The Relationship of Matrix Metalloproteinase-9 and Microbleeds on T2*-Weighted Gradient-Echo MRI in Acute Lacunar Infarction

ABSTRACT

BACKGROUND: Hypointense cerebral lesions on T2*-weighted gradient-echo MRI (GRE) have been known to be related with microbleeds or advanced microangiopathy with potential for further bleeding. It has also been suggested that matrix metalloproteinases (MMPs) may play a role in blood brain barrier disruption, edema formation and hemorrhagic transformation. In this study, we investigated the relationship between microbleeds detected by GRE, MMPs and neurological worsening in acute lacunar infarctions. METHODS: Eighty-eight patients with acute lacunar infarctions, defined by TOAST classification, were included. GRE (1.5T, TR 500 ms TE 15 ms) was performed within 48 hours after stroke symptom onset. MMPs were measured by standard quantitative sandwich enzyme-linked immunosorbent assays (ELISA). Clinical characteristics, neurologic scale and MMP-9 levels were compared between groups with or without hypointense lesions in GRE (microbleeds). Neurological worsening was defined as deterioration from baseline in the score on the NIHSS by one or more points 14 days after the onset of a lacunar infarction. RESULTS: Eleven of 88 patients (12.5%) undergoing GRE demonstrated evidence of microbleeds in the ischemic region. In the groups with microbleeds, the ESR level (p=0.048) and MMP-9 activity (p=0.001) were significantly increased, and neurological worsening was more prominent (p=0.018). CONCLUSIONS: This study suggests that microbleeds detected by GRE are related with elevated MMP-9 and neurological worsening. Therefore, the finding of microbleeds in GRE, increased MMP-9 activity and elevated ESR level might be useful factors for predicting the progression of acute lacunar infarctions.