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MISTIE Sends a Mixed Message of Hope in Intracerebral Hemorrhage


HONOLULU—A minimally invasive treatment for evacuating blood clots caused by intracerebral hemorrhage (ICH) appears to reduce mortality, but, overall, did not improve function among patients at one year, researchers reported here at the 2019 International Stroke Conference, sponsored by the American Stroke Association.

In the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE 3) trial, about 45 percent of patients who underwent the combination of surgery and catheter-based clot evacuation and about 41 percent of patients treated medically achieved a modified Rankin Scale (mRS) score of 0–3—an indication of good functioning—but that difference failed to reach statistical significance,  Daniel F. Hanley, MD, FAAN, professor of acute neurology at Johns Hopkins University in Baltimore, told Neurology Today At the Meetings.

There were nine deaths among the 256 patients who were assigned to receive the surgical treatment compared with 15 deaths among the 250 patients treated medically (p=0.037), Dr. Hanley reported in his oral, late-breaker presentation.

Outcomes were enhanced if surgeons made a concerted effort to get more than an average amount of the clot out of the brain, co-author Issam A. Awad, MD, director of neurovascular surgery at the University of Chicago Medicine and Biological Sciences told Neurology Today At the Meetings. Dr. Awad said that if 50 percent or more of the clot was removed, there was a benefit in mortality, but if more than 70 percent was removed to a point where less than 15 mL of the clot remained, there was also a benefit in function.

Dr. Hanley said that there was a 10.5 percent difference in achieving an mRS score of 0–3 in favor of the surgery technique if the clot volume was below 15 mL when compared with the medically-treated controls (p=0.03).

The researchers noted that the minimally invasive treatment can be taught to those who have not attempted the procedure before the trial. In MISTIE III, 88 percent of the doctors were performing their first procedure. There is currently no effective surgical treatment for intracerebral hemorrhage, which is the most common type of lethal brain bleed. The MISTIE procedure avoids the damage of traditional craniotomy by using imaging to guide placement of a soft tube into the blood clot through a small hole in the skull to remove large amounts of blood and toxic blood components. It uses a low mechanical impact procedure with suction and up to three days of gentle irrigation with the clot-busting drug alteplase.

Alteplase was delivered every eight hours and up to nine doses were permitted, but they used an average of three doses, Dr. Awad said in his presentation. He suggested that many of the doctors, after removing a substantial amount of clot, decided to stop before reaching the 15 mL threshold.

"The more clot removed, the better the patient's outcome was," Dr. Awad said. "For every mL removed beyond 15 mL, there was a subsequent 10 percent chance of further improvement in functional outcomes."

"The trial confirmed that removal of the blood clot using the MISTIE procedure can be done safely as compared to supportive therapy. But there was no difference in functional recovery between those in the surgery group and the medical group," said Dr. Hanley. "The trial results do suggest that patients have improved functional recovery when the blood clot size is reduced to about 3 tablespoonsful or less of blood. This will require further study, but, at a minimum, the trial data provide a sound basis to avoid limiting care in patients with large brain blood clots."

Commenting on the study, Louise D. McCullough, MD, PhD, chair of neurology at the McGovern Medical School at the University of Texas at Houston Health Science Center, and vice-chair of the International Stroke Conference, told Neurology Today At the Meetings: "Before MISTIE III we weren't really sure how much blood we could leave in the head after an intracerebral hemorrhage. You could potentially make things worse if you were extracting normal brain tissue and trying to get every last bit of blood out. I think this study showed that if you can get to 15 mL, you are going to do really well. Less is more."

"So I think this is really useful if we are going to design trials going forward because we did see an efficacy signal in the group of patients with less than 15 cc of blood left in the brain," she continued.

"I think we still need a trial that would show functional benefit. That is what matters to patients.

However, ICH is a terrible disease, there is no treatment for it, and there may be a signal that this can work for patients, especially those with no other option. I think that because it was easy to train doctors to do this procedure and there was very little downside in terms of increased mortality, this might be performed in selected patients," Dr. McCullough said.

"We would prefer to see a clinical trial done with the refinements suggested by MISTIE 3, but at the very least they should be done in conjunction with a registry. I think my own institution will continue to do this because it is all we have to offer these patients, and I think all these cases should be done in a registry," she said.

The National Institute of Neurological Disorders and Stroke funded the study and Genentech Inc. donated alteplase. Dr. Hanley has served as a consultant and on the advisory boards of BrainScope, Neurotrope, Portola Pharmaceuticals, Op2Lysis, and HeadSense. Dr. Awad had no disclosures.


ISC Abstract LB4: Hanley DF, Zuccarello M, Awad IA, et al, for MISTIE 3 Investigators. MISTIE 3 trial results.