Minocycline Reduces Stroke Damage in Late-Presenting Patients

HOLON, Israel, Oct. 1 -- Patients with acute ischemic stroke had significantly better neurologic and functional outcomes when started on the antibiotic minocycline within 24 hours of onset of symptoms, researchers reported.

Although the patients arrived at the emergency department after the therapeutic window for tissue-plasminogen activator (tPA) had slammed shut, patients who received a five-day course of minocycline had National Institute of Health Stroke Scale scores that were one-fourth those seen with patients who received a placebo, said Yair Lampl, M.D., of the Edith Wolfson Medical Center here, and colleagues.

At three months, the patients who had received minocylcine (Minocin, Dynacin, Myrac) had a mean NIHSS score of 1.6, indicating little or no disability, compared with 6.5, near the upper limit for mild disability, for patients treated with placebo, the investigators reported in the Oct. 2 issue of Neurology.

"The improvement was already apparent within a week of the stroke," said Dr. Lampl, who is also with Tel Aviv University.

Minocycline treatment was not, however, associated with lower risk of death, myocardial infarction, recurrent strokes, or hemorrhagic transformation, the investigators said.

Minocycline, a semi-synthetic derivative of tetracycline, is thought to have both anti-inflammatory and anti-apoptotic properties. It has been shown to have a significant and beneficial neurorprotective effect in animal models of multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, they said.

To see whether minocycline at 200 mg daily (a dose previously shown to be safe) could be beneficial in patients with acute ischemic stroke, the authors conducted an open-label, evaluator-masked trial.

Patients were enrolled from among all who presented to the emergency department with acute ischemic stroke at least six hours but no later than 24 hours after the onset of symptoms.

The patients were randomly assigned, based on their identity card numbers, to receive usual post-stroke care plus either oral minocycline 200 mg or placebo for five days.

The outcome measures were neurologic deficits, global functional abilities, and the level of handicap scored using the NIHealth Stroke Scale, modified Rankin scale, and Barthel Index. The patients were evaluated by a staff member blinded to treatment assignment at baseline and at one week, one month, and three months.

A total of 152 patients with a mean age of 66.7 were enrolled.

The average time to treatment was approximately 12 hours in both the minocycline and placebo groups.

No patients were lost to follow-up or dropped out because of adverse events during the study, but 14 died during follow-up: five in the minocycline group, and nine in the placebo group.

There were no significant differences between the groups at baseline in either age, gender, or stroke etiology, but patients assigned to minocycline had received sulfonylureas on a four to one ratio compared with patients assigned to placebo, and significantly more controls had received ACE inhibitors than treatment-group patients.

The authors found that at three months mean NIHSS scores were significantly lower among minocycline-treated patients, at 1.6 + 1.9, compared with 6.5 + 3.8 for placebo-treated patients (P