Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial.
BACKGROUND
Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke.


METHODS
We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 microg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core.


RESULTS
All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis.


CONCLUSIONS
Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes.
Shyu
Woei-Cherng
WC
Neuro-Medical Scientific Center, Buddhist Tzu-Chi General Hospital, Tzu-Chi University, Hualien, Taiwan.
Lin
Shinn-Zong
SZ
Lee
Chau-Chin
CC
Liu
Demeral David
DD
Li
Hung
H
D000208:Acute Disease; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016179:Granulocyte Colony-Stimulating Factor