- Division of Neurosurgery, University of California, San Diego, CA
- Department of Neurology and Neurosurgery, University of Lille North of France, Lille, France
- Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
Clark C. Chen
Division of Neurosurgery, University of California, San Diego, CA
DOI:10.4103/2152-7806.132589Copyright: © 2014 Hatefi D This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Hatefi D, Hirshman B, Leys D, Lejeune J, Marshall L, Carter BS, Kasper E, Chen CC. Hemicraniectomy in the management of malignant middle cerebral artery infarction: Lessons from randomized, controlled trials. Surg Neurol Int 15-May-2014;5:72
How to cite this URL: Hatefi D, Hirshman B, Leys D, Lejeune J, Marshall L, Carter BS, Kasper E, Chen CC. Hemicraniectomy in the management of malignant middle cerebral artery infarction: Lessons from randomized, controlled trials. Surg Neurol Int 15-May-2014;5:72. Available from: http://sni.wpengine.com/surgicalint_articles/hemicraniectomy-in-the-management-of-malignant-middle-cerebral-artery-infarction-lessons-from-randomized-controlled-trials/
Territorial middle cerebral artery (MCA) infarcts are among the most devastating forms of ischemic cerebral disease.[
At present, there have been seven published, RCTs evaluating hemicraniectomy as treatment for malignant MCA infarction.
The first study was termed “HeADDFIRST” (Hemicraniectomy and durotomy on deterioration from infarction-related swelling trial) and was only published as an abstract.[
The second RCT reported was a pooled analysis of one year outcome data from three European multicenter hemicraniectomy RCTs: The French DECIMAL (decompressive craniectomy in malignant MCA infarcts) trial, the German DESTINY (decompressive surgery for the treatment of malignant infarction of the MCA) trial, and the Dutch HAMLET (hemicraniectomy after MCA infarction with life-threatening edema trial). While the inclusion criteria and exclusion criteria of these three studies differed (see below), the clinical results from 93 patients fulfilling the following criteria were pooled: Age 18-60 years, NIHSS (National Institutes of Health Stroke Scale) >15, Infarct >50% of the MCA territory (or approximately >145 ccs), and randomization within 45 h of symptoms. Of note, patients with significant preexisting morbidities were excluded from this analysis (e.g. life expectancy <3 years). In this pooled analysis, hemicraniectomy was associated with a statistically significant reduction of mortality from 75% to 24%. The modified Rankin Scale (mRS,[
Seven months after the publication of the pooled result, the outcome of the German DESTINY trial and the French DECIMAL trials were separately published. The German DESTINY trial[
The French DECIMAL trial[
The Dutch HAMLET trial[
There last two RCT that included patients age >60 years. The first study was reported by Zhao et al.[
The German DESTINY II trial[
Functional outcome of patients surviving territorial MCA infarct after hemicraniectomy as measured by the modified Rankin Scale (mRS). Percent of patients with each mRS scale are shown on the X-axis. Red triangles indicate the demarcation of independent function based on mRS≥3. The mRS of patients >60 from Zhao et al.[
“The only good reason to doubt hemicraniectomy as a treatment for malignant infarcts in the increased proportion of patients with [severe disability].” Didier Leys and Jean-Paul Lejeune, University of Lille North of France
Given the RCT data, the only good reason to doubt hemicraniectomy as a treatment for malignant infarcts is the increased proportion of patients with a mRS 4 (i.e. these patients are unable to attend to their own bodily needs without assistance and are unable to walk unassisted) in patients who underwent the procedure. This is really an issue, but the question is whether we can refuse to offer decompressive surgery to a patient with a large MCA infarct, if there is a high probability of developing malignant infarct, when the treatment increased the probability of being fully independent from 2% to 14%, and of having no or minimal dependency from 21% to 43%? Even if hemicraniectomy for large MCA infarcts still leaves unanswered questions, it should be considered as an important step in the treatment of patients suffering from territorial MCA infarct.
The hemicraniectomy RCTs represent only one step in defining the optimal treatment for large MCA infarcts. There will likely be improvements in the future. First, for such a severe disorder, it is likely that one-year follow-up is too short to evaluate the outcome. There are reports of significant improvements after one year. Second, the selection of patients suitable for surgery will probably improve in the future. Third, registries of patients treated by hemicraniectomy will probably be useful to better identify the best candidates, exactly as we did with intravenous thrombolysis. Finally, more research is needed to better identify patients who should not be treated surgically, and to identify complementary strategies. We should bear in mind that improvements are made by small successive steps nowadays (e.g. in cancer), rarely by a single, important discovery that changes the world, as were the discovery of antirabies vaccination or of penicillin.
“Despite its general applicability, mRS tells us nothing about some of the fundamental issues that most would consider to impact human dignity, such as bowel and bladder control.” Lawrence Marshall, University of California, San Diego.
There are a number of observations that we can gleam from the hemicraniectomy RCTs. First, mortality and morbidity is clearly reduced by hemicraniectomy for patients under the age of 60. Given the variable inclusion criteria and the different time allowance in the trials, pooling the data would be frowned upon by statisticians. Nevertheless, what is encouraging is that hemicraniectomy moved certain patients up the continuum of better functional outcomes in all RCTs for patients under the age of 60. Conversely, hemicraniectomy should not be performed in patients aged >60 as there is no evidence of benefit. Second, there are suggestions that outcome after hemicraniectomy may be improved if the procedure is performed earlier. Of the three European trials, the most unfavorable outcome was observed in the HAMLET trial, where patients underwent DHC within 96 h of presentation.
What could be done better to improve the future hemicraniectomy RCT design? First we need uniform entry criteria. Critical variables to consider include patient age, infarct volume, time to procedure, clinical status (e.g. pupillary reactivity), and whether Intracranial pressure (ICP) monitoring was instituted. The last variable is of particular importance as it can be used to guide the timing of hemicraniectomy. Additionally, we need to use better measures of functional outcome than just the mRS. Despite its general applicability, mRS tells us nothing about some of the fundamental issues that most would consider to impact human dignity, such as bowel and bladder control.
Morbidity and mortality
Irrespective of age, all seven RCTs publications consistently demonstrated that decompressive hemicraniectomy decrease the mortality associated with malignant, territorial MCA infarct from 46-75% to 12-27%, with absolute mortality risk reduction of a half to a third. The picture for morbidity reduction was more mixed. While DECIMAL and DESTINY trials demonstrated that the likelihood of a survivor incurring deficit with mRS≥3 was reduced from approximate 50-25%, such reduction was not observed in the HAMLET, DESTINY II, or the Chinese study. The most notable difference between the latter studies and the former involved the age of the patient population and the timing of the decompression. The HAMLET study allowed randomization up to 96 h post-ictus, while the Chinese and the DESTINY II study involved patients aged >60. Thus, a reasonable interpretation of the data set is that decompressive hemicraniectomy may reduce morbidity in select patient populations. Irrespective of interpretation, the objective data show that patients who survive territorial infarct after decompressive craniectomy have an approximately 30-95% likelihood of living with significant disability characterized by mRS≥3.
The decision of choosing to live with a significant disability versus opting for comfort care when facing the consequences of a territorial MCA infarct is a highly personal one. In one extreme, some patients may opt for the chance to live irrespective of consequences. On the other end of the spectrum, some patients may rather choose to pass away peacefully if there is likelihood of a significant morbidity. Reasons against decompression may range from not wanting to be a financial burden to their family to not wanting to be remembered as someone who slowly wasted away to the unwillingness to cope with significant morbidity. Most patients fall in the spectrum of views defined by these two extreme poles. It is interesting to consider that when patients who suffered territorial infarct and survived after hemicraniectomy were posed the question of whether they would have undergone surgery if they had knowledge of their subsequent clinical course, only 50% of these patients reported that they would have opted for surgery.[
The scenario of an elderly (aged >60) who presents with a territorial MCA infarct without an advance directive or health proxy is a particularly challenging one. On the one hand, independent studies (Chinese and DESTINY II) suggest that the likelihood of functional independence after decompression was <10%. As such, an argument can be made not to perform the surgery. On the other hand, death is irreversible. It is the practice of the senior editor of this article (CCC) to review the overall clinical condition of the patient with the intensive care specialists and neurologists as to determine surgical risk and likelihood of functional recovery. Discussions are then held with the family members or health proxy as to the appropriateness of the surgery.
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