Association between plasma levels of hyaluronic acid and functional outcome in acute stroke patients

Background: Activation of hyaluronic acid (HA) and associated enzyme synthesis has been demonstrated in experimental stroke animal models. Our study aimed to investigate the plasma levels of HA in acute stroke patients and the associations between HA levels and functional outcome. Methods: This was a multicenter case-control study. Acute stroke patients and age-and sex-matched non-stroke controls were recruited. Plasma levels of HA in acute stroke patients were determined at <48 hours and at 48 to 72 hours after stroke onset by standard ELISA. Favorable functional outcome was defined as modified Rankin scale <= 2 at 3 months after stroke. Results: The study included 206 acute stroke patients, including 43 who had intracerebral hemorrhage and 163 who had ischemic stroke, and 159 controls. The plasma levels of HA in the acute stroke patients were significantly higher than those in the controls (219.7 +/- 203.4 ng/ml for <48 hours and 343.1 +/- 710.3 ng/ml for 48 to 72 hours versus 170.4 +/- 127.9 ng/ml in the controls; both P < 0.05). For intracerebral hemorrhage patients, HA <= 500 ng/ml (<48 hours) was an independent favorable outcome predictor (P = 0.016). For ischemic stroke patients, an inverted U-shaped association between plasma HA (48 to 72 hours) and outcome was noted, indicating that ischemic stroke patients with too high or too low plasma HA levels tended to have an unfavorable outcome. Conclusion: HA plasma level was elevated in patients with acute stroke, and can predict 3-month functional outcome, particularly for patients with intracerebral hemorrhage.