Among patients with acute ischemic stroke treated with thrombolysis, pre-treatment cerebral microbleeds (CMBs) predict a higher risk for symptomatic intracerebral hemorrhage (ICH) and poor functional outcome, according to a study published in Neurology.
ICH is the most feared complication of thrombolysis with intravenous (IV) recombinant tissue plasminogen activator (rtPA) for acute stroke therapy, and symptomatic ICH is associated with poor functional outcome.1 CMBs on pre-treatment magnetic resonance imaging (MRI) represent small vessel disease at risk for spontaneous ICH.2 Whether CMBs predict symptomatic ICH after IV rtPA remains unclear, as several studies report conflicting findings.
Andreas Charidimou, MD, MSc, PhD, of Massachusetts General Hospital in Boston, and Ashkan Shoamanesh, MD, of McMaster University in Canada, together with the International META-MICROBLEEDS initiative performed an updated review and meta-analysis of the published data on CMBs and their relationship with post-rtPA symptomatic ICH and functional outcomes at 3 to 6 months.
A total of 8 studies were evaluated. Definitions of symptomatic ICH differed between studies, but most studies considered ICH symptomatic if it was associated with an increase of at least 2 to 4 points in the NIH Stroke Scale score within the first week. The authors defined poor functional outcome as modified Rankin Scale score >2.
Of 2601 patients with acute stroke treated with IV rtPA, 24% had CMBs. The risk of symptomatic ICH after rtPA among patients with CMBs was double that of patients without CMBs (5% vs 3%; odds ratio [OR], 2.18; P =.021).
Of the 8 studies analyzed, 4 (n =1665) reported 3- to 6-month functional outcomes after thrombolysis. Poor functional outcome occurred more frequently among patients with CMBs than among patients without (52% vs 41%; OR, 1.58; P =.002).
“The main limitation of this study is that the authors could not obtain information about other risk factors for symptomatic ICH, and therefore their analysis could not be adjusted for those risk factors,” Nicolas Raposo, MD, of the University of Toulouse in France and author of a related editorial, said in an interview with Neurology Advisor. Risk factors that increase the likelihood of symptomatic ICH include older age, large infarct volume, and high blood glucose levels.
Although the presence of CMBs is associated with a higher risk of symptomatic ICH and poor functional outcome after IV rtPA for acute ischemic stroke, the researchers concluded that “this risk seems acceptable and should probably not discourage recanalization therapies in this patient population.”
“However, a crucial question remains: among patients with pre-treatment CMBs, do patients who are treated with IV thrombolysis have worse outcomes than those who are not?” Dr Raposo said. “Randomized controlled trials are needed to answer this question.”
Disclosures: Dr Raposo and Dr Charidimou do not report any relevant disclosures. Dr Shoamanesh receives funding from the Marta an Owen Boris Chair in Stroke Research and Care.
- Raposo N, Curtze S. Cerebral microbleeds in acute ischemic stroke: A red flag for IV thrombolysis. Neurology. 2016 Sept 14. doi:10.1212/WNL.0000000000003216.
- Charidimou A, Shoamanesh A; International META-MICROBLEEDS Initiative. Clinical relevance of microbleeds in acute stroke thrombolysis: Comprehensive meta-analysis. Neurology. 2016 Sept 14; doi: 10.1212/WNL.0000000000003207.