Decompressive craniectomy for malignant middle cerebral artery infarction outcome

J.Sales-Llopis

Neurosurgery Service, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain.

A meta-analysis was performed to approximate the efficacy of decompressive craniectomy (DC) for treating malignant middle cerebral artery infarction (MCI), considering age and time to surgery. A systematic literature review was conducted on Medline, Embase, and Cochrane library databases to August 1, 2018. Death and severe disability at 3, 6, 12, and 36 months follow-up were assessed, comparing best medical therapy with DC.

18 studies were eligible for inclusion and represented 987 individuals who received DC. Nine of these were randomized controlled trials (RCTs) (n = 374 DC). Early DC (<48 hours from onset of stroke) reduced mortality (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.11, 0.29; P < 0.00001) but not unfavourable outcome (modified Rankin Scale [mRS] >4) (OR = 1.38, 95% CI = 0.47, 4.11; P = 0.56) at 12 months follow-up. This survival benefit was maintained regardless of age.

Early DC reduces mortality but does not appear to improve favorable outcomes in patients younger or older than 60 years after MCI. RCTs incorporating quality of life assessments are warranted for MCI patients, in addition to defining the optimal timing and benefits of DC in older patients ¹⁾.

According to PRISMA guidelines, Li et al from the Department of Neurosurgery, The Clinical Medical College of Yangzhou University, China searched databases containing articles published in English (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese (Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for randomized controlled trials (RCTs) of decompressive hemicraniectomy published before January, 2016. They extracted data on patient characteristics, methodological quality, and outcome measures. The outcomes assessed included mortality and good functional outcome (GFO). We did a subgroup analysis to determine the effect of age and surgical timing on mortality and functional outcomes.

14 studies were included in this metaanalysis, including 830 patients with severe middle cerebral artery infarction. In the total population, mortality was lower in the decompressive hemicraniectomy group than in the conventional treatment group at 6 months after onset (odds ratio [OR] 0·19, 95% CI 0·11-0·33; p<0·0001), and at 12 months (OR 0·18, 0·11-0·28; p<0·0001). The pooled OR of GFO was 3·15 (95% CI 1·49-6·69; p=0·003) at 6 months, and 1·95 (1·19-3·19; p=0·008) at 12 months. Survival with moderately severe disability was higher in the decompressive hemicraniectomy group at 6 months (OR 3·90, 95% CI 2·23-6·83; p<0·0001) and 12 months (OR 4·36, 2·55-7·36; p<0·0001). However, with regard to survival with severe disability, no significant differences were observed (p=0·55 at 6 months, p=0·81 at 12 months). In the subgroup analysis, compared with conventional treatment, decompressive hemicraniectomy significantly decreased mortality in patients older than 60 years (p<0·0001) and 60 years or younger (p<0·0001). With regard to survival with moderately severe or severe disability, significant differences were observed between treatment groups both in patients older than 60 years (p=0·0002) and 60 years or younger (p=0·0002). No significant differences between treatment groups were found in the subgroup analysis of surgical timing.

Compared with conventional treatment, decompressive hemicraniectomy could significantly reduce mortality and improve prognosis both in patients older than 60 years and those aged 60 years or younger with severe middle cerebral artery infarction. However, compared with conventional treatment, more patients who receive decompressive hemicraniectomy might survive with moderately severe or severe disability ²⁾.

Wang et al searched PUBMED, EMBASE and the Cochrane Central Register of Controlled Trials. Other sources, including internet-based clinical trial registries and grey literature, were also searched. After searching the literature, two investigators independently performed literature screening, assessing the quality of the included trials and extracting the data. The outcome measures included the composite outcome of death or dependence and the risk of death. Ten RCT were included: seven RCT were on malignant middle cerebral artery infarction (MCAI) and three were on severe traumatic brain injury (TBI). Decompressive craniectomy significantly reduced the risk of death for patients suffering malignant MCAI (risk ratio [RR] 0.46, 95% confidence interval [CI]: 0.36-0.59, P<0.00001) in comparison with no reduction in the risk of death for patients with severe TBI (RR: 0.83, 95% CI: 0.48-1.42, P=0.49). However, there was no significant difference in the composite risk of death or dependence at the final follow-up between the decompressive craniectomy group and the conservative treatment group for either malignant MCAI or severe TBI. The present meta-analysis indicates that decompressive craniectomy can significantly reduce the risk of death for patients with malignant MCAI, although no evidence demonstrates that decompressive craniectomy is associated with a reduced risk of death or dependence for TBI patients ³⁾.

93 patients were included in a pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS<or=4 (75%vs 24%; pooled absolute risk reduction 51% [95% CI 34-69]), an mRS<or=3 (43%vs 21%; 23% [5-41]), and survived (78%vs 29%; 50% [33-67]), indicating numbers needed to treat of two for survival with mRS<or=4, four for survival with mRS<or=3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials.

In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient ⁴⁾.

Alexander et al. searched MEDLINE, EMBASE and Cochrane library databases for randomised controlled trials (RCTs) enrolling patients suffering SO-MCAi comparing conservative management to DHC administered within 96 hours after stroke symptom onset. Outcomes were death and disability measured by the modified Rankin Scale (mRS). We used a random effects meta-analytical approach with subgroup analyses (time to treatment and age). We applied GRADE methods to rate quality/confidence/certainty of evidence.

7 RCTs were eligible (n=338 patients). We found DHC reduced death (69-30% in medical vs surgical groups, 39% fewer), and increased the number of patients with mRS of 2-3 (slight to moderate disability: 14-27%, increase of 13%), those with mRS 4 (severe disability: 10-32%, increase of 22%) and those with mRS 5 (very severe disability 7-11%: increase of 4%) (all differences p<0.0001). We judged quality/confidence/certainty of evidence high for death, low for functional outcome mRS 0-3, and moderate for mRS 0-4 (wide CIs and problems in concealment, blinding of outcome assessors and stopping early).

DHC in SO-MCAi results in large reductions in mortality. Most of those who would otherwise have died are left with severe or very severe disability: for example, inability to walk and a requirement for help with bodily needs, though uncertainty about the proportion with very severe, severe and moderate disability remains (low to moderate quality/confidence/certainty evidence) ⁵⁾.

Li et al., searched English and Chinese databases for randomized controlled trials or observational studies published before August 2016. Outcomes included good functional outcome (GFO), mortality, and National Institutes of Health Stroke Scale and Barthel index scores.

This meta-analysis included 25 studies (1727 patients). There were statistically significant differences between decompressive hemicraniectomy (DHC) and conventional treatment (CT) groups in terms of GFO (P < 0.0001), mortality (P < 0.00001), and National Institutes of Health Stroke Scale and Barthel index scores (P < 0.0001) at different follow-up points. Significant differences were observed between the groups in survival with moderately severe disability (P < 0.00001); no differences were observed in survival with severe disability. In the subgroup analysis, in the DHC group, GFO was less in patients >60 years old (9.65%) versus ≤60 years old (38.94%); more patients >60 years old had moderately severe or severe disability (55.27%) compared with patients ≤60 years old (44.21%).

DHC could significantly improve GFO and reduces mortality of patients of all ages with malignant MCA infarction compared with CT, without increasing the number of patients surviving with severe disability. However, patients in the DHC group more frequently had moderately severe disability. Patients >60 years old with malignant MCA infarction had a higher risk of surviving with moderately severe or severe disability and less GFO ⁶⁾.

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct and Web of Science. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI).

RESULTS: The overall OR for mRS 6 (death) at 6 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.19 (95% CI: 0.10-0.37). The frequency of patients with mRS 2, 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 3.29 (95% CI: 1.76-6.13). The overall OR for mRS 6 (death) at 12 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.17 (95% CI: 0.10-0.29). The frequency of patients with mRS 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 4.43 (95% CI: 2.27-8.66). In the long run it was also observed that the number of patients with a mRS score of 2 was significantly higher in the decompressive surgery cohort an OR of 4.51 (95% CI: 1.06-19.24).

The results imply that surgical intervention decreased mortality of patients with fatal middle cerebral artery infarct at the expense of increasing the proportion suffering from substantial disability at the conclusion of follow up ⁷⁾.

A literature search was conducted using Medline, Embase, PubMed and the Cochrane Library. Randomised controlled trials and meta-analysis that fulfilled the inclusion criteria and answered the clinical question were evaluated.

Twelve papers were identified and considered appropriate to answer the clinical question. These included 8 prospective randomised controlled trials and 4 meta-analysis. A critical review of these papers was conducted.

In patients 60 years of age or younger, DC within 48 hours of stroke onset significantly reduced risk of death and major disability (mRS >3) compared to maximal medical therapy only. In older patients (>60 years) DC also significantly improved survival but the majority of survivors were left with major disability (mRS 4-5). DC performed more than 48 hours after symptom onset does not appear to be superior to best medical management. The decision to perform decompressive surgery needs to be made on a case-by-case basis, taking into account the degree of disability patients and their carers are willing to accept ⁸⁾.

Decompressive hemicraniectomy (DH) in malignant middle cerebral artery infarction reduces mortality significantly but evidence for long-term functional benefit is sparse and contradictory.

There is currently a debate regarding how routinely such surgery should be performed in the clinical setting, considering the very high rate of disability and functional dependence among survivors.

Several large, randomized trials in malignant middle cerebral artery infarction have firmly established the benefit of decompressive hemicraniectomy (DHC) as a treatment of malignant middle cerebral artery territory infarction (MMI). Further studies since then have not only better characterized the diagnosis and predictors of MMI, but have also shown that this benefit extends to patients with additional clinical and demographic characteristics. Future randomized studies should continue to evaluate the benefit of a DHC in other subgroups, and assess neurocognitive and psychosocial secondary outcomes ⁹⁾.

According to the current literature, decompression craniectomy in older patients can increase survival without most severe disabilities, although, most survivors need assistance in most bodily needs. Involvement of the dominant hemisphere results in aphasia that might partly recover in younger patients, although, considering the neuropsychological deficits caused by infarctions of the nondominant hemisphere, involvement of the dominant hemisphere does not pose as a contraindication for decompression craniectomy. Furthermore, there is convincing evidence that surgery should be performed within 48 h after the onset of symptoms and the size of the craniectomy should be at least 12 cm as a minimum. An additional lobectomy or the resection of the temporal muscle, however, can only be part of individual treatment options. Conceding the weak evidence, it is recommended to close the dura by some form of a duraplasty avoiding cerebrospinal fluid leakages or scarring between the cortex and the scalp leading to injuries during reimplantation of the bone-flap. Complications associated with decompression surgery (hemorrhages, infections, 'sinking skin-flap syndrome', cerebrospinal fluid leakages, hydrocephalus, seizures), with the infarction itself, or with those that occur during the ICU course (cardiac and pulmonary complications) appear acceptable and are mostly treatable, especially considering the fatal course of conservative treatment. Key Message: This review summarizes the current state of the literature about decompression craniectomy of patients with malignant stroke addressing, in particular, critical surgical issues, and thus, help surgeons to make decisions confidently for/or against performing surgery ¹⁰⁾.

Malignant middle cerebral artery infarction is a life-threatening sub-type of ischemic stroke that may only be survived at the expense of permanent disability. Decompressive hemicraniectomy is an effective surgical therapy to reduce mortality and improve functional outcome without promoting most severe disability. Evidence derives from three European randomized controlled trials in patients up to 60 years. The recently finished DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY - II trial gives now high-level evidence for the effectiveness of decompressive hemicraniectomy in patients older than 60 years. Nevertheless, pressing issues persist that need to be answered in future clinical trials, e.g. the acceptable degree of disability in survivors of malignant middle cerebral artery infarction, the importance of aphasia, and the best timing for decompressive hemicraniectomy. This review provides an overview of the current diagnosis and treatment of malignant middle cerebral artery infarction with a focus on decompressive hemicraniectomy and outlines future perspectives ¹¹⁾.

A prospective randomized study was carried out of a series of 46 consecutive patients with malignant middle cerebral artery territory infarction. Patients were divided randomly into 2 groups: group I, 27 patients who were followed until obvious deterioration of level of consciousness; group II, 19 patients who were operated on prophylactically in 6 hours of presentation even with no clear deterioration of level of consciousness or radiologic findings. Patients were assessed clinically using the Glasgow Coma Scale, motor power by the United Kingdom Medical Research Council, and functionally by the National Institutes of Health Stroke Scale and modified Rankin Scale. Radiologically, patients had primary magnetic resonance imaging on admission, followed by computed tomography scan. Infarction behavior including volume of infarct area, midline shift, and secondary hemorrhage were calculated.

At final follow-up, both groups showed good improvement in level of consciousness, motor power, and functional outcome; however, statistically significant neurologic improvement was shown in group II. Functional outcome also showed statistically significant improvement (P < 0.05) in this ultraearly decompression group (group II). There was a significant difference in mortality in both groups; more than half (52%) of group I died as a result of delay in surgery or its other consequences. Another significant difference was in the progression of infarction volume, which was observed more in group I (statistically insignificant).

Despite the possible complications from surgery, early decompressive craniotomy (within 6 hours of ictus without waiting for neurologic deterioration) has a significant impact on prognosis. Delay in transferring the patient, diagnosing the condition, or taking the decision of surgery significantly affects mortality and overall outcome ¹²⁾.

Jüttler et al. randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization.

Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group.

Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.) ¹³⁾.

A total of 60 patients with malignant MCA infarction were prospectively enrolled. 36 (60%) patients underwent DH and 24 (40%) patients received best medical therapy alone. Both groups were followed-up for 1 year for improvement in disability and aphasia using modified Rankin score (mRS) and Western Aphasia Battery respectively. Good outcome was defined as mRS ≤ 3. Secondary analysis using mRS ≤ 4 was also performed.

An absolute risk reduction of 45% was observed in mortality at 1 year; 38% (14/36) in the surgical group died versus 83% (20/24) in the medical group. Good outcome at 1 year was achieved in 20% (7/35) patients in the surgical group compared with none in the medical group (P = 0.025). Repeated measures regression suggested increased proportion of patients improving over time (discharge, 3, 6 and 12 months). Surgery reduced the odds of moderate to severe disability (mRS ≥ 4) by 93.5% (odds ratio: 0.064, 95% confidence interval: 0.01-0.045, P = 0.006).

DH in malignant MCA infarction not only reduces mortality but also increases chances of a better functional outcome. The benefit of surgery in motor and aphasia recovery is progressive and sustained until 1 year ¹⁴⁾.

Between February 2008 and October 2011, 131 patients were diagnosed with malignant MCA infarctions. We divided these patients into two groups: patients who underwent decompressive craniectomy (n = 58) and those who underwent conservative care (n = 73). A cut-off point of 70 years of age was set, and the study population was segregated into those who fell above or below this point. Mortality rates and functional outcome scores were assessed, and a modified Rankin Scale (mRS) score of > 3 was considered to represent a poor outcome.

Mortality rates were significantly lower at 29.3% (one-month mortality rate) and 48.3% (six-month mortality rate) in the craniectomy group as compared to 58.9% and 71.2%, respectively, in the conservative care group (p < 0.001, p = 0.007). Age (≥70 years vs. < 70 years) did not statistically differ between groups for the six-month mortality rate (p = 0.137). However, the pre-operative National Institutes of Health Stroke Scale (NIHSS) score did contribute to the six-month mortality rate (p = 0.047).

Decompressive craniectomy is effective for patients with a malignant MCA infarction regardless of their age. Therefore, factors other than age should be considered and the treatment should be individualized in elderly patients with malignant infarctions ¹⁵⁾.

DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II is a randomised controlled trial including patients 61-years and older with malignant middle cerebral artery infarcts. Patients are randomised to either maximum conservative treatment alone or in addition to early hemicraniectomy within 48 h after symptom onset. The trial uses a sequential design with a maximum number of 160 patients to be enrolled (ISRCTN 21702227).

In the face of an ageing population, the potential benefit of hemicraniectomy in older patients is of major clinical relevance, but remains controversial.

The results of this trial are expected to directly influence decision making in these patients ¹⁶⁾.

Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66).

Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency ¹⁷⁾.

conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score < or =3) at 6 months' follow-up (primary outcome) between the 2 treatment groups.

RESULTS: After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score < or =3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (P=0.18 and P=0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (P<0.0001).

In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy ¹⁸⁾.

DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat.

A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23).

DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials ¹⁹⁾.

In an open, prospective trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infarction. Initial clinical presentation was assessed by the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Scale (GCS). All survivors were reexamined 3 months after surgical decompression, with the clinical evaluation graded according to the Rankin Scale (RS) and Barthel Index (BI). We analyzed the influence of early decompressive surgery (<24 hours after symptom onset, based on clinical status at admission and initial CT findings) versus late surgery (>24 hours after first reversible signs of herniation) on mortality, functional outcome, and the length of time of critical care therapy was needed.

In total, 46 patients (73%) survived. Despite complete hemispheric infarction, no survivor suffered from complete hemiplegia or was permanently wheelchair bound. In patients with speech-dominant hemispheric infarction (n=11), only mild to moderate aphasia was present. The mean BI score was 65, and RS score revealed severe handicap in 13% of the patients. In 31 patients with early decompressive surgery, mortality was 16% and BI score 68.8. Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed (7.4 versus 13.3 days, P<0.05).

In general, the outcome of patients treated with craniectomy in severe ischemic hemispheric infarction was surprisingly good. In addition, early decompressive surgery may further improve outcome in these patients ²⁰⁾.

Patients who had experienced a recent minor stroke were asked to complete a questionnaire containing 2 parts: demographic information, including patient age, sex, years of education, working status, religion, and economic status, and acceptable level of disability based on modified Rankin Scale (mRS) with corresponding illustrations to explain mRS levels.

Patient age was identified as an independent determinant of the worst acceptable mRS score with a negative correlation. For nondominant hemispheric malignant infarction, the worst acceptable mRS score was significantly lower (mean ± SD 2.0 ± 1.3) for the oldest patients (>70 years old) compared with patients <60 years old (mean ± SD 3.0 ± 0.6) and 60-70 years old (mean ± SD 3.0 ± 0.8). For dominant hemispheric malignant infarction with language impairment, all age groups showed a significantly lower value for worst acceptable mRS score (mean ± SD 1.8 ± 1.1 for patients <60 years old, 1.8 ± 1.2 for patients 60-70 years old, and 1.0 ± 1.4 for patients >70 years old).

Patients showed different attitudes toward disability according to their age. Patients >70 years old showed the lowest worst acceptable mRS score after surgical treatment of malignant infarction. Language impairment with dominant hemispheric infarction further decreased the worst acceptable mRS score ²¹⁾.

In a nationwide survey of decompressive hemicraniectomy for malignant middle cerebral artery infarction in Japan, less than one-tenth of candidates with malignant MCA infarction in Japan underwent decompressive surgery, and the vast majority of patients were elderly. Age was not found to be an independent factor for immediate mortality in this study, and performing surgery in the elderly may be justified based on additional evidence of functional improvements.

Although there is convincing evidence that decompressive craniectomy can significantly reduce mortality rate and improve neurological outcome in young patients (<60 years) ²²⁾ , many surgeons are still hesitant to recommend hemicraniectomy for stroke patients.

Several studies have evaluated the use of decompressive hemicraniectomy (DHC) in malignant middle cerebral artery infarction (MMCAI). In the United Kingdom (UK), the National Institute for Health and Care Excellence (NICE) has set criteria for selection of patients for DHC in MMCAI.

Basu et al. set out to survey the attitudes and practice of neurosurgeons and stroke physicians within the UK towards DHC in MMCAI.

An electronic survey of questions on management of MMCAI in various clinical scenarios was submitted to the academic committees of the Society of British Neurological Surgeons (SBNS) and the British Association of Stroke Physicians (BASP) for approval, prior to dissemination through the consultant members. Responses were collected over two months.

78 responses, from 51 neurosurgeons and 27 stroke physicians, were included in final analysis. 54% and 24% of all respondents would recommend DHC in patients aged 60-70 and 70-80 years, respectively. 60% would advocate surgery between 48-72 hours and 27% beyond 72 hours. 36% indicated DHC with pre-operative GCS 15/15. These findings do not conform to current NICE guidelines. Stroke physicians were statistically more likely to recommend DHC in patients over 60 years (p = 0.032) and in those with dominant multi-territorial infarcts (p = 0.042) and accept a higher post-operative modified Rankin Scale (mRS) (p = 0.034) compared to neurosurgeons.

In view of evidence from recent trials and differences in NICE guidelines and current clinical practice within the UK, based on survey results, it is important to re-evaluate NICE guidelines ²³⁾.

DESTINY-S is a multicenter, international, cross-sectional survey among 1,860 physicians potentially involved in the treatment of malignant MCA infarction. Questions concerned the grade of disability, the hemisphere of the stroke, and the preferred treatment for malignant MCA infarction.

mRS scores of 3 or better were considered acceptable by the majority of respondents (79.3%). Only few considered a mRS score of 5 still acceptable (5.8%). A mRS score of 4 was considered acceptable by 38.0%. Involved hemisphere (dominant vs. non-dominant) was considered a major clinical symptom influencing treatment decisions in 47.7% of respondents, also reflected by significantly different rates for DHC as preferred treatment in dominant versus non-dominant hemispheric infarction (46.9 vs. 72.9%). Significant differences in acceptable disability and treatment decisions were found among geographic regions, medical specialties, and respondents with different work experiences.

Little consensus exists among physicians regarding acceptable outcome and therapeutic management after malignant MCA infarction, and physician's recommendations do not correlate with available evidence. We advocate for a decision-making process that balances scientific evidence, patient preference, and clinical expertise ²⁴⁾.

In a review, twenty-one patients were included from 2004 to 2017, according to the protocol for the management of ischaemic stroke that is implemented in our institution. The relatives were interviewed by telephone. The functional outcome at discharge, 3 months, 1 year, and at present was measured using the modified Rankin scale (mRS).

Patient age was shown to be directly related to the mRS (r=0.56; p=0.035) and 37.5% achieved a good outcome (mRS≤3); 78.9% of the interviewed relatives would repeat the surgical decision.

We present a 21 patients group where the best outcome was achieved in patients ≤60 years old. The severe neurological sequelae in patients with malignant infarction subjected to decompressive hemicraniectomy are tolerated and accepted by most families to the benefit of survival. We must not let this family satisfaction hide the prognosis, having to contextualize it within the real ambulatory situation of the patients ²⁵⁾.

Over the past 10 years in France, decompressive craniectomy (DC) has been increasingly performed for malignant middle cerebral artery infarction (MCI) regardless of age. However, in-hospital mortality remains considerable, as about one-quarter of patients died within the first weeks. For those who survive beyond 6 months, the risk of death significantly decreases. Early mortality is especially high for comatose patients above 60 years operated in inexperienced centers. Most of those who remain in good functional status tend to undergo a cranioplasty within the year following DC ²⁶⁾.

Kilic et al. identified consecutive patients diagnosed with MMCAI who underwent decompressive craniectomy (DC). Clinical and demographic data were obtained from electronic medical records, including: age, sex, preoperative Glasgow Coma Scale (GCS) score, surgery timing, postoperative GCS scores, and modified Rankin Scale (mRS) scores. Results: This study included 27 stroke patients (aged 38⁻80 years) operated within 72 h of the onset of neurological symptoms. Sixteen, five, and six patients underwent DC within 24 h, between 24 and 48 h, and after 48 h after onset of symptoms, respectively. Five patients died after the surgery. Patients who underwent DC within 24 h and 24⁻48 h had better mean GCS scores than those who underwent DC after 48 h (p = 0.000, p = 0.015). In addition, patients who underwent DC within 24 h had better mean postoperative mRS scores (p = 0.000) than other patients. Patients older than 60 years had significantly lower GCS scores (p = 0.027) and higher mRS scores (p = 0.033) than younger patients. Conclusion: Our findings support that DC had satisfying outcomes in patients who underwent DC within 24 h. Older age and lower Glasgow Coma Scale scores among DC patients with MMCAI are associated with high morbidity and mortality ²⁷⁾.

Funchal et al. evaluated 14 patients admitted to a tertiary hospital with malignant middle cerebral artery infarctions, from October 2010 to February 2015, who underwent DC and had ICP monitoring. Patients with and without episodes of ICP elevation were compared.

Fourteen patients were submitted to DC and had ICP monitoring following the procedure during the period. Ten patients (71.4%) had at least one episode of sustained elevated ICP in the first seven days after surgery. Maximal ICP levels had no correlation with age, time to hemicraniectomy or Glasgow Coma Scores at admission, but had a trend toward correlation with the National Institutes of Health Stroke Scale score at admission (p = 0.1). Ventriculitis occurred in 21.4% of the patients.

High ICP episodes and ventriculitis were common in patients following hemicraniectomy for malignant middle cerebral artery strokes. Therefore, the implications of ICP and benefits of the procedure should be firmly established ²⁸⁾.

The primary objective was to compare 1-year mortality between patients receiving DHC for malignant MCA infarction at our institution based on hospital of origin. We retrospectively reviewed the medical records of all patients treated for malignant MCA infarction with DHC at our institution over a 3-year period. One-year mortality rates and time to surgery were comparable regardless of whether the patient first attended the tertiary referral centre or a peripheral centre ²⁹⁾.

From January 2005 to December 2014, a total of 75 patients with acute MCA IS underwent decompressive craniectomy. Median age was 55 years (interquartile range 44-64) with male preponderance (66%) and median National Institute of Health Stroke Scale score 21 points (interquartile range 18-24). A considerable proportion of these patients (38.7%) received intravenous thrombolysis. The majority (70%) of patients suffered right MCA IS, and decompressive surgery was performed within 48 hours of symptom onset in 50 (67%) of the patients. Favorable functional outcome was achieved in 25 (33.3%) patients at 6 months. Right MCA stroke (odds ratio 9.158; 95% confidence interval 1.881-44.596, P = 0.006) and early decompression surgery (odds ratio 4.011; 95% confidence interval 1.058-15.208, P = 0.041) were independent predictors of favorable functional outcome at 6 months.

Early decompression craniectomy, especially in right MCA ischemic stroke, is associated with better favorable functional outcome. ³⁰⁾.

The records of 101 patients with large hemispheric infarctions undergoing DC were retrospectively reviewed. Twenty-seven patients had additional ACA and/or PCA infarcts. Sequential CTs were used for postoperative follow-up. Intracranial pressure (ICP) was monitored via a ventricular catheter in comatose patients. The main aim of treatment was to keep midline shift below 10 mm and ICP below 20 mmHg. If midline shift increased despite preceding DC, repeat surgery with removal of clearly necrotic tissue was considered. For the current analysis, Glasgow Coma Scale (GCS) at 14 days and modified Rankin Scale (mRS) at 3 months were used as outcome parameters. mRS 2 and 3 were defined as “moderate disability”, mRS 4 as “severe disability”, and mRS 5 and 6 as “poor outcome”. These outcome parameters were correlated to age, gender, side, vascular territory, and time delay after stroke, GCS at the time of decompression, maximum ICP, maximum midline shift, and delay of maximum shift.

The median age of the 39 female and 62 male patients was 56 years (range, 5-79 years). Overall, 12 patients died in the acute stage (11.9%). Twenty-three (22.8%) patients recovered to moderate disability at 3 months (mRS ≤ 3), 45 (44.6%) to severe disability and 33 (32.6%) suffered a poor outcome (mRS 5 or 6). Twenty patients (19.8%) required additional necrosectomy due to secondary increasing midline shift and/or intracranial hypertension. Patients recovering to moderate disability at 3 months were in the median 10 years younger than patients with less favorable outcome (P < 0.001) and had a higher GCS prior to surgery (P < 0.001). Eleven of the 27 patients with infarctions exceeding the MCA territory needed secondary surgery, indicating a higher necrosectomy rate as for isolated MCA infarction. At 3 months, the distribution of the outcomes in terms of mRS was comparable between the patients suffering from extended infarctions and patients having isolated MCA stroke. Infarctions exceeding the territory of the middle cerebral artery were seen in 30% of the group recovering to moderate disability and thus as frequent as in the groups suffering a less favorable outcome.

Intensified postoperative management including possible secondary decompression with necrosectomy may further reduce case fatality rate of patients with large hemispheric infarction. Age above 60 years and severely reduced level of consciousness are the most significant factors heralding unfavorable recovery. Patients suffering infarctions exceeding the MCA territory have a comparable chance of favorable recovery as patients with isolated MCA infarction ³¹⁾.

A total of 99 consecutive patients with the diagnosis of large hemispheric infarctions and the indication for decompressive hemicraniectomy were included. We retrospectively evaluated patient characteristics (gender, age and selected preoperative risk factors), stroke characteristics (side, stroke volume and existing mass effect) and surgical characteristics (size of the bone flap, initial complication rate, time to cranioplasty, complication rate following cranioplasty, type of implant, number of revision surgeries and mortality).

Frequency of hydrocephalus development was 10% in our cohort. Patients who developed a hydrocephalus had an earlier time point of bone flap reimplantation compared to the control group (no hydrocephalus=164±104days, hydrocephalus=108±52days, p<0.05). Additionally, numbers of revision surgeries after cranioplasty was associated with hydrocephalus with a trend towards significance (p=0.08).

Communicating hydrocephalus is frequent in patients with malignant middle cerebral artery infarction after decompressive hemicraniectomy. A later time point of cranioplasty might lead to a lower incidence of required shunting procedures in general as we could show in our patient cohort ³²⁾.

Jeon et al. studied 70 patients with malignant middle cerebral artery infarctions (MMI) who underwent hemicraniectomies. Midline shift was measured preoperatively and postoperatively using computed tomography (CT). Consciousness level was evaluated using the Glasgow Coma Scale on postoperative day 1. Patient survival was assessed six months after stroke onset.

The median time interval between preoperative and postoperative CT was 8.3 hours (interquartile range, 6.1-10.2 hours). Reduction in midline shift was associated with higher postoperative Glasgow Coma Scale scores (P<0.05). Forty-three patients (61.4%) were alive at six months after the stroke. Patients with reductions in midline shifts following hemicraniectomy were more likely to be alive at six months post-stroke than those without (P<0.001). Reduction of midline shift was associated with lower mortality at six months after stroke, after adjusting for age, sex, National Institutes of Health Stroke Scale score, and preoperative midline shift (adjusted hazard ratio, 0.71; 95% confidence interval, 0.62-0.81; P<0.001).

Reduction in midline shift following hemicraniectomy was associated with improved consciousness and six-month survival in patients with MMI. Hence, it may be an early indicator of effective decompression following hemicraniectomy ³³⁾.

A retrospective cohort study was carried out including 46 patients who underwent DHC at the Karolinska University Hospital University Hospital between 2004 and 2014. The maximum time to surgery was 5 days after symptom debut. The primary endpoint was a dichotomised score on the modified Rankin Scale (mRS) 3 months after surgery, with favourable outcome defined as mRS ≤ 4.

When the study population was dichotomised according to the primary endpoint, a significant difference between the groups was seen in preoperative Glasgow Coma Score (GCS), blood glucose levels and the infarction's involvement of the basal ganglia (p < 0.05). In a logistic regression model, preoperative GCS contributed significantly with a 59.6 % increase in the probability of favourable outcome for each point gained in preoperative GCS (p = 0.035).

The results indicate that preoperative GCS, blood glucose and the infarction's involvement of the basal ganglia are strong predictors of clinical outcome. These factors should be considered when assessing the probable outcome of DHC, and additional research based on these factors may contribute to improved inclusion criteria for DHC ³⁴⁾.

53 patients underwent decompressive craniectomy after malignant MCA infarction between January 2012 and May 2014 at tertiary care hospital.

They were analyzed for preoperative clinical condition, timing of surgery, cause of infarction, and location and extension of infarction. The outcome was assessed in terms of mortality and scores like modified Rankin scale (mRS).

Totally, 53 patients aged between 22 and 80 years (mean age was 54.92 ± 11.8 years) were analyzed in this study. Approximately, 60% patients were older than 60 years. Approximately, 74% patients operated within 48 h (25 patients) had mRS 0-3 at discharge while 56% patients operated after 48 h had mRS 0-3 at discharge which is not significant statistically. 78% patients aged below 60 years had mRS 0-3 at discharge while only 38% patients aged above 60 years had mRS 0-3 at discharge which was statistically significant (P < 0.008).

Decompressive craniectomy has reduced morbidity and mortality especially in people aged below 60 years and those operated within 48 h of malignant MCA stroke though those operated outside 48 h of stroke also fare well neurologically, there is no reason these patients should be denied surgery ³⁵⁾.

A retrospective case review study was conducted to compare patients treated with medical therapy and decompressive surgery for malignant MCA infarction in Hospital Kuala Lumpur over a period of 5 years (from January 2007 to December 2012). A total of 125 patients were included in this study; 90 (72%) patients were treated with surgery, while 35 (28%) patients were treated with medical therapy. Outcome was assessed in terms of mortality rate at 30 days, Glasgow Outcome Score (GOS) on discharge, and modified Rankin scale (mRS) at 3 and 6 months.

Decompressive craniectomy resulted in a significant reduction in mortality rate at 30 days (P < 0.05) and favorable GOS outcome at discharge (P < 0.05). Good functional outcome based on mRS was seen in 48.9% of patients at 3 months and in 64.4% of patients at 6 months (P < 0.05). Factors associated with good outcome include infarct volume of less than 250 ml, midline shift of less than 10 mm, absence of additional vascular territory involvement, good preoperative Glasgow Coma Scale (GCS) score, and early surgical intervention (within 24 h) (P < 0.05). Age and dominant hemisphere infarction had no significant association with functional outcome.

Decompressive craniectomy achieves good functional outcome in, young patients with good preoperative GCS score and favorable radiological findings treated with surgery within 24 h of ictus ³⁶⁾.

Twenty-seven patients with malignant middle cerebral artery infarction who were treated with DC were studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral blood flow, and cerebral blood volume were evaluated preoperatively and within the first 24 hours after DC.

There was a global trend toward improved cerebral hemodynamics after DC. Preoperative and postoperative absolute mean transit times were associated with mortality at 6 months, and the ratio of post- and preoperative cerebral blood flow was significantly higher in patients with favorable outcomes than those with unfavorable outcomes. Patients who underwent surgery 48 hours after stroke, those with midline brain shift>10 mm, and those who were >55 years showed no significant improvement in any perfusion CT parameters.

DC improves cerebral hemodynamics in patients with malignant middle cerebral artery infarction, and the level of improvement is related to outcome. However, some patients did not seem to experience any additional hemodynamic benefit, suggesting that perfusion CT may play a role as a prognostic tool in patients undergoing DC after ischemic stroke ³⁷⁾.

Antuña-Ramos et al. analysed 21 patients one year after malignant middle cerebral artery infarction who have undergone decompressive craniectomy determine the degree of retrospective satisfaction, they asked relatives and patients whether, now that the patient's current sequelae are known, they would have still agreed to a decompressive craniectomy.

The physical sphere is felt to be more disrupted than that concerning emotional aspects. There are no differences in the quality of life between patients who have the right or the left hemisphere affected. Patients with a better functional situation report a better quality of life. Altogether, 81% of patients said they were satisfied.

Despite the fact that all the patients show a loss of quality of life after a decompressive craniectomy, most of them seem to be satisfied with the treatment they have received, even in cases in which the dominant hemisphere is compromised or in those with a moderate-severe disability ³⁸⁾.

Patients with malignant MCA territory infarction treated in our hospital between January 1997 and March 2003 were included in this retrospective analysis. The National Institutes of Health Stroke Scale (NIHSS) assessed neurologic status at admission, operation, and at 1 week after surgery. All patients were followed up for assessment of functional outcome by the Barthel Index (BI) and the modified Rankin Scale (RS) at 3 to 9 months after infarction.

Twenty-five patients underwent decompressive craniectomy. The mortality was 7.7% in younger patients (ages <60 years) compared with 33.3% in elderly patients (ages >/=60 years) (P > .05). All patients had significant decrease of NIHSS after surgery (P < .001). At follow-up, younger patients who received surgery had significantly better outcome with mean BI of 75.42 and Rankin score of 3.00; however, none of the elderly survivors had a BI score above 60 or a Rankin score below 4.

Decompressive craniectomy in younger patients with malignant MCA territory infarction improves both survival rates and functional outcomes. Although survival rates were improved after surgery in elderly patients, functional outcome and level of independence were poor ³⁹⁾.

Carter et al. tested the hypothesis that decompressive hemicraniectomy for massive nondominant cerebral infarction is lifesaving in a series of 14 patients presenting with right hemispheric infarction and clinical signs of uncal herniation and impending death. We have further analyzed, in prospective follow-up examinations, the levels of physical, psychiatric, and social disabilities in these patients.

The methods used included retrospective analysis to determine rates of immediate mortality and morbidity after surgical intervention. Prospective follow-up data were obtained to determine the level of recovery in surviving patients after 1 year. Standardized measures of outcome to assess physical, psychiatric, and social recovery included the Barthel Index, Zung Depression Scale, and Reintegration to Normal Living Index.

With decompressive hemicraniectomy, we were able to prevent death secondary to transtentorial herniation in all cases; 11 patients experienced long-term survival after the procedure, and three deaths were related to non-neurological causes. We observed that 8 of the 11 surviving patients were at home, were functioning with minimal to moderate assistance, and had Barthel scores greater than 60. The remaining three patients were severely disabled. Seven of the 11 survivors were able to walk at 1 year after undergoing the procedure. Depression and failure to reintegrate socially were experienced by most patients.

This series confirms the lifesaving nature of hemicraniectomy in patients deteriorating because of cerebral edema after infarction. In patients younger than 50 years, recovery to a state of near-independence is possible ⁴⁰⁾.

The optimal timing of decompressive craniectomy in pediatric patients after presentation with malignant middle cerebral artery infarction is unknown. A previously healthy 6-year-old Japanese girl who had good outcome after emergency decompressive craniectomy 116 h after malignant middle cerebral artery infarction. This case suggests that the timing of decompressive craniectomy can be delayed until deterioration of neurological findings and, compared with adults, a more prolonged time course for surgical intervention might be acceptable ⁴¹⁾.