Surgical Decompression for Space-Occupying Cerebral Infarction
Outcomes at 3 Years in the Randomized HAMLET Trial
Background and Purpose—We assessed whether the effects of surgical decompression for space-occupying hemispheric infarction, observed at 1 year, are sustained at 3 years.
Methods—Patients with space-occupying hemispheric infarction, who were enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial within 4 days after stroke onset, were followed up at 3 years. Outcome measures included functional outcome (modified Rankin Scale), death, quality of life, and place of residence. Poor functional outcome was defined as modified Rankin Scale >3.
Results—Of 64 included patients, 32 were randomized to decompressive surgery and 32 to best medical treatment. Just as at 1 year, surgery had no effect on the risk of poor functional outcome at 3 years (absolute risk reduction, 1%; 95% confidence interval, −21 to 22), but it reduced case fatality (absolute risk reduction, 37%; 95% confidence interval, 14–60). Sixteen surgically treated patients and 8 controls lived at home (absolute risk reduction, 27%; 95% confidence interval, 4–50). Quality of life improved between 1 and 3 years in patients treated with surgery.
Conclusions—In patients with space-occupying hemispheric infarction, the effects of decompressive surgery on case fatality and functional outcome observed at 1 year are sustained at 3 years.
- decompressive surgery
- malignant cerebral infarction
- space-occupying hemispheric infarction
A pooled analysis of 3 European randomized trials has shown that in patients with space-occupying hemispheric infarction, surgical decompression initiated within 48 hours of stroke onset strongly reduces the risk of death and increases the chance of a favorable functional outcome at 1 year. However, this large reduction in case fatality comes at the expense of an increased risk of moderately severe or severe disability at 1 year,1 and the majority of survivors have global cognitive impairment.2 Some authors have therefore expressed concerns about the effect of decompressive surgery on long-term quality of life.3 It is unknown whether the effects of surgery at 1 year are sustained over a longer follow-up period. We assessed outcomes 3 years after inclusion in the randomized Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET).
The design of HAMLET (ISRCTN94237756) has been reported previously.1 In brief, adult patients ≤60 years of age with space-occupying hemispheric infarction were randomly assigned to surgical decompression or to best medical treatment. The trial was approved by institutional review boards, and written informed consent was obtained for each patient.
The primary outcome measure was functional outcome as measured with the modified Rankin Scale at 1 year, dichotomized between good (modified Rankin Scale, 0–3) and poor (modified Rankin Scale, 4, 5, or death). Predefined secondary outcome measures included functional outcome at 3 years, and case fatality, functional dependence assessed with the Barthel Index, quality of life assessed with the Medical Outcomes Study 36-item short-form health survey and a visual analogue scale, symptoms of depression measured by the Montgomery and Åsberg Depression Rating Scale, and caregiver strain assessed with the caregiver strain index at 1 and at 3 years.
A study nurse visited each patient and their caregivers to assess all outcome measures at 1-year and 3-years follow-up, open to treatment allocation. Predefined subgroup analyses were done with regard to the interval from stroke onset to treatment (≤48 versus >48 hours).
Mean differences, absolute risk reductions, and corresponding 95% confidence intervals were calculated. The independent t test, Mann–Whitney test, χ2-test, paired t test, or McNemar test were performed where appropriate. Comparisons between 1 and 3 years were performed only in patients with outcome data at both time points.
Sixty-four patients were included, of whom 32 were randomized to decompressive surgery. All patients received the treatment to which they were assigned. Baseline characteristics and outcomes at 1 year have been published previously.1
The mean duration of follow-up was 3.1 years (SD, 0.1). After 3 years, 8 patients in the surgical group and 20 in the medical group had died, one more than at 1 year in each group. One patient in the surgical group was lost to follow-up (Figure 1).
The Table shows all outcomes at 3 years. Surgical patients had a lower case fatality rate than controls. The risk of a poor outcome did not differ between groups. Quality of life was acceptable for the majority of survivors in both groups.
Figure 2 shows the distribution of scores on the modified Rankin Scale after 1 and 3 years. Differences between 1 and 3 years for other outcome measures are presented in Table I in the online-only Data Supplement. Surgical patients had a statistically significant improvement in the physical summary score of the 36-item short-form health survey and on the visual analogue scale, an effect not observed in medical patients.
Results of subgroup analyses were comparable to the overall analysis (see Figure I and Tables II and III in the online-only Data Supplement).
This study shows that the effects of decompressive surgery on case fatality and functional outcome in patients with space-occupying hemispheric infarction are sustained for up to 3 years. In HAMLET, decompressive surgery reduced the risk of death at 1 and 3 years but had no effect on the chance of a good functional outcome. Quality of life improved between 1 and 3 years in patients treated with surgery.
Previous reports on outcome in randomized trials of decompressive surgery for space-occupying hemispheric infarction were limited to the first year after stroke.1,4 Observational studies have been limited by a short period of follow-up5 or the use of short and long periods combined.6
Meta-analyses that have demonstrated a benefit of decompressive surgery were limited to treatment in the first 48 hours.1 In HAMLET, patients could be enrolled within 96 hours after stroke onset. Subgroup analyses in patients enrolled in HAMLET within 48 hours were limited by smaller patient numbers but are consistent with the overall findings of our study.
Recovery after ischemic stroke generally follows a nonlinear pattern, with the highest rate of recovery in the first weeks, and little improvement after 6 months.7 We found improvement in activities of daily living and quality of life after surgical decompression between 1 and 3 years after the infarct. A similar improvement was observed in medically treated patients, but this did not reach statistical significance, possibly because of the smaller sample size. Recovery in young patients surviving a severe stroke apparently may take a long time, and outcome assessments in these patients should probably not be limited to the first year.
This study has limitations. Although HAMLET was the largest randomized trial in this field, its sample size was insufficient to detect small differences between groups and small changes over time. In addition, comparisons between treatment groups other than those with regard to case fatality or functional outcome should be interpreted with caution because of the large differences in case fatality between the groups. Finally, outcome assessment at 3 years was unblinded.
We thank M. van Buuren, research nurse, for all outcome assessments. The members of the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial steering committee have been published previously.1
Sources of Funding
Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial was supported by the Dutch Heart Foundation (grant number 2002B138).
Drs Geurts and van der Worp are currently supported by the Dutch Heart Foundation (2010B239 and 2010T075, respectively). The other authors report no conflict.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.002014/-/DC1.
- Received May 1, 2013.
- Accepted June 3, 2013.
- © 2013 American Heart Association, Inc.
- Hofmeijer J,
- Kappelle LJ,
- Algra A,
- Amelink GJ,
- van Gijn J,
- van der Worp HB