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Impact of an immune modulator fingolimod on acute ischemic stroke.

Abstract
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.
AuthorsYing Fu, Ningnannan Zhang, Li Ren, Yaping Yan, Na Sun, Yu-Jing Li, Wei Han, Rong Xue, Qiang Liu, Junwei Hao, Chunshui Yu, Fu-Dong Shi
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 51 Pg. 18315-20 (Dec 23 2014) ISSN: 1091-6490 [Electronic] United States
PMID25489101 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine
Topics
  • Adult
  • Aged
  • Brain Ischemia (drug therapy)
  • Case-Control Studies
  • Female
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents (adverse effects, therapeutic use)
  • Lymphocyte Subsets
  • Male
  • Middle Aged
  • Propylene Glycols (adverse effects, therapeutic use)
  • Single-Blind Method
  • Sphingosine (adverse effects, analogs & derivatives, therapeutic use)
  • Stroke (drug therapy)

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