Peripheral lymphocytes entering brain ischemic regions orchestrate inflammatory responses, catalyze tissue death, and worsen clinical outcomes of
acute ischemic stroke (AIS) in preclinical studies. However, it is not known whether modulating
brain inflammation can impact the outcome of patients with AIS. In this open-label, evaluator-blinded, parallel-group clinical pilot trial, we recruited 22 patients matched for clinical and MRI characteristics, with anterior cerebral circulation occlusion and onset of
stroke that had exceeded 4.5 h, who then received standard management alone (controls) or standard management plus
fingolimod (
FTY720,
Gilenya, Novartis), 0.5 mg per day orally for 3 consecutive days. Compared with the 11 control patients, the 11
fingolimod recipients had lower circulating lymphocyte counts, milder neurological deficits, and better recovery of neurological functions. This difference was most profound in the first week when reduction of National Institutes of Health
Stroke Scale was 4 vs. -1, respectively (P = 0.0001).
Neurological rehabilitation was faster in the
fingolimod-treated group. Enlargement of lesion size was more restrained between baseline and day 7 than in controls (9 vs. 27 mL, P = 0.0494). Furthermore, rT1%, an
indicator of microvascular permeability, was lower in the
fingolimod-treated group at 7 d (20.5 vs. 11.0; P = 0.005). No
drug-related serious events occurred. We conclude that in patients with acute and anterior cerebral circulation occlusion
stroke, oral
fingolimod within 72 h of disease onset was safe, limited secondary tissue injury from baseline to 7 d, decreased microvascular permeability, attenuated neurological deficits, and promoted recovery.