Neal S. Parikh, MD
Citing the potential utility of silent brain infarcts (SBI) as both a possible stroke risk factor and a surrogate outcome in stroke trials, Dr. Gupta and colleagues performed a systematic review and meta-analysis to evaluate the precise association between SBI and subsequent stroke.
The authors selected studies of adults who had baseline MRI-ascertained SBI and at least 12 months of follow-up for clinical stroke. Studies were vetted and abstracted in a rigorous, pre-specified manner. Meta-analyses were performed with random effects modelling, which controls for occult heterogeneity between individual study samples. The risks of selection bias and publication bias were assessed and found to be low.
The authors selected studies of adults who had baseline MRI-ascertained SBI and at least 12 months of follow-up for clinical stroke. Studies were vetted and abstracted in a rigorous, pre-specified manner. Meta-analyses were performed with random effects modelling, which controls for occult heterogeneity between individual study samples. The risks of selection bias and publication bias were assessed and found to be low.
Thirteen studies were ultimately included. All studies defined SBI as T2 hyperintense lesions at least three millimeters in size, with various methods employed to distinguish SBI from leukoaraiosis and dilated perivascular spaces. Clinical ischemic stroke was typically defined as a neurological deficit lasting greater than 24 hours in the absence of hemorrhage. Not all studies distinguished between ischemic and hemorrhagic stroke.
A total of 14,764 subjects were included, and the mean follow-up for clinical stroke was 76 months. Most subjects were middle-aged or elderly. 3,007 (20%) had SBI on MRI. The crude relative risk of clinical stroke in patients with SBI was 2.94 (95% confidence interval (CI), 2.24-3.86). Eight of the 13 studies provided covariate-adjusted hazard ratios (HR); the aggregate adjusted HR was 2.08 (95% CI, 1.69-2.56).
Subgroup analyses found that the association between SBI and subsequent stroke was present in both stroke-free community-dwelling patients and in patients with prevalent stroke. In both groups, patients with SBI experienced a two-fold increased risk of subsequent stroke.
The major limitations of their study are: variable definitions of SBI as diagnosed on MRIs of variable magnetic field strength, variable inclusion of relevant covariates, inconsistent reporting of ischemic versus hemorrhagic stroke, non-tissue based definition of ischemic stroke, and outdated cohorts (e.g. not subject to contemporary maximum medical therapy of vascular risk factors). These limitations do not, on the whole, negate the study’s findings.
There appears to be a clear, positive association between SBI and subsequent stroke. In current clinical practice, incidental SBIs do not prompt thorough stroke mechanism evaluation or personalized secondary prevention. Our evolving understanding of this entity will surely impact our practice patterns.
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