VENOST
A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study
Year of Publication: 2017
Authors: Taskin Duman, MD, Derya Uluduz, ..., and VENOST Study Group
Journal: Journal of Stroke and Cerebrovascular Diseases
Citation: Journal of Stroke and Cerebrovascular Diseases, Vol.(), No.(), 2017: pp-. 10.1016/j.jstrokecerebrovasdis.2017.04.070
Link: https://www.researchgate.net/publication...he_VENOST_Study
PDF: https://www.researchgate.net/profile/Meh...saWNhdGlvbiJ9fQ
PDF: Clinical Question
To characterize the clinical characteristics, risk factors, and outcomes of Caucasian patients with cerebral venous thrombosis (CVT) in a large, multicenter study, comparing these features across age and sex distributions.
Bottom Line
The VENOST study, a large multicenter observational study of Caucasian CVT patients, found clinical and radiological features consistent with previous studies, but identified different predisposing factors, notably a higher incidence of puerperium and lower oral contraceptive use. Malignancy, older age, and hemorrhagic infarcts were associated with worse outcomes, while epileptic seizures had no negative impact.
Major Points
- The study included 1144 patients with confirmed CVT from 35 national stroke centers in Turkey, with data collected retrospectively (2000-2013) and prospectively (after 2013).
- 67.9% of patients were women, but male patients were more prevalent in the older age group (>50 years) (27.8% vs 16.6% in women; P<.001).
- The most frequent symptoms were headache (87.2%), nausea and vomiting (27.7%), visual field defects (26.5%), and epileptic seizures (23.7%). Headache was the sole symptom in 25.1% of patients.
- Gynecological factors (puerperium 18.3%, oral contraceptive use 13.9%, pregnancy 9.5%) comprised the largest etiological group in women. Oral contraceptive use was not a prevalent risk factor in this cohort.
- Prothrombotic conditions (26.4%), mainly MTHFR mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders.
- Infection-associated etiology was found in 8.1% of patients and malignancy-related in 5.2%; both were significantly higher in men and older age groups (P<.001).
- Parenchymal involvement (constitutively hemorrhagic infarcts), malignancy, and older age were associated with higher modified Rankin Scale (mRS) scores (worse outcome).
- Epileptic seizures had no effect on prognosis. Patients with focal neurological deficit and altered consciousness had unfavorable prognosis.
- Most patients were anticoagulated (83.9%) in the early period with intravenous heparin (69.6%) or subcutaneous low-molecular weight heparin (14.3%).
- At 1-month follow-up, 78.4% of patients had mRS 0-1, 11.7% had mRS 2, and 10.0% had mRS 3-5. No patients had mRS 6 due to CVT.
- Outcome was favorable in patients with no parenchymal lesions and worst in patients with hemorrhagic infarcts. Outcome was favorable in infectious-related CVT but unfavorable in malignancy.
Design
Study Type: National, multicenter, retrospective and prospective, hospital-based observational study
Randomization:
Enrollment Period: Data collected between 2000 and 2015. Retrospective enrollment for 2000-2013, prospective enrollment after 2013.
Follow-up Duration: Up to 12 months (follow-up visits recorded after 1, 3, 6, and 12 months if available).
Centers: 35
Countries: Turkey
Sample Size: 1144
Analysis: Continuous data summarized as mean±standard deviation or median with interquartile range; categorical data as frequency and percent. Independent sample t-test for continuous variables, Pearson chi-square or likelihood ratio test for categorical data. Multivariate logistic regression for odds ratios (OR) for prognostic factors. SPSS v.22 statistical package used.
Inclusion Criteria
- Patients aged more than 18 years.
- Radiologically confirmed cerebral venous and sinus thrombosis (CVST) based on clinical presentation and thrombosis on cranial CT, MRI, MRV, and DSA.
- Caucasian patients.
Exclusion Criteria
- 49 patients were excluded as their data were inconclusive.
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Female, n (%) | 787 (67.9) | |
| Male, n (%) | 357 (32.1) | |
| Age group 18-36, n (%) | 533 (46.6) | |
| Age group 37-50, n (%) | 380 (33.2) | |
| Age group 51+, n (%) | 231 (20.2) | |
| Mode of onset - Acute, n (%) | 530 (47.1) | |
| Mode of onset - Subacute, n (%) | 383 (34.0) | |
| Mode of onset - Chronic, n (%) | 213 (18.9) | |
| Isolated headache, n (%) | 287 (25.1) | |
| Headache, n (%) | 997 (87.2) | |
| Nausea and vomiting, n (%) | 317 (27.7) | |
| Epileptic seizures, n (%) | 271 (23.7) | |
| Visual field defect, n (%) | 303 (26.5) | |
| Focal neurological deficit, n (%) | 208 (18.2) | |
| Altered consciousness, n (%) | 204 (17.8) | |
| Cranial nerve palsies, n (%) | 128 (11.2) | |
| Radiological workup - Cranial MRI, n (%) | 60 (5.3) | |
| Radiological workup - Cranial MRV, n (%) | 41 (3.6) | |
| Radiological workup - Cranial MRI + MRV, n (%) | 1015 (89.1) | |
| Radiological workup - Cerebral angiography, n (%) | 23 (2.0) | |
| Number of sinuses involved - 1 sinus, n (%) | 551 (48.2) | |
| Number of sinuses involved - 2 sinuses, n (%) | 387 (33.8) | |
| Number of sinuses involved - More than 2 sinuses, n (%) | 206 (18.0) | |
| Involved sinuses - Isolated transverse sinuses, n (%) | 292 (25.5) | |
| Involved sinuses - Isolated sagittal sinuses, n (%) | 168 (14.7) | |
| Involved sinuses - Isolated sigmoid sinuses, n (%) | 37 (3.2) | |
| Involved sinuses - Isolated cortical veins, n (%) | 24 (2.1) | |
| Involved sinuses - Isolated jugular sinuses, n (%) | 16 (1.4) | |
| Involved sinuses - Isolated cavernous sinuses, n (%) | 9 (0.8) | |
| Involved sinuses - Transverse sinuses, n (%) | 840 (73.4) | |
| Involved sinuses - Sigmoid sinuses, n (%) | 455 (39.8) | |
| Involved sinuses - Sagittal sinuses, n (%) | 445 (38.9) | |
| Involved sinuses - Internal jugular vein, n (%) | 178 (15.6) | |
| Involved sinuses - Cortical veins, n (%) | 42 (3.7) | |
| Involved sinuses - Cavernous sinuses, n (%) | 19 (1.7) | |
| Parenchymal involvement - No lesion, n (%) | 685 (59.9) | |
| Parenchymal involvement - Infarction, n (%) | 218 (19.1) | |
| Parenchymal involvement - Hemorrhagic infarction, n (%) | 198 (17.3) | |
| Parenchymal involvement - Intracerebral hemorrhage, n (%) | 43 (3.8) | |
| Gynecological causes - Oral contraceptive use, n (%) | 108 (13.9) | |
| Gynecological causes - Pregnancy, n (%) | 74 (9.5) | |
| Gynecological causes - Puerperium, n (%) | 142 (18.3) | |
| Infections - Paracranial (focal), n (%) | 70 (6.1) | |
| Infections - Systemic, n (%) | 23 (2.0) | |
| History of VTE - Cerebral, n (%) | 26 (1.9) | |
| History of VTE - Deep venous thrombosis, n (%) | 34 (3.0) | |
| History of VTE - Other, n (%) | 4 (0.8) | |
| Malignancy, n (%) | 59 (5.2) | |
| Family history of VTE, n (%) | 11 (1.0) | |
| MTHFR mutation heterozygote, n (%) | 37 (5.1) | |
| MTHFR mutation homozygote, n (%) | 46 (6.3) | |
| Hyperhomocysteinemia, n (%) | 45 (4.8) | |
| Prothrombin mutation, n (%) | 19 (2.6) | |
| Protein C/S deficiency, n (%) | 47 (5.0) | |
| Factor V Leiden mutation, n (%) | 37 (5.1) | |
| Thrombocytosis, n (%) | 10 (1.1) | |
| Polisitemia vera, n (%) | 7 (0.7) | |
| Anticardiolipin Ab, n (%) | 6 (0.6) | |
| PAI mutation, n (%) | 10 (1.4) | |
| Antithrombin III deficiency, n (%) | 5 (0.5) | |
| Hyperfibrinogenemia, n (%) | 3 (0.3) | |
| Antiphospholipid Ab, n (%) | 11 (1.3) | |
| Activated protein C resistance, n (%) | 14 (1.5) | |
| High ANA titers, n (%) | 17 (1.5) | |
| Behçet's disease, n (%) | 108 (9.4) | |
| SLE, n (%) | 15 (1.4) | |
| Idiopathic, n (%) | 281 (24.6) |
Arms
| Field | Observational CVT cohort |
|---|---|
| Intervention | Observational registry: imaging-confirmed cerebral venous thrombosis patients across 35 Turkish centers (2000–2015). Anticoagulation and other treatments per physician discretion. |
| Duration | Up to 3 months follow-up (and beyond in some patients) |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional outcome at 3 months (mRS 0–1) in Caucasian patients with cerebral venous thrombosis, with description of clinical, radiological, and etiological features. | Primary | ||||
| mRS score 0-1 at 1st month visit | Secondary | 787 (78.4%) | |||
| mRS score 2 at 1st month visit | Secondary | 117 (11.7%) | |||
| mRS score 3-5 at 1st month visit | Secondary | 100 (10.0%) | |||
| mRS score 0-1 at 3rd month evaluation | Secondary | 764 (90.6%) | 0.128 | ||
| mRS score 2 at 3rd month evaluation | Secondary | 45 (5.3%) | 0.263 | ||
| mRS score >3 at 3rd month evaluation | Secondary | 33 (3.9%) | <.001 | ||
| mRS score 0-1 at 6th month follow-up | Secondary | 712 (91.5%) | 0.011 | ||
| mRS score 2 at 6th month follow-up | Secondary | 37 (4.8%) | 0.938 | ||
| mRS score >3 at 6th month follow-up | Secondary | 29 (3.7%) | <.001 | ||
| mRS score 0-1 at 12th month outcome | Secondary | 643 (93.1%) | 0.057 | ||
| mRS score 2 at 12th month outcome | Secondary | 22 (3.2%) | 0.518 | ||
| mRS score >3 at 12th month outcome | Secondary | 26 (3.8%) | <.001 | ||
| Outcome favorable in patients with no parenchymal lesions (mRS 0-1) | Secondary | 62.2% of patients with no parenchymal lesions | |||
| Outcome unfavorable in patients with focal neurological deficit (mRS >=3) | Secondary | 3.264 | |||
| Outcome unfavorable in patients with altered consciousness (mRS >=3) | Secondary | 5.856 | |||
| Outcome favorable in patients without headache (mRS 0-1) | Secondary | 13.2% of patients without headache | 0.014 (for comparison with headache patients) | ||
| Outcome favorable for transverse sinus involvement (mRS 0-2) | Secondary | 73.4% of patients had transverse sinus involvement | 0.026 | ||
| Outcome unfavorable for SSS involvement (mRS >=3) | Secondary | 4.228 | 0.001 | ||
| Outcome favorable for infectious-related CVST (mRS 0-2) | Secondary | 8.1% of patients had infection-associated CVST | |||
| Outcome unfavorable for malignancy-related CVST (mRS >=3) | Secondary | 3.307 | 0.003 | ||
| mRS 0-1 at 1 month (favorable) | Adverse | 787/1004 (78.4%) | |||
| mRS 2 at 1 month (minimal disability) | Adverse | 117/1004 (11.7%) | |||
| mRS 3-5 at 1 month (dependent) | Adverse | 100/1004 (10.0%) | |||
| mRS 6 (death due to CVST) at 1 month | Adverse | 0 (0%) | |||
| Observational study - no AE table | Adverse | Multicenter observational cohort - no systematic AE collection | |||
Criticisms
- The study has an observational nature, lacking uniform evaluation for etiology and treatment options, which may introduce bias.
- There were high dropout rates from long-term follow-up (e.g., 60.4% at 1 year).
- The study does not represent the entire CVST patient population, nor is it a random sample, which limits generalizability.
- Specific details on acute and maintenance treatment duration and dosages, beyond initial anticoagulation, are not uniformly provided for all patients.
- Information on acquired or congenital thrombophilic abnormalities was collected only if available, not uniformly.
- The study identified Behçet's disease as an underlying etiology more frequently than Western countries, but the impact of this specific etiology on overall outcomes is not fully explored.
- The authors mention that the proportion of women was higher in the older age group and acute onset was more common in younger ages, and chronic onset in older age, which could confound some age-related findings.
Subgroup Analysis
Patients were compared by sex and age groups (less than 37 years of age, 37-50 years, and more than 50 years) for clinical symptoms, etiological factors, vascular involvement, and frequency of parenchymal involvement. Prognostic factors (aged >50 years, parenchymal involvement, malignancy, SSS involvement, focal neurological deficit, altered consciousness) were evaluated for association with higher mRS scores (mRS ≥3) using multivariate logistic regression.
Based on: VENOST (Journal of Stroke and Cerebrovascular Diseases, 2017)
Authors: Taskin Duman, MD, Derya Uluduz, ..., and VENOST Study Group
Citation: Journal of Stroke and Cerebrovascular Diseases, Vol.(), No.(), 2017: pp-. 10.1016/j.jstrokecerebrovasdis.2017.04.070
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