Cerebral Venous Thrombosis Among Bangladeshi Population: A Systematic Review

Cerebral venous thrombosis (CVT) is a rare cause of stroke which remains unsung among Bangladeshi physicians and the general population. Our objective was to provide a comprehensive review of published data on Bangladeshi CVT patients. We searched all-electronic databases for Bangladeshi studies on CVT until November 2023, including literature in all languages. This study reviews the age of onset, gender distribution, radiological characteristics, and outcomes of Bangladeshi CVT patients. We included 13 studies (two observational and 11 case reports) that evaluated 102 CVT patients and found that women suffered CVT significantly higher than men (59.8% vs 40.2%; P =0.04), respectively. The overall age of the study population was 36.6±6.8, and men were significantly older than women (45.4±12.3 vs. 32.4±8.3; P<0.001). The most commonly affected sites were the superior sagittal sinus and transverse sinus thrombosis. Rivaroxaban was primarily used for long-term anticoagulation after initial low molecular weight heparin therapy. Furthermore, most studies observed an excellent clinical outcome with completed recanalisation on early follow-up angiography in three studies. In Bangladesh, women 1.5 times more commonly suffer from CVT and 13 years earlier than men. Although this review found that prompt diagnosis and anticoagulation therapy provides good clinical outcome, we recommended further studies to evaluate the long-term outcome, especially the safety and efficacy of oral anticoagulants, with recanalisation and recurrence rate.

Although CVT carries a complex pathogenesis, it is often (~50% of cases) associated with more than one risk factor, and 15% of patients are of unknown aetiology, which is why diagnosis of CVT can be challenging and requires a high index of clinical suspicion [3][4][5].Additionally, chronic sinusitis and pathogen dissemination from nasal infections could be potential sources of CVT development, especially TS thrombosis, which may be caused by mastoid and middle ear infections [6,7].Furthermore, existing literature found that female gender-specific risk factors, especially pregnancy and puerperium and oral contraceptives, are potential risk factors for CVT in women [2][3][4]8].Furthermore, the American Heart Association-American Stroke Association (AHA-ASA) guidelines proposed using full-dose unfractionated or low molecular weight heparin, followed by oral anticoagulation therapy with warfarin for 6-12 months, prompt management to maximize the chance of a favourable outcome [9].
In Bangladesh, there are seldom studies on CVT, which is why there is a paucity of evidence on the prevalence, potential risk factors and prognosis of CVT following long-term anticoagulation treatment.This systematic review will focus on the age of onset, gender distribution and outcome of CVT among the Bangladeshi population to observe the age of CVT onset among sexes.

Search strategy
A literature search was conducted in the all-electronic database, including PubMed, Web of Science, Google Scholar, and BanglaJOL, for all published papers on Bangladeshi CVT of all age groups till November 2023.
The Medical Subject Headings (MeSH) terms were "cerebral venous thrombosis", "CVT", "cerebral venous sinus thrombosis", "CVST", and Boolean terms were "AND" and "OR" to link search terms with for the disease.

Study eligibility criteria
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Figure 1) [10].The systematic review included literature on Bangladeshi CVT patients published in any language and all published studies covering case reports as well as case series on Bangladeshi CVT.However, duplicate literature was excluded from the study.

Data extraction and statistical analysis
The initial search results obtained a total of 85 existing published papers, and after careful evaluation, 13 studies (Table 1) were included in the review [11][12][13][14][15][16][17][18][19][20][21][22][23].Study variables were extracted using structured data sheets and recorded into a database.A MedCalc statistical software package was utilised to calculate the age of CVT onset and gender distribution from included studies.A statistical significance was considered if a P value <0.05.

Outcome
The majority of the published papers observed good clinical outcomes except in one study where Saha and colleagues stated patient mortality was due to early discharge against medical advice [13-18-23].Although most of the studies observed a good prognosis, only three studies reported completed recanalisation on follow-up angiography [15,18,23].

Discussion
This study revealed that women have a higher likelihood (1.5 times) of experiencing CVT than men, and they tend to suffer from it about 13 years earlier than men.The SSS and TS are the most commonly affected sinuses.Additionally, we observed that long-term anticoagulation treatment with either warfarin or rivaroxaban is safe and effective.
This systematic review highlights a paucity of data on CVT among Bangladeshi patients, indicating the need for further research to raise awareness among Bangladeshi clinicians and patients.Although we observed that women are significantly younger than men, similar to previous studies, the age of CVT onset in Bangladeshi women is earlier than in European women (32.4 vs 37 years, respectively) [24][25][26][27].Furthermore, Ranjan and coworkers found that European women suffered CVT three times more than men, whereas Bangladeshi women suffered CVT 1.5 times more commonly than men, results similar to other South Asian studies [25][26][27][28].However, the comparatively low CVT prevalence among Bangladeshi women might be due to lower socioeconomic status and off-limits healthcare facilities.
Although the exact pathophysiology is still unclear, several published papers observed that gender-specific risk factors (especially pregnancy, puerperium, and oral pill) are potential predictors of women's CVT, a result of concordance with the current study findings [4,24,29,30].Nonetheless, like our review findings, Christiansen et al. and Zuurbier et al. found obesity and Martinelli et al. found hyperhomocysteinemia is a potential risk factor for adult CVT [8,[31][32].The CVT diagnosis required a high degree of clinical suspicion confirmed by angiography, either computed tomography (CT) or magnetic resonance imaging (MRI) venography [3,28].Several published papers reported the most common involvement of SSS and TS thrombosis, similar to our findings [3,5,[25][26].Most of our studies utilised MR venography to diagnose CVT, which is helpful in either emergency or subacute cases to confirm the deep venous thrombosis and had better sensitivity and specificity over CT venography [28,[33][34].

Strength and limitations
There is seldom a study on CVT in Bangladesh, which is why this systematic review generates substantial evidence based on published papers among Bangladeshi CVT patients.Further, we first describe the differences in the age of CVT onset between men and women and the prevalence of CVT among Bangladeshis.Like any study, we need to acknowledge limitations, specifically the inclusion of case reports and observational studies in the review, which are potential for bias.However, the lack of studies due to the rare CVT disease mitigates the risk of outcome bias.Although follow-up angiographic evaluation of CVT might be a concern, the low socioeconomic conditions and good clinical profile on follow-up minimise the risk of outcome bias.

Conclusions
This systematic review observed that Bangladeshi women are significantly younger and suffer CVT 1.5 times higher than men.Considering the rarity of CVT and the paucity of enough power evidence on Bangladeshi CVT, this systematic review findings provide substantial evidence regarding the diagnosis and management of CVT.However, we recommended large-scale studies to evaluate the long-term outcome, especially the safety and efficacy of the anticoagulants, recanalisation, and recurrence of CVT.

FIGURE 1 :
FIGURE 1: PRISMA flow diagram according to PRISMA 2020 guidelines illustrates different phases of systematic review.PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses[10]