A novel rat model for cerebral venous sinus thrombosis: verification of similarity to human disease via clinical analysis and experimental validation.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. METHODS: This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague-Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. RESULTS: The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. CONCLUSIONS: We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.

Clinical Profile and Long-Term Outcome in Neonatal Cerebral Sinus Venous Thrombosis.

BACKGROUND: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT. METHODS: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined. RESULTS: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment. CONCLUSIONS: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis, and type of cerebral injury. These results can help guide further studies in neonatal CSVT aiming to decrease morbidity and mortality with the goal of improving long-term neurological outcomes.

The clinical analysis and treatment strategy of endovascular treatment for cerebral venous sinus thrombosis combined with intracerebral hemorrhage.

Cerebral venous sinus thrombosis (CVST) combined with intracerebral hemorrhage(ICH) is a special subgroup, and whether intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) therapy should be carried out is controversial because of previous hemorrhage and possible delayed hemorrhage.The aim of this study was to analyze the safety and effectiveness of endovascular treatment of CVST with ICH and further discuss the treatment strategy. This is a retrospective study of 56 cases admitted from January 2010 to June 2019 diagnosed with CVST combined with ICH, and all were treated with endovascular treatment including IST with or without MT. We reviewed the clinical, radiological, and outcome data of all patients. The percentage of cases that showed complete and partial recanalization were 67.8% and 26.9% after endovascular treatment. ICH exacerbation occurred in 5 cases during thrombolysis. The percentage of cases with good outcome was 87.5% at discharge. 51 cases were followed up at sixth month. 49 cases had a mRS score of 0-2,and 2 cases had a mRS score of 3-4 at sixth month.Our data suggest that endovascular treatment may improve clinical and radiological outcome in most patients of CVST with ICH, but confirmation in prospective, controlled studies is warranted.

Endoplasmic reticulum stress and oxidative stress contribute to neuronal pyroptosis caused by cerebral venous sinus thrombosis in rats: Involvement of TXNIP/peroxynitrite-NLRP3 inflammasome activation.

Cerebral venous sinus thrombosis (CVST) is a rare type of stroke, which is life-threatening in severe cases. However, considerably less attention has been concentrated on the mechanism of neural cell damage after CVST. This study aims to investigate the role of endoplasmic reticulum stress, oxidative stress, and pyroptosis in a well-established rodent model of CVST. Rat brains were harvested at 0 h, 6 h, days 1, days 3, days 7, and days 14 post-CVST for measurement of corresponding indexes. Endoplasmic reticulum stress sensors (including protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme-1α (IRE1α)), oxidative stress markers (thioredoxin-interacting protein (TXNIP) and peroxynitrite), NLRP3, caspase p20, IL-1ß, and gasdermin D (GSDMD, an indicator of pyroptosis) were separately evaluated by Western-blot and Immunohistochemistry/Immunofluorescence. Co-immunoprecipitation and Fluorescent double-labeling were employed to probe into the relationship between TXNIP/peroxynitrite and NLRP3 inflammasome. In the damaged cortex region, profuse p-PERK, p-IRE1α, TXNIP were produced and predominantly localized in neurons accompanied by a small amount expressed in microglia and astrocytes. The levels of 3-nitrotyrosine (3-NT, as a footprint of peroxynitrite), NLRP3, caspase p20, IL-1ß, and GSDMD were distinctly elevated post-CVST and cellular localization of peroxynitrite, NLRP3, caspase p20, and IL-1ß was largely observed in neurons and/or microglia. Importantly, sites of enhanced TXNIP and 3-NT immunoreactivity were colocalized with increased NLRP3 staining, indicating the involvement of TXNIP and peroxynitrite in NLRP3 inflammasome activation and subsequent pyroptosis. Besides, co-immunoprecipitation also hinted that there might be an interaction or causality between TXNIP/peroxynitrite and NLRP3 inflammasome. We concluded that endoplasmic reticulum stress and oxidative stress may jointly lead to neuronal NLRP3 inflammasome activation and pyroptosis after CVST.

Cerebral Venous Thrombosis: A Comprehensive Review.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a relatively rare, potentially fatal neurological condition that can be frequently overlooked due to the vague nature of its clinical and radiological presentation. A literature search on PubMed using the keyword "Cerebral sinus venous thrombosis" was performed. We searched for the epidemiology, risk factors, pathophysiology, clinical features, diagnosis, and treatment of CSVT. All full-text articles in the last 10 years, in adults (>18 years), and the English language were included. We aim to give a comprehensive review of CSVT, with a primary focus on the management of the disease. SUMMARY: The literature search revealed 404 articles that met our criteria. CSVT is a relatively rare condition that accounts for approximately 1% of all forms of stroke. They can be subdivided into acute, subacute, and chronic forms based on the time of onset of clinical symptoms. It is a multifactorial disease, and the major forms of clinical presentation include isolated intracranial hypertension syndrome, focal neurological deficits, and cavernous sinus syndrome. MRI with magnetic resonance venogram (MRV) is considered the gold standard for diagnosis. Anticoagulation with heparin or low-molecular-weight heparin is the mainstay of treatment. Endovascular management is indicated for those cases with severe symptoms or worsening of symptoms despite anticoagulation therapy. Favorable outcomes have been reported in patients who receive early diagnosis and treatment. CONCLUSION: CSVT is a potentially fatal neurological condition that is often under-diagnosed due to its nonspecific presentation. Timely diagnosis and treatment can reduce morbidity and mortality, remarkably improving the outcome in affected individuals.

Acute Seizures in Cerebral Venous Sinus Thrombosis: Risk Factors and Prognosis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) often presents with acute seizures, and recurrent seizures may also be seen in the long term in some patients. The purpose of this retrospective study was to investigate the frequency and type of acute seizures and to define the risk factors. METHODS: Sixty-two patients diagnosed with CVST between September 2007 and October 2018 were retrospectively evaluated for the occurrence of acute seizures. Seizures which developed as a presenting symptom or occurred within 2 weeks of diagnosis were defined as acute seizures. Demographic, clinical, and radiologic characteristics were compared between patients with or without acute seizures. RESULTS: Twenty (32.3%) of the 62 CVST patients had acute seizures. Univariate analysis revealed a significant association between acute seizures and aphasia (P=0.03), motor deficit (P<0.001), sensory deficit (P=0.018), severe (≥3) modified Rankin Scale scores on admission (P=0.017), sagittal sinus thrombosis (P=0.037), cortical vein thrombosis (P<0.001), supratentorial lesions (P<0.001), and hemorrhagic lesions (P<0.001). Multivariate regression analysis identified supratentorial lesions (P=0.015, odds ratio: 9.131, 95% confidence interval: 1.525-54.687) and cortical vein thrombosis (P=0.034, odds ratio: 5.802, 95% confidence interval: 1.146-29.371) as independent factors for acute seizures. Although 25% of patients with acute seizures had recurrent seizures during hospitalization, only 2.6% of the 38 patients with long-term follow-up had recurrent seizures. CONCLUSIONS: Approximately one third of patients with CVST had acute seizures. Cortical vein thrombosis, supratentorial, and especially hemorrhagic lesions were the most significant risk factors associated with acute seizures. Although seizure recurrence may occur early in the course, long-term recurrence is rare in CVST.

Successful treatment of a massive sinus thrombosis in a Chinese woman with antithrombin III deficiency: a case report and review of the literature.

: The incidence of antithrombin III (AT III) deficiency is very rare. The most common complication of AT III deficiency is deep venous thrombosis, which causes a low incidence of intracranial sinus thrombosis. We presented a 31-year-old Chinese woman patient who had a family history of AT III deficiency admitted to our hospital. She had a history of pulmonary embolism. She took rivaroxaban for a long time to prevent thrombosis. After giving birth, she stopped taking the medication for half a year and suffered from drug withdrawal symptoms. Four months after drug withdrawal, she suddenly fell into a coma. After diagnosis, it was found to be caused by a subarachnoid hemorrhage. Finally, she was diagnosed with sagittal and transverse sinus thrombosis. After treatment with mechanical thrombectomy, she fully recovered. In sum, we concluded that mechanical thrombectomy was efficient for AT III deficiency and treating thrombosis.

Significance of recanalization of sinuses and resolution of parenchymal lesion in cerebral venous sinus thrombosis.

In cerebral venous sinus thrombosis (CVST), the degree of recanalization may determine resolution of parenchymal lesion and clinical outcome. The aim of our study was to evaluate the relationship of recanalization with resolution of MRI lesion and clinical outcome. The patients with CVST diagnosed on the basis of magnetic resonance venography (MRV) were included prospectively. Risk factors, clinical features, and MRI and MRV findings were noted. MRI and MRV were repeated at 6 months and the change in parenchymal lesion and grade of recanalization (I, II, III) were noted. Patients were evaluated clinically at three and six months. Complete recovery was considered if modified Rankin Scale (mRS) score was 0. Thirty-three CVST patients were included, 12 (36.4%) of whom were females. Recanalization occurred in 29 (87.9%), which was complete (grade III) in 6 (21%). Sigmoid sinus (52%) recanalized more frequently. Resolution of parenchymal lesion on repeat MRI occurred in 13.3% (4/30) patients, and they had no sequelae. Degree of recanalization was not related to resolution of neurological sequelae, MRI lesion at follow up and burden of thrombosis at baseline. Varying degree of recanalization occurred in 87.9% patients with CVST, and resolution of parenchymal lesion occurred in 13.3%. Clinical outcome however was not related to recanalization.

Radiological evaluation in patients with clinical suspicion of cerebral venous sinus thrombosis presenting with nontraumatic headache - a retrospective observational study with a validation cohort.

BACKGROUND: Clinical suspicion of cerebral venous sinus thrombosis (CVST) is imprecise due to non-specific symptoms such as headache. The aim was to retrospectively assess the diagnostic value of nonenhanced CT (neCT) in patients with nontraumatic headache and clinically suspected CVST. METHODS: A retrospective consecutive series of patients referred 2013-2015 for radiology were evaluated. Eligible patients had nontraumatic headache and suspicion of CVST stated in the referral, investigated with CT venography (CTV) and nonenhanced CT (neCT). neCT scans were re-evaluated for the presence of CVST or other pathology. All CTVs were checked for the presence of CVST. The validation cohort consisted of 10 patients with nontraumatic CVT (2017-2019). RESULTS: Less than 1% (1/104) had a suspected thrombus on neCT, confirmed by subsequent CTV. The remaining 99% had a CTV excluding CVST. Eleven percent had other imaging findings explaining their symptoms. In the patient with CVST, the thrombosed dural sinus was high attenuating (maximum HU 89) leading to the suspicion of CVST confirmed by CTV. The validation cohort (n = 10) confirmed the presence of a high attenuating (HU > 65) venous structure in the presence of a confirmed thrombus in all patients presenting within 10 days (suspicion written in referral, 10%). CONCLUSIONS: Despite clinical suspicion, imaging findings of CVST in nontraumatic headache are uncommon. Evaluating neCT for high attenuation in dural sinuses, followed by CTV for confirmation in selected cases seems reasonable. CVST should be recognized by all radiologists and requires a high level of awareness when reading neCT for other indications.

Clinical and epidemiological profile of cerebral venous thrombosis. A Multicenter retrospective study in Aseer Region Saudi Arabi.

OBJECTIVE: To assess the epidemiological pattern and correlates with the clinical outcome of Cerebral venous thrombosis (CVT) in Abha, Kingdom of Saudi Arabia. METHODS: A retrospective record_based cohort design was conducted including all patients admitted with diagnosis of CVT in 2 main tertiary hospitals in Aseer Region between 2015 to the end of 2018. The study hospitals were Aseer Central Hospital and Armed Forces Hospitals Southern Region. The data were collected by structured data sheets, including sociodemographic data. Assessment of known risk factors for CVT, clinical presentation, treatment received, and clinical outcome after treatment were extracted. RESULTS: The study included 119 patients with CVT, whose ages ranged from 15 to 97 years, with a mean age of 35.5-/+14.1 years. Majority of the patients were females (81.5%). Headache was the most presenting (82.4%) symptom, followed by vomiting (30.3%) and a decreased level of consciousness. Thirty_three cases (27.7%) had complications, and recanalization was recorded among 92 cases (94.8%) based on follow up vascular imaging. CONCLUSION: The study revealed that most of the cases of CVT had favorable clinical outcome and recanalization, especially those who had a shorter duration untildiagnosis. Young females were the most affected group.

Dural Arteriovenous Fistula Complicated with Cerebral Venous Sinus Thrombosis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is always confused with dural arteriovenous fistula (DAVF) in clinical practice; however, both of them are very rare cerebral vascular diseases. In this report, we provide one case of DAVF combined with CVST. CASE DESCRIPTION: A 75-year-old woman complained of headache with nausea and vomiting for 4 days. Magnetic resonance venography revealed filling defect in the torcular, left transverse, and sigmoid sinus, which strongly suggested sinus thrombosis. The patient underwent anticoagulation treatment for 9 days. However, the manifestation was not alleviated, magnetic resonance imaging detected the lesion was enlarged, and the midline shifted to the left. Digital subtraction angiography examination detected that one fistula classified as Borden type IA was fed by the left superficial temporal artery and drained into the left transverse and sigmoid sinus. Endovascular embolization with ethylene vinyl alcohol was conducted. CONCLUSIONS: Follow-up at 6 months indicated that the patient recovered without any sequelae.

Establishment of a Rat Model of Superior Sagittal-Sinus Occlusion and Recanalization via a Thread-Embolism Method.

There are many uncontrollable factors in the pathogenesis of cerebral venous sinus thrombosis (CVST). In order to further explore the pathophysiology and morphology of CVST, it is necessary to establish a highly compatible CVST animal model that can standardize the site and stage of venous thrombosis. The present study employed the insertion of a self-made thread embolism into the superior sagittal sinus (SSS) to establish a rat model of SSS occlusion that emulates CVST. The thread embolism was removed after 6 h of SSS occlusion in order to achieve recanalization. After successful preparation of the model, the cerebral blood flow (CBF) status and ultrastructural changes of the blood-brain barrier (BBB) were monitored. This CVST model was able to achieve continuously high occlusion of SSS. The parasagittal venous-collateral circulation underwent extensive compensation and recombination, which alleviated blood flow stasis and brain tissue hypoxia caused by restricted reflux. Removing SSS occlusion significantly improved cerebral circulation, reduced brain edema, and accelerated the receding of brain edema. This study established a new model of acute occlusion and recanalization of SSS in rats via a thread-embolism method, which standardized the ischemic site and stage of venous thrombosis. In addition, our study suggests that promoting collateral circulation may be a potential treatment for promoting brain protection.

Neonatal cerebral sinovenous thrombosis.

Cerebral sinovenous thrombosis (CSVT) is a focal or diffuse disruption of cerebral blood flow secondary to occlusion of cerebral veins and/or sinuses. The challenge of CSVT during the neonatal age has led to a great interest in this condition among neonatologists, child neurologists, and pediatric neuroradiologists. The highly variable clinical spectra, etiologies, and prognosis require fine medical skills and a high level of suspicion. Nevertheless, the diagnosis is often delayed or missed altogether. Differences in brain vulnerability at different stages of maturation may explain the spectrum of associated brain lesions, which varies with gestational age. Treatment is controversial and reported clinical outcomes vary widely. The controversial treatment of CSVT with anticoagulant therapy is based only on case series and expert consensus, there is lack of safety data.

T2*-Weighted MRI Detected Dilated Cerebral Veins in a Patient with Acute-Phase Cerebral Venous Sinus Thrombosis-A Case Report.

We describe a 45-year-old man who presented with nausea, vomiting, and strong occipital headache on the right side. Although no abnormalities on neurological examination or computed tomography imaging were found on admission, peripheral blood cell counts showed polycythemia (hemoglobin 20.6 g/dL) and electrocardiography demonstrated atrial fibrillation. Therefore, anticoagulant treatment with heparin was started immediately. On the following day, the occipital headache continued. Brain T2*-weighted (T2*WI) magnetic resonance imaging (MRI) and, to a lesser extent, susceptibility-weighted imaging showed dilation of numerous cortical veins, suggesting the possibility of cerebral venous thrombosis (CVT). MR venography (MRV) showed a deficit of the right transverse sinus. Contrast-enhanced MRI revealed partial defects of the right transverse sinus, and led to the definite diagnosis of CVT, and the anticoagulation therapy was continued. On day 7 the headache disappeared, and MRV on day 16 showed the recanalization of the right transverse sinus. There were no complications subsequent to the CVT. On day 25, the patient was discharged with no after-effect. We speculate that the dilation of cortical veins on T2*WI is a helpful sign in detecting acute-phase CVT.

Incidence of Dural Venous Sinus Thrombosis in Patients with Glioblastoma and Its Implications.

OBJECTIVE: Glioblastoma (GBM) is associated with increased risk of developing dural venous sinus thrombosis (DVST), which often goes undiagnosed as symptoms are readily attributed to tumor. The purpose of this study was to investigate the incidence of DVST, potential predictive features on imaging, complications, its effect on survival, and time of greatest risk for developing DVST. METHODS: A retrospective search of patients with GBM who had surgery followed by chemotherapy and/or radiation therapy between 2009 and 2015 at our institution was performed. Magnetic resonance imaging studies of the brain were reviewed on volumetric postgadolinium T1-weighted sequences for DVST. Tumors were characterized using the Visually Accessible REMBRANDT (Repository for Molecular Brain Neoplasia Data) Images classification, and identified thromboses were tracked for propagation, regression, or resolution. Statistical analyses were directed at identifying clinical predictors and survival differences between the DVST and no-DVST groups. RESULTS: In total, 163 cases totaling 1637 scans, were reviewed; 12 patients (7.4%) developed DVST, of whom 11 presented with thrombus before any treatment. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratios were significantly associated with thrombus development (P = 0.02 and P = 0.02, respectively). In patients who developed DVST, thrombosis was more likely to develop ipsilateral to tumor side (P = 0.01) and was associated with a greater likelihood of developing extracranial venous thromboembolism (P = 0.012). There were no venous infarcts and no significant difference in survival between groups (P = 0.83). CONCLUSIONS: Patients with GBM have increased risk of developing DVST, independent of surgical treatment or chemoradiation. DVST presence does not affect survival. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratio on preoperative imaging were the most significant predictors of DVST development.

Behçet's disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study.

OBJECTIVE: This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçet's disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS: VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS: BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS: BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).