Fulminant Extra- And Intracranial Arteriovenous Thrombosis And Non-aneurysmal Subarachnoid Hemorrhage Following COVID-19 Infection.

PURPOSE: Coronavirus disease of 2019 (COVID-19) is associated with increased risk of stroke and intracranial hemorrhage. This first report of fulminant panvascular arteriovenous thrombosis with subarachnoid hemorrhage (SAH) in a post-COVID-19 infection is attributed to extensive arteriovenous inflammation leading to arterial rupture following vasculitis. CASE REPORT: We report a rare case of extensive extra- and intra-cranial cerebral arteriovenous thrombosis following COVID-19 infection, presenting as fatal non-aneurysmal subarachnoid hemorrhage. The clinical course, biochemical and radiological evaluation is discussed. The other possible etiological differentials which were analysed and ruled out during case management are also detailed. CONCLUSION: A high degree of suspicion for COVID-19 induced coagulopathy leading to extensive non- aneurysmal, non-hemispheric SAH and malignant intracranial hypertension should be entertained. Our experience and previous reports on non-aneurysmal SAH in such patients show a poor prognosis.

SARS-CoV-2 Possible Etiology of Cerebral Venous Thrombosis in a Teenager: Case Report and Review of Literature.

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers.

MRI-negative myelitis associated with cerebral venous thrombosis after COVID-19 infection.

Transverse myelitis and cerebral venous thrombosis represent some of the described neurological complications of coronavirus disease. A woman in her early 30s presented with headache, left-sided sensory symptoms and voiding difficulty. The patient also reported dry cough, fever, nasal congestion, anosmia and ageusia 2 weeks before presentation. The clinical examination showed sensory disturbances on the left side of the body, starting from the lower abdomen and extending to the left leg, which was consistent with transverse myelitis. The laboratory assessment confirmed a previous infection with coronavirus disease and excluded autoimmune entities. Radiological investigations revealed left transverse sinus thrombosis with no spinal cord abnormalities. The treatment was started with therapeutic anticoagulation and intravenous high-dose steroids. The patient showed significant improvement, and the neurological deficits resolved after 3 months. This is the first documented case of imaging-negative myelitis associated with cerebral venous thrombosis after coronavirus disease.

[Cerebral venous thrombosis associated with COVID-19]. / Tserebral'nye venoznye trombozy, assotsiirovannye s COVID-19.

The literature reports that cerebral venous thrombosis (CVT) develops in 1-1.5% of patients with COVID-19. Recently, a new syndrome named vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described. VITT is a rare side-effect of COVID-19 vaccination that also causes CVT. The article presents an overview of the above problem and a clinical case of a patient with CVT that developed within a month after the first component of the Sputnik V vaccination and COVID-19.

Concomitant Guillain-Barré syndrome and cerebral venous thrombosis complicating a SARS-CoV-2 infection: a case report.

Cerebral venous thrombosis associated to acute inflammatory axonal polyneuropathy during infection with SARS-CoV-2 (coronavirus-2) is unusual. We describe the case of a 66-year-old patient with typical clinical and electrophysiological criteria of acute axonal motor neuropathy, who was positive for SARS-CoV-2. The symptoms started with fever associated with respiratory symptoms, and complicated one week later by headaches, and general weakness. The examination showed bilateral peripheral facial palsy, predominantly proximal tetraparesis, and areflexia with tingling of limbs were found. The whole was concomitant with the diagnosis of an acute polyradiculoneuropathy. Electrophysiologic evaluation confirmed the diagnosis. Cerebrospinal fluid examination showed albuminocytologic dissociation, and brain imaging revealed sigmoid sinus thrombophlebitis. Neurological manifestations improved during treatment with plasma exchange and anticoagulants. Our case draws attention to the occurrence of cerebral venous thrombosis and Guillain-Barré syndrome (GBS) in patients with COVID-19. The neuro-inflammation induced by the systemic immune response to infection, can lead to neurological manifestations. Further studies should be conducted on the full clinical spectrum of patients with COVID-19 with neurological symptoms.

Inflammation in Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that impairs people's wellbeing and quality of life. Inflammation is considered to play an important role in CVT initiation and progression. Several studies have reported the important role of leukocytes, proinflammatory cytokines, and adherence molecules in the CVT-related inflammatory process. Moreover, inflammatory factors exacerbate CVT-induced brain tissue injury leading to poor prognosis. Based on clinical observations, emerging evidence shows that peripheral blood inflammatory biomarkers-especially neutrophil-to-lymphocyte ratio (NLR) and lymphocyte count-are correlated with CVT [mean difference (MD) (95%CI), 0.74 (0.11, 1.38), p = 0.02 and -0.29 (-0.51, -0.06), p = 0.01, respectively]. Moreover, increased NLR and systemic immune-inflammation index (SII) portend poor patient outcomes. Evidence accumulated since the outbreak of coronavirus disease-19 (COVID-19) indicates that COVID-19 infection and COVID-19 vaccine can induce CVT through inflammatory reactions. Given the poor understanding of the association between inflammation and CVT, many conundrums remain unsolved. Further investigations are needed to elucidate the exact relationship between inflammation and CVT in the future.

Cerebral venous thrombosis during the COVID-19 Pandemic: A multi-center experience.

OBJECTIVE: To describe the clinical characteristics and outcomes of CVT in patients with history of recent COVID-19 infection or vaccination. METHODS: We reviewed demographic, clinical, and radiographic characteristics of non-pyrogenic, non-traumatic CVT cases at our multi-center institution between March 2020 and December 2021. Patients were grouped according to their history of recent COVID-19 infection or vaccination into group-I (+COVID-19 association) and group-II (-COVID-19 association). RESULTS: Fifty-one patients with CVT were included, of which 14 (27.4%) had a positive COVID-19 association: 10 with infection and 4 with mRNA-COVID-vaccine. Nine patients in group-I had COVID-19 infection or vaccine within 30 days of CVT diagnosis, including 3 patients with active infection at the time of CVT diagnosis. Half of the patients in group-I (n = 7,50.0%) and 32.4% (n = 12) of group-II were male, and mean age was 52.6 years in group-I and 51.4 years in group-II. Fever at presentation was noted in one patient who had active COVID infection (I=1 (7.1%), II= 0 (0%)). Higher rates of comorbidities were observed in group-II: hypertension (I= 2 (14.3%), II= 13 (35.1%)), deep venous thrombosis(I=1(7.1%), II= 10 (27.0%)), pulmonary emboli (I=1(7.1%), II= 8(21.6%)), or stroke(I=0(0%), II= 6(16.4%)). Three patients had thrombocytopenia at the time of CVT diagnosis (5.4%) and most patients (n = 37, 72.5%) were treated medically with anticoagulation. Complication rate during hospitalization was 17.6% (n = 6), and no mortality was noted. CONCLUSION: Twenty-seven percent of CVT patients were associated with COVID-19 infection or vaccination, and the majority presented within 30 days of infection/vaccination.

Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore.

Importance: Reports of cerebral venous thrombosis (CVT) after messenger RNA (mRNA)-based SARS-CoV-2 vaccination has caused safety concerns, but CVT is also known to occur after SARS-CoV-2 infection. Comparing the relative incidence of CVT after infection vs vaccination may provide a better perspective of this complication. Objective: To compare the incidence rates and clinical characteristics of CVT following either SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Design, Setting, and Participants: Between January 23, 2020, and August 3, 2021, this observational cohort study was conducted at all public acute hospitals in Singapore, where patients hospitalized with CVT within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) were identified. Diagnosis of SARS-CoV-2 infection was based on quantitative reverse transcription-polymerase chain reaction or positive serology. National SARS-CoV-2 infection data were obtained from the National Centre for Infectious Disease, Singapore, and vaccination data were obtained from the National Immunisation Registry, Singapore. Exposures: SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Main Outcomes and Measures: Clinical characteristics, crude incidence rate (IR), and incidence rate ratio (IRR) of CVT after SARS-CoV-2 infection and after mRNA SARS-CoV-2 vaccination. Results: Among 62 447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58 989 (94.5%) were male; the median (range) age was 34 (0-102) years; 6 CVT cases were identified (all were male; median [range] age was 33.5 [27-40] years). Among 3 006 662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1 626 623 (54.1%) were male; the median (range) age was 50 (12-121) years; 9 CVT cases were identified (7 male individuals [77.8%]; median [range] age: 60 [46-76] years). The crude IR of CVT after SARS-CoV-2 infections was 83.3 per 100 000 person-years (95% CI, 30.6-181.2 per 100 000 person-years) and 2.59 per 100 000 person-years (95% CI, 1.19-4.92 per 100 000 person-years) after mRNA-based SARS-CoV-2 vaccination. Six (66.7%) received BNT162b2 (Pfizer-BioNTech) vaccine and 3 (33.3%) received mRNA-1273 (Moderna) vaccine. The crude IRR of CVT hospitalizations with SARS-CoV-2 infection compared with those who received mRNA SARS-CoV-2 vaccination was 32.1 (95% CI, 9.40-101; P < .001). Conclusions and Relevance: The incidence rate of CVT after SARS-CoV-2 infection was significantly higher compared with after mRNA-based SARS-CoV-2 vaccination. CVT remained rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety.

Neonatal Cerebral Venous Thrombosis following Maternal SARS-CoV-2 Infection in Pregnancy.

A possible consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the development of an exacerbated thrombophilic status, and cerebral venous thrombosis (CVT) is a rare but possible complication of SARS-CoV-2 infection reported both in adults and in children. The present case report describes the clinical course of a term neonate showing extended CVT of unclear origin, whose mother had developed SARS-CoV-2 infection during the third trimester of pregnancy. We speculate that the prothrombotic status induced by maternal SARS-CoV-2 infection may have played a pathophysiological role in the development of such severe neonatal complication. Further investigations are required to confirm such hypothesis.

First Report of Cerebral Venous Thrombosis Following Inactivated-Virus Covid Vaccination (Sinopharm and Sinovac).

Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease, which has been reported with covid infection as well as covid vaccines, particularly AstraZeneca and Janssen vaccines. We present four consecutive cases of CVT after receiving either Sinopharm or Sinovac vaccine, both of which are composed of an inactivated-virus. All the patients recovered well with anticoagulation and discharged with a good functional outcome. This is the first case series reporting CVT following the administration of these vaccines.

Brain venography performance following the pause of Ad.26.COV2.S COVID-19 vaccine administration.

Cases of cerebral venous thrombosis (CVT) associated with vaccine induced thrombotic thrombocytopenia (VITT) were reported following administration of the adenoviral vector COVID-19 vaccines, resulting in a pause in Ad.26.COV2.S vaccine administration in the United States, beginning on April 14, 2021. We aimed to quantify and characterize an anticipated increase in brain venograms performed in response to this pause. Brain venogram cases were retrospectively identified during the three-week period following the vaccine pause and during the same calendar period in 2019. For venograms performed in 2021, we compared COVID vaccinated to unvaccinated patients. There was a 262% increase in venograms performed between 2019 (n = 26) and 2021 (n = 94), compared to only a 19% increase in all radiologic studies. Fifty-seven percent of patients in 2021 had a history of COVID-19 vaccination, with the majority being Ad.26.COV2.S. All patients diagnosed with CVT were unvaccinated. COVID vaccinated patients lacked platelet or D-dimer measurements consistent with VITT. Significantly more vaccinated versus unvaccinated patients had a headache (94% vs 70%, p = 0.0014), but otherwise lacked compelling CVT presentations, such as decreased/altered consciousness (7% vs 23%, p = 0.036), neurologic deficit (28% vs 48%, p = 0.049), and current/recent pregnancy (2% vs 28%, p = 0.0003). We found a dramatic increase in brain venograms performed following publicity of rare COVID-19 vaccine associated CVT cases, with no CVTs identified in vaccinated patients. Clinicians should carefully consider if brain venogram performance is indicated in COVID-19 vaccinated patients lacking thrombocytopenia and D-dimer elevation, especially without other compelling CVT risk factors or symptoms.

Cerebral venous thrombosis and myeloproliferative neoplasms: A three-center study of 74 consecutive cases.

The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations prompted the current retrospective review of 74 cases of CVT (median age = 44 years, range 15-85; 61% females) associated with myeloproliferative neoplasms (MPNs), seen at the Mayo Clinic, Catholic University of Rome, and University of Florence, between 1991 and 2021. Disease-specific frequencies were 1.3% (39/2893), 1.2% (21/1811) and 0.2% (3/1888) for essential thrombocythemia, polycythemia vera and primary myelofibrosis, respectively. Cerebral venous thrombosis occurred either prior to (n = 20, 27%), at (n = 32, 44%) or after (n = 22) MPN diagnosis. A total of 72% of patients presented with headaches. Transverse (51%), sagittal (43%) and sigmoid sinuses (35%) were involved with central nervous system hemorrhage noted in 10 (14%) patients. In all, 91% of tested patients harbored JAK2V617F. An underlying thrombophilic condition was identified in 19 (31%) cases and history of thrombosis in 10 (14%). Treatment for CVT included systemic anticoagulation alone (n = 27) or in conjunction with aspirin (n = 24), cytoreductive therapy (n = 14), or both (n = 9). At a median follow-up of 5.1 years (range 0.1-28.6), recurrent CVT was documented in three (4%) patients while recurrent arterial and venous thromboses and major hemorrhage were recorded in 11%, 9% and 14%, respectively. Follow-up neurological assessment revealed headaches (n = 9), vision loss (n = 1) and cognitive impairment (n = 1). The current study lends clarity to MPN-associated CVT and highlights its close association with JAK2V617F, younger age and female gender. Clinical features that distinguish COVID vaccine-related CVT from MPN-associated CVT include, in the latter, lower likelihood of concurrent venous thromboses and intracerebral hemorrhage; as a result, MPN-associated CVT was not fatal.

Concerning the unexpected prothrombotic state following some coronavirus disease 2019 vaccines.

Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5--14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford-AstraZeneca vaccine (and probably by Janssen/Johnson & Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccine-induced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome.

Coronavirus disease (COVID-19) complicated by rhino-orbital-cerebral mucormycosis presenting with neurovascular thrombosis: a case report and review of literature.

Among the ever-increasing literature of the coronavirus disease 2019 (COVID-19), there have been reports on several complications in association with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), such as secondary bacterial and fungal infections. We report a 61-year-old woman with a past history of diabetes mellitus who presented to our hospital suffering from COVID-19 infection. During the course of her hospitalization, the patient developed chemosis and proptosis in both eyes, ultimately leading to a diagnosis of invasive rhino-orbital-cerebral mucormycosis and cerebrovascular thrombosis. This study strengthens the possible association between the occurrence of COVID-19 and invasive mucormycosis infection, providing new impetus for further investigations to substantiate this correlation.

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.