The risk profiles of pregnancy-related cerebral venous thrombosis: a retrospective study in a comprehensive hospital.

OBJECTIVES: To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). METHODS: A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. RESULTS: PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). CONCLUSIONS: The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.

Factors associated with venous collaterals in patients with cerebral venous thrombosis.

OBJECTIVES: To identify the factors associated with venous collaterals in Thai patients with cerebral venous thrombosis. MATERIALS AND METHODS: This retrospective 20-year cohort study enrolled patients diagnosed with cerebral venous thrombosis between January 2002 and December 2022. Data was collected from the electronic medical record, and venous collaterals were independently reviewed by two neuroradiologists using the Qureshi classification. Patients with and without venous collaterals were compared. Significant factors (P<0.05) in the univariate analysis were recruited into the multivariate logistic regression analysis to determine independently associated factors. RESULTS: Among 79 patients with cerebral venous thrombosis, the prevalence of venous collaterals at the initial neuroimaging was 25.3%. In the univariate analysis, patients with cerebral venous thrombosis and venous collaterals were significantly younger (37.0±13.9 years vs. 44.9±17.4 years, P = 0.048), more often had occlusion in the superior sagittal sinus (80.0% vs. 54.2%, P = 0.041), and were associated with hormonal exposure (35.0% vs. 6.8%, P = 0.002). Multivariate logistic regression analysis revealed occlusion in the superior sagittal sinus (adjusted odds ratio [aOR] 3.581; 95% confidence interval [95% CI] 1.941-13.626; P = 0.044) and hormonal exposure (aOR 7.276, 95% CI 1.606-32.966, P = 0.010) as independent factors associated with venous collaterals in cerebral venous thrombosis. CONCLUSIONS: In this cohort, the prevalence of venous collaterals was 25.3%. Occlusion in the superior sagittal sinus and hormonal exposure were independently associated with venous collaterals in patients with cerebral venous thrombosis.

Intracranial dural arteriovenous fistulas: association with cerebral venous thrombosis, baseline aggressiveness, and clinical outcomes. A retrospective multicenter study on 263 consecutive patients and literature review.

OBJECTIVE: The pathogenesis of intracranial dural arteriovenous fistulas (icDAVFs) is controversial. Cerebral vein thrombosis (CVT) and venous hypertension are recognized predisposing factors. This study aimed to evaluate the incidence of association between icDAVF and CVT and describe baseline aggressiveness and clinical outcomes for icDAVFs associated with CVT. The authors also performed a literature review of studies reporting icDAVF associated with CVT. METHODS: Two hundred sixty-three consecutive patients in two university hospitals with confirmed icDAVFs were included. A double-blind imaging review was performed to determine the presence or absence of CVT close or distant to the icDAVF. Location, type (using the Cognard classification), aggressiveness of the icDAVF, clinical presentation, treatment modality, and clinical and/or angiographic outcomes at 6 months were also collected. All prior brain imaging was analyzed to determine the natural history of onset of the icDAVF. RESULTS: Among the 263 included patients, 75 (28.5%) presented with a CVT concomitant to their icDAVF. For 18 (78.3%) of 23 patients with previous brain imaging available, CVT preceding the icDAVF was proven (6.8% of the overall population). Former/active smoking (OR 2.0, 95% CI 1.079-3.682, p = 0.022) and prothrombogenic status (active inflammation or cancer/coagulation trouble) were risk factors for CVT associated with icDAVF (OR 3.135, 95% CI 1.391-7.108, p = 0.003). One hundred eighty-seven patients (71.1%) had a baseline aggressive icDAVF, not linked to the presence of a CVT (p = 0.546). Of the overall population, 11 patients (4.2%) presented with spontaneous occlusion of their icDAVF at follow-up. Seven patients (2.7%) died during the follow-up period. Intracranial DAVF + CVT was not associated with a worse prognosis (modified Rankin Scale score at 3-6 months: 0 [interquartile range {IQR} 0-1] for icDAVF + CVT vs 0 [IQR 0-0] for icDAVF alone; p = 0.055). CONCLUSIONS: This was one of the largest studies focused on the incidence of CVT associated with icDAVF. For 6.8% of the patients, a natural history of CVT leading to icDAVF was proven, corresponding to 78.3% of patients with previous imaging available. This work offers further insights into icDAVF pathophysiology, aiding in identifying high-risk CVT patients for long-term follow-up imaging. Annual imaging follow-up using noninvasive vascular imaging (CT or MR angiography) for a minimum of 3 years after the diagnosis of CVT should be considered in high-risk patients, i.e., smokers and those with prothrombogenic status.

Factors associated with the initial intracranial hemorrhage occurrence in patients with cerebral venous thrombosis.

OBJECTIVES: Studies focusing on intracranial hemorrhage (ICH) in patients with cerebral venous thrombosis (CVT) are limited; thus, we aimed to identify factors associated with the occurrence of ICH in Thai patients with CVT. METHODS: This retrospective cohort study recruited patients with CVT admitted to a tertiary university-based hospital between 2002 and 2022. The baseline characteristics, clinical presentations, radiographic findings, and etiologies were compared between the ICH and non-ICH groups. The factors with p < 0.2 in the univariate analysis were further analyzed using multivariable logistic regression analysis to identify independent factors associated with ICH in patients with CVT. RESULTS: Of 228 screenings, 202 patients were eligible. The incidence rate of ICH was 36.63%. The ICH group showed a higher prevalence of focal neurological deficits (63.51% vs. 26.56%, p < 0.001), seizures (68.92% vs. 21.88%, p < 0.001), dependency status at admission (60.81% vs. 39.84%, p = 0.004), superior sagittal sinus thrombosis (71.62% vs. 39.07%, p < 0.001), superficial cortical vein thrombosis (36.49% vs. 10.16%, p < 0.001), and hormonal use (17.57% vs. 7.03%, p = 0.021) than the non-ICH group. In contrast, the ICH group showed a lower prevalence of isolated increased intracranial pressure (10.81% vs. 21.88%, p = 0.048) than the non-ICH group. Seizures (adjusted odds ratio [aOR], 4.537; 95% confidence interval [CI], 2.085-9.874; p < 0.001), focal neurological deficits (aOR, 2.431; 95% CI, 1.057-5.593; p = 0.037), and superior sagittal sinus thrombosis (aOR, 1.922; 95% CI, 1.913-4.045; p = 0.045) were independently associated with ICH in the multivariable logistic regression analysis. CONCLUSIONS: Seizures, focal neurological deficits, and superior sagittal sinus thrombosis are associated with ICH in patients with CVT.

Dural Arteriovenous Fistulas With or Without Cerebral Venous Thrombosis: A Cross-Sectional Analysis of 511 Patients.

BACKGROUND AND OBJECTIVES: Recent studies suggest a bidirectional relationship of dural arteriovenous fistula (DAVF) with cerebral venous thrombosis (CVT). We aimed to compare the characteristics of patients with DAVF with or without CVT and to analyze the risk factors for the coexistence of CVT in a DAVF population. METHODS: A total of 511 adult patients with DAVF were enrolled consecutively in our hospital from February 2019 through November 2022. Demographic data, clinical manifestations, and imaging characteristics were reviewed in detail. The patients with DAVF were divided into two groups: DAVF with CVT (DAVF-CVT) group and without CVT (DAVF alone) group. Univariate logistic regression and multivariate logistic regression were used to analyze the risk factors for the coexistence of CVT and DAVF. RESULTS: CVT was found in 19.8% of patients with DAVF. In univariate analysis, compared with the DAVF-alone group, the DAVF-CVT group was more likely to have tinnitus ( P = .001), blurred vision ( P < .001), visual field loss ( P = .001), focal neurological deficits ( P = .002), seizures ( P = .008), and cognitive impairment ( P = .046) and less likely to have spinal cord/brain stem dysfunction ( P = .004). In addition, there were significant differences in age ( P = .009), sex ( P = .019), the occurrence of venous cerebral infarction ( P = .001), and DAVF location ( P < .001) between the two groups. Furthermore, multivariate analysis showed that blurred vision, venous cerebral infarction, large sinus DAVF, and multiple DAVF were risk factors for the coexistence of CVT in patients with DAVF, with the odds ratio of 2.416 (95% CI 1.267-4.606, P = .007), 6.018 (95% CI 1.289-28.100, P = .022), 5.801 (95% CI 2.494-13.496, P < .001), and 5.640 (95% CI 2.122-14.989, P = .001), respectively. CONCLUSION: CVT occurred in approximately one fifth of patients with DAVF. Blurred vision, venous cerebral infarction, large sinus DAVF, and multiple DAVF may be the risk factors for predicting the coexistence of CVT in patients with DAVF.

Post cerebral venous thrombosis headache - Prevalence, mechanisms and risk factors.

INTRODUCTION: Headache after cerebral venous thrombosis (post-CVT headache [PCH]) is a common complaint during follow-up. Risk factors and their pathophysiology are not well known. We studied PCH prevalence in CVT patients, its pathophysiology, and possible risk factors. MATERIALS AND METHODS: We performed a retrospective observational study of patients admitted to a tertiary hospital between 2006 and 2019 with CVT and at least one follow-up appointment. We diagnosed PCH when patients reported headaches during the follow-up visit. Recanalization was retrospectively assessed by two neuroradiologists using the first available follow-up MRI/ MRV, and the PRIORITy-CVT study classification. RESULTS: Of 131 patients, sixty (60/131, 45.8 %) reported PCH at the 3-month follow-up. Of these PCH, 9 had previous migraine (9/60, 5.0 %) and 13 previous tension-type headaches (13/60, 21.6 %), before CVT. Forty-four (44/60, 73.3 %) PCH patients had de novo headache: 21 (21/60, 35.0 %) de novo tension-type headaches; 6 (6/60, 10.0 %) de novo migraine; 6 [(6/60, 10.0 %) secondary headache disorders: 3 due to dural arteriovenous fistula, 2 due to intracranial hypertension, and 1 recurrent CVT], and 11 other headache types. Most patients had at least partial recanalization, with no difference in PCH frequency amongst recanalization subgroups (p = 0.598). Premorbid depression (p = 0.009, OR 7.9, 95 % CI 1.6-31.4) increased the odds ratio of PCH, while superior sagittal sinus thrombosis (p = 0.005, OR 0.15, 95 % CI 0.03-0.56) decreased it. DISCUSSION: Our study shows that PCH is a common finding after CVT and elucidates potential risk factors. PCH is common in patients with previous or de novo primary headache. In PCH patients without previous headache, secondary causes of headache, namely related to CVT complications, should be excluded. PCH is also increased in patients with premorbid depression. There was no statistically significant difference in PCH amongst the PRIORITy-CVT recanalization subgroups, but most patients had at least partial recanalization.

Risk and Prognosis of Cancer in Patients With Cerebral Venous Thrombosis Compared With the Danish General Population.

BACKGROUND: Whether cerebral venous thrombosis (CVT) is a marker of cancer in clinical practice remains unknown. Little is known about the prognosis of cancer detected subsequent to CVT. METHODS: We used Danish nationwide registries (1996-2019) to identify patients with a first-time primary inpatient diagnosis of CVT without a history of cancer (N=811, 65% women, median age 42 years). We assessed the risk of an incident cancer diagnosis using standardized incidence ratios (SIRs). This measure contrasts the number of observed cancers among patients with CVT to the number of expected cancers where patients with CVT have the same cancer risk as the general population. We used Kaplan-Meier survival analysis and Cox regression to compare the survival of patients with both cancer and CVT with the survival of patients with cancer but without CVT, matched on cancer site, sex, age, and year of cancer diagnosis. RESULTS: Observing 43 incident cancer cases during follow-up, the overall SIR was unity (SIR, 1.04 [95% CI, 0.75-1.40]). However, the risk was ≈7-fold the expected level in the first 3 months following CVT diagnosis (SIR, 7.00 [95% CI, 3.02-13.80]) and ≈2-fold the expected level from 3 to 12 months following CVT diagnosis (SIR, 2.21 [95% CI, 0.89-4.56]). By 12 months following CVT diagnosis, the risk resembled the expected level (SIR, 0.76 [95% CI, 0.50-1.09]). Survival among cancer patients with prior CVT versus cancer patients without prior CVT was 91% versus 87% after 6 months and 65% versus 70% after 5 years. The adjusted hazard ratio of death was 0.78 (95% CI, 0.44-1.38). CONCLUSIONS: Patients with CVT were not at overall increased risk of a cancer diagnosis, except in the first 3 months after diagnosis during which period the risk was elevated ≈7-fold. The estimate from this early period, however, was based on only a few cancer diagnoses. Unlike other forms of venous thrombosis, a prior diagnosis of CVT did not negatively impact cancer survival.

Seizures in cerebral venous thrombosis - A retrospective analysis of a tertiary centre cohort.

BACKGROUND: Seizures are common in cerebral venous thrombosis (CVT). The occurrence of acute symptomatic seizures (ASS) has implications for patients' management, with some patients developing unprovoked late seizures (ULS). We aimed to determine risk factors for the development of ASS, ULS, and seizure recurrence (SR) in patients with CVT. METHODS: We performed an observational retrospective analysis of 141 patients with CVT. We recorded the occurrence of seizures, their time relation to the first-symptom onset, and their relation with demographic, clinical, CVT risk factors, and radiological findings. Seizure recurrence (total recurrency, recurrent ASS, and recurrent LS), potential risk factors, and the use of antiepileptic drugs (AED) were also analysed. RESULTS: Thirty-two (22.7%) patients developed seizures: 23 (16.3%) were ASS and 9 (6.3%) ULS. After multivariable logistic regression, seizure patients had more focal deficits (p = 0.033), parenchymal lesion (p < 0.001), sagittal sinus thrombosis (p = 0.007). In ASS, more frequent focal deficits (p = 0.001), encephalopathy (p = 0.001), mutation in V Leiden factor (p = 0.029), and parenchymal brain lesions (p < 0.001) were observed. ULS patients were younger (p = 0.049) and took more hormonal contraceptives (p = 0.047). Thirteen (9.2%) patients suffered SR (2 recurrent ASS only, 2 recurrent LS only, 2 both acute and recurrent LS), which was more frequent in patients with focal deficits (p = 0.013), infarct with haemorrhagic transformation (p = 0.002), or previous ASS (p = 0.001). CONCLUSION: The occurrence of seizures in patients with CVT is related to focal deficits, structural parenchymal lesions, and superior sagittal sinus thrombosis. SR is frequent, even in patients under AED. This shows the important impact that seizures have on CVT and its long-term management.

Prevalence of Venous Infarction in Patients With Cerebral Venous Thrombosis: Baseline Diffusion-Weighted MRI and Follow-Up MRI.

BACKGROUND: A venous pattern of infarction on neuroimaging is used as a clue to undiagnosed cerebral venous thrombosis (CVT); prevention of venous infarction is a goal of CVT management; and venous infarction is a factor used for clinical prognostication. Despite widespread use of the term venous infarct, the prevalence of true venous infarction is unclear. Our primary aim was to determine the prevalence of venous infarction in patients with CVT. We also measured the prevalence of diffusion abnormality without infarction, vasogenic edema, and intracranial hemorrhage. METHODS: Single-center, retrospective cohort study using a registry of 110 consecutive patients admitted to hospital with cerebral venous thrombosis between 2004 and 2014. Inclusion criteria were brain magnetic resonance imaging (MRI) and contrast-enhanced venography at presentation, and repeat brain MRI ≥1 month later. Exclusion criteria were dural arteriovenous fistula, arteriovenous malformation, cavernous sinus thrombosis, or previous neurosurgical procedure. Main outcome was proportion of patients with venous infarction (irreversible ischemic injury) diagnosed using diffusion-weighted MRI at presentation, confirmed using T2-weighted fluid-attenuated inversion recovery MRI ≥1 month later, and reported with 95% CI using the Wilson score interval method. We also report the prevalence of transient diffusion MRI abnormality without infarction, vasogenic edema, and intracranial hemorrhage. RESULTS: Seventy-three patients met the inclusion criteria, and after exclusions, the final study population was 59 patients with median age 41 years (interquartile range, 32-57). Venous infarction occurred in 12% (7/59 [95% CI, 6%-23%]) of patients, and final infarct volume was >1 mL in only 5.1% (3/59) of patients. An additional 8% (5/59 [95% CI, 4%-18%]) of patients had a transient diffusion MRI abnormality without infarction. Prevalence of cerebral vasogenic edema and intracranial hemorrhage were 66% (39/59 [95% CI, 53%-77%]) and 54% (32/59 [95% CI, 41%-66%]), respectively. CONCLUSIONS: In patients with CVT, venous infarction is uncommon and venous infarcts are typically very small. Vasogenic edema and hemorrhage are more common consequences of CVT.

Age of onset of cerebral venous thrombosis: the BEAST study.

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, ~12 years younger, in those with multiple (⩾1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors.

Intracranial hypertension after cerebral venous thrombosis-Risk factors and outcomes.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a special cerebrovascular disease that accounts for around 0.5%-1.0% of all strokes and often occurs in younger adults. Intracranial hypertension is the most frequent symptom of acute CVT due to venous occlusion. This study aimed to ascertain the risk factors for intracranial hypertension after CVT and to investigate whether intracranial hypertension at diagnosis may affect patient outcomes. METHODS: We performed a retrospective cohort analysis of all patients treated for acute/subacute CVT at our department between 2018 and 2021. Logistic regression analysis was performed to identify potential risk factors associated with intracranial hypertension after CVT and clinical outcomes at the 6-month follow-up. RESULTS: A total of 293 acute/subacute CVT survivors were eligible for inclusion, with 245 patients (83.60%) experiencing concomitant intracranial hypertension at diagnosis. In the multivariable regression analysis, hereditary thrombophilia (OR 2.210, 95% CI 1.148-4.254, p = 0.018) and thrombosis location of superior sagittal sinus (SSS) and right lateral sinus (LS) (OR 4.115, 95% CI 1.880-9.010, p = 0.000) were independently associated with intracranial hypertension. 83.67% of patients with intracranial hypertension after CVT had favorable functional outcomes (mRS score, 0-2), whereas they more often had residual visual impairment (15.51% vs. 4.17%, p = 0.036) at follow-up. The risk factors for residual visual impairment were papilledema (OR 2.971, 95% CI 1.231-7.170, p = 0.015) and visual disturbances at diagnosis (OR 2.869, 95% CI 1.123-7.327, p = 0.028), thrombosis location (SSS and right LS [OR 10.811, 95% CI 4.208-27.773, p = 0.000]; SSS and left LS [OR 3.139, 95% CI 1.409-6.995, p = 0.005]), and CVT recurrence (OR 4.763, 95% CI 1.556-14.584, p = 0.006). CONCLUSIONS: Intracranial hypertension is the most common clinical symptom of acute CVT. At follow-up, patients with intracranial hypertension after CVT were more prone to develop residual visual impairment.

Clinical and prognostic characteristics of cerebral venous thrombosis at high altitude: a single-center retrospective study of Tibet.

OBJECTIVE: Data regarding diagnosis, management, and prognosis of patients with cerebral venous thrombosis (CVT) from high altitude are limited. The aim of the present study is to identify the clinical features, risk factors, and outcomes of cerebral venous thrombosis (CVT) in Tibet. METHODS: We retrospectively included patients with a diagnosis of CVT consecutively admitted to Tibet Autonomous Region People's Hospital between July 2015, and September 2022. The risk factors, clinical and radiological presentations, treatment and outcomes were analyzed. RESULTS: A total of 38 patients with CVT were included in this study. The median age was 31 years, and females accounted for 63.2%. Patients of Tibetan nationality accounted for 71.1% (n = 27) and the median altitude of residence in Tibet was 3800 m (3657, 4054). Headache was the most common symptom (92.1%). The most common risk factors of CVT were infection in the past 4 weeks (34.2%) and pregnancy or puerperium (23.7%). Lateral sinus (transverse and/or sigmoid sinus) (68.4%) and superior sagittal sinus (55.3%) were the most commonly involved. The D-dimer increased in 31 patients (81.6%). All three patients who died in hospital and during follow-up had risk factor of recent infection. Favorable outcome at follow-up with a median length of 454 days (189, 1059) was observed in 85.3% of patients. CONCLUSIONS: CVT at high altitude is more common in young patients and women, with various clinical manifestations and risk factors. Recent infection is the most common risk factor and may increase the mortality of CVT at high altitude. The long-term prognosis of CVT at high altitude is favorable.

Risk factors of impaired employability after cerebral venous thrombosis.

AIMS: Cerebral venous thrombosis (CVT) is a major cause of stroke in young and middle-aged adults. This study aimed to evaluate the prevalence of post-CVT employability decline and identify factors associated with unemployment. METHODS: We identified patients first diagnosed with acute/subacute CVT at Xuanwu Hospital, Capital Medical University (January 2018 to June 2021) and invited all survivors to a clinical 6-months follow-up visit after onset. Baseline data were collected from all patients at admission. A modified Rankin Scale (mRS) and employment status were used to assess functional outcomes. Multivariate logistic regression was used to identify independent factors associated with unemployment. RESULTS: A total of 303 CVT patients were eligible for this study, 131 (42.23%) patients could not return to work 6-month after discharge. After adjusting for age and sex in multivariate analysis, motor deficits, aphasia, mental disorders, CVT recurrence, National Institutes of Health Stroke Scale (NIHSS) score at admission, and mRS 0-2 at 6-month follow-up were independently associated with employment after CVT. Among 263 patients whose mRS showed a favorable outcome, 102 patients were unable to return to their previous work and the risk factors for impaired ability to return to work were aphasia and CVT recurrence. CONCLUSIONS: Impaired employability after CVT was associated with motor deficits, aphasia, mental status disorders, and NIHSS score at admission. Even if they recover from CVT without physical disability, patients with a good functional prognosis have a higher risk of employment failure due to their higher rates of aphasia and CVT recurrence.

Incidence of Cerebral Venous Thrombosis: A Population-Based Study, Systematic Review, and Meta-Analysis.

BACKGROUND: Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks may have changed in the post-COVID era. METHODS: We examined CVT incidence using linked administrative data in British Columbia, Canada (population 5.2 million). To contextualize our findings, we also examined CVT incidence in the published literature and searched MEDLINE and EMBASE for article titles and abstracts up to Nov 2, 2021 on CVT incidence in adults. We performed abstract screening and full-text review prior to data extraction and explored associations between CVT incidence and year of study, geographic location, and study quality with meta-analyses and meta-regression. A random-effects restricted maximum likelihood model was used. Publication bias was assessed using the Egger tests and using visual inspection of the funnel plot for symmetry. RESULTS: There were 554 unique CVT cases (mean age 50.9 years, 55.4% women) in British Columbia from 2000 to 2017; overall annual incidence was 8.7 (95%CI' 8.0-9.4) per million. Incidence increased over time in men across the entire study period, and from 2011 to 2017 in women. We identified 22 other studies on CVT incidence before 2020 (21/23 total studies included in meta-analysis). Annual incidence overall was 12.1 (95% CI' 9.9-14.3) per million with significant between-study heterogeneity (I2 98.8%, Qp-value<0.001). There were no significant associations on meta-regression between incidence and study year, study quality score, or gross national income per capita of the study country. Visual inspection of the funnel plot and a significant Egger test (z=2.8, P<0.01) suggested possible publication bias. CONCLUSIONS: Incidence of CVT in Canadian data increased over time but remained lower than in other population-based studies. Significant heterogeneity exists in the literature, which may be subject to publication bias.

Contemporary Incidence and Burden of Cerebral Venous Sinus Thrombosis in Children of the United States.

BACKGROUND: The incidence of cerebral venous thrombosis (CVT) in children of the United States is unknown, and it is uncertain how the burden of CVT hospitalizations in children changed over the last decade. METHODS: We conducted a retrospective cohort study using the State Inpatient Database and Kid's inpatient database. All new CVT cases in children (0-19 years) in the New York 2006 to 2018 State Inpatient Database (n=705), and all cases of CVT in the entire US contained in the 2006 to 2019 Kid's inpatient database (weighted n=6115) were identified using validated International Classification of Diseases (ICDs) codes. Incident counts were combined with census data to compute incidence. Between-group differences in incidence were tested using 2-proportions Z-test, and Joinpoint regression was used to trend incidence over time. RESULTS: Across the study period, 48.2% of all incident CVT cases and 44.6% of all CVT admissions nationally were in girls. Of all incident cases, 27.2% were infants and 65.8% of these infants were neonates. Average incidence across the study period was (1.1/100 000/year, SE:0.04) but incidence in infants (6.4/100 000/year) was at least 5 times the incidence in other age groups (1-4 years: 0.7/100 000/year, 15-19 years: 1.2/100 000/year). Incidence and national burden of CVT admissions was higher in girls in adolescents 15 to 19 years, but overall burden was higher in boys in other age groups. Age- and sex-standardized CVT incidence increased by 3.8% annually (95% CI, 0.2%-7.6%), while the overall burden of admissions increased by 4.9% annually (95% CI, 3.6%-6.2%). CONCLUSIONS: CVT incidence in New York and national burden of CVT increased significantly over the last decade.

Headache at the chronic stage of cerebral venous thrombosis.

BACKGROUND: Headache is the most frequent symptom of cerebral venous thrombosis (CVT) but there is limited information about the frequency and phenotype of headache, weeks to months after cerebral venous thrombosis (post-cerebral venous thrombosis headache, PCH). OBJECTIVE: To assess the frequency, characteristics and predictors of PCH. METHODS: In this cross-sectional study, the frequency and characteristics of PCH were assessed in cerebral venous thrombosis survivors. Patients were interviewed between six months and five years after the cerebral venous thrombosis diagnosis. Clinical and imaging characteristics at the time of cerebral venous thrombosis diagnosis, as well as history of headache prior to cerebral venous thrombosis were compared in subjects with (GroupPCH) and without PCH (Groupcontrol). RESULTS: Subjects (n = 100; 82% women) were assessed, on average, at 1.1 ± 1.6 years of follow-up. PCH was present in 59% of the patients, phenotypes of tension-type-like headache were present in 31/59 (52.6%) and of migraine-like headache in 16/59 (27.1%). History of primary headache prior to cerebral venous thrombosis was significantly more common (OR: 6.4; 95% CI: 1.7-36.3) in GroupPCH (33.9%) than in Groupcontrol (7.3%). CONCLUSION: PCH was present in more than half of the patients. History of prior headache may be a risk factor for PCH. Prospective studies are required to confirm these findings and determine mechanisms, as well as interventions for prevention and treatment of PCH.

Late epileptic seizures following cerebral venous thrombosis: a systematic review and meta-analysis.

BACKGROUND: Identifying late epileptic seizures (LS) following cerebral venous thrombosis (CVT) can be useful for prognosis and management. We systematically reviewed the literature to identify risk factors for LS due to CVT. METHODS: We systematically searched PubMed, Scholar, and Scopus databases (May 2021) to identify studies reporting data on prevalence and risk factors for CVT-LS. The methodological quality was assessed with the Ottawa-Newcastle Scale. The risk of developing CVT-LS was summarized in meta-analyses and expressed as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using random-effects models. RESULTS: Out of the 332 records retrieved, four studies were eventually included with a total of 1309 patients with CVT and 142 (11%) with CVT-LS. The most relevant predictors of CVT-LS were symptomatic seizures (OR 5.66, 95% CI 3.83-8.35), stupor/coma (OR 6.81, 95% CI 1.18-39.20), focal neurologic signs (OR 6.81, 95% CI 1.18-39.2), hemorrhagic component (OR 3.52, 95% CI 2.45-5.06), and superior sagittal sinus involvement (OR 1.52, 95% CI 1.04-2.21). CONCLUSION: There are several risk factors for CVT-LS that should be considered in clinical practice. Further high-quality studies are warranted to develop predictive models for individualized risk stratification and prediction of CVT-LS.

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.

Thyroid dysfunction in cerebral venous thrombosis: a retrospective cohort study.

BACKGROUND: Cerebral venous thrombosis (CVT) is a multifactorial disease with a variety of related conditions and risk factors. Thyroid dysfunction-especially hyperthyroidism-has been linked to CVT, but this is mainly based on case reports ranging back to 1913, while systematic investigations addressing this issue are lacking. Therefore, we investigated the frequency and clinical characteristics of thyroid dysfunction in a large single-center cohort of CVT patients. METHODS: We retrospectively identified all consecutive patients with aseptic CVT treated at our center between 2006 and 2020. Clinical information was extracted from our electronic medical documentation system. Thyroid-stimulating hormone (TSH) had been routinely measured at admission, free thyroid hormones and thyroid autoantibodies were analyzed whenever available. RESULTS: Of 120 patients with imaging-confirmed CVT, our main analysis included 107 patients (mean age 42 ± 16 years, 74% female) in whom TSH measurements were available. Nineteen patients (17.8%, 95% confidence interval 10-25%) had thyroid dysfunction. Two had newly diagnosed hyperthyroidism (1.9%, 95% confidence interval 0-4%) caused by Graves' disease, but without typical symptoms for this condition. Seventeen patients (15.9%, 95% confidence interval 9-23%) had hypothyroidism (12 previously diagnosed with ongoing thyroid hormone replacement therapy; 5 with newly diagnosed subclinical hypothyroidism). Clinical CVT characteristics were similar comparing patients with versus without thyroid dysfunction. CONCLUSION: We observed a remarkably high prevalence of thyroid dysfunction in CVT patients. Whether this finding reflects a causal relationship warrants further studies. Despite that, the frequent coexistence of both diseases argues for TSH screening in CVT patients.