key: cord-1020632-p71plr9d authors: Domingo, Ricardo A; Ramos-Fresnedo, Andres; Perez-Vega, Carlos; Tripathi, Shashwat; Pullen, Michael W.; Martinez, Jaime L.; Erben, Young M.; Meschia, James; Tawk, Rabih G. title: Cerebral Venous Thrombosis during the COVID-19 Pandemic: A Multi-Center Experience date: 2022-04-19 journal: Clin Neurol Neurosurg DOI: 10.1016/j.clineuro.2022.107256 sha: 6eaab4a68c13302792a1d06c52f510bcde0d062c doc_id: 1020632 cord_uid: p71plr9d 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. Cerebral venous thrombosis (CVT) is commonly associated with conditions such as trauma, infection, pregnancy, dehydration, leukemia, hormone replacement therapy and neoplasms. [1] [2] [3] [4] However, 30% of all CVTs are considered spontaneous. 5 Advances in diagnostic imaging techniques have led to an increased CVT incidence of 1.32-1.57/100,000 person-years. 6 Spontaneous CVT is commonly seen in young adults and may have variable clinical manifestations ranging from headaches to seizures, focal neurological deficits, and altered mental status. 3, 4 Although it may present as a benign incidental finding on imaging, severe cases can result in devastating neurological sequalae and death due to increased intracranial pressure, venous stroke, and hemorrhagic conversion. 6 Management is mainly with anticoagulant therapy with occasional need for endovascular and surgical treatment in certain cases. 5, 6 Hence, early diagnosis is paramount to minimize morbidity and mortality. COVID-19 infection has been associated with a prothrombotic state, leading to complications such as deep venous thrombosis, pulmonary emboli, and CVT. 10 Most recently, reports of patients presenting with CVT following COVID-19 vaccination have suggested a potential association between CVT and this preventive practice. [11] [12] [13] Although multiple studies have looked at CVT in COVID-19 patients [10] [11] [12] [14] [15] [16] [17] [18] [19] , the influence of COVID infection or vaccination in patients presenting with CVT and their potential manifestations is understudied. We aim to describe the clinical and radiographic characteristics, as well as management and outcomes of CVT in patients with a prior COVID infection or vaccination who were treated at our institutions during the COVID pandemic. J o u r n a l P r e -p r o o f 4 Electronic medical records of 335 consecutive adult patients with a presumed diagnosis of nonpyrogenic thrombosis of the intracranial venous system treated at our 3 main centers between March 1, 2020, and December 1, 2021 were reviewed. Inclusion criteria were as follows: 1) International Classification of Diseases (ICD) code I67.6, 163.6; 2) confirmed diagnosis of CVT by Magnetic Resonance Venography (MRV) or Computed Tomography Venography (CTV), 3) Available COVID-19 PCR test results and vaccination history. Patients with CVT due to recent trauma, cranial surgery, bacterial sinus infection, and chronic CVT were excluded (Figure 1 ). This study was approved by the Institutional Review Board #20-004849, waiving patient consents in view of its retrospective nature. Demographic and clinical data were extracted from the electronic medical records at the time of presentation with CVT. The following variables were obtained: age, sex, past medical history, vital signs at presentation (systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, heart rate, and respiration rate), presenting symptoms, Glasgow coma scale (GCS), platelet count, hypercoagulable state (included Factor V Leiden, Prothrombin gene mutation, pro-thrombotic protein deficiencies, homocystinuria, active systemic cancer, supplemental estrogen use, and antiphospholipid antibody syndrome), and use of anticoagulation or antiplatelet medication. Data on past medical history included hypertension (HTN), diabetes mellitus (DM), deep vein thrombosis (DVT), pulmonary embolus (PE), and prior stroke. Presenting symptoms included headaches, seizures, focal neurologic deficit(s), altered mental status, or asymptomatic (incidental finding on imaging). Fever was considered an oral, transtympanic, axillary or rectal temperature of C or higher recorded at least once during patient's hospitalization Radiographic variables were collected from review of available imaging of the brain vasculature (MRV or CTV). The following variables were collected: location (cortical veins, venous sinus involvement, or both), extensive thrombosis (defined as 3 or more sinuses involved), and radiographic presentation (thrombosis with or without venous stroke and hemorrhagic conversion). J o u r n a l P r e -p r o o f 5 Management and treatment details were collected from the progress and procedural notes including medical management with anticoagulation, endotracheal intubation, intravenous thrombolysis with tissue plasminogen activator (tPA), and mechanical thrombectomy. Functional outcomes were assessed at discharge and last follow-up using the modified Rankin Scale (mRS), which ranges from 0 (no symptoms) to 6 (death). Other variables included length of stay, complications during hospitalization, hemorrhagic conversion, ischemic stroke, mortality, and follow-up time. Patients were classified according to their COVID-19 association prior to diagnosis of CVT into group I (positive COVID-19 association defined as a positive COVID-19 infection that was confirmed by testing or a recent COVID-19 vaccination) or group II (negative COVID-19 association defined as no history of COVID-19 infection or vaccination); recent vaccination was considered as <30 days prior to CVT diagnosis and the date of the second dose was used to calculate the time. The extracted data from the medical records were summarized using descriptive statistics, including percentages and counts for categorical data. Fisher exact and Mann-Whitney U test were used where appropriate Significance was considered at α ≤ 5 (two-sided). R (version 3.6.0) was utilized to analyze patient data. Fifty-one patients with confirmed diagnosis of non-pyogenic, non-traumatic CVT were included in this study. Demographic and clinical characteristics at presentation are summarized in Table 1 , while management and outcomes are summarized in Table 2 , and Table 3 , respectively. Ten patients had recent history of COVID-19 infection, including 3 patients with active infection at the time of CVT diagnosis. The most common presenting symptom was headache (n=3, 30%), followed by focal neurological deficit (n=3, 30%), syncope (n=2, 20%), and seizures (n=1, 10%). One patient presented with fever corresponding to a case of active Nevertheless, we did not observe a difference in the outcomes according to sex (P = 0.41). Recent studies on COVID-19 patients suggested that CVT presents at a younger age in this population when compared to the general population, with multiple reports of CVT in COVID-19 patients younger than 40 years. 26, 27 Although no statistical significance was achieved on comparative analysis, various trends were observed: the mean age was similar between the 2 groups and patients without COVID-19 association had higher rates of comorbidities including Evaluation and management of cerebral venous thrombosis Risk factors governing the development of cerebral vein and dural sinus thrombosis after craniotomy in patients with intracranial tumors Diagnosis and management of cerebral venous thrombosis Diagnosis and treatment of cerebral venous thrombosis: a review Management and outcome of spontaneous cerebral venous sinus thrombosis in a 5-year consecutive single-institution cohort Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association Path to reopening surgery in the COVID-19 pandemic: neurosurgery experience Effects of the covid-19 pandemic on neurological diseases. 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