Keywords Stroke - Decompressive Craniectomy - Infarction, Middle Cerebral Artery
Palavras-chave Acidente Vascular Cerebral - Craniectomia Descompressiva - Infarto da Artéria Cerebral
Média
INTRODUCTION
Ischemic stroke remains the second leading cause of death and disability globally.[1 ] In middle income regions, such as Brazil and other Latin American countries, the
lifetime risk of stroke is even higher and the number of deaths from stroke has increased
in the last three decades.[2 ]
[3 ] Moreover, stroke care is not well stablished in most of these countries and the
proportion of patients who receive any kind of recanalization therapy is still around
1%.[3 ] In this context, the management of patients with malignant middle cerebral artery
infarction (MMCAI)—a very disabling entity that corresponds to approximately 10% of
supratentorial strokes and has mortality as high as 80% when clinically treated—is
of paramount importance.[4 ]
[5 ]
Decompressive craniectomy (DC) was evaluated as a life-saving measure to alleviate
brain swelling and improve outcomes in the setting of MMCAI in several European clinical
trials and has been proved to be effective in preventing death and severe morbidity.[6 ]
[7 ]
[8 ]
[9 ]
[10 ] However, there are no randomized trials in developing countries and only a few studies
evaluated outcomes of patients treated in these regions, most before the randomized
trials era.
In this study, we aimed to evaluate the functional outcome of patients with MMCAI
treated with DC at an academic tertiary stroke center in Brazil.
METHODS
Population
Patients were retrospectively selected from a stroke registry. The study was approved
by the Ethics Committee of Hospital das Clínicas – Ribeirão Preto Medical School and
all patients included on the stroke registry gave informed consent. We included all
patients older than 18 years admitted between January 2014 and December 2017, who
were treated with DC for management of MMCAI, defined as infarction on more than half
of the middle cerebral artery territory. The exclusion criteria were: i) lacking enough
information on the registry or medical records and ii) indication for the DC different
from malignant edema (e.g. symptomatic hemorrhagic transformation).
Clinical assessment
Patients with suspected stroke were assessed and treated according to Brazilian and
international guidelines and the institutional protocol.[11 ]
[12 ]
[13 ]
[14 ] When eligible, intravenous thrombolysis and mechanical thrombectomy (MT) were performed.
Those at risk of MMCAI were monitored preferably on intensive care unit or stroke
unit and clinically reevaluated frequently. Additional imaging was performed according
to the clinical discretion.
Eligibility to DC per local protocol included being younger than 60-years-old, clinical
signs of total anterior circulation syndrome according to Bamford et al.'s classification,[15 ] reduced level of consciousness as scored on National Institutes of Health Stroke
Scale (NIHSS) subitem 1a, and noncontrast computerized tomography (NCCT) evidence
of involvement of more than 50% of MCA territory, or infarct size bigger than 145 cm3 on the diffusion weighted imaging (DWI) sequence. The indication of surgical treatment
followed the local protocol, along with the neurologist and neurosurgeon's joint decision.
The surgical technique was decided according to the current practice.[16 ]
[17 ]
[18 ] Given the severity of the condition, some patients were treated beyond the predefined
time and age limits, based on clinical judgment on premorbid condition, and neurological
and imaging exams at the moment of the decision.
Upon hospital admission, clinical data were assessed and recorded, including NIHSS
score and Glasgow coma scale (GCS), baseline systolic and diastolic blood pressure,
and baseline serum glucose. The following demographic data were also systematically
obtained: age, sex, cardiovascular risk factors, and previous functional status.
Time to events (brain imaging, thrombolysis, thrombectomy, and surgery) were recorded,
as well as the type of recanalization therapy and site of arterial occlusion. The
stroke etiology was classified according to the Trial of Org 10172 in Acute Stroke
Treatment criteria.[19 ]
The initial NCCT was performed at admission in all cases and retrospectively reviewed
regarding arterial territory involved (only MCA or additional anterior or posterior
cerebral artery territory involvement), the Alberta stroke programme early Computed
Tomography score (ASPECTS),[20 ] hemorrhagic transformation and signs of brain herniation. When available, digital
subtraction angiography and MT were also evaluated. The last imaging before surgery
indication was also assessed according to the same criteria.
Outcomes assessment
The modified Rankin scale (mRS) was assessed at discharge, 3-months and 1-year after
stroke. In the cases which lacked data at 1-year, it was considered the closest date
to 1-year available. Favorable functional outcome was defined as mRS ≤ 4.
Given the high morbidity of the disease and high dependency of survivors, it was also
evaluated the patients' destiny after discharge: whether to home, rehabilitation hospital,
or institutionalization at a support hospital.
Statistical analysis
Continuous variables were described as central tendency measures and dispersion, means
(± ) and standard deviations (SD), or medians and interquartile ranges (IQR). Categorical
variables were shown as percentages. We used the Statistical Package Social Sciences
version 24 (SPSS, IBM Corp. Armonk, NY) version 24 for all analysis. A p -value < 0.05 (two-sided) was used as the threshold for statistical significance.
RESULTS
During the study period, 58 patients with supratentorial ischemic stroke treated with
DC were identified. There were 4 patients excluded due to hemorrhagic transformation
as the main indication for the surgery and other one due to the lack of information
on the medical records. We included 53 patients on the final analysis. The mean age
was 54.6 ± 11.6 years and 64.2% were men. At admission, the median NIHSS was 20 (16–24)
and the median GCS was 12 (10–14). The right hemisphere was the affected in most cases
(60.4%). The most common comorbidities were arterial hypertension (66%) and diabetes
mellitus (32%).
The median time from symptoms to admission was 4.8 (3–9.7) hours and the median time
from symptoms to surgery was 33.8 (24.7–44.2) hours. Among the patients, 45 (84.9%)
were treated within 48 hours from symptoms onset. The complete clinical and demographics
characteristics are summarized in [Table 1 ].
Table 1
Baseline clinical characteristics.
Characteristicsa
n = 53
Clinical
Male sex
34 (64.2)
Age (years)
54.6 ± 11.6
Time of admission to surgery (hours)
26.6 (14.6–37.0)
Time of symptoms to surgery (hours)
33.8 (24.7–44.2)
Length of hospital stay (days)b
25 (14–46.5)
Glucose at admission (mg/dL)b
124 (109–179)
Systolic blood pressure at admission (mmHg)
148 ± 27.7
Diastolic blood pressure at admission (mmHg)
88 ± 17
Neurological exam and brain imaging
NIHSS at admissionb
20 (16–24)
GCS at admissionb
12 (10–14)
Left hemisphere
21 (39.6)
ASPECTS at admissionb
6 (4–7.5)
Midline shift before surgery (mm)b
5 (2–7)
Previous pathologic history
Hypertension
35 (66)
Diabetes mellitus
17 (32)
Renal failure
2 (3.8)
Atrial fibrillation
10 (18.9)
Congestive heart failure
13 (24.5)
Tobacco use
30 (56.6)
Alcohol abuse
15 (28.3)
Previous stroke
8 (15.1)
Coronary disease
3 (5.7)
Site of arterial occlusion
Middle cerebral artery
20 (37.7)
Intracranial internal carotid artery
11 (20.8)
Tandem occlusion
14 (26.4)
Unknown
8 (15.1)
Recanalization therapy
Intravenous thrombolysis
14 (26.4)
Mechanical thrombectomy
18 (34)
Stroke etiology
Atherosclerosis
14 (26.4)
Cardioembolism
16 (30.2)
Other known causes
7 (13.2)
Abbreviations: ASPECTS, Alberta stroke program early computed tomography score; GCS, Glasgow coma
scale; NIHSS, national institute of health stroke scale. Notes:
a Values expressed as mean ± standard deviation or absolute number (percentage of total).
b Values expressed as median (interquartile range).
We identified an in-hospital mortality rate of 30.2%. The surviving patients stayed
in-hospital for 31 (18.5–42.5) days. At discharge, 16 (43.2%) patients went to home,
10 (27%) were discharged to rehabilitation hospital and then to home, and 11 (29.7%)
were transferred to a support hospital, where they could receive nursing care and
eventually could be discharged to a nursing home or their own.
During the in-hospital period, the most common complications were infectious, accounting
for 75.5% of all patients. Acute kidney injury (37.7%) and seizures (24.5%) also had
high prevalence. The in-hospital complications are listed in [Table 2 ].
Table 2
In-hospital complications.
Complicationsa
n = 53
Seizures
24.5% (13)
Surgery-related complications
30.2% (16)
Urinary tract infections
18.9% (10)
Surgical site infections
24.5% (13)
Acute kidney injury
37.7% (20)
Pneumonia
58.5% (31)
Any infection
75.5% (40)
Venous thromboembolism
9.4% (5)
Note : a Values expressed as percentage (absolute number).
The functional outcome was described in [Figure 1 ]. After a median of 337 (157–393) days, 25 (47.1%) patients had a favorable outcome
(mRS ≤ 4). When considering only those patients aged 60 years or younger treated within
48 hours from symptoms onset (n = 29), the proportion of favorable outcome increases
to 55.1% ([Figure 2 ]). In this scenario, there was no survival with severe disability (mRS 5) and the
mortality rate was 44.8%.
Figure 1 Modified Rankin scale (mRS) distribution at discharge, after 3-months, and after
1-year of stroke.
Figure 2 Modified Rankin scale (mRS) distribution at discharge, after 3-months, and after
1-year of stroke in the subgroup of patients younger than 60 years treated with decompressive
craniectomy within 48 hours from symptom onset.
DISCUSSION
Although the role of decompressive craniectomy on management of MMCAI has been studied
in several randomized controlled trials (RCT) that showed its benefits on mortality
and even on the prevention of severe disability, ethical and social concerns remain
about when this procedure is recommended.[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[21 ] As shown on the metanalysis from the first three RCTs, up to 42% of survivals in
the group of patients treated with DC had moderate to severe disabilities.[9 ] It is important to consider that these studies included only patients from high-income
European countries and that there are unquestionably differences on socioeconomic
aspects, as well as on the health care between European and middle-income countries,
including Latin American ones. Those differences pose limitations for the extrapolation
of data regarding treatment outcomes, especially regarding severe disabling diseases
that requires continuous multidisciplinary attention and even financial support, such
as stroke. There is only one RCT from a middle-income country that included patients
older than 18 years without upper age limit, and it found that 58% of survivals in
the surgery group had moderate to severe disabilities (mRS 4 or 5) after 12-months
of follow-up.[21 ] However, the different inclusion criteria make it difficult to compare them.
In our study, we aimed to evaluate the outcomes of DC in real-world situations, considering
the socioeconomics limitations inherent to a middle-income country. Our data shows
similar distribution to those found on the first RCT. There was a reduction of the
expected mortality rates if they had not been treated with DC at the expense of a
high proportion of survivals with great disability. However, the magnitude of this
effect appears to be more important on the RCT, as evidenced by the greater mortality
(39 vs. 22%) and smaller proportion of survivals with mRS ≤ 3 (21 vs. 43%) in our
population.[9 ]
There are limited data about DC and stroke in middle-income countries. In the only
study from Brazil that evaluated functional outcome measured by the mRS, Vital et
al. included 60 patients, divided in two age groups (< 60 years and ≥ 60 years) and
identified overall mortality of 55% after 90 days, while 38% were mRS ≤ 4 in the same
period.[22 ] In China, Chen et al. described a population of 60 patients, with a 27% mortality
rate at 1-year.[23 ] In a cohort of 31 patients with MMCAI treated with DC, 39% were dead after 1-year
and 52% had mRS ≤ 4.[24 ] In India, Rai et al. evaluated 36 stroke patients treated with DC in a cohort of
60 patients and identified a mortality rate of 38% at 1-year and good outcome defined
as mRS ≤ 4 in 53% of the patients, although the median time from symptoms to surgery
was 56 hours.[25 ]
Our results are similar to those found on these retrospective observational studies,
but worse than the results found on RCT. In the pooled analysis of individual data
from the first three RCT, 75% of the patients in the surgery group had mRS ≤ 4 and
22% were dead at 1-year of follow-up.[9 ] The worse outcomes can be attributed to several factors. The most obvious ones are
the inclusion of patients beyond 48 hours from symptoms and older than 60 years, but
some differences are a result of the real-world character from our study and from
socioeconomic discrepancies between the countries involved, such as the inherent greater
prevalence of comorbidities in our population and differences in health assistance
and rehabilitation.
Limitations of our study include its retrospective design and the possible selection
bias related to the moment of treatment decision, which might have led to the exclusion
of patients with severe comorbidities and poor prognosis at baseline. However, our
population and our results reflect a real-world scenario, with all its implications.
Our follow-up time was longer than most retrospective studies in order to better reflect
the continuous improvement of the surviving patients, and to offer a fair possibility
of comparison to the randomized trials.
In conclusion, decompressive craniectomy is a life-saving measure in the setting of
MMCAI, and its effects remains important in the scenario of a middle-income country
in real-world situations. After 1-year of follow-up, there was a great reduction in
expected mortality and an improvement in the proportion of surviving patients without
severe disabilities.
