Recanalization in Cerebral Venous Thrombosis

If you have a blood clot in a vein in your brain, they don't bother telling you what the results are; just a better chance of favorable outcome if you get recanalized. Once again missing the whole point of stroke research; what interventions get us to 100% recovery. Every research article should be written and evaluated in that light. Not this beating around the bush and quoting statistics like they are useful to stroke survivors.
https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.022129?platform=hootsuite

A Systematic Review and Meta-Analysis

Diana Aguiar de Sousa

,

Lia Lucas Neto

,

Patrícia Canhão

and

José M. Ferro

Originally published18 Jul 2018Stroke. 2018;49:1828-1835

Abstract

Background and Purpose—

The role of recanalization of the occluded dural sinus or vein in the outcome of patients with cerebral venous thrombosis (CVT) is not established. We aimed to systematically review, in patients with CVT, (1) the recanalization rate and its association with (2) clinical outcome and (3) CVT recurrence.

Methods—

Systematic search in MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane Library, and clinicaltrials.gov (inception to September 2017). We considered cohort studies reporting the recanalization rate in adult patients with CVT treated with anticoagulation. Reported rates of venous recanalization at the last follow-up, functional outcome defined using the modified Rankin scale at last follow-up dichotomized for favorable (0–1) and unfavorable (2–6) outcome, and recurrence rate of CVT according to recanalization status were extracted independently by 2 authors. Meta-analyses of proportions were performed using Freeman-Tukey double arcsine transformation. Functional outcomes according to the recanalization status were compared using meta-analysis and ordinal logistic regression. We conducted sensitivity analyses for time to assessment of recanalization and study quality.

Results—

Four hundred sixty-eight studies were identified, and 19 studies were included. (1) We found report of 694 patients with recanalization in the follow-up among 818 cases of CVT. The overall pooled proportion of patients achieving recanalization was 85% (95% confidence interval, 80–89; I²=58%). In studies with higher methodological quality, the recanalization rate was 77% (95% confidence interval, 70–82; I²=0%). (2) There was a significant increase in the chance of favorable outcome (modified Rankin scale, 0–1) in patients with recanalization with a pooled odds ratio of 3.3 (95% confidence interval, 1.2–8.9; I²=32%) in the random effects meta-analysis and a common odds ratio of 3.3 (95% confidence interval, 1.7–6.3) in the ordinal logistic regression. (3) Data on CVT recurrence according to recanalization was scarce.

Conclusions—

The overall rate of recanalization in patients receiving anticoagulation was 85%, but exclusion of severe patients from follow-up imaging is a plausible source of bias. Lack of venous recanalization was associated with worse clinical outcome.

Introduction

Thrombosis of the cerebral veins and sinuses (cerebral venous thrombosis [CVT]) is a distinct cerebrovascular disorder with a highly variable and unpredictable clinical course and in which, despite treatment, death or dependence occurs in ≈15% of patients with CVT.¹

The clot itself is the primary target of current CVT treatments. However, although evidence from animal models of CVT suggests that early venous recanalization has an impact on brain tissue damage,² the hypothesis that reopening of occluded sinuses and veins improves clinical outcome is not established in patients with CVT. Venous recanalization, that is, recanalization of sinuses or veins, may improve regional perfusion and, therefore, allow salvage of threatened tissues. However, several factors may weaken this relationship, particularly if this occurs too late to benefit affected tissues or if collateral circulation, common in the venous territories, protects perfusion. Besides, recanalization of sinuses may not restore drainage effectively if veins or microcirculation remain occluded.

Cohort studies evaluating rate and temporal profile of recanalization in patients with CVT receiving standard therapeutic anticoagulation have shown variable results. A prior systematic review published in 2006 highlighted the scarcity of data and the subsequent poor quality of the estimated recanalization rates.³ Importantly, studies assessing the relationship between venous recanalization and prognosis in patients with CVT have shown conflicting results.^4–6 One possible explanation could be the variable extent and function of collateral circulation, which was not analyzed in these cohorts. However, an independent effect of venous collateral circulation on the prognosis of patients with CVT has not been shown previously.⁷

As described for low-extremity deep vein thrombosis,⁸ recanalization may also influence the risk of CVT recurrence. This association has already been suggested in a large cohort of pediatric patients with CVT⁹ but remains to be shown in adult patients.

We performed a systematic review of the published evidence to better estimate, in patients with CVT receiving standard anticoagulation treatment, (1) the recanalization rate and its association with (2) clinical outcome and (3) CVT recurrence.

Methods

For the purpose of this systematic review, we followed the MOOSE (Meta-Analysis of Observational Studies in Epidemiology)¹⁰ proposal and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)¹¹ guidelines. The authors declare that all supporting data are available within the article and its online-only Data Supplement.

Eligibility Criteria

We considered published observational cohort studies reporting original data on the recanalization status after acute CVT in adults, using noninvasive imaging (computed tomographic venography or magnetic resonance imaging). Cohort studies including at least 10 patients with evaluation for the recanalization status were accepted. We did not exclude studies a priori owing to poor quality. Articles in English, German, French, Spanish, Italian, and Portuguese were accepted. Series of pediatric patients or traumatic CVT were excluded. Cohorts in which >10% of patients received endovascular treatment or were not anticoagulated were also excluded.

Definitions

We considered imaging outcomes in follow-up, assessed using computed tomographic venography or magnetic resonance (complete recanalization, partial recanalization, and no recanalization), and clinical outcomes (full modified Rankin scale [mRS] score in the last available follow-up; recurrent CVT).

We used the following definitions of outcomes for data extraction and analysis:

To assess the quality of the author’s definitions of complete, partial, and absent recanalization of each individual occluded sinus or vein, we compared them with the following standard: complete recanalization defined as blood flow without any interruption, partial recanalization defined as small interruptions of continuous blood flow and narrowing of the venous lumen, and absent recanalization defined as interrupted blood flow.

Recanalization at the patient level was considered when there was recanalization of at least 1 sinus or vein in an individual patient with CVT. No recanalization was defined as total absence of any type of recanalization in any previously thrombosed sinus or vein in an individual patient with CVT. Complete recanalization was considered when all previously thrombosed structures met the criteria of complete recanalization. Whenever the criteria for complete recanalization were not fulfilled but at least 1 vessel displayed any type of recanalization, we considered this as partial recanalization.

We considered the earliest proof of recanalization in the imaging studies as the time point of recanalization.

Clinical outcomes were defined using the mRS in the last available follow-up. Favorable outcome was defined as complete recovery, demonstrated by mRS 0 to 1.

CVT recurrence was defined as new CVT diagnosis confirmed with imaging in a patient with prior CVT.

Search Strategy

A systematic search using combinations of keywords was performed in Pubmed, Cochrane Library, and clinicaltrials.gov from inception to September 10, 2017. The developed search strategy for all databases combined the terms sinus, thrombosis, cerebral, vein/venous or intracranial, and recanaliz* or recanalis*, as described in the online-only Data Supplement. Potential eligible studies and selected studies’ reference lists were crosschecked for additional studies.

Study Selection

Reports retrieved through electronic identification were screened for potential eligibility by title and abstract analysis. The full text of potentially eligible studies was screened for appropriateness for inclusion by 2 independent authors (D.A.d.S., L.L.N.). Disagreements were solved by consensus or by a third independent party (P.C., J.M.F.).

Data Collection Process

Two independent parties (D.A.d.S., L.L.N.) extracted data from included studies’ full text to a specially designed form. Disagreements were solved by consensus or by a third independent party (P.C., J.M.F.). Corresponding authors were contacted for additional information if needed.

Data Items

For the selected studies, we extracted the following data: country, study design, year of publication, study setting, number of patients, median/mean follow-up, number of patients with follow-up noninvasive imaging, imaging method used for assessment of recanalization, number of patients with recanalization (complete/partial) and no recanalization at the last follow-up, number of patients with recanalization (complete/partial) according to time point(s), mean/median time between diagnosis and last follow-up imaging, predictors of recanalization, number of patients with recurrent CVT according to recanalization status, clinical outcome (mRS) according to recanalization status, and mortality rate according to recanalization status.

Assessment of Study Quality

The studies eligible for inclusion in the meta-analysis were assessed for quality of study design and data reporting, according to the grading of recommendations, assessment, development, and evaluation approach¹² (Table I in the online-only Data Supplement).

Summary Measures

The primary outcomes were recanalization rate in the last imaging follow-up in patients with CVT, functional outcome according to recanalization status and recurrence rate of CVT according to recanalization status. The secondary outcome was rate of partial and complete recanalization in the last imaging follow-up and mortality rate according to recanalization status.

Sensitivity analyses were conducted by excluding studies with recanalization assessment after <3 months and studies in which quality was classified as low.

Synthesis of Results/Statistical Analysis

We calculated the pooled incidence of recanalization per 100 individuals with CVT and 95% confidence intervals (CIs) using meta-analysis of proportions. A random effects model with Freeman-Tukey double arcsine transformation was used for pooling the proportions. Heterogeneity among studies was assessed with Cochran Q test. The percentage of total variation across studies because of heterogeneity was evaluated by the I² measure. The presence of publication bias was interrogated by funnel plots. Extracted pooled incidences of dichotomized functional outcomes and recurrence rates according to recanalization status were pooled using a random effects model (DerSimonian Laird) owing to the presumed heterogeneity between individual study estimates and compared using odds ratio (OR). Overall incidences of functional outcomes according to the recanalization status were compared using proportional odds ordinal logistic regression to analyze shifts across the full range of the mRS. A P value of 0.05 was considered statistically significant. All analyses were conducted using Stata Statistical Software Release 14 (StataCorp, College Station, TX).

Results

We identified 468 nonduplicate references using our search strategy in Pubmed, Cochrane Library, and clinicaltrials.gov ( online-only Data Supplement), and 11 additional studies were obtained from manually reviewing references. We excluded 403 publications after evaluation of titles and abstracts using the predefined inclusion and exclusion criteria. We retrieved 65 studies in full text for detailed evaluation and verification of overlaps in study populations. Finally, we selected 19 studies.^{4–6,13–28} A MOOSE/PRISMA flowchart summarizes study selection, including the reasons for exclusion (Figure 1). Details of the studies are displayed in the Table.