Brush Sign Is Associated With Increased Severity in Cerebral Venous Thrombosis

We used longitudinal data from 2 cohorts of adult patients with diagnosis of acute CVT: patients admitted to Hospital Santa Maria, Lisbon, between January 2010 and April 2018 (Cohort 1) and to Inselspital, Bern, between October 2009 and April 2018, included in the Bernese Stroke Registry (Cohort 2). In Cohort 1, data were collected retrospectively from January 2010 to April 2014 and prospectively between May 2014 and April 2018. Both registries were approved by the local medical ethical committees. Patients included in the prospective studies provided written informed consent. In the retrospective registry, the institutional review board waived the requirement of informed consent. The data that support the findings of this study are available from the corresponding author on reasonable request. Inclusion criteria, MRI parameters, clinical, imaging, and statistical analysis methods are provided in the online-only Data Supplement.

From the 148 CVT patients admitted during the study period, 30 patients were excluded because they did not meet the imaging inclusion criteria or had concomitant intracranial disease. One hundred eighteen patients were included: 62 patients from Cohort 1 and 56 patients from Cohort 2. There were 91 females and 27 males (female/male ratio, 3:1). Patient characteristics were comparable in both cohorts (Table I in the online-only Data Supplement).

BS was identified in 17 patients (14%): 10 (16%) in T2* (Figure 1) and 7 (13%) in SWI (Figure 2). The interrater reliability (κ) for BS identification was 0.97 in Cohort 1 and 1.00 in Cohort 2. Besides the medullary veins, other veins draining into the deep system were engorged in multiple cases (Table II in the online-only Data Supplement). Demographic data and imaging findings are summarized in Table I in the online-only Data Supplement.

Higher thrombus load was significantly associated with BS (P<0.0001; Figure I in the online-only Data Supplement). Brain lesion was more common in patients with BS (odds ratio, 6.4; 95% CI, 1.9–21.1; P=0.002).

In BS-positive patients, thrombosis of the straight sinus or deep venous system, particularly the vein of Galen and ipsilateral internal cerebral vein, was significantly more frequent (Table I in the online-only Data Supplement). All patients with BS had thrombosis involving at least one of the following topographies: superior sagittal sinus, straight sinus, or veins of the deep venous system. When considering only patients with thrombosis of at least one of these vessels, the proportion of positive BS in patients evaluated with T2*WI or SWI was 25% (10/40) and 27% (7/26), respectively. A follow-up MRI was available for 81% of patients (96/118). In 10 out of 17 patients, the signal was absent in follow-up evaluations. No de novo BS was identified in the follow-up.

The median time from symptom onset to MRI evaluation was 5 days both in patients with or without BS. All patients received standard treatment with anticoagulation. CVT manifested by isolated intracranial hypertension was more common in patients not having BS (odds ratio, 6.0; 95% CI, 1.6–22.4; P=0.007). Clinical manifestation with focal neurological deficits was more frequent in patients with BS (odds ratio, 4.2; 95% CI, 1.4–12.7; P=0.01). Functional outcome at 3 months was available for 87% of patients (103/118). Favorable outcome (modified Rankin Scale score <2) at 3 months was similar in patients with positive BS and in the remaining cases (P=0.84).

One main finding in this study is that an abnormal vessel hypointensity at paramagnetic-sensitive MR sequences involving the medullary veins, previously described as BS, occurs in 14% of patients with acute CVT. BS was originally described as a unilateral change in patients with occlusion of the middle cerebral artery.² In these CVT cohorts, a bilateral sign was observed in 10 out of 17 positive BS cases, and thrombosis of midline venous structures was evident in all patients. The characteristics of BS were highly consistent, and the interrater agreement was excellent.

Second, this sign was associated with higher thrombus load and with ipsilateral parenchymal brain lesion, both in patients assessed with T2*WI and SWI and for hemorrhagic and nonhemorrhagic lesions. Clinical manifestations were also more severe in patients with BS.

No significant association was observed between the presence of BS and functional outcome measured by the modified Rankin Scale. Future studies are necessary to evaluate whether the BS is associated with worse cognitive and vocational outcomes, which are often affected in patients achieving independence.⁷

Positive BS likely represents increased deoxyhemoglobin in the deep veins, due to increased oxygen extraction fraction, together with engorgement of the medullary and subependymal veins, related with the development of collateralization between the superficial and the deep venous systems of the brain. We noticed that BS disappeared on follow-up imaging in most patients, suggesting this sign can be susceptible to fast changes due to improvement of the tissue metabolic status. This observation, also previously documented in patients with ischemic stroke, can be related in CVT both with early venous recanalization or improvement of collateral circulation, which may become sufficient in preventing progression of tissue damage.⁸ Further studies are needed to confirm whether BS is associated with hypoperfusion and evaluate if longer persistence of BS predicts worse functional outcome.

The key strength of this study is the relatively large sample size and multicenter design, pooling registries of 2 university hospitals that include serial clinical and imaging assessment. The use of 2 different paramagnetic sequences also increases the applicability of the findings. However, several limitations are worth noting, the most important being related with the retrospective design of this analysis. MRI was performed at 2 centers with a different imaging setup and protocol, which required an individual analysis of each cohort for all variables. Additionally, an impact of field strength in the detection of T2*-BS is likely and, therefore, these results cannot be generalized to MRIs performed using 1.5T scanners. Exclusion of patients with severe neurological deficit or dying early, unable to perform acute MRI evaluation, is a potential source of bias. Functional outcome at 3 months was missing in 13% of cases, and we cannot exclude a differential loss to follow-up that might have influenced the association. Yet, clinical follow-up was available for all patients with positive BS, limiting the risk that this confounding would affect our results in a meaningful way.

This case series describes BS in paramagnetic MRI sequences in patients with acute CVT, which was a finding present in approximately one in 7 patients. We demonstrate an association between BS and extent of thrombosis, parenchymal brain lesion, and clinical manifestation with focal neurological deficits, suggesting that BS can represent a marker of severity in the setting of increased intracranial venous pressure related with CVT and should prompt close monitoring during the acute phase.