are required to confirm these findings.