Editorial
Hemicraniectomy
A Second Chance on Life for Patients With Space-Occupying
MCA Infarction
Stephan A. Mayer, MD, FCCM
reported was the phase II National Institute of Health–
sponsored Hemicraniectomy And Durotomy On Deterioration
From Infarction Related Swelling Trial (HeADDFIRST).8
HeADDFIRST randomized 26 patients between the ages of
18 and 75 between the years 2000 to 2003. Patients were
enrolled if they presented with CT evidence of a massive
(⬎180 mL) MCA infarction, with randomization to surgery
or continued medical therapy triggered by the subsequent
development of midline shift (defined as ⱖ7 mm septal or
⬎4 mm pineal gland displacement). The investigators reported a nonsignificant reduction in mortality from 46% with
medical therapy to 27% in the surgically treated group.8
Functional outcomes were not reported, however, leaving
open to question the issue of quality of life in these survivors.
Somewhat unconventionally, 3 European hemicraniectomy
trials, including the DESTINY and DECIMAL trials, reported a
pooled analysis of their 1-year outcomes in March of 2007,
before individual publication of their main results.9 This turn
of events resulted from termination of enrollment in the
DESTINY and DECIMAL trials last year after it became
clear that survival was improved with surgery. The DESTINY and DECIMAL investigators combined their data with
the ongoing HAMLET10 trial in an attempt to get the most
definitive data to the scientific community as soon as possible. Importantly, all 3 of these studies restricted enrollment to
patients ⱕ60 years of age, and the timing of surgery to ⬍48
hours after stroke onset.
The aforementioned pooled analysis reported by Vahedi et
al earlier this year is a landmark publication because it is the
first to demonstrate that hemicraniectomy can be a life-saving
procedure.9 A total of 93 patients were randomized to surgical
or medical therapy and evaluated with the modified Rankin
Scale (mRS) at 1 year. Hemicraniectomy more than doubled
the chances of survival, from 29% to 78%. This staggering
absolute risk reduction of 49% was highly significant and
translates into a number needed to treat of 2 to avoid one
fatality.
Thus, it seems clear that hemicraniectomy can save lives,
at least in younger patients if the surgery is performed early.
But what was the quality of recovery among those who
survived? In the acute phase of a severe stroke the decision to
proceed with hemicraniectomy is usually made by families,
based on the patient’s wishes and best interests. In this regard
the pooled analysis by Vahedi et al9 also provides useful
information that cannot be gleaned from the individual trial
results reported in this issue of Stroke. First, hemicraniectomy
did not appear to increase the risk of complete dependency,
misery, and hopelessness. Exactly 2 patients in the surgical
and medical groups (⬇5%) were bedbound and severely
See related articles, pages 2506 –2517 and 2518 –2525.
o-called “malignant” middle cerebral artery (MCA) territory infarction is the most devastating form of ischemic
stroke. With conventional medical therapy, including endotracheal intubation, blood pressure control, osmotherapy,
hyperventilation, and barbiturate anesthesia for refractory
intracranial hypertension, mortality rates of up to 80% have
been reported.1–3 Death or neurological devastation results
from progressive swelling of the infarct, brain tissue shifts,
compartmentalized elevation of intracranial pressure, and the
extention of ischemia to adjoining vascular territories.
Decompressive hemicraniectomy and duroplasty for malignant MCA territory infarction is intended to prevent the
death spiral by normalizing intracranial pressure, restoring
compromised flow in the penumbra and adjacent vascular
territories, and restoring the midline position of the brain stem
and diecephalon. The procedure is not new, but was performed rarely for MCA infarction before the 1990s, primarily
because of concerns that it would result in survival with
overwhelming neurological impairment and handicap. With
improvements in postoperative critical care, however, there
has been a resurgence of interest in hemicraniectomy over the
past 10 years. Several case series and nonrandomized casecontrol studies have suggested that hemicraniectomy can
improve survival,4,5 but the evidence has been far from
definitive, particularly regarding the extent of residual handicap in those who survive the procedure. Given the lack of
evidence from clinical trials to date, hemicraniectomy has
remained one of the most controversial and hotly debated
topics in stroke care. Is it “radical surgery” that only leads to
more pain and suffering, or a beneficial procedure that can
give some patients a second chance on life?
In this issue of Stroke, the results of 2 of the 5 recently
organized trials designed to evaluate the efficacy of hemicraniectomy for MCA infarction—the DESTINY and DECIMAL trials—are reported.6,7 But before we look into the
results of these studies, it is important to review the recent
history of hemicraniectomy clinical trials. The first trial to be
S
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The opinions in this editorial are not necessarily those of the editors or
of the American Heart Association.
From the Division of Neurocritical Care, Departments of Neurology
and Neurosurgery, Columbia University College of Physicians and
Surgeons, New York, NY.
Correspondence to Stephan A. Mayer, MD, Neurological Institute, 710
West 168th Street, Box 39, New York, NY 10032. E-mail sam14@
columbia.edu
(Stroke. 2007;38:2410-2412.)
© 2007 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.107.494203
2410
Mayer
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disabled (mRS level of 5) at 1 year. The proportion of patients
alive with minimal-to-moderate disability (mRS 0 to 3),
however, was significantly increased from 21% to 43%.
Viewed another way, hemicraniectomy resulted in a 49%
absolute risk reduction in death, and an absolute increase in
the proportion of patients rated as mRS 2 of 12%, mRS 3 of
10%, and mRS 4 of 29%. Thus, for every 10 hemicraniectomies performed for MCA infarction, 5 patients will escape
death, and at 1 year 1 of these patients will have mild
disability, 1 will have moderate disability, and 3 will have
moderate-to-severe disability (ie, unable to walk independently). This information may be helpful for explaining the
anticipated outcome of this procedure to families.
With this backdrop, the more detailed reports of the
DESTINY and DECIMAL trials in this issue of Stroke allow
for a more nuanced and critical appraisal of the data reported
in the pooled analysis. The most clinically pertinent issues
involve patient selection and the timing of surgery. The fact
remains that not every patient with an MCA infarct develops
fatal brain edema, and the factors that contribute to a
malignant course are poorly understood. The most consistently identified clinical risk factors for death after MCA
infarction include a high initial National Institute of Health
Stroke Scale (NIHSS) score, larger infarct volume, younger
age, and early signs of transtentorial herniation.11,12 The
DECIMAL investigators performed MRI preoperatively and
used a diffusion-weighted imaging lesion volume of ⬎145
mL as one of their inclusion criteria. Importantly, they noted
that among the 8 patients screened but not randomized
because their stroke was smaller than 145 mL, none died,
which confirms a prior report identifying this threshold as a
risk factor for malignant ischemic edema.13 Conversely, no
patient with a baseline lesion volume exceeding 210 mL
survived without a hemicraniectomy. Unfortunately, infarct
volume cannot be quantified precisely without advanced
image analysis tools. There is a need for larger imaging
studies to systematically evaluate lesion volume, midline
shift, cisternal effacement, vessel patency, and other potential
predictors of malignant edema after MCA infarction.
The optimal timing of hemicraniectomy remains uncertain.
There has been an ongoing debate over whether to operate as
soon as the diagnosis of MCA infarction is made, or to wait
for signs of early symptomatic mass effect, which might
perhaps spare some patients the procedure if they have a
stable course. The mean interval between onset and surgery in
the DESTINY and DECIMAL trials was ⬇24 hours, and the
pooled analysis by Vahedi et al found no additional benefit
with surgery performed within 24 hours compared with
surgery performed later (both studies required that surgery
take place no more than 6 hours after randomization).9 A
systematic review of 129 published cases of hemicraniectomy
for MCA infarction also found no difference in outcome if
surgery was performed within 24 hours or at a later time
point,5 in contrast to a single center study that reported better
results with early surgery.4 These data indicate that for alert
patients who lack significant shift or mass effect on imaging,
careful clinical monitoring is appropriate until a change in
level of consciousness or other signs of intracranial mass
effect develop. In contrast to the classic teaching that brain
Hemicraniectomy: A Second Chance on Life
2411
edema peaks in intensity 3 days after stroke, some patients
with MCA infarction deteriorate from mass effect several
days later. Because the DESTINY and DECIMAL studies did
not include patients enrolled beyond 48 hours, the benefit of
hemicraniectomy as a late “salvage” procedure in patients
who were initially managed medically remains uncertain.
Involvement of the dominant hemisphere has often been
used in the past as an excuse to deny patients hemicraniectomy as a life saving procedure, with the logic being that
global aphasia is a fate worse than death.14 For several years
there has been an increasing sentiment in the stroke community that this concept is outmoded.15 Neglect resulting from
nondominant lesions is known to limit the degree of active
participation in rehabilitation programs and is associated with
poor functional recovery and social reintegration, thus making it just as disabling as aphasia.16 Moreover, significant
improvement in aphasia can occur in dominant hemisphere
stroke treated with hemicraniectomy.17 A prespecified subset
analysis in the DECIMAL trial showed no difference in the
mRS scores of survivors with or without aphasia,7 and the
pooled analysis by Vahedi et al showed that the benefit of
surgery for preventing death or moderate-to-severe disability
(mRS) was similar regardless of the presence or absence of
aphasia at baseline.9 In the DESTINY trial all surgical
survivors agreed with the decision to undergo surgery in
retrospect, including the slightly more than half of patients
still experiencing aphasia.6 These data indicate that involvement of the dominant hemisphere is no longer an acceptable
reason for withholding hemicraniectomy from otherwise
appropriate candidates.
Perhaps the most common question that will vex clinicians
in the near future will be the issue of age. In the aforementioned systematic review of published hemicraniectomy
cases, younger age (in this case dichotomized at 50 years)
was the only preoperative clinical determinant of survival
with good functional outcome.5 A prespecified analysis in the
DECIMAL trial confirmed that younger age was a stronger
determinant of favorable outcome than infarct volume among
surgically treated patients.7 However, the DESTINY and
DECIMAL trials only provide us with information on the
benefits of hemicraniectomy for patients younger than age 60.
Given the striking survival benefit, it is now clear that studies
to determine whether patients aged 60 to 80 can also benefit
from hemicraniectomy are now urgently needed. Until that
time, clinicians will need to struggle with where to “draw the
line” in terms of offering hemicraniectomy as a treatment
option for older patients, who clearly have worse functional
outcomes after hemicraiectomy,18 and who are at increased
risk for complications in the intensive care unit (ICU). The
detailed data reported in the DECIMAL trial confirms that
hemicraniectomy patients can experience a vast array of
medical problems, including nosocomial infections, venous
thromboembolism, and seizures. The importance of meticulous intensive care for restoring patients to health after
hemicraniectomy cannot be emphasized enough. The ICU
protocol provided in Table 2 of the DESTINY trial provides
an excellent starting point in this regard.6
The DESTINY and DECIMAL trials are not without flaws,
of course, including their small size, the presence of several
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September 2007
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protocol violations, and the fact that approximately half of the
patients in each trial was enrolled by a single center. The
biggest doubt that remains, however, has to do with the fact
that the clinical management was unblinded to treatment
modality. It is well established that survival in critically ill
stroke patients is largely determined by decisions regarding
whether to aggressively pursue care, or to withhold or
withdraw support. It is entirely possible that unconscious
biases among the investigators could have influenced this
decision-making. It is notable that in the DECIMAL trial
100% of the surgically treated patients received mechanical
ventilation, compared with only 61% of the medically treated
patients,7 which suggests that decisions to withhold life
support may have played a role in the early demise of some
of these patients. This conundrum cannot be solved, unfortunately, because there is no practical way to blind caregivers in
the ICU to treatment in a hemicraniectomy trial. What this
points to is the importance of ICU support after surgery for
determining who lives and who dies.
In terms of interpreting the results of the DESTINY and
DECIMAL trials, however, the lack of blinding may not
matter. Until now, massive MCA infarction has essentially
been a guarantee of death or devastation. Let us agree that
hemicraniectomy combined with aggressive ICU support can
give many patients with MCA infarction a second chance on
life, compared with supportive care alone combined with a
possibly more nihilistic attitude. Tell this to your patients, and
let them decide.
Disclosures
None.
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KEY WORDS: decompressive surgery
䡲
MCA infarction
Hemicraniectomy: A Second Chance on Life for Patients With Space-Occupying MCA
Infarction
Stephan A. Mayer
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Stroke. 2007;38:2410-2412; originally published online August 9, 2007;
doi: 10.1161/STROKEAHA.107.494203
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