Keywords:
stroke - brain edema - decompressive craniectomy
Palavras-chave:
acidente vascular cerebral - edema encefálico - craniectomia descompressiva
Mortality in extensive ischemic stroke (EIS) in the territory of the middle cerebral
artery (MCA) can reach up to 80% according to some controlled studies[1],[2]. Transtentorial herniation is the most common cause of death[3]. In view of this scenario, the selection of patients for early prophylactic decompressive
craniectomy (DC) surgery is an essential measure in the treatment of acute neurovascular
syndrome in emergency neurological services worldwide[4].
EIS is said to be malignant when there is neurological deterioration secondary to
extensive cerebral infarction and consequent encephalic edema, which in turn usually
occurs between the second and fifth day after the stroke[5],[6],[7]. The patient may present clinical signs of intracranial hypertension, such as headache,
nausea, vomiting, anisocoria, epileptic crisis, mental confusion, lowering of consciousness
level and coma[8],[9],[10].
Two forms of malignant ischemic stroke management are recognized: isolated conservative
treatment (CT) and surgical treatment associated to clinical measures, such as osmotherapy
with mannitol or hypertonic saline[11],[12],[13],[14]. The first multicenter randomized controlled trials that sought to evaluate the
benefit of DC surgery were the HAMLET (Hemicraniectomy After Middle cerebral artery
infarction with Life-threatening Edema trial) in 2006, the DECIMAL (DEcompressive
Craniectomy In MALignant MCA Infarction) and the DESTINY I (Decompressive Surgery
for the Treatment of Malignant Infarction of the Middle Cerebral Artery) in 2007.
They established benefits in the survival of patients under 60 years of age undergoing
early surgical decompression for malignant stroke, when compared to CT. However, such
studies did not assess the quality of life of these survivors. Often, the survival
of patients undergoing DC was accompanied by serious sequelae, such as tetraparesis,
aphasia, chronic pain and depression. The choice of treatment in the EIS has become
a real dilemma for neurologists, neurosurgeons and intensive care specialists, mainly
with the advent of new knowledge from so-called Palliative Medicine[15],[16],[17]. Therefore, this study aimed to evaluate the functional outcome of patients with
malignant ischemic stroke treated in a neurological emergency center in the Northeast
of Brazil, submitted to DC surgery or not.
METHODS
This was a prospective cohort study, in which all patients with MCA malignant ischemic
stroke treated by the neurological emergency service of the General Hospital of Fortaleza
City, Ceará State, Brazil, from November 1st, 2015 to December 30th, 2016, were evaluated. The inclusion criteria were diagnosis of ischemic stroke with
an ictus of 48 hours or less, an extensive ischemic area measured with cranial CT
(>50% of MCA territory), neurological deterioration and clinical signs of intracranial
hypertension.
The initial sample of 29 patients was divided into two groups: 10 patients who were
treated with DC surgery and 19 who continued receiving gold-standard conservative
treatment in the stroke unit, with the support of the specialized multidisciplinary
team, including neurologists, nurses, physiotherapists, occupational therapists, speech
therapists and dentists. Two patients from the craniectomized group and two patients
from the non-craniectomized group were lost from the follow-up, thus providing a final
sample of 25 individuals.
The patients were monitored by the Neurology and Neurosurgery team during hospitalization
and reassessed by telephone, after six months, by the Neurology team. The functional
status of both groups was compared to the modified Rankin Scale (mRS). The favorable
functional outcome of mild impairment (mRS 0–3) was adopted as the primary outcome.
A mRS between 4 and 5 represents moderate to severe disability, which together with
an mRS of 6, comprised the total of unfavorable outcomes. The magnitude of the neurological
deficit was quantified with the standard National Institutes of Health Stroke Scale
(NIHSS), stratified as mild (0–10), moderate (11–18) and severe (>18). The level of
consciousness was measured with the Glasgow Coma Scale (GCS) score, as severe (≤8),
moderate (between 9 and 12) and mild (between 13 and 15).
Data were analyzed using the IBM SPSS version 23 software. Absolute and relative frequencies
were calculated for the qualitative variables and mean and standard deviation for
the quantitative variables. The quantitative measures were evaluated for normality
using the Shapiro-Wilk test. Student’s t-test, the Mann-Whitney test and the chi-squared
test were used to examine the association between variables. The results were presented
in graphs and tables. For all the inferential procedures used, a significance level
of 5% was adopted.
RESULTS
In the sample analyzed, most patients with EIS in both groups were women, representing
70.6% of the patients that received the conservative treatment and 50% of the patients
that underwent craniectomy. Ages ranged from 21 to 67, with the majority corresponding
to the age group between 21 and 59 (75.0% in CD group and 88.2% in CT group), as presented
in [Figure 1]. Regarding origin, 62.5% of the surgical patients and 70.5% of the non-surgical
patients lived in Fortaleza City, as presented in [Table 1].
Figure 1 Distribution by age of patients treated conservatively and surgically in a neurological
emergency center after malignant ischemic stroke.
Table 1
Sociodemographic and etiological profile of the patients affected by malignant ischemic
stroke of a neurological emergency center.
|
Variable
|
Group
|
|
Craniectomy
|
Conservative
|
|
Sex
|
|
Male
|
4
|
50.0
|
5
|
29.4
|
|
Female
|
4
|
50.0
|
12
|
70.6
|
|
Age group
|
|
21-60
|
6
|
75.0
|
15
|
88.2
|
|
≥60
|
2
|
25.0
|
2
|
11.8
|
|
Origin
|
|
Fortaleza City
|
5
|
62.5
|
12
|
70.5
|
|
Metropolitan region
|
2
|
25.0
|
0
|
0
|
|
Countryside of the state
|
1
|
12.5
|
5
|
29.5
|
|
Associated factor
|
|
Systemic hypertension
|
5
|
62.5
|
11
|
64.7
|
|
Diabetes mellitus
|
1
|
12.5
|
4
|
23.5
|
|
Dyslipidemia
|
1
|
12.5
|
3
|
17.6
|
|
Previous stroke
|
0
|
0
|
3
|
17.6
|
|
Sedentary lifestyle
|
7
|
87.5
|
13
|
76.5
|
|
Family history of stroke
|
3
|
37.5
|
6
|
35.6
|
|
Chagas disease
|
0
|
0
|
2
|
11.8
|
|
Oral contraceptive use
|
0
|
0
|
1
|
5.9
|
|
Obesity
|
1
|
12.5
|
1
|
5.9
|
|
Congestive heart failure
|
1
|
12.5
|
5
|
29.4
|
|
Arrhythmia
|
1
|
12.5
|
1
|
5.9
|
|
Traumatic brain injury
|
1
|
12.5
|
0
|
0
|
|
Valvopathies
|
0
|
0
|
1
|
5.9
|
|
Migraine
|
1
|
12.5
|
2
|
11.8
|
|
Smoker
|
3
|
37.5
|
13
|
76.5
|
|
Previous Rankin
|
|
0-1
|
8
|
100
|
16
|
94.1
|
|
4
|
0
|
0
|
1
|
5.9
|
|
Mechanism
|
|
Cardioembolic
|
3
|
37.5
|
5
|
29.5
|
|
Cryptogenic
|
5
|
62.5
|
11
|
64.7
|
|
Large vessels
|
0
|
0
|
1
|
5.8
|
The most prevalent risk factors in both populations were systemic hypertension, sedentary
lifestyle and smoking. Most patients treated in the referral service were sedentary
(n=20). Smoking ranked as the second risk factor (n=16), followed by systemic hypertension
(n=15), as shown in [Table 1]. Some patients presented more than one factor. Regarding the previous functionality,
evaluated with the modified Rankin Scale (mRS), [Table 2] shows that most patients had no significant disability and that all the patients
that had craniectomy were functionally independent regarding activities of daily living.
One individual in the surgical group (3.5%) had a moderately severe disability (mRS=4)
prior to the stroke.
Table 2
Clinical profile of the patients affected by malignant ischemic stroke of a neurological
emergency center.
|
Variable
|
Group
|
|
Craniectomy (n=8)
|
Conservative (n=17)
|
|
n
|
%
|
n
|
%
|
|
Onset of symptoms-admission
|
|
≤4.5 hours
|
2
|
25.0
|
6
|
35.3
|
|
4.5–6 hours
|
0
|
0
|
5
|
29.4
|
|
>6 hours
|
6
|
75.0
|
6
|
35.3
|
|
Side affected
|
|
Right
|
2
|
25.0
|
9
|
52.9
|
|
Left
|
6
|
75.0
|
8
|
47.0
|
|
Glasgow Coma Scale score -admission
|
|
Serious
|
2
|
25.0
|
4
|
23.5
|
|
Moderate
|
5
|
62.5
|
6
|
35.3
|
|
Mild
|
1
|
12.5
|
7
|
41.2
|
|
NIHSS score - admission
|
|
Moderate
|
3
|
37.5
|
8
|
47.1
|
|
Serious
|
5
|
62.5
|
9
|
52.9
|
|
Banford score - admission
|
|
LACS
|
1
|
12.5
|
0
|
0
|
|
PACS
|
0
|
0
|
4
|
23.5
|
|
TACS
|
7
|
87.5
|
13
|
76.5
|
|
Thrombolysis
|
|
Yes
|
0
|
0
|
0
|
0
|
|
No
|
8
|
100
|
17
|
100
|
|
Presence of anisocoria
|
3
|
37.5
|
4
|
23.5
|
|
Final Rankin score
|
|
0–3
|
3
|
37.5
|
5
|
29.4
|
|
4–6
|
5
|
62.5
|
12
|
70.6
|
|
Physiotherapy time
|
|
>=3 months
|
4
|
66.7
|
6
|
35.3
|
|
<3 months
|
2
|
33.3
|
11
|
64.7
|
Most patients were able to reach the neurological referral service within the therapeutic
window period for intravenous thrombolytic administration (4.5 hours after onset of
symptoms), totaling 11 cases (38%). Nine patients (31%) arrived between 4.5–8 hours
after the onset of symptoms, and nine (31%) patients arrived with an interval of more
than 8 hours. Only one patient received thrombolytic therapy with alteplase. According
to the etiological investigation of the stroke, 16 cases of the total sample had no
defined etiology. Seven patients had cardioembolic etiology and only one case presented
large vessels mechanism ([Table 1]).
Regarding the clinical manifestations at the time of admission, all the patients
presented motor and sensory symptoms. Twenty patients presented speech changes and
visual changes. In addition, 64% of the patients had altered levels of consciousness.
Only five patients had headaches, three had a seizure episode, and vomiting was reported
in 20% of the cases ([Table 3]). At admission, 25% of the craniectomized patients and 23.5% of non-craniectomized
patients arrived at the hospital with a Glasgow Coma Scale score considered severe
(GCS<8); 62.5% of the surgical patients and 35.3% of the non-surgical patients had
a moderate score (9–12), and 12.5% of the craniectomized patients and 41.2% of the
non-craniectomized patients presented a mild GCS (13–15). Regarding the magnitude
of the neurological damage calculated by the NIHSS score, no individual was classified
as mild NIHSS (0–10), 11 patients had moderate NIHSS (11–18), and the majority of
patients (n=14) had NIHSS considered severe >18). In relation to the cerebral hemisphere
involved, the majority of craniectomized patients had their left side affected (n=6),
whereas most of conservative patients had their right hemisphere more affected (n=9)
([Table 1]).
Table 3
Clinical manifestation of patients with malignant ischemic stroke treated at a neurological
emergency center.
|
Clinical manifestation
|
n
|
%
|
|
Motor
|
25
|
100
|
|
Sensitive
|
25
|
100
|
|
Aphasia
|
20
|
80
|
|
Visual
|
20
|
80
|
|
Consciousness
|
16
|
64
|
|
Headache
|
5
|
20
|
|
Vomiting
|
5
|
20
|
|
Convulsive crisis
|
3
|
12
|
|
Hemineglect
|
4
|
16
|
Regarding the functionality of the patients with malignant stroke at the 6-month
follow-up, [Figure 2] shows the percentage of all functional outcomes according to the mRS, whereas [Table 4] divides the two groups into favorable outcome (mRS 0–3), unfavorable outcome (mRS
4–5) and death (mRS=6). Most patients who received conservative treatment evolved
to death (52.8%). In addition, 37.5% (3/8) of the craniectomized patients and 29.4%
(5/17) of the non-craniectomized patients achieved a favorable outcome of mild disability
(mRS 0–3), whereas 37.5% (3/8) of the patients in the craniectomized group and 17.6%
(3/17) of the non-craniectomized group had moderate to severe disability (mRS 4–5)
after six months. Mortality (mRS=6) was 2.1% (2/8) among surgical patients and 52.9%
(9/17) among those treated conservatively. Of those who died, 81.8% presented a cause
of death related to brain herniation. One patient died of sudden cardiac arrest 10
months after discharge. The mean time between the stroke and death was 6.8 days.
Figure 2 Functional capacity measured with the mRS after 6 months in two therapeutic groups
(Decompressive Craniectomy vs. Conservative) of patients with malignant ischemic stroke.
Table 4
Stratification of the modified Rankin Scale at the end of the 6-month follow-up in
patients with ischemic stroke treated in a neurological emergency center.
|
Variables
|
Craniectomy
|
Conservative
|
p-value
|
|
RANKIN
|
0-3
|
3 (37.5)
|
5 (29.4)
|
0.420
|
|
4-5
|
3 (37.5)
|
3 (17.7)
|
|
6
|
2 (25.0)
|
9 (52.9)
|
DISCUSSION
The average age of patients in our sample was 50.0±10.9, whereas in the study by
Vital et al.[18] it was 63 (32-83). Patients were allocated to the groups within 48 hours of the
stroke, with this time being 30 hours for the DECIMAL study, 96 hours for the HAMLET,
36 hours for the DESTINY I and 48 hours for the DESTINY II. The mean time between
the onset of symptoms and admission to the emergency room was 7 hours (range 2-25).
In the studies by Bongiorni et al.[19] at the Hospital de Clínicas de Porto Alegre, Brazil, the average was 13.2±1.4 hours.
The mean NIHSS admission score in the DECIMAL study was 22.5 for the surgery group
and 23.4 for the non-surgery group, whereas in the present sample it was 20.7 and
19.9, respectively, showing that the patients of the present study were in a less
serious condition upon arrival at the neurological referral service.
In the study by Mattos et al.[20], patients with GCS<8 in the preoperative examination showed a tendency for poor
outcomes, which represented a quarter of the craniectomized patients in the present
study. The mean ictus-craniectomy interval for the patients of the present study was
39.7 hours, whereas in the DECIMAL it was 20.5 hours (interval between 7 and 43 hours).
In studies on MCA hemispheric infarction, Fiorot Junior et al.[21] published that the mean age of patients was 59.1±18.0, whereas in our sample it
was 50.0±10.9, with 46.6±13.2 in the DC group and 51.8±9.3 in the CT group. When risk
factors were analyzed, 31.0% of the craniectomized patients and 22% of the non-craniectomized
DECIMAL patients were hypertensive, whereas in the present study these figures were
62% and 64.7%, respectively, thus showing an unsatisfactory control of modifiable
risk factors, such as hypertension.
The cardioembolic mechanism was the most prevalent in the present sample, found in
37.5% in the surgical group and 29.5% in the non-surgical group. The mean time between
symptom onset and therapeutic decision among patients with hemispheric infarction
in the study by Fiorot Junior et al.[21] was 33 hours for craniectomized patients and 37 hours for non-craniectomized patients,
whereas, in our study, 26.5 and 31 hours, respectively. In the DESTINY I study, these
values were 24.4 ± 6.9 and 23.8 ± 7.8 hours, showing that the time for making decisions
about the type of treatment in our hospital is similar to international data.
In the analysis of functionality between the two therapeutic groups, the present study
showed that the favorable outcome (mRS 0-3) after 6 months was better among the patients
who underwent DC surgery when compared to those on CT, numerically corresponding to
37.5% (3/8) of the craniectomized patients compared to 29.4% (5/17) of the non-craniectomized
patients. The proportion of patients with moderate to severe disability (mRS 4-5)
was higher in the surgical group (37.5%) than in the non-surgical group (17.7%), proving
that survival is accompanied by a reduction in functionality. Furthermore, the number
of deaths (mRS=6) among the patients who underwent DC (25% mortality) was lower when
compared to those on CT (52.9% mortality). Studies of DC in patients with traumatic
brain injury showed that the procedure, even after clinical signs of brain herniation,
can still lead to better functional outcomes compared to conservative treatment[22]. Although this has not shown such benefit in stroke studies, in our sample, even
with a rate of 37.5% of patients in the CD group with anisocoria, CD brought a favorable
outcome (mRS) for 37.5% of them. In the international literature, the DESTINY I study,
with the inclusion of 32 patients, revealed a statistically significant reduction
in mortality: 15 (88%) of the 17 patients randomized to hemicraniectomy versus 7 (47%)
of the 15 patients randomized to conservative therapy survived after 30 days (p≤0.02).
In the study by Kim et al.[23] on the attitude of patients as to their disability after MCA hemispheric stroke,
55% of patients considered an mRS score of 3 to be the worst disability acceptable.
In sum, it is concluded that although DC surgery is a procedure that reduces mortality,
the increased survival is accompanied by serious functional disability. Accordingly,
it is important for the medical team to inform family members about the risks, susceptibilities
and likely postoperative functional outcome for patients, considering that many of
them will require lifelong special and individualized care.
