February 12, 2007 (San Francisco) — Pooled analysis of 3 trials of randomized patients confirms mortality is reduced with decompressive surgery after malignant infarction of the middle cerebral artery (MCA) and establishes that surgery increases the number of patients who survive with a good functional outcome.
That the surgery decreases mortality in these major strokes has been known for some time, but what has not been clear is the quality of life for those survivors, said Werner Hacke, MD, from the University of Heidelberg, Germany, who presented results on behalf of researchers from the pooled DESTINY, DECIMAL, and HAMLET trials.
In this analysis, "decompressive surgery increases the probability of survival without increasing the number of very severely disabled survivors, or in short, decompressive surgery is likely to increase functional outcome among survivors," Dr. Hacke concluded.
The results were presented here at the International Stroke Conference 2007, coinciding with online publication February 9 in Lancet Neurology.
Devastating Choice
Malignant infarction of the middle cerebral artery is a devastating stroke, associated with a mortality of up to 80% stemming from life-threatening space-occupying edema that develops usually between the second and fifth day after stroke onset. Nonrandomized studies have suggested convincingly that mortality can be significantly reduced in these patients, down to levels of 20% to 30% with decompressive surgery. The surgery involves hemicraniectomy, removing a large bone flap from the skull, and duraplasty, allowing the swelling brain to expand without obstruction.
What was not clear is whether this reduced mortality simply increased the number of survivors with poor functional outcome, Dr. Hacke said. Uncontrolled studies had suggested it did not, but the problem has been the fact that randomizing these patients is a delicate and difficult proposition.
"Think: you have a 50-year-old mother of 4 and you go into a randomization process and she is randomized to conservative therapy. You know the chance she will die is 70%, 80%, and we knew from our series — and everyone accepts that — we can cut it down to 30%, 20%" with this surgery, he said. However, that survival may be in a hopelessly vegetative state. The upshot he said, is that "you don't want to randomize a single patient more" than is needed to have clear results.
This study was a novel approach to getting an answer as rapidly as possible and represents a pooled analysis of 3 randomized studies that were enrolling these patients: the Hemicraniectomy After Middle Cerebral Artery Infarction with Life-Threatening Edema (HAMLET) trial, being conducted in the Netherlands; the German Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) trial; and the French Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarcts (DECIMAL) trial.
The principal investigators met while the trials were still ongoing to prospectively design the protocol for the pooled analysis, including all patients aged between 18 and 60 years who were treated within 48 hours of stroke onset. Pooled data on a total of 93 patients, roughly one third from each contributing trial, were analyzed by an independent group, Peter M. Rothwell, MD, and colleagues at Oxford University, United Kingdom.
The primary outcome measure was the score on the modified Rankin Scale (mRS) at 1 year, dichotomized between favorable (0 – 4) and unfavorable (5 and death). Secondary end points were case fatality at 1 year and dichotomization of the mRS between 0 and 3 and 4 to death.
Their results confirmed that more patients in the decompressive-surgery group survived in numbers similar to those seen in previous series, and more survived with relatively good outcomes compared with control patients. Numbers needed to treat were 2 for survival, 2 for the primary end point of mRS < 4, and 4 for an mRS score of < 3, indicating moderate disability. All differences were highly statistically significant.
Functional Outcome and Survival With Decompressive Surgery vs Control
|
End point
|
Decompressive Surgery Group, %
|
Control Group, %
|
Pooled Absolute Risk Reduction, % (95% CI)
|
Number Needed to Treat
|
|
mRS < 4 at 12 mo
|
75
|
24
|
51
(34–69) |
2
|
|
mRS < 3 at 12 mo
|
43
|
21
|
23
(5-41) |
4
|
|
Survival at 12 mo
|
78
|
29
|
50
(33-67) |
2
|
The effect of surgery was consistent across all the trials and in all subgroups, including patients younger than and older than 50 years of age, with and without aphasia, and in those randomized within less than 24 hours or more than 24 hours after stroke onset.
Their results have some limitations, Dr. Hacke noted; among these is the lack of information on patients older than 60 years of age. The decision to perform surgery should still be made on an individual basis in each patient.
However, he told Medscape that in the German DESTINY trial, they had a structured interview with surviving patients and their caregivers, including questions on whether they would make the same decision again to have the surgery done, given their current condition or that of their relative. "And we have 100% yes, we are happy that we have done it," he said, "and that was very reassuring."
Not a "Bridge Too Far"
Commenting on these findings for Medscape, Robert J. Adams, MD, from the Medical College of Georgia, in Augusta, called these findings a "real contribution." As a treatment option, decompressive surgery is highly invasive, and some neurosurgeons are reluctant to perform it, he said. The first time Dr. Adams proposed this surgery to a neurosurgeon formerly at his institution, the surgeon said, "Basically, this is a bridge too far," Dr. Adams said. "Well I think what we saw today is that it's not a bridge too far."
He will be looking to the published results for some guidance on patient selection, he said, "because that's been an issue too — who to do this in or when to advocate it being done."
Jan Paul Muizelaar, MD, PhD, a neurosurgeon at the University of California, Davis, agreed that neurosurgeons are often reluctant to perform this procedure. These new findings, he said, will change some neurosurgeon's minds — including his own. "I think those neurologists who ask us to do it now have much more fodder to convince us that it is good for the patients.
"I really feel that the gold standard for almost everything should be randomized trials, and this was a good randomized trial, a good analysis that shows no, we are not just keeping people alive in hopeless conditions where they need to be shipped off to nursing homes. A good number of them can go back home, and I think that's very important knowledge," he said.
Based on these results, the surgery will probably be offered in all patients to 60 years of age and then in a more selective way to older patients, Dr. Muizelaar added.
Philip Gorelick, MD, from the University of Illinois at Chicago and chair of the International Stroke Conference Program Committee, pointed out that although older patients also face this complication, it often affects younger patients with MCA infarctions and poor collateral circulation because they have not experienced the brain shrinkage that older patients have by the time they have this type of stroke.
"Early decompressive surgery is a life-saving procedure that may also reduce neurological morbidity as judged by the modified Rankin Scale," he told Medscape. "The decision to undergo such surgery, however, should be made on an individual case-by-case basis. Patient preference must be carefully considered as part of the decision-making process, as there is still risk that the patient will survive with a poor neurological outcome and require extensive nursing care."
Dr. Hacke reports no conflict of interest. He and Dr. Adams are members of the editorial board for Medscape Neurology and Neurosurgery.
Lancet Neurol. Published online February 9, 2007.
Medscape Medical News © 2007 Medscape
Cite this: Susan Jeffrey. Decompressive Surgery After MCA Stroke Reduces Death, Improves Functional Outcome - Medscape - Feb 12, 2007.
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