A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis.

BACKGROUND: To analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). METHODS: This is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. RESULTS: A total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. CONCLUSIONS: CSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

Sex Differences and Clinical Outcomes of Patients with Coronavirus Disease 2019 Infection and Cerebral Venous Sinus Thrombosis: A Systematic Review.

Cerebral venous sinus thrombosis (CVST) is a rare neurovascular condition that has been observed in individuals with coronavirus disease 2019 (COVID-19). This systematic review aimed to explore the sex differences and characteristics of concurrent COVID-19 and CVST cases. A total of 212 CVST patients were included in the study. Women with CVST had a slightly higher mean age compared to men (47.359 years vs 46.08 years). Women were more likely to report symptoms such as fever (56.1%) and decreased sense of smell or taste (71.4%), while men more frequently experienced nausea or vomiting (55.6%), headache (62.9%), and seizures (72%). Notably, current smokers, who were predominantly men, had a higher occurrence of CVST. On the other hand, women had a higher likelihood of CVST risk factors such as oral contraceptive pill (OCP) use and autoimmune diseases. Treatment approaches also showed sex-based differences. Unfractionated heparin was administered more often to women with CVST (63.2%). The in-hospital mortality rate for CVST patients was 21.3%, with men having a significantly higher mortality rate than women (65.2% vs 34.8%, P = .027). Survival analysis revealed that factors such as smoking history, diabetes mellitus, hypertension, OCP use, COVID-19 symptoms, CVST symptoms, and the need for intubation significantly influenced survival outcomes. Understanding these sex differences in COVID-19-related CVST is crucial for accurate diagnosis and effective management, ultimately leading to improved patient outcomes. Our findings highlight the importance of considering sex as a factor in the evaluation and treatment of individuals with COVID-19 and concurrent CVST.

[The clinical characteristics of neutrophil extracellular trap in patients with severe cerebral venous sinus thrombosis and its prognostic value in acute and subacute patients].

Objective: To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. Methods: This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (P<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (P<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients (P values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%CI: 0.638~0.962, P=0.032), the best cut-off value was 13.5 µg/L, the sensitivity was 100%, and the specificity was 58.8%. Conclusions: A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Full sample analysis of cerebral venous sinus thrombosis in ophthalmology inpatients.

PURPOSE: We hope that by analyzing the clinical features of cerebral venous sinus thrombosis (CVST), we can help ophthalmologists reduce misdiagnosis or delayed diagnosis. DESIGN: We evaluated 47 patients with CVST in terms of clinical manifestations. METHODS: All cases were analyzed in terms of risk factors, clinical symptoms, ophthalmic examination, imaging examination and lumbar puncture. RESULTS: The body mass indices (BMIs) of 41 patients (87.2%; 95% CI, 77.7-96.8%) were≥24, which is overweight by Chinese standards. There were 22 patients (46.8%; 95% CI, 32.5-61.1%) with BMIs≥28, who were considered obese. Thirteen were hypertensive (27.7%; 95% CI, 14.9-40.5%). The initial symptoms included blurred vision (23, 48.9%; 95% CI, 34.6-63.2%), amaurosis fugax (13, 27.7%; 95% CI, 14.9-40.5%), headache (11 patients, 23.4%; 95% CI, 11.3-35.5%), dizziness (3, 6.4%; 95% CI, -0.6-13.4%), and bilateral diplopia (3, 6.4%; 95% CI, -0.6-13.4%). There were 9 patients (9, 19.2%; 95% CI, 7.9-30.4%) with blindness, 23 patients (48.9%; 95% CI, 34.6-63.2%) with pupillary abnormalities, and 40 patients (85.1%; 95% CI, 74.9-95.2%) with papilledema. Forty-three of the 45 patients who successfully underwent a routine lumbar puncture showed high intracranial pressure (91.7%; 95.6% CI, 89.6-101.6%). Finally, two cases are reported in greater detail for illustrative purposes. CONCLUSION: The main reasons interfering with the diagnosis of CVST might be its nonspecific ocular symptoms and the physicians' clinical thought process being limited to the scope of common ophthalmological diseases.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.

Role of Decompressive Craniectomy in the Treatment of Malignant Cerebral Venous Sinus Thrombosis: A Single Center Consecutive Case Series Study in China.

OBJECTIVE: Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST. METHODS: Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months. RESULTS: In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23-63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0-1), 2 (14.29%) patients had moderate disability (mRS 2-3), and 5 (35.71%) patients had severe disability (mRS 4-5). CONCLUSIONS: Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL).

Thrombosis and Bleeding in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: A Systematic Review of Published Cases.

INTRODUCTION: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic reaction to COVID-19 (coronavirus disease 2019) adenoviral vector vaccines. Its distinct bleeding and thrombotic patterns compared with other platelet consumptive disorders remain unclear. METHODS: We performed a systematic review of the literature (PubMed and Embase) up to July 31, 2022, including case reports and case series providing nonaggregate data of VITT patients. Accurate VITT diagnosis required fulfillment of the following criteria: (1) endorsement by the authors, (2) consistent vaccine type and timing, (3) presence of thrombocytopenia and thrombosis, (4) detection of anti-platelet factor 4 antibodies. Data are presented as frequencies with 95% confidence intervals (CIs) calculated with the exact binomial method. RESULTS: We retrieved 143 eligible studies, describing 366 patients. Of 647 thrombotic events, 53% (95% CI: 49-56) were venous thromboses at unusual sites and 30% (95% CI: 27-34) were cerebral venous sinus thromboses (CVSTs). The ratio of venous-to-arterial events was 4.1. Thromboses in most sites were associated with at least another thrombotic event, with the exception of CVST and CNS arterial thrombosis (isolated in 49 and 39% of cases, respectively). Bleeding occurred in 36% (95% CI: 31-41) of patients; 68% (95% CI: 59-75) of bleeding events were intracranial hemorrhages (ICHs). Overall mortality was 24% (95% CI: 19-29), and 77% (95% CI: 58-90) in patients with isolated CVST complicated by ICH. CONCLUSION: VITT displays a venous-to-arterial thrombosis ratio comparable to heparin-induced thrombocytopenia. However, VITT is characterized by a higher prevalence of CVST and ICH, which contribute to the increased bleeding frequency and mortality.

Profile and Outcome of Prospective Non-Septic Lateral Sinus Thrombosis Patients from a Stroke Unit of a Developing Country.

Background: Due to effective treatment of middle ear infections there is a change in etiologies causing lateral sinus thrombosis (LST) and outcome. There is a paucity of literature describing homogenous group of patients with nonseptic LST (NS-LST). Objective: To describe the clinical profile, risk factors, outcome of patients of NS-LST seen at a single center from South India. Methods and Materials: Prospective, observational study of 100 patients of NS-LST patients, diagnosed by magnetic resonance imaging (MRI) seen at the stroke unit. Results: During 2 years, 100 patients of NS-LST (isolated: combined: 27:73) (male: female: 44:56), mean age: 31.45 ± 11.13 years, were seen. Subacute presentation (74%) with headache, seizures, focal deficits, and features of raised intracranial pressure were presenting features. Hyperhomocysteinemia (61%), anemia (57%), postpartum state (41%), OCP use (37%), and low VitB12 (32%) were commonly seen risk factors. Imaging with MRI compared withcomputerized tomography (CT) had better diagnostic sensitivity (100% vs. 67%), detection of parenchymal (81% vs. 67%)/hemorrhagic (79% vs. 74%) lesions, and cortical vein thrombosis (31% vs. 15.46%). Treatment with anticoagulation and supportive therapy resulted in good outcome (mRS (0-2)) at 3 months in 81%.There were four deaths, all during admission (one - isolated, three - combined) and 11 patients underwent decompressive surgery. Patients with low GCS level of sensoriumat admission, hemiparesis, combined LST, cerebellar involvement, and decompressive craniectomy had a poor outcome. Conclusion: This single-center large cohort study of NS-LST patients brings out the clinical features, risk factors (peculiar to developing countries), and the superiority of MRI in the diagnosis. Majority of patients have good outcome, with low mortality with 10% requiring decompressive surgery.

[Clinical analysis of 11 cases of otogenic intracranial complications treated by multidisciplinary collaboration].

Objective:To analyze the clinical diagnosis, treatment ，and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University（Qingdao） from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.

Translabyrinthine Craniotomy Is Associated with Higher Risk of Asymptomatic Dural Venous Sinus Thrombosis in Vestibular Schwannoma Resection.

OBJECTIVE: Characterize the incidence, risk factors, and patient outcomes of dural venous sinus thrombosis identified on postoperative imaging after retrosigmoid or translabyrinthine craniotomy for vestibular schwannoma resection. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary academic referral center. PATIENTS: Eighty-one patients 19 to 82 years of age with vestibular schwannomas, 58% female. INTERVENTIONS: Retrosigmoid or translabyrinthine craniotomy with postoperative magnetic resonance imaging/magnetic resonance venography. MAIN OUTCOME MEASURES: Association between operative approach, age, sex, body mass index, tumor size, dominant sinus, operative time, laterality, and perioperative cerebrospinal fluid (CSF) leaks with rate of thrombosis. RESULTS: Translabyrinthine craniotomy was associated with the highest relative risk of thrombosis (odds ratios [OR] = 19.82, 95% confidence interval [CI] = 1.75-224, p = 0.007), followed by male sex (OR = 5.53, 95% CI = 1.63-18.8, p = 0.035). Other patient and demographic risk factors were not associated with increased rates of dural venous thrombosis, nor was there an association with postoperative CSF leak. 81% (25/31) of thrombi had resolved within 3 years of surgery. CONCLUSIONS: Translabyrinthine approach and male sex most strongly predicted postoperative dural venous thrombosis after postauricular craniotomy for vestibular schwannoma resection. PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: Better understanding of risk factors and management of dural venous thrombosis after vestibular schwannoma surgery. LEARNING OBJECTIVE: Characterize clinically significant risk factors for dural venous thrombosis in vestibular schwannoma surgery. DESIRED RESULT: Identification of patient and operative risk factors for dural venous thrombosis. LEVEL OF EVIDENCE: III. INDICATE IRB OR IACUC: Exempt.

Dynamic Evolution of Catatonia in the Context of Cerebral Venous Sinus Thrombosis.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2023;25(4):22f03471. Author affiliations are listed at the end of this article.

Post-operative segmental cerebral venous sinus thrombosis: risk factors, clinical implications, and therapeutic considerations.

Cerebral venous sinus thromboses (CVSTs) are rare complications of neurosurgical interventions and their management remains controversial as most of cases appear clinically silent. Here, we analyzed our institutional series of patients with CVSTs evaluating clinical and neuroradiological characteristics, risk factors, and outcome. From the analysis of our institutional PACS, we collected a total of 59 patients showing postoperative CVSTs after supratentorial or infratentorial craniotomies. For every patient, we collected demographics and relevant clinical and laboratory data. Details on thrombosis trend were retrieved and compared along the serial radiological assessment. A supratentorial craniotomy was performed in 57.6% of cases, an infratentorial in 37.3%, while the remaining were a single cases of trans-sphenoidal and neck surgery (1.7%, respectively). A sinus infiltration was present in almost a quarter of patients, and in 52.5% of cases the thrombosed sinus was exposed during the craniotomy. Radiological signs of CVST were evident in 32.2% of patients, but only 8.5% of them developed a hemorrhagic infarct. CVST-related symptoms were complained by 13 patients (22%), but these were minor symptoms in about 90%, and only 10% experienced hemiparesis or impaired consciousness. The majority of patients (78%) remained completely asymptomatic along the follow-up. Risk factors for symptoms occurrence were interruption of preoperative anticoagulants, infratentorial sinuses involvement and evidence of vasogenic edema and venous infarction. Overall, a good outcome defined mRS 0-2 was observed in about 88% of patients at follow-up. CVST is a complication of surgical approaches in proximity of dural venous sinuses. CVST usually does not show progression and courses uneventfully in the vast majority of cases. The systematic use of post-operative anticoagulants seems to not significantly influence its clinical and radiological outcome.

Antibodies against platelet factor 4 and the risk of cerebral venous sinus thrombosis in patients with vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector-based vaccines against SARS-CoV-2. This syndrome is caused by antibodies against platelet factor 4 (PF4; CXCL4) that lead to platelet activation and is characterized by thrombocytopenia and thrombosis in unusual locations, including cerebral venous sinus thrombosis (CVST). VITT can be classified based on anti-PF4 antibodies properties in vitro: those that require PF4 to activate platelets (PF4-dependent) and those that can activate platelets without additional PF4 (PF4-independent) in the serotonin release assay. OBJECTIVES: We aim to characterize the relationship of VITT platelet-activating profiles with CVST. METHODS: We conducted a retrospective cohort study involving patients with confirmed VITT who were tested between March and June 2021. Data were collected with an anonymized form and cases were identified as VITT with high clinical suspicion according to platelet activation assays. Anti-PF4 antibody binding regions on PF4 were further characterized with alanine scanning mutagenesis. RESULTS: Of the patients with confirmed VITT (n = 39), 17 (43.6%) had PF4-dependent antibodies and 22 (56.4%) had PF4-independent antibodies. CVST occurred almost exclusively in PF4-independent patients (11 of 22 vs 1 of 17; P < .05). Additionally, PF4-independent antibodies bound to 2 distinct epitopes on PF4, the heparin-binding region and a site typical for heparin-induced thrombocytopenia antibodies, whereas PF4-dependent antibodies bound to only the heparin-binding region. CONCLUSION: These findings suggest that VITT antibodies that cause PF4-independent platelet activation represent a unique subset of patients more likely to be associated with CVST, possibly due to the 2 different types of anti-PF4 antibodies.

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries.

BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

Características de la trombosis venosa cerebral en pacientes de dos hospitales universitarios de Colombia en el período 2018-2020 / Characteristics of cerebral venous thrombosis in patients from two university hospitals in Colombia between 2018-2020

Introducción. La trombosis venosa cerebral es una causa infrecuente de enfermedad cerebrovascular que viene en aumento a nivel mundial. A pesar de ello, actualmente, en Colombia no se cuenta con estudios suficientes que nos permitan caracterizar epidemiológicamente la enfermedad en nuestra población para identificar los factores de riesgo y las complicaciones más frecuentes en nuestro medio. Objetivo. Describir las características clínicas, demográficas y radiológicas, y los factores de riesgo de una serie de pacientes con trombosis venosa cerebral de dos hospitales de Colombia. Materiales y métodos. Es un estudio descriptivo retrospectivo de pacientes hospitalizados, atendidos en el servicio de neurología de dos hospitales de Bogotá desde diciembre de 2018 hasta diciembre del 2020. Resultados. Se incluyeron 33 pacientes. Las frecuencias más altas correspondieron a mujeres en edad fértil, en puerperio (n=7; 33,3 %) y pacientes con patologías autoinmunes (n=10; 30,3 %). El síntoma inicial más común fue la cefalea (n=31; 93,9 %), seguido de focalización neurológica (n=9; 27,2%) y crisis epiléptica (n=8; 24,2 %). El 51 % (n=17) de los pacientes tuvo un examen físico normal. El infarto venoso cerebral se presentó en el 21,1 % (n=7), la hemorragia subaracnoidea en el 12,1 % (n=4) y el hematoma intraparenquimatoso en el 9 % (n=3) del total de pacientes. El 60,6 % (n=20) quedó con nivel independiente en la escala funcional de Barthel. Ningún paciente falleció. Conclusiones. Se encontraron características sociodemográficas, clínicas y radiológicas similares a lo reportado en la literatura mundial. Con respecto a las diferencias, se encontró en nuestro estudio compromiso de la circulación venosa cerebral profunda en un porcentaje ligeramente mayor a lo descrito, pero sin aumento de complicaciones, ni mortalidad.

Introduction. Cerebral venous thrombosis is an uncommon cause of cerebrovascular disease, which has been increasing worldwide. In Colombia, there are not enough recent studies that allow us to determine epidemiological characteristics of the disease in our population to identify more frequent risk factors and complications according to our living conditions. Objective. To describe clinical, demographic, and radiographic characteristics, and risk factors in a cohort of patients with cerebral venous thrombosis attended at two hospitals in Colombia. Materials and methods. Retrospective descriptive study with patients treated in the hospitalization neurology service of two hospitals in Bogotá, Colombia from December 2018 to December 2020. Results. Thirty-three patients were included. There was a higher incidence of cerebral venous thrombosis in women of childbearing age in the puerperium (n=7; 33.3%) and associated with autoimmune diseases (n=10; 30.3%). The most common initial symptom was headache (n=31; 93.9 %), followed by neurological focal signs (n=9; 27.2%) and seizures (n=8; 24.2%). Fifty-one percent (n=17) of the patients had a normal physical examination. Cerebral venous infarction occurred in 21.1 % (n=7), subarachnoid hemorrhage in 12.1 % (n=4), and intraparenchymal hematoma in 9 % (n=3) of all the patients. Sixty-point six percent (n=20) of the patients had a total independent Barthel functional scale. None of those died. Conclusions. We found similar sociodemographic, clinical, and radiography characteristics to those reported in the world literature. Regarding the differences, deep cerebral venous circulation was higher than that described in previous studies but without complications increase or mortality.

Investigation of anti-PF4 versus anti-PF4/heparin reactivity using fluid-phase enzyme immunoassay for 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia (HIT), autoimmune HIT, vaccine-induced immune thrombotic thrombocytopenia, and spontaneous HIT.

BACKGROUND: Four platelet-activating anti-platelet factor 4 (PF4) disorders have been recognized: classic heparin-induced thrombocytopenia (cHIT), autoimmune heparin-induced thrombocytopenia (aHIT), spontaneous heparin-induced thrombocytopenia (SpHIT), and vaccine-induced immune thrombotic thrombocytopenia (VITT). All test immunoglobulin G (IgG) positive using solid-phase enzyme immunoassay (solid-EIA) against PF4/heparin (PF4/H) and/or PF4 alone. Fluid-phase EIA (fluid-EIA) should better discriminate between anti-PF4 and anti-PF4/H antibodies since conformationally altered PF4 bound to solid phase is avoided. OBJECTIVES: To compare anti-PF4 vs anti-PF4/H antibody profiles for anti-PF4 disorders using solid- and fluid-EIA. METHODS: We developed a novel fluid-EIA to measure anti-PF4 vs anti-PF4/H antibodies. RESULTS: Using fluid-EIA, 27 of 27 (100%) cHIT sera tested IgG positive with PF4/H, but only 4 of 27 (14.8%) tested positive against PF4 alone; all 27 exhibited heparin-enhanced binding. In contrast, 17 of 17 (100%) VITT sera tested IgG positive against PF4 alone, with markedly reduced binding against PF4/H; this distinct VITT antibody profile was not evident using solid-EIA. All 15 aHIT sera and all 11 SpHIT sera tested IgG positive against PF4 alone, with variable reactivity in PF4/H-EIA (heparin-enhanced binding in 14 of 15 and 10 of 11 aHIT and SpHIT sera, respectively). Remarkably, 1 SpHIT patient with a VITT-mimicking fluid-EIA profile (PF4 >> PF4/H) also clinically resembled patients with VITT (postviral cerebral vein/sinus thrombosis), with anti-PF4 reactivity correlating inversely with platelet count recovery; moreover, the single aHIT patient with a VITT-mimicking fluid-EIA profile also developed postviral cerebral vein/sinus thrombosis. CONCLUSION: cHIT and VITT sera showed opposite fluid-EIA profiles (cHIT: PF4/H >> PF4, with most testing negative against PF4 alone; VITT: PF4 >> PF4/H, with most testing negative against PF4/H). In contrast, all aHIT and SpHIT sera reacted against PF4 alone but with variable (usually enhanced) reactivity against PF4/H. VITT-mimicking clinical/serologic profiles occurred in only a minority of patients with SpHIT and aHIT.