[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal
Original Article
Long-term outcome of decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A prospective observational study Vinod Kumar Rai, Rohit Bhatia, Kameshwar Prasad, M. V. Padma Srivastava, Shaily Singh, Neha Rai, Ashish Suri1 Departments of Neurology, and 1Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
Abstract
Address for correspondence: Dr. Rohit Bhatia, Department of Neurology, Room No. 3, 6th Floor, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India. E-mail: [email protected] Received : 21-12-2013 Review completed : 15-01-2014 Accepted : 26-01-2014
Background: Malignant middle cerebral artery (MCA) infarction is associated with high mortality and morbidity. Decompressive hemicraniectomy (DH) reduces mortality significantly but evidence for long-term functional benefit is sparse and contradictory. Materials and Methods: 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. Results: 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). Conclusions: 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. Key words: Decompressive hemicraniectomy, malignant middle cerebral artery infarction, ischemic stroke
Introduction Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.128273
26
About 10-15% patients with middle cerebral artery (MCA) territory cerebral infarction suffer from progressive clinical deterioration because of increased brain swelling, raised intracranial pressure, and subsequent herniation. [1-3] Such space occupying infarction is commonly referred to as malignant MCA infarction. Edema associated with these infarcts is usually observed between the 2nd and 5th day after the index event and Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
is associated with a poor prognosis. [2,4] Previously described series, have observed fatality rates of about 80%, and most survivors were left severely disabled.[1,2] Unfortunately, medical management for malignant MCA infarction is generally ineffective, necessitating a surgical approach for its relief.[5] A pooled analysis of individual patient data of the three randomized controlled trials showed that surgical decompression reduced the risk of death or disability, defined as modified Rankin Score (mRS) ≥3.[6] However, only those patients who were operated within 48 h from symptom onset and who were ≤60 years old were included in the analysis. Although decompressive hemicraniectomy (DH) has shown to reduce mortality significantly among patients compared to medical therapy alone, there has been concern that life is preserved at the potentially unacceptable cost of marked functional disability.[7] Although various prognostic factors affecting the outcome after DH have been identified, the strength of association is not well-established. It is also important to realize that most of the published data comes from western populations where long-term stroke rehabilitation facilities exist and stroke units are well-established. We aimed to assess the long-term functional outcome (motor as well as language) of our patients undergoing DH for malignant MCA infarction, compared with those managed with best medical treatment alone, in real life situations where care and support following discharge is provided by family members at home.
Materials and Methods This was a non-randomized, prospective, observational cohort study conducted between January 2010 and June 2011 in the department of Neurology at the All India Institute of Medical Sciences, New Delhi, a tertiary referral center in India. The study protocol was approved by the Institutional Ethics Committee and written informed consent was obtained from all participants. All admitted patients with life threatening malignant MCA infarction indicated to undergo DH [Supplemental Appendix e-1] on the basis of clinical assessment (National Institute of Health Stroke Scale [NIHSS], Glasgow coma scale [GCS]) and neuroimaging (computed tomography head) were prospectively enrolled. Patients who died within 24 h of presentation, those with dilated and fixed pupils at presentation, GCS < 6, mRS ≥ 2 prior to the current stroke and known metabolic cause for altered sensorium were excluded to reduce the risk of bias. All patients meeting the inclusion criteria but not undergoing surgery due to any of the reasons cited below were included in the control group (best medical management); (1) no consent; Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
Appendix e-1: Clinical and radiologic criteria commonly used for referring ischemic stroke patients for decompressive craniectomy Patients with Ischemic stroke with at least one of following NIHSS score ≥16 GCS score 5 mm was more common in the surgical group (17 [47%] vs. 4 [17%]) [Table 1]. Significantly high mortality was noted in the medical management group within the hospital, at 3 months, 6 months and 12 months follow up. 62% (15/24) patients died during the hospital stay in medical management group as compared to 13% (5/36) deaths in the hemicraniectomy group. Cumulative risk of death reached up to 83% (20/24) in medical group as compared with 38% (14/36) in the surgical group by 1 year suggesting an absolute risk reduction of 45% in mortality [Table 2]. Log rank test for equality of the survivor function showed significantly higher deaths (20) than expected. Since surgical group patients were younger in age with greater midline shift, cox regression was used to compute adjusted hazard rate [Table 3]. Risk of death in the surgical group was 63% less when compared to the medical group (Hazard Ratio of 0.37 [95% CI: 0.20, 0.69; P = 0.002]) [Figure 1]. Functional outcome measured by dichotomized mRS at 3 and 4 was significantly better in the surgical group at 3 months, 6 months and 1 year follow-up. Good outcome was achieved by 20% patients in the surgical group at 1 year as compared to none in medical group. 53% patients achieved mRS ≤ 4 in the surgery group as compared to 8% in medical group at 1 year follow-up [Table 4 and Supplemental Figure e-1]. Proportion of patients for dichotomized mRS at every time point was calculated in the surgically treated group. Repeated measures regression for dichotomized mRS ≤ 3 and mRS ≤ 4 were applied to see the change in the 28
proportion of patients improving over time (discharge, 3, 6 and 12 months). On average, between any two consecutive time points, 1.98% (95% CI: 1.1%-2.8%, P < 0.0001) more patients achieved a mRS ≤ 3 and 3.7% (95% CI: 2.2%-5.1%, P < 0.0001) achieved mRS of ≤ 4, suggesting significant improvement with time. Table 1: Characteristics of patients in decompressive hemicraniectomy (surgical) and medical management alone (medical) groups
Patient characteristics
Surgical Medical Significance group N=36 group N=24 (P)
Age mean in years (%) 44.63±12.23 Male 27 (75) HTN 17 (47.22) DM 7 (19.44) Dyslipidaemia 11 (30.56) RHD 10 (27.78) Smoking 21 (58.33) Etiology of stroke (%) Large artery disease 5 (13.89) Cardio-embolic 10 (27.78) Unknown (incomplete 21 (58.33) evaluation) GCS 10.44±2.75 NIHSS 18.97±3.34 Aphasia 16 (44.44) Midline shift >5 mm 17 (47.22)
57.12±19.28 16 (66) 15 (62.50) 5 (20.83) 4 (16.67) 7 (29.17) 11 (45.83)
0.003 0.483 0.245 0.895 0.224 0.152 0.342
8 (33.33) 7 (29.17) 9 (37.50)
0.152 0.152 0.152
9.95±4.02 18.41±3.83 7 (29.17) 4 (16.67)
0.580 0.722 0.233 0.048
SD - Standard deviation, HTN - Hypertension, DM - Diabetes mellitus, TIA - Transient ischemic attack, GCS - Glasgow coma scale, NIHSS - National Institute of Health Stroke Scale, RHD - Rheumatic heart disease
Table 2: Cumulative risk of death in medical versus surgical group
Discharge
3 months
6 months
12 months
Medical group (24) 0.62 (15/24) 0.79 (19/24) 0.83 (20/24) 0.83 (20/24) Surgery group (36) 0.13 (5/36) 0.22 (8/36) 0.33 (12/36) 0.38 (14/36) Absolute risk 0.49 0.57 0.50 0.45 reduction RR 0.78 0.28 0.40 0.46 RR - Relative risk
Table 3: Adjusted analysis for death and disability at 1 year
Adjusted analysis for death at 1 year Variables HR P value
95% CI
Surgery Age Midline shift >5 mm Aphasia GCS
0.20-0.69 0.99-1.02 0.92-1.09 0.62-2.23 0.74-0.97
0.37 1.00 1.00 1.17 0.84
0.002 0.251 0.961 0.627 0.017
Adjusted analysis for disability (m RS≥4) at 1 year Variables OR P value 95% CI Surgery Age Midline shift >5 mm Aphasia GCS
0.064 1.04 3.18 2.54 0.71
0.006 0.111 0.167 0.278 0.059
0.01-0.45 0.99-1.09 0.62-16.35 0.47-13.75 0.49-1.01
GCS - Glasgow coma scale, HR - Hazard ratio, OR - Odds ratio, CI - Confidence interval
Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
All 25 patients of left MCA stroke were aphasic at the time of the first assessment (discharge or 1 month after stroke). Out of the 25 patients, 16 were in the surgery group and 9 were in medical group. 11 patients died before 3 months follow-up (8 in medical group, 3 in the surgical group). 1 year follow-up data of language assessment (on OPD basis) was available for only 6 patients, all from surgical group. Progressive improvement in aphasia was observed over time on the mean AQ score (Western Aphasia Battery). Maximum improvement was seen in first 3 months of follow-up [Supplemental Table e-1]. Among 36 patients who underwent DH, 21 (58.33%) achieved good outcome (mRS ≤ 4) and 15 (41.66%) had a poor outcome at 1 year. No significant differences were observed between the two groups among baseline variables [Supplemental Table e-2]. In the post-operative period, ten patients developed fever of which six patients were diagnosed to have aspiration or ventilator associated pneumonia, three urinary tract infection and in one patient source of infection could
not be identified. Surgical site examination and NCCT head were done to rule out any infection, subdural or epidural hematoma or collection; none of which were Table 4: Comparison of functional outcome (dichotomized mRS) in medical and surgical group
Medical Decompressive Significance management surgery (n=36) (P value) alone (n=24) (%) (%) Good outcome defined as mRS≤4 (months) 3 6 12 Good outcome defined as mRS≤3 (months) 3 6 12
12.5 (3) 16.67 (4) 8.3 (2)
58.33 (21) 63.89 (23) 52.78 (19)
0.0001 0.0001 0.0001
0 (0) 0 (0) 0 (0)
2.78 (1) 16.67 (6) 19.44 (7)
0.410 0.035 0.025
mRS - Modified Rankin score
1.00
Supplemental Table e-1: Recovery of aphasia in the surgical group over follow-up of 1 year
First asses 3 months 6 months 12 months
Repeated measure ANOVA, F=126.6, P=0.0001, AQ - Aphasia quotient
0.00
0.50
Subjects Mean AQ Improvement post (SD) hoc analysis (pairwise comparison)
0.25
0.75
Time
0
5
10
analysis time
15
Figure 1: Survival estimates adjusted for age and midline shift
19.44
surgery 1 yr (n=36)
33.33
medical 1 yr (n=24) 8.33 8.33
8.33
38.88
mRS1
83.33
mRS2 16.66
surgery 6 mths (n=36)
47.2
2.8
mRS3
33.33
mRS4 16.66 0
medical 6 mths (n=24)
mRS5
83.33
mRS6 surgery 3 mths (n=36) 2.8
12.5
medical 3 mths (n=24) 0
55.5
19.5
25 20
22.2
62 40
60
80
100
Figure e-1: Modified Rankin score distribution in both groups at 3 months, 6 months and 1 year
Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
25 8 7 6
2.6 (7.9) 39.6 (10) 50.5 (11.5) 60 (7.9)
First 3 months=0.0001 3-6 months, P=0.065 3-12 months, P=0.070 6-12 months, P=0.087
Supplemental Table e-2: Characteristics of patients with good outcome and bad outcome in decompressive hemicraniectomy group dichotomized at mRS 4
Patient characteristics
Good Bad Significance outcome outcome (P value) (mRS≤4) (mRS>4) n=19 n=17
Age mean±SD years Male (%) HTN (%) DM (%) Dyslipidaemia (%) RHD (%) Smoking (%) GCS, mean (SD) NIHSS, mean (SD) Aphasia (%) Midline shift (%) Time to surgery, mean (SD) Early surgery ( 4) in selected patients 60 years of age or younger with a massive hemispheric infarction and edema.[12] This meta-analysis involving 134 patients who were 60 years of age or younger suggested that surgical decompression reduced the risk of death at the end of follow-up (OR: 0.19, 95% CI: 0.09-0.37) and the risk of death or disability defined as mRS > 4 at 12 months (OR: 0.26, 95% CI: 0.13-0.51). Death or disability defined as mRS > 3 at the end of follow-up was no different between the treatment arms (OR: 0.56, 95% CI: 0.27-1.15). Since all the trials were stopped early, possibility of an overestimation of the effect size was expressed. In a review of 13 uncontrolled studies of 138 patients, being older than 50 years was a strong predictor of poor functional outcome after surgical decompression. 30
However timing of the operation, side of the infarct and the involvement of other vascular territories did not affect the outcome.[13] In a recent review of uncontrolled studies, just 6 (8%) of 72 patients older than age 60 years had a favorable outcome after surgery, as compared with 77 (54%) of 143 younger patients.[14] In our study, age was not identified as a predictor of outcome of surgery as only a small number of patients (n = 3) aged > 60 years were operated. A large prospective study enrolling 330 patients with post stroke aphasia showed that Stationary language function in 95% was reached within 2 weeks in those with initial mild aphasia, within 6 weeks in those with moderate, and within 10 weeks in those with severe aphasia.[15] In our study, we found progressive improvement in AQ up to 1 year follow-up. This suggests surgical intervention may have a beneficial effect on recovery of aphasia beyond 3 months. Similar results have been observed in a previously published study.[16] Limitations of our study include younger patients in the surgical group at baseline (however adjusted analysis done showed similar results), slightly less severe stroke as compared to previous trials and unavailability of quantitative measure of infarct volume. However, our results reflect a real world scenario out of context of randomized clinical trials as our patients continued to receive best medical management during the hospital stay, irrespective of not being operated. The follow-up period was long to ascertain true outcome after such large strokes. Furthermore, our patients were cared for at home by family members. This is a more realistic situation of understanding the outcome in resource limited setting like ours where patients don’t spend time in dedicated rehabilitation centers. In the future, we also wish to ascertain caregiver burden and patients perception of the illness with a larger multicenter study.
Conclusion DH in large MCA stroke patients leads to markedly improved survival and better functional outcome (motor and language) at 1 year. The benefit of surgery in motor and aphasia recovery is progressive and sustained until 1 year. Results of the present study suggests that 3 months or 6 months outcome assessment may be insufficient to understand the true benefit of this life saving surgery and at least 1 year follow-up should be recommended for measuring its functional benefit. The results are valid in real life situations, out of context of randomized controlled trials.
References 1.
Berrouschot J, Sterker M, Bettin S, Köster J, Schneider D. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
conservative intensive care. Intensive Care Med 1998;24:620-3. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. ‘Malignant’ middle cerebral artery territory infarction: Clinical course and prognostic signs. Arch Neurol 1996;53:309-15. 3. Rieke K, Schwab S, Krieger D, von Kummer R, Aschoff A, Schuchardt V, et al. Decompressive surgery in space-occupying hemispheric infarction: Results of an open, prospective trial. Crit Care Med 1995;23:1576-87. 4. Ropper AH, Shafran B. Brain edema after stroke. Clinical syndrome and intracranial pressure. Arch Neurol 1984;41:26-9. 5. Hofmeijer J, van der Worp HB, Kappelle LJ. Treatment of space-occupying cerebral infarction. Crit Care Med 2003;31:617-25. 6. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: A pooled analysis of three randomised controlled trials. Lancet Neurol 2007;6:215-22. 7. Puetz V, Campos CR, Eliasziw M, Hill MD, Demchuk AM, Calgary Stroke Program. Assessing the benefits of hemicraniectomy: What is a favourable outcome? Lancet Neurol 2007;6:580. 8. Kerrtesz A. Western Aphasia Battery. New York: Grune and Stratton; 1982. 9. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB, et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): A multicentre, open, randomised trial. Lancet Neurol 2009;8:326-33. 10. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery 2.
infarction (DECIMAL Trial). Stroke 2007;38:2506-17. 11. Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): A randomized, controlled trial. Stroke 2007;38:2518-25. 12. Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev 2012;1:CD003435. 13. Gupta R, Connolly ES, Mayer S, Elkind MS. Hemicraniectomy for massive middle cerebral artery territory infarction: A systematic review. Stroke 2004;35:539-43. 14. Arac A, Blanchard V, Lee M, Steinberg GK. Assessment of outcome following decompressive craniectomy for malignant middle cerebral artery infarction in patients older than 60 years of age. Neurosurg Focus 2009;26:E3. 15. Pedersen PM, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Aphasia in acute stroke: Incidence, determinants, and recovery. Ann Neurol 1995;38:659-66. 16. Kastrau F, Wolter M, Huber W, Block F. Recovery from aphasia after hemicraniectomy for infarction of the speech-dominant hemisphere. Stroke 2005;36:825-9. How to cite this article: Rai VK, Bhatia R, Prasad K, Padma Srivastava MV, Singh S, Rai N, et al. Long-term outcome of decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A prospective observational study. Neurol India 2014;62:26-31. Source of Support: Nil, Conflict of Interest: None declared.
Announcement
“QUICK RESPONSE CODE” LINK FOR FULL TEXT ARTICLES The journal issue has a unique new feature for reaching to the journal’s website without typing a single leƩer. Each arƟcle on its first page has a “Quick Response Code”. Using any mobile or other hand-held device with camera and GPRS/other internet source, one can reach to the full text of that parƟcular arƟcle on the journal’s website. Start a QR-code reading soŌware (see list of free applicaƟons from hƩp://Ɵnyurl.com/yzlh2tc) and point the camera to the QR-code printed in the journal. It will automaƟcally take you to the HTML full text of that arƟcle. One can also use a desktop or laptop with web camera for similar funcƟonality. See hƩp://Ɵnyurl.com/2bw7fn3 or hƩp://Ɵnyurl.com/3ysr3me for the free applicaƟons. Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
31
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Original Article
Long-term outcome of decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A prospective observational study Vinod Kumar Rai, Rohit Bhatia, Kameshwar Prasad, M. V. Padma Srivastava, Shaily Singh, Neha Rai, Ashish Suri1 Departments of Neurology, and 1Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
Abstract
Address for correspondence: Dr. Rohit Bhatia, Department of Neurology, Room No. 3, 6th Floor, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India. E-mail: [email protected] Received : 21-12-2013 Review completed : 15-01-2014 Accepted : 26-01-2014
Background: Malignant middle cerebral artery (MCA) infarction is associated with high mortality and morbidity. Decompressive hemicraniectomy (DH) reduces mortality significantly but evidence for long-term functional benefit is sparse and contradictory. Materials and Methods: 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. Results: 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). Conclusions: 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. Key words: Decompressive hemicraniectomy, malignant middle cerebral artery infarction, ischemic stroke
Introduction Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.128273
26
About 10-15% patients with middle cerebral artery (MCA) territory cerebral infarction suffer from progressive clinical deterioration because of increased brain swelling, raised intracranial pressure, and subsequent herniation. [1-3] Such space occupying infarction is commonly referred to as malignant MCA infarction. Edema associated with these infarcts is usually observed between the 2nd and 5th day after the index event and Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
is associated with a poor prognosis. [2,4] Previously described series, have observed fatality rates of about 80%, and most survivors were left severely disabled.[1,2] Unfortunately, medical management for malignant MCA infarction is generally ineffective, necessitating a surgical approach for its relief.[5] A pooled analysis of individual patient data of the three randomized controlled trials showed that surgical decompression reduced the risk of death or disability, defined as modified Rankin Score (mRS) ≥3.[6] However, only those patients who were operated within 48 h from symptom onset and who were ≤60 years old were included in the analysis. Although decompressive hemicraniectomy (DH) has shown to reduce mortality significantly among patients compared to medical therapy alone, there has been concern that life is preserved at the potentially unacceptable cost of marked functional disability.[7] Although various prognostic factors affecting the outcome after DH have been identified, the strength of association is not well-established. It is also important to realize that most of the published data comes from western populations where long-term stroke rehabilitation facilities exist and stroke units are well-established. We aimed to assess the long-term functional outcome (motor as well as language) of our patients undergoing DH for malignant MCA infarction, compared with those managed with best medical treatment alone, in real life situations where care and support following discharge is provided by family members at home.
Materials and Methods This was a non-randomized, prospective, observational cohort study conducted between January 2010 and June 2011 in the department of Neurology at the All India Institute of Medical Sciences, New Delhi, a tertiary referral center in India. The study protocol was approved by the Institutional Ethics Committee and written informed consent was obtained from all participants. All admitted patients with life threatening malignant MCA infarction indicated to undergo DH [Supplemental Appendix e-1] on the basis of clinical assessment (National Institute of Health Stroke Scale [NIHSS], Glasgow coma scale [GCS]) and neuroimaging (computed tomography head) were prospectively enrolled. Patients who died within 24 h of presentation, those with dilated and fixed pupils at presentation, GCS < 6, mRS ≥ 2 prior to the current stroke and known metabolic cause for altered sensorium were excluded to reduce the risk of bias. All patients meeting the inclusion criteria but not undergoing surgery due to any of the reasons cited below were included in the control group (best medical management); (1) no consent; Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
Appendix e-1: Clinical and radiologic criteria commonly used for referring ischemic stroke patients for decompressive craniectomy Patients with Ischemic stroke with at least one of following NIHSS score ≥16 GCS score 5 mm was more common in the surgical group (17 [47%] vs. 4 [17%]) [Table 1]. Significantly high mortality was noted in the medical management group within the hospital, at 3 months, 6 months and 12 months follow up. 62% (15/24) patients died during the hospital stay in medical management group as compared to 13% (5/36) deaths in the hemicraniectomy group. Cumulative risk of death reached up to 83% (20/24) in medical group as compared with 38% (14/36) in the surgical group by 1 year suggesting an absolute risk reduction of 45% in mortality [Table 2]. Log rank test for equality of the survivor function showed significantly higher deaths (20) than expected. Since surgical group patients were younger in age with greater midline shift, cox regression was used to compute adjusted hazard rate [Table 3]. Risk of death in the surgical group was 63% less when compared to the medical group (Hazard Ratio of 0.37 [95% CI: 0.20, 0.69; P = 0.002]) [Figure 1]. Functional outcome measured by dichotomized mRS at 3 and 4 was significantly better in the surgical group at 3 months, 6 months and 1 year follow-up. Good outcome was achieved by 20% patients in the surgical group at 1 year as compared to none in medical group. 53% patients achieved mRS ≤ 4 in the surgery group as compared to 8% in medical group at 1 year follow-up [Table 4 and Supplemental Figure e-1]. Proportion of patients for dichotomized mRS at every time point was calculated in the surgically treated group. Repeated measures regression for dichotomized mRS ≤ 3 and mRS ≤ 4 were applied to see the change in the 28
proportion of patients improving over time (discharge, 3, 6 and 12 months). On average, between any two consecutive time points, 1.98% (95% CI: 1.1%-2.8%, P < 0.0001) more patients achieved a mRS ≤ 3 and 3.7% (95% CI: 2.2%-5.1%, P < 0.0001) achieved mRS of ≤ 4, suggesting significant improvement with time. Table 1: Characteristics of patients in decompressive hemicraniectomy (surgical) and medical management alone (medical) groups
Patient characteristics
Surgical Medical Significance group N=36 group N=24 (P)
Age mean in years (%) 44.63±12.23 Male 27 (75) HTN 17 (47.22) DM 7 (19.44) Dyslipidaemia 11 (30.56) RHD 10 (27.78) Smoking 21 (58.33) Etiology of stroke (%) Large artery disease 5 (13.89) Cardio-embolic 10 (27.78) Unknown (incomplete 21 (58.33) evaluation) GCS 10.44±2.75 NIHSS 18.97±3.34 Aphasia 16 (44.44) Midline shift >5 mm 17 (47.22)
57.12±19.28 16 (66) 15 (62.50) 5 (20.83) 4 (16.67) 7 (29.17) 11 (45.83)
0.003 0.483 0.245 0.895 0.224 0.152 0.342
8 (33.33) 7 (29.17) 9 (37.50)
0.152 0.152 0.152
9.95±4.02 18.41±3.83 7 (29.17) 4 (16.67)
0.580 0.722 0.233 0.048
SD - Standard deviation, HTN - Hypertension, DM - Diabetes mellitus, TIA - Transient ischemic attack, GCS - Glasgow coma scale, NIHSS - National Institute of Health Stroke Scale, RHD - Rheumatic heart disease
Table 2: Cumulative risk of death in medical versus surgical group
Discharge
3 months
6 months
12 months
Medical group (24) 0.62 (15/24) 0.79 (19/24) 0.83 (20/24) 0.83 (20/24) Surgery group (36) 0.13 (5/36) 0.22 (8/36) 0.33 (12/36) 0.38 (14/36) Absolute risk 0.49 0.57 0.50 0.45 reduction RR 0.78 0.28 0.40 0.46 RR - Relative risk
Table 3: Adjusted analysis for death and disability at 1 year
Adjusted analysis for death at 1 year Variables HR P value
95% CI
Surgery Age Midline shift >5 mm Aphasia GCS
0.20-0.69 0.99-1.02 0.92-1.09 0.62-2.23 0.74-0.97
0.37 1.00 1.00 1.17 0.84
0.002 0.251 0.961 0.627 0.017
Adjusted analysis for disability (m RS≥4) at 1 year Variables OR P value 95% CI Surgery Age Midline shift >5 mm Aphasia GCS
0.064 1.04 3.18 2.54 0.71
0.006 0.111 0.167 0.278 0.059
0.01-0.45 0.99-1.09 0.62-16.35 0.47-13.75 0.49-1.01
GCS - Glasgow coma scale, HR - Hazard ratio, OR - Odds ratio, CI - Confidence interval
Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
All 25 patients of left MCA stroke were aphasic at the time of the first assessment (discharge or 1 month after stroke). Out of the 25 patients, 16 were in the surgery group and 9 were in medical group. 11 patients died before 3 months follow-up (8 in medical group, 3 in the surgical group). 1 year follow-up data of language assessment (on OPD basis) was available for only 6 patients, all from surgical group. Progressive improvement in aphasia was observed over time on the mean AQ score (Western Aphasia Battery). Maximum improvement was seen in first 3 months of follow-up [Supplemental Table e-1]. Among 36 patients who underwent DH, 21 (58.33%) achieved good outcome (mRS ≤ 4) and 15 (41.66%) had a poor outcome at 1 year. No significant differences were observed between the two groups among baseline variables [Supplemental Table e-2]. In the post-operative period, ten patients developed fever of which six patients were diagnosed to have aspiration or ventilator associated pneumonia, three urinary tract infection and in one patient source of infection could
not be identified. Surgical site examination and NCCT head were done to rule out any infection, subdural or epidural hematoma or collection; none of which were Table 4: Comparison of functional outcome (dichotomized mRS) in medical and surgical group
Medical Decompressive Significance management surgery (n=36) (P value) alone (n=24) (%) (%) Good outcome defined as mRS≤4 (months) 3 6 12 Good outcome defined as mRS≤3 (months) 3 6 12
12.5 (3) 16.67 (4) 8.3 (2)
58.33 (21) 63.89 (23) 52.78 (19)
0.0001 0.0001 0.0001
0 (0) 0 (0) 0 (0)
2.78 (1) 16.67 (6) 19.44 (7)
0.410 0.035 0.025
mRS - Modified Rankin score
1.00
Supplemental Table e-1: Recovery of aphasia in the surgical group over follow-up of 1 year
First asses 3 months 6 months 12 months
Repeated measure ANOVA, F=126.6, P=0.0001, AQ - Aphasia quotient
0.00
0.50
Subjects Mean AQ Improvement post (SD) hoc analysis (pairwise comparison)
0.25
0.75
Time
0
5
10
analysis time
15
Figure 1: Survival estimates adjusted for age and midline shift
19.44
surgery 1 yr (n=36)
33.33
medical 1 yr (n=24) 8.33 8.33
8.33
38.88
mRS1
83.33
mRS2 16.66
surgery 6 mths (n=36)
47.2
2.8
mRS3
33.33
mRS4 16.66 0
medical 6 mths (n=24)
mRS5
83.33
mRS6 surgery 3 mths (n=36) 2.8
12.5
medical 3 mths (n=24) 0
55.5
19.5
25 20
22.2
62 40
60
80
100
Figure e-1: Modified Rankin score distribution in both groups at 3 months, 6 months and 1 year
Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
25 8 7 6
2.6 (7.9) 39.6 (10) 50.5 (11.5) 60 (7.9)
First 3 months=0.0001 3-6 months, P=0.065 3-12 months, P=0.070 6-12 months, P=0.087
Supplemental Table e-2: Characteristics of patients with good outcome and bad outcome in decompressive hemicraniectomy group dichotomized at mRS 4
Patient characteristics
Good Bad Significance outcome outcome (P value) (mRS≤4) (mRS>4) n=19 n=17
Age mean±SD years Male (%) HTN (%) DM (%) Dyslipidaemia (%) RHD (%) Smoking (%) GCS, mean (SD) NIHSS, mean (SD) Aphasia (%) Midline shift (%) Time to surgery, mean (SD) Early surgery ( 4) in selected patients 60 years of age or younger with a massive hemispheric infarction and edema.[12] This meta-analysis involving 134 patients who were 60 years of age or younger suggested that surgical decompression reduced the risk of death at the end of follow-up (OR: 0.19, 95% CI: 0.09-0.37) and the risk of death or disability defined as mRS > 4 at 12 months (OR: 0.26, 95% CI: 0.13-0.51). Death or disability defined as mRS > 3 at the end of follow-up was no different between the treatment arms (OR: 0.56, 95% CI: 0.27-1.15). Since all the trials were stopped early, possibility of an overestimation of the effect size was expressed. In a review of 13 uncontrolled studies of 138 patients, being older than 50 years was a strong predictor of poor functional outcome after surgical decompression. 30
However timing of the operation, side of the infarct and the involvement of other vascular territories did not affect the outcome.[13] In a recent review of uncontrolled studies, just 6 (8%) of 72 patients older than age 60 years had a favorable outcome after surgery, as compared with 77 (54%) of 143 younger patients.[14] In our study, age was not identified as a predictor of outcome of surgery as only a small number of patients (n = 3) aged > 60 years were operated. A large prospective study enrolling 330 patients with post stroke aphasia showed that Stationary language function in 95% was reached within 2 weeks in those with initial mild aphasia, within 6 weeks in those with moderate, and within 10 weeks in those with severe aphasia.[15] In our study, we found progressive improvement in AQ up to 1 year follow-up. This suggests surgical intervention may have a beneficial effect on recovery of aphasia beyond 3 months. Similar results have been observed in a previously published study.[16] Limitations of our study include younger patients in the surgical group at baseline (however adjusted analysis done showed similar results), slightly less severe stroke as compared to previous trials and unavailability of quantitative measure of infarct volume. However, our results reflect a real world scenario out of context of randomized clinical trials as our patients continued to receive best medical management during the hospital stay, irrespective of not being operated. The follow-up period was long to ascertain true outcome after such large strokes. Furthermore, our patients were cared for at home by family members. This is a more realistic situation of understanding the outcome in resource limited setting like ours where patients don’t spend time in dedicated rehabilitation centers. In the future, we also wish to ascertain caregiver burden and patients perception of the illness with a larger multicenter study.
Conclusion DH in large MCA stroke patients leads to markedly improved survival and better functional outcome (motor and language) at 1 year. The benefit of surgery in motor and aphasia recovery is progressive and sustained until 1 year. Results of the present study suggests that 3 months or 6 months outcome assessment may be insufficient to understand the true benefit of this life saving surgery and at least 1 year follow-up should be recommended for measuring its functional benefit. The results are valid in real life situations, out of context of randomized controlled trials.
References 1.
Berrouschot J, Sterker M, Bettin S, Köster J, Schneider D. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
[Downloaded free from http://www.neurologyindia.com on Thursday, March 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for this journal Rai, et al.: Decompressive hemicraniectomy in malignant MCA stroke
conservative intensive care. Intensive Care Med 1998;24:620-3. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. ‘Malignant’ middle cerebral artery territory infarction: Clinical course and prognostic signs. Arch Neurol 1996;53:309-15. 3. Rieke K, Schwab S, Krieger D, von Kummer R, Aschoff A, Schuchardt V, et al. Decompressive surgery in space-occupying hemispheric infarction: Results of an open, prospective trial. Crit Care Med 1995;23:1576-87. 4. Ropper AH, Shafran B. Brain edema after stroke. Clinical syndrome and intracranial pressure. Arch Neurol 1984;41:26-9. 5. Hofmeijer J, van der Worp HB, Kappelle LJ. Treatment of space-occupying cerebral infarction. Crit Care Med 2003;31:617-25. 6. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: A pooled analysis of three randomised controlled trials. Lancet Neurol 2007;6:215-22. 7. Puetz V, Campos CR, Eliasziw M, Hill MD, Demchuk AM, Calgary Stroke Program. Assessing the benefits of hemicraniectomy: What is a favourable outcome? Lancet Neurol 2007;6:580. 8. Kerrtesz A. Western Aphasia Battery. New York: Grune and Stratton; 1982. 9. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB, et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): A multicentre, open, randomised trial. Lancet Neurol 2009;8:326-33. 10. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery 2.
infarction (DECIMAL Trial). Stroke 2007;38:2506-17. 11. Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): A randomized, controlled trial. Stroke 2007;38:2518-25. 12. Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev 2012;1:CD003435. 13. Gupta R, Connolly ES, Mayer S, Elkind MS. Hemicraniectomy for massive middle cerebral artery territory infarction: A systematic review. Stroke 2004;35:539-43. 14. Arac A, Blanchard V, Lee M, Steinberg GK. Assessment of outcome following decompressive craniectomy for malignant middle cerebral artery infarction in patients older than 60 years of age. Neurosurg Focus 2009;26:E3. 15. Pedersen PM, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Aphasia in acute stroke: Incidence, determinants, and recovery. Ann Neurol 1995;38:659-66. 16. Kastrau F, Wolter M, Huber W, Block F. Recovery from aphasia after hemicraniectomy for infarction of the speech-dominant hemisphere. Stroke 2005;36:825-9. How to cite this article: Rai VK, Bhatia R, Prasad K, Padma Srivastava MV, Singh S, Rai N, et al. Long-term outcome of decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A prospective observational study. Neurol India 2014;62:26-31. Source of Support: Nil, Conflict of Interest: None declared.
Announcement
“QUICK RESPONSE CODE” LINK FOR FULL TEXT ARTICLES The journal issue has a unique new feature for reaching to the journal’s website without typing a single leƩer. Each arƟcle on its first page has a “Quick Response Code”. Using any mobile or other hand-held device with camera and GPRS/other internet source, one can reach to the full text of that parƟcular arƟcle on the journal’s website. Start a QR-code reading soŌware (see list of free applicaƟons from hƩp://Ɵnyurl.com/yzlh2tc) and point the camera to the QR-code printed in the journal. It will automaƟcally take you to the HTML full text of that arƟcle. One can also use a desktop or laptop with web camera for similar funcƟonality. See hƩp://Ɵnyurl.com/2bw7fn3 or hƩp://Ɵnyurl.com/3ysr3me for the free applicaƟons. Neurology India | Jan-Feb 2014 | Vol 62 | Issue 1
31
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
