Neurocrit Care DOI 10.1007/s12028-014-0056-y
ORIGINAL ARTICLE
Long-Term Outcome and Quality of Life After Craniectomy in Speech-Dominant Swollen Middle Cerebral Artery Infarction Jarle Sundseth • Antje Sundseth • Bente Thommessen • Lars G. Johnsen • Marianne Altmann • Wilhelm Sorteberg Karl-Fredrik Lindegaard • Jon Berg-Johnsen
•
Ó Springer Science+Business Media New York 2014
Abstract Background Decompressive craniectomy in malignant middle cerebral artery infarction (MMCAI) reduces mortality. Whether speech-dominant side infarction results in less favorable outcome is unclear. This study compared functional outcome, quality of life, and mental health among patients with speech-dominant and non-dominant side infarction. Methods All patients undergoing decompressive craniectomy for MMCAI were included. Demographics, side of infarction, and speech-dominant hemisphere were recorded. Outcome at follow-up was assessed by global functioning (modified Rankin Scale score), neurological impairment (National Institutes of Health Stroke Scale score), dependency (Barthel Index), anxiety and depression
J. Sundseth (&) W. Sorteberg K.-F. Lindegaard J. Berg-Johnsen Department of Neurosurgery, Oslo University Hospital Rikshospitalet, Postboks 4950 Nydalen, 0424 Oslo, Norway e-mail: [email protected] J. Sundseth A. Sundseth M. Altmann K.-F. Lindegaard J. Berg-Johnsen Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway A. Sundseth B. Thommessen M. Altmann Department of Neurology, Medical Division, Akershus University Hospital, Lørenskog, Norway
(Hospital Anxiety and Depression scale), and quality of life (Short Form-36). Results Twenty-nine out of 45 patients (mean age ± SD, 48.1 ± 11.6 years; 58 % male) were alive at follow-up, and 26 were eligible for analysis [follow-up, median (interquartile range): 66 months (32–93)]. The speechdominant hemisphere was affected in 13 patients. Outcome for patients with speech-dominant and non-dominant side MMCAI was similar regarding neurological impairment (National Institutes of Health Stroke Scale score, mean ± SD: 10.3 ± 7.0 vs. 8.9 ± 2.7, respectively; p = 0.51), global functioning [modified Rankin Scale score, median (IQR): 3.0 [2–4] vs. 4.0 [3–4]; p = 0.34], dependence (Barthel Index, mean ± SD: 16.2 ± 5.0 vs. 13.1 ± 4.8; p = 0.12), and anxiety and depression (Hospital Anxiety and Depression scale, mean ± SD: anxiety, 5.0 ± 4.5 vs. 7.3 ± 5.8; p = 0.30; depression, 5.0 ± 5.2 vs. 5.9 ± 3.9; p = 0.62). The mean quality of life scores (Short Form-36) were not significantly different between the groups. Conclusions There was no statistical or clinical difference in functional outcome and quality of life in patients with speech-dominant compared to non-dominant side infarction. The side affected should not influence suitability for decompressive craniectomy. Keywords Decompressive craniectomy Malignant Middle cerebral artery infarction Speech-dominant Outcome Quality of life
L. G. Johnsen Department of Orthopedic Surgery, St. Olav’s University Hospital, Trondheim, Norway
Introduction
L. G. Johnsen Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
A small proportion of supratentorial cerebral infarctions (1–10 %) manifest as life–threatening, space-occupying
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cerebral edema with a peak usually 2–5 days after stroke onset [1–3]. In 1996, Hacke and colleagues defined this type of ischemic stroke as ‘‘malignant middle cerebral artery infarction’’ (MMCAI) [4]. The mortality is approximately 80 % despite optimal intensive care treatment [4– 6], and the patients are in general 10 years younger than the average stroke patient [4]. Decompressive craniectomy was first described by Harvey Cushing in 1905 [7], and introduced as surgical treatment in MMCAI in 1956 [8]. Several nonrandomized trials have suggested that decompressive craniectomy is a life-saving surgical procedure in acute brain swelling [6, 9– 11]. Three recent prospective, randomized controlled European trials, DEcompressive Craniectomy In MALignant middle cerebral artery infarction (DECIMAL) [12], DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY (DESTINY) [13], Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) [14, 15], and their pooled analysis [16] revealed a substantially reduced mortality. The newly published data from the DESTINY II trial, which only included patients older than 60 years, also showed significantly increased survival in those who were operated with decompressive craniectomy compared with best medical treatment [17]. There remain, however, several unanswered questions regarding timing of surgery, cut-off age, long-term benefits on quality of life (QoL), and possible benefits of surgery on speech-dominant versus non-dominant side MMCAI. The definition of a favorable functional outcome is under debate [18]. Concern has been raised about the longterm QoL in these patients [19], and especially when the speech-dominant hemisphere is affected [9, 20]. Several studies have even excluded patients with left or speechdominant hemisphere infarction [21–24] in the belief that these patients benefit less from decompressive surgery. What is meant by a favorable functional outcome should preferably be answered by the individual patients and their closest relatives or caregivers. This study was conducted to assess and compare functional outcome, dependency, QoL, and mental health among patients with speech-dominant and non-dominant side MMCAI treated with decompressive craniectomy in our department during a 12-year time period 1998–2010.
Methods Study Design and Participants All patients operated with decompressive craniectomy due to MMCAI at the Department of Neurosurgery, Oslo University Hospital Rikshospitalet, Oslo, Norway between
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May 1998 and October 2010, were included in the study. Our department serves patients from a well-defined catchment area with 2.7 million people in southeast Norway. Data Collection Patients were identified through a search of all patients admitted with the diagnosis of stroke, and by reviewing all relevant surgical reports in the patients’ medical records. Data were collected by reviewing medical records and interviewing the patients and their close relatives or caregivers. Through interviews, we obtained whether the patients had aphasia, were right- or left-handed, as well as their marital status, working status, comorbidities (hypertension, heart disease, diabetes, depression, previous stroke or transient ischemic attack, cancer), and functional level before stroke onset, as assessed by the modified Rankin Scale (mRS) score [25, 26]. Data obtained retrospectively from the patients’ medical records included the infarction territory, time from stroke onset to decompressive craniectomy, and time of death. Time from stroke onset to hospitalization was obtained from the emergency medical services (EMS) records. The patients’ speech-dominant side was determined on the basis of aphasia after stroke onset and at follow-up, and whether the patients were rightor left-handed. Follow-up was conducted as home visits, or outpatient evaluations at Oslo University Hospital Rikshospitalet. Patients, who lived far from the hospital or were poor functioning, were assessed during home visits (n = 18). The remaining patients were assessed at the outpatient department (n = 9). Home visits were conducted by JS and AS, and outpatient evaluations by JS, BT, and MA. Outcome Our primary outcome was the mRS score, a measure of global functioning. The mRS ranges from 0 (no symptoms) to 6 (death). In accordance with the HAMLET trial [15], a mRS score B 3 was considered as a good functional outcome. Secondary outcome measures were: (1) neurological impairment, assessed by the National Institutes of Health Stroke Scale (NIHSS) score [27], with a higher score indicating increased functional impairment; (2) dependence, assessed by the Barthel Activities of Daily Living Index (Barthel Index) [28, 29], where a score of 0 indicates complete dependence and a score of 20 independence; (3) cognitive impairment, by using the Mini Mental State Examination (MMSE) [30], where a low score indicates cognitive impairment; (4) outcome after severe brain injury, assessed by the Glasgow Outcome Scale (GOS)
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[31], ranging from 1 (death) to 5 (low disability); (5) mental health, evaluated with the Hospital Anxiety and Depression (HAD) scale [32], where a HAD-A (anxiety) or HAD-D (depression) subscores of 8–10 points was considered as a possible case of anxiety or depression, and a subscore C11 points as a definite case [32], and (6) QoL, assessed by the Short Form-36 (SF-36) [33]. The baseline SF-36 scores were calculated for the eight subscales physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), mental health (MH) and the two summary scales physical component summary (PCS), and mental component summary (MCS). Each subscale in SF36 is scored from 0 to 100, with high scores representing good function. The data were compared with the U.S. general population scores from 1998 (with a normal score defined as 50 points). These subscales are indicated PF-US norm, RP-US norm, BP-US norm, GH-US norm, VT-US norm, SF-US norm, RE-US norm, and MH-US norm, and reflect the outcome in our patients compared with the normal U.S. general population score of 50 points. For scoring of the SF-36, we used QualityMetric Health OutcomesTM Scoring Software 2.0 (QualityMetric Incorporated, Lincoln, USA). Finally, all patients were asked the following question: ‘‘Knowing your outcome after the probable life-saving decompressive craniectomy procedure, would you retrospectively consent to the treatment you have received’’? Answer options were ‘‘yes’’, ‘‘no’’, or ‘‘do not know’’. Ethical Considerations The study was approved by the Regional Committee for Medical and Health Research Ethics and the data protection official for research. The patients or their closest relatives were contacted by JS by phone and informed about the study. All agreed to receive an informational letter about the trial, and all but one accepted participation. Written consent was given by the patients, close relatives, or legal guardians. Surgical Procedure Decompressive Craniectomy A standard frontotemporoparietal craniectomy was performed, whereupon the dura mater was opened in a stellate fashion. A dura substitute (Neuro-PatchÒ Aesculap AG, Am Aesculap-Platz, 78532 Tuttlingen) was then placed over the cerebral cortex, and the opened dura repositioned over the substitute. No patients underwent resection of brain tissue. During the later years, a second dura substitute was positioned between the dura and the temporal muscle
in order to facilitate surgical dissection of the temporal muscle during cranioplasty. The subcutis and cutis were closed separately. A subcutaneous drainage (AbdovacTM Wellspect HealthCare, PO Box 14, SE-43121, Mo¨lndal, Sweden) and an intracranial pressure sensor (Johnson & Johnson Plaza, New Brunswick, NJ 08933) were placed to ease the postoperative intensive care monitoring. Connective tissue and blood were removed from the bone flap before it was cleansed in sterile H2O2 and NaCl 9 mg/ml. The flap was thereafter dried with sterile gauze, packed in two layers of sterile instrument pouch (3M Health Care 9097 St. Paul, MN 55144-1000, USA), and placed in an ultra-freezer (Forma Scientific Inc. SA mod. 925, 401 Mill Creek Rd, Marietta, OH 45750) at -86 °C. Statistical Analysis Categorical variables are presented as absolute values and percentages. Continuous normally distributed data are presented as mean and standard deviation (SD). Betweengroup differences were determined by v2 statistics or Fischer exact test, as appropriate, and unpaired 2-sample t test. Time intervals and mRS score are presented as medians and interquartile ranges (IQR), and between-group differences were analyzed by Mann–Whitney U test. The between-group difference in good outcome is presented as odds ratio (OR) with 95 % confidence interval (CI), adjusted for age and NIHSS score on admission with multivariable regression analysis. A p value < 0.05 was used as a level of significance. All statistical analyses were performed using SPSS 18.0.
Results Patient Cohort From May 1998 to October 2010, a total of 45 patients (58 % male) with MMCAI were operated with decompressive craniectomy. Their mean age (SD) was 48.1 (11.6) years (range 19–74 years). The mean age of females was 48.8 (11.4) years (range 21–74 years), and of males 47.5 (12.0) years (range 19–66 years). The median time from stroke onset to decompressive craniectomy was 46.7 h (IQR 30.7–72.7). The left hemisphere was affected in 17 patients (38 %). Information about the patient being rightor left-handed before stroke onset was available in 43 patients. The speech-dominant side was affected in 19 patients (42 %), and the non-dominant side in 24 patients (53 %). Information about the territory affected was available in 44 patients; in one patient, the radiological diagnosis could not be used with certainty to determine the affected territory. The middle cerebral artery (MCA) was
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Neurocrit Care Table 1 Patient demographics at stroke onset
Table 2 Outcome at follow-up in the speech-dominant and nondominant side groups
Dominant side (N = 13)
Non-dominant side p (N = 13) value
Age, mean (SD)
42.2 (13.7)
50.4 (7.4)
0.07
Male n (%)
10 (77)
8 (62)
0.56
mRS score, median (IQR) 3 (2–4)
4 (3–4)
0.34
0.76
mRS score B 3 n (%)
6 (46)
6 (46)
0.65
0.28
NIHSS score, mean (SD) GOS score, mean (SD)
10.3 (7.0) 3.8 (0.7)
8.9 (2.7) 3.3 (0.6)
0.51 0.10
GOS score B 3 n (%)
5 (39)
10 (77)
0.06
Barthel index, mean (SD)
16.2 (5.0)
13.1 (4.8)
0.12
HAD-A score, mean (SD) 5.0 (4.6)
7.3 (5.8)
0.30
HAD-D score, mean (SD) 5.0 (5.2)
5.9 (3.9)
0.62
MMSE score, mean (SD)
26.5 (2.7)
0.40
Premorbid mRS score, 1.0 (2.5) mean (SD) NIHSS on admission, 15.8 (5.5) mean (SD) Timea in hours, median (IQR)
0.7 (2.5) 13.7 (4.0)
46.7 (30.7–72.7) 51.7 (38.0–79.1)
0.34
Territory n (%) MCA
10 (77)
11 (85)
MCA + ACA
2 (15)
2 (15)
MCA + PCA
1 (8)
0
0.86
b
Comorbidity n (%) Cancerc
0
2 (15)
Hypertension
2 (15)
3 (23)
0.31 0.30
Heart disease
3 (23)
1 (8)
0.50
Previous stroke or TIAd
2 (15)
1 (8)
0.96
Diabetes
1 (8)
2 (15)
0.54
Depression
1 (8)
1 (8)
ACA indicates anterior cerebral artery, MCA middle cerebral artery, mRS modified Rankin Scale, PCA posterior cerebral artery, TIA transient ischemic attack a Time from stroke onset to decompressive craniectomy b
Prior to stroke
c
Known prior to craniectomy and considered stable disease: one patient with breast cancer, and one with testicular cancer d
Without sequelae
affected in 32 patients (71 %), MCA and the anterior cerebral artery (ACA) in 10 patients (22 %), and MCA and the posterior cerebral artery (PCA) in two patients (4 %). Surviving Patients Eligible for Follow-up Fourteen patients (31 %) died during primary hospitalization at a median of 7 days after decompressive surgery (range 3–44 days), while two patients (4 %) died during the follow-up time period. A 74-year-old woman died after 510 days for unknown reasons, and a 47-year-old woman after 1,921 days from burn injuries at a nursing home. Two out of the 29 surviving patients were not eligible for follow-up. A tourist who had her bone flap replaced 24 days after stroke onset was repatriated soon thereafter and lost to follow-up. The other patient refused to participate in the study. In one patient with right-sided infarction, information about speech involvement pre- and postoperatively was unavailable. He was, therefore, excluded from further analyses.
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Dominant Non-dominant p value side (N = 13) side (N = 13)
25.0 (5.1)
GOS Glasgow Outcome Scale, HAD-A Hospital Anxiety and Depression scale—anxiety subscore, HAD-D Hospital Anxiety and Depression scale—depression subscore, mRS modified Rankin Scale, MMSE Mini Mental State Examination, NIHSS National Institutes of Health Stroke Scale
The remaining 26 patients were followed for a median of 66 months (IQR 32–93). The speech-dominant (dominant side group) and non-dominant hemisphere (nondominant side group) was affected in 13 patients each. The patients’ demographics and NIHSS score at admission are presented in Table 1. All patients included in the present study had their cryopreserved bone flaps replaced after a median of 105 days (IQR 81–123). Nineteen of the 26 surviving patients eligible for follow-up (73 %) were married or living in cohabitation prior to stroke, and 20 patients (77 %) were working full time. At follow-up, 13 (50 %) were still married, but none of the patients had resumed to their previous work. Only one patient was in a facilitated, reduced work situation. Outcome At follow-up, patients in the speech-dominant and nondominant side group had a median mRS score (IQR) of 3.0 (2–4) vs. 4 (3–4), respectively (p = 0.34). We found no statistical or clinical difference regarding NIHSS score [mean (SD): 10.3 (7.0) vs. 8.9 (2.7), p = 0.51], GOS score [mean (SD): 3.8 (0.7) vs. 3.3 (0.6), p = 0.10], Barthel Index [mean (SD): 16.2 (5.0) vs. 13.1 (4.8), p = 0.12], HAD-A score [mean (SD): 5.0 (4.5) vs. 7.3 (5.8), p = 0.30], and HAD-D score [mean (SD): 5.0 (5.2) vs. 5.9 (3.9), p = 0.62] (Table 2). Six out of 13 patients in each group had a good outcome at follow-up [OR (95 % CI): 1.00 (0.21–4.67), p = 1.00]. Still, after adjustment for age and NIHSS score on admission, there was no statistical or clinical difference between the groups [OR (95 % CI): 0.75 (0.13–4.18), p = 0.74].
Neurocrit Care Table 3 Quality of life at follow-up assessed by Short Form-36 Dominant side Non-dominant side p value (N = 11) (N = 13) PF, mean (SD)
53.2 (41.7)
22.7 (21.4)
PF-US norma, mean (SD)
37.5 (17.5)
24.7 (9.0)
RP, mean (SD)
38.6 (46.6)
69.2 (25.3)
RP-US norma, mean (SD) 38.9 (13.2)
47.5 (7.2)
BP, mean (SD)
59.4 (27.3)
43.2 (32.5)
BP-US norma, mean (SD) 45.3 (11.7)
38.4 (13.9)
GH, mean (SD)
71.3 (26.6)
59.5 (27.1)
GH-US norma, mean (SD) 50.5 (12.5)
45.0 (12.7)
VT, mean (SD)
63.2 (24.9)
44.4 (22.9)
VT-US norma, mean (SD) 52.9 (11.8)
44.0 (10.8)
SF, mean (SD)
68.2 (33.7)
73.1 (31.0)
SF-US norma, mean (SD)
43.3 (14.6)
45.4 (13.5)
RE, mean (SD)
36.4 (50.5)
43.6 (39.4)
RE-US norma, mean (SD) 35.2 (15.9)
37.5 (12.5)
MH, mean (SD)
77.1 (22.4)
66.2 (26.5)
MH-US norma, mean (SD) 51.1 (12.7)
44.9 (15.0)
Table 4 Functional outcome related to time from stroke onset to surgery and age mRS score B 3 mRS score > 3 p (N = 12) (N = 14) value
0.12 0.12
Time to surgery in hours, 58 (34–80) median (IQR)
49 (32–62)
0.71
Age < 50 n (%)
6 (43)
0.70
7 (58)
0.19
mRS indicates modified Rankin Scale
0.25
Age and Time
0.11
The age [mean (SD)] of the patients in the speech-dominant and non-dominant side group was 42.2 (13.7) and 50.4 (7.4) years (p = 0.07), and the time from stroke onset to surgery [median (IQR)] was 46.7 (30.7–72.7) and 51.7 (38.0–79.1) h (p = 0.34), respectively. There was no difference in the proportion of those younger or older than 50 years having a good functional outcome (mRS score B 3) at follow-up (p = 0.70), or the time from stroke onset to surgery in patients with mRS score B 3 versus mRS score > 3 (p = 0.71) (Table 4).
0.82 0.73 0.23
PCS, mean (SD)
42.2 (8.0)
36.9 (8.4)
0.08
MCS, mean (SD)
47.7 (6.7)
46.8 (9.1)
0.87
BP bodily pain, GH general health, MCS mental component summary, MH mental health, PCS physical component summary, PF physical functioning, RE role-emotional, RP role-physical, SF social functioning, VT vitality
Discussion
a
Data compared to U.S. general population in 1998 where 50 points were set as the normal score
Twenty-four patients were able to complete the SF-36 questionnaire. We found no statistical or clinical difference between patients with speech-dominant and non-dominant side MMCAI regarding any of the eight subscales or the two summary scales (Table 3). Patients with speech-dominant side MMCAI performed similar to the general U.S. population scores from 1998 (with a normal score defined as 50 points) in the categories general health [mean (SD) 50.5 (12.5)], vitality [52.9 (11.8)], and mental health [51.1 (12.7)] (Table 3). At follow-up, 77 % of patients with non-dominant side infarction suffered from hemispatial neglect. Two patients (19 and 23 years) with global aphasia regained almost normal speech function, and two (21 and 41 years) were able to speak understandable sentences at follow-up. Knowing their outcome, 10 patients (77 %) with speechdominant and 12 (92 %) with non-dominant side infarction would retrospectively consent to the treatment they received (p = 0.12). Three patients in the dominant side group were uncertain whether they would consent to treatment retrospectively; one patient in the non-dominant side group would not consent.
The present study could not confirm the hypothesis that surgery on speech-dominant side MMCAI results in less favorable outcome at follow-up. No statistical or clinical differences were found between patients with speechdominant and non-dominant side MMCAI regarding our primary outcome measure, the mRS score, or any of the secondary outcome measures. The groups were balanced regarding demographics, comorbidity, and affected territory of the brain. Retrospect agreement to treatment with craniectomy was high in both groups in corroboration with earlier studies [15, 34]. Aphasia The controversy whether to perform decompressive craniectomy on patients with speech-dominant side infarction emerges from the assumption that aphasia with the loss of ability to communicate results in poor outcome [22]. Some previous studies have excluded patients with speech-dominant side infarction [21–24]. A significant improvement in aphasic symptoms over time has, however, been observed among patients with MMCAI in the speech-dominant hemisphere operated with decompressive craniectomy [6, 35, 36]. In the present study, the NIHSS aphasia subscore was used to evaluate the degree of speech impairment. We observed that two out of 13 patients (19 and 23 years) with speech-dominant side infarction and global aphasia had
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regained almost normal speech function, and an additional two patients (21 and 41 years) were able to speak understandable sentences at follow-up. This corresponds well with the results of Kastrau and colleagues, who found a more pronounced improvement of the aphasic syndrome in young age [35]. Cortical language activation in stroke patients recovering from aphasia studied on functional MRI has shown that language activity significantly increases in the right hemisphere [37]. However, age was not significantly correlated to improvement. Others have found that the right-hemisphere shift seems to be an ineffective attempt of the brain to improve speech function after speech-dominant side infarction, and that improvement of the post-stroke dominant side language patterns gives the best language function recovery [38]. Mood Disorders and Neglect Although most patients with speech-dominant side infarction in the present study remained aphasic, they achieved a similar functional outcome and were not more dependent than patients with infarction in the non-dominant hemisphere. The admission NIHSS scores were higher in the speech-dominant side group which we believe may be explained by the fact that seven out of 42 possible points of the scale are directly related to measurement of language compared with only two points related to neglect. Thus, a probable explanation for our results could be that hemispatial neglect, most often seen when the non-dominant side is affected, may be as disabling as aphasia [39, 40]. The HAMLET investigators found that 78 % of patients randomized to surgery suffered from depression at 1-year follow-up [15]. Several authors have studied whether depression and mood disorders are related to the hemisphere affected. While Carson and colleagues found no support for the hypothesis that the risk of depression after stroke is dependent on the location of the brain lesion [41], others have found that patients with infarctions in the non-dominant hemisphere were at high risk of depression and severe cognitive impairment [42, 43]. Lesions in the non-dominant hemisphere affect verbal and non-verbal memory as well as learning [44, 45] which may result in problems with emotional processing [46–49], and are associated with affective disorders [50]. However, our study did not reveal statistical or clinical differences in the level of anxiety and depression between patients in the speech-dominant and non-dominant side group. Quality of Life Patients with speech-dominant side MMCAI scored as high on physical function, vitality, general, and mental health,
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and had no more bodily pain than patients in the nondominant side group. Social function was equal in the two groups. Interestingly, patients with speech-dominant side MMCAI considered themselves as ‘‘normal’’ regarding general health, vitality, and mental health when compared to the U.S. general population scores with a score of 50 set as normal. Our pooled data on the SF-36 summary scores PCS and MCS were similar to the findings in the HAMLET trial [15].
Age and Timing of Surgery Age is the strongest predictor of mortality and poor functional outcome in patients with MMCAI [11]. All the European randomized controlled trials DECIMAL [12], DESTINY [13], and HAMLET [14, 15] included only patients 60, but their definition of dominant and non-dominant hemisphere was related to the side affected, and not to speech involvement. Thus, there are unanswered questions about when to intervene surgically in MMCAI, and especially concerning the benefit of surgery on speech-dominant versus non-dominant side [55]. The recently published DESTINY-S trial concluded that there is little consensus among physicians regarding therapeutic management and what constitutes acceptable outcome in patients with MMCAI [56]. In 48 % of the respondents, the decision on treatment strategy actually was influenced by the hemisphere affected [56]. Limitations The present study is a retrospective observational cohort study. The retrospective analysis may have suffered from anticipated deficiencies related to loss of patient information. A single follow-up within a large time interval may also have influenced our results. Somewhat younger patients with speech-dominant side MMCAI and the relatively small sample size preclude firm conclusions about our results. Age may have influenced the decision-making whether to operate patients with speech-dominant side MMCAI, based on the notion that they achieve a less favorable outcome compared to patients with non-dominant side infarction. The SF-36 results of our patients with aphasia should be interpreted with caution, as there is some uncertainty about the understanding and processing of the questionnaire in aphasic patients.
Conclusions The main results of the present study were that decompressive craniectomy in patients with speech-dominant side MMCAI compared with non-dominant side MMCAI does not result in poorer functional outcome, QoL, or mental health. The similar clinical outcome may be explained by the typical non-dominant side sequelae neglect that may be
as disabling for the patient as aphasia. Knowing their outcome, most patients in both groups retrospectively consented to the treatment they received. Based on these data, the side affected does not influence suitability for decompressive craniectomy after MMCAI. Acknowledgments foundation.
Gidske and Peter Jacob Sørensens research
Conflict of interest of interest.
The authors declare that they have no conflict
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Neurocrit Care 15. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB, HAMLET investigators. 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. 16. Vahedi K, Hofmeijer J, Juettler E, DECIMAL, DESTINY, and HAMLET investigators, 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. 17. Ju¨ttler E, Unterberg A, Woitzik J, DESTINY II investigators, et al. Hemicraniectomy in older patients with extensive middlecerebral-artery stroke. N Engl J Med. 2014;370:1091–100. 18. 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. 19. Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol. 2009;8:949–58. 20. Robertson SC, Lennarson P, Hasan DM, Traynelis VC. Clinical course and surgical management of massive cerebral infarction. Neurosurgery. 2004;55:55–62. 21. Carter BS, Ogilvy CS, Candia GJ, Rosas HD, Buonanno F. Oneyear outcome after decompressive surgery for massive nondominant hemispheric infarction. Neurosurgery. 1997;40:1168–76. 22. Delashaw JB, Broaddus WC, Kassell NF, et al. Treatment of right hemispheric cerebral infarction by hemicraniectomy. Stroke. 1990;21:874–81. 23. Erban P, Woertgen C, Luerding R, Bogdahn U, Schlachetzki F, Horn M. Long-term outcome after hemicraniectomy for space occupying right hemispheric MCA infarction. Clin Neurol Neurosurg. 2006;108:384–7. 24. Leonhardt G, Wilhelm H, Doerfler A, et al. Clinical outcome and neuropsychological deficits after right decompressive hemicraniectomy in MCA infarction. J Neurol. 2002;249:1433–40. 25. Rankin J. Cerebral vascular accidents in patients over the age of 60. II. Prognosis. Scott Med J. 1957;2:200–15. 26. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7. 27. Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864–70. 28. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J. 1965;14:61–5. 29. Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Stud. 1988;10:61–3. 30. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-mental state’’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98. 31. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1:480–4. 32. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70. 33. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–83. 34. Benejam B, Sahuquillo J, Poca MA, et al. Quality of life and neurobehavioral changes in survivors of malignant middle cerebral artery infarction. J Neurol. 2009;256:1126–33. 35. 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.
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36. Woertgen C, Erban P, Rothoerl RD, Bein T, Horn M, Brawanski A. Quality of life after decompressive craniectomy in patients suffering from supratentorial brain ischemia. Acta Neurochir (Wien). 2004;146:691–5. 37. Cao Y, Vikingstad EM, George KP, Johnson AF, Welch KM. Cortical language activation in stroke patients recovering from aphasia with functional MRI. Stroke. 1999;30:2331–40. 38. Szaflarski JP, Allendorfer JB, Banks C, Vannest J, Holland SK. Recovered vs. not-recovered from post-stroke aphasia: the contributions from the dominant and non-dominant hemispheres. Restor Neurol Neurosci. 2013;31:347–60. 39. Goto A, Okuda S, Ito S, et al. Locomotion outcome in hemiplegic patients with middle cerebral artery infarction: the difference between right- and left-sided lesions. J Stroke Cerebrovasc Dis. 2009;18:60–7. 40. Paolucci S, Antonucci G, Pratesi L, Traballesi M, Lubich S, Grasso MG. Functional outcome in stroke inpatient rehabilitation: predicting no, low and high response patients. Cerebrovasc Dis. 1998;8:228–34. 41. Carson AJ, MacHale S, Allen K, et al. Depression after stroke and lesion location: a systematic review. Lancet. 2000;356: 122–6. 42. Curry WT Jr, Sethi MK, Ogilvy CS, Carter BS. Factors associated with outcome after hemicraniectomy for large middle cerebral artery territory infarction. Neurosurgery. 2005;56:681– 92. 43. Schmidt H, Heinemann T, Elster J, et al. Cognition after malignant media infarction and decompressive hemicraniectomy—a retrospective observational study. BMC Neurol. 2011;11:77. 44. De Renzi E, Nichelli P. Verbal and non-verbal short-term memory impairment following hemispheric damage. Cortex. 1975;11:341–54. 45. Gillespie DC, Bowen A, Foster JK. Memory impairment following right hemisphere stroke: a comparative meta-analytic and narrative review. Clin Neuropsychol. 2006;20:59–75. 46. Almeida OP, Burton EJ, Ferrier N, McKeith IG, O’Brien JT. Depression with late onset is associated with right frontal lobe atrophy. Psychol Med. 2003;33:675–81. 47. Tranel D, Bechara A, Denburg NL. Asymmetric functional roles of right and left ventromedial prefrontal cortices in social conduct, decision-making, and emotional processing. Cortex. 2002;38:589–612. 48. Dalby RB, Chakravarty MM, Ahdidan J, et al. Localization of white-matter lesions and effect of vascular risk factors in lateonset major depression. Psychol Med. 2010;40:1389–99. 49. Dalby RB, Frandsen J, Chakravarty MM, et al. Depression severity is correlated to the integrity of white matter fiber tracts in late-onset major depression. Psychiatry Res. 2010;184:38–48. 50. Chan D, Anderson V, Pijnenburg Y, et al. The clinical profile of right temporal lobe atrophy. Brain. 2009;132:1287–98. 51. Uhl E, Kreth FW, Elias B, et al. Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. J Neurol Neurosurg Psychiatry. 2004;75:270–4. 52. Holtkamp M, Buchheim K, Unterberg A, et al. Hemicraniectomy in elderly patients with space occupying media infarction: improved survival but poor functional outcome. J Neurol Neurosurg Psychiatry. 2001;70:226–8. 53. Malm J, Bergenheim AT, Enblad P, et al. The Swedish Malignant Middle cerebral artery Infarction Study: long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care. Acta Neurol Scand. 2006;113:25–30.
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ORIGINAL ARTICLE
Long-Term Outcome and Quality of Life After Craniectomy in Speech-Dominant Swollen Middle Cerebral Artery Infarction Jarle Sundseth • Antje Sundseth • Bente Thommessen • Lars G. Johnsen • Marianne Altmann • Wilhelm Sorteberg Karl-Fredrik Lindegaard • Jon Berg-Johnsen
•
Ó Springer Science+Business Media New York 2014
Abstract Background Decompressive craniectomy in malignant middle cerebral artery infarction (MMCAI) reduces mortality. Whether speech-dominant side infarction results in less favorable outcome is unclear. This study compared functional outcome, quality of life, and mental health among patients with speech-dominant and non-dominant side infarction. Methods All patients undergoing decompressive craniectomy for MMCAI were included. Demographics, side of infarction, and speech-dominant hemisphere were recorded. Outcome at follow-up was assessed by global functioning (modified Rankin Scale score), neurological impairment (National Institutes of Health Stroke Scale score), dependency (Barthel Index), anxiety and depression
J. Sundseth (&) W. Sorteberg K.-F. Lindegaard J. Berg-Johnsen Department of Neurosurgery, Oslo University Hospital Rikshospitalet, Postboks 4950 Nydalen, 0424 Oslo, Norway e-mail: [email protected] J. Sundseth A. Sundseth M. Altmann K.-F. Lindegaard J. Berg-Johnsen Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway A. Sundseth B. Thommessen M. Altmann Department of Neurology, Medical Division, Akershus University Hospital, Lørenskog, Norway
(Hospital Anxiety and Depression scale), and quality of life (Short Form-36). Results Twenty-nine out of 45 patients (mean age ± SD, 48.1 ± 11.6 years; 58 % male) were alive at follow-up, and 26 were eligible for analysis [follow-up, median (interquartile range): 66 months (32–93)]. The speechdominant hemisphere was affected in 13 patients. Outcome for patients with speech-dominant and non-dominant side MMCAI was similar regarding neurological impairment (National Institutes of Health Stroke Scale score, mean ± SD: 10.3 ± 7.0 vs. 8.9 ± 2.7, respectively; p = 0.51), global functioning [modified Rankin Scale score, median (IQR): 3.0 [2–4] vs. 4.0 [3–4]; p = 0.34], dependence (Barthel Index, mean ± SD: 16.2 ± 5.0 vs. 13.1 ± 4.8; p = 0.12), and anxiety and depression (Hospital Anxiety and Depression scale, mean ± SD: anxiety, 5.0 ± 4.5 vs. 7.3 ± 5.8; p = 0.30; depression, 5.0 ± 5.2 vs. 5.9 ± 3.9; p = 0.62). The mean quality of life scores (Short Form-36) were not significantly different between the groups. Conclusions There was no statistical or clinical difference in functional outcome and quality of life in patients with speech-dominant compared to non-dominant side infarction. The side affected should not influence suitability for decompressive craniectomy. Keywords Decompressive craniectomy Malignant Middle cerebral artery infarction Speech-dominant Outcome Quality of life
L. G. Johnsen Department of Orthopedic Surgery, St. Olav’s University Hospital, Trondheim, Norway
Introduction
L. G. Johnsen Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
A small proportion of supratentorial cerebral infarctions (1–10 %) manifest as life–threatening, space-occupying
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cerebral edema with a peak usually 2–5 days after stroke onset [1–3]. In 1996, Hacke and colleagues defined this type of ischemic stroke as ‘‘malignant middle cerebral artery infarction’’ (MMCAI) [4]. The mortality is approximately 80 % despite optimal intensive care treatment [4– 6], and the patients are in general 10 years younger than the average stroke patient [4]. Decompressive craniectomy was first described by Harvey Cushing in 1905 [7], and introduced as surgical treatment in MMCAI in 1956 [8]. Several nonrandomized trials have suggested that decompressive craniectomy is a life-saving surgical procedure in acute brain swelling [6, 9– 11]. Three recent prospective, randomized controlled European trials, DEcompressive Craniectomy In MALignant middle cerebral artery infarction (DECIMAL) [12], DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY (DESTINY) [13], Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) [14, 15], and their pooled analysis [16] revealed a substantially reduced mortality. The newly published data from the DESTINY II trial, which only included patients older than 60 years, also showed significantly increased survival in those who were operated with decompressive craniectomy compared with best medical treatment [17]. There remain, however, several unanswered questions regarding timing of surgery, cut-off age, long-term benefits on quality of life (QoL), and possible benefits of surgery on speech-dominant versus non-dominant side MMCAI. The definition of a favorable functional outcome is under debate [18]. Concern has been raised about the longterm QoL in these patients [19], and especially when the speech-dominant hemisphere is affected [9, 20]. Several studies have even excluded patients with left or speechdominant hemisphere infarction [21–24] in the belief that these patients benefit less from decompressive surgery. What is meant by a favorable functional outcome should preferably be answered by the individual patients and their closest relatives or caregivers. This study was conducted to assess and compare functional outcome, dependency, QoL, and mental health among patients with speech-dominant and non-dominant side MMCAI treated with decompressive craniectomy in our department during a 12-year time period 1998–2010.
Methods Study Design and Participants All patients operated with decompressive craniectomy due to MMCAI at the Department of Neurosurgery, Oslo University Hospital Rikshospitalet, Oslo, Norway between
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May 1998 and October 2010, were included in the study. Our department serves patients from a well-defined catchment area with 2.7 million people in southeast Norway. Data Collection Patients were identified through a search of all patients admitted with the diagnosis of stroke, and by reviewing all relevant surgical reports in the patients’ medical records. Data were collected by reviewing medical records and interviewing the patients and their close relatives or caregivers. Through interviews, we obtained whether the patients had aphasia, were right- or left-handed, as well as their marital status, working status, comorbidities (hypertension, heart disease, diabetes, depression, previous stroke or transient ischemic attack, cancer), and functional level before stroke onset, as assessed by the modified Rankin Scale (mRS) score [25, 26]. Data obtained retrospectively from the patients’ medical records included the infarction territory, time from stroke onset to decompressive craniectomy, and time of death. Time from stroke onset to hospitalization was obtained from the emergency medical services (EMS) records. The patients’ speech-dominant side was determined on the basis of aphasia after stroke onset and at follow-up, and whether the patients were rightor left-handed. Follow-up was conducted as home visits, or outpatient evaluations at Oslo University Hospital Rikshospitalet. Patients, who lived far from the hospital or were poor functioning, were assessed during home visits (n = 18). The remaining patients were assessed at the outpatient department (n = 9). Home visits were conducted by JS and AS, and outpatient evaluations by JS, BT, and MA. Outcome Our primary outcome was the mRS score, a measure of global functioning. The mRS ranges from 0 (no symptoms) to 6 (death). In accordance with the HAMLET trial [15], a mRS score B 3 was considered as a good functional outcome. Secondary outcome measures were: (1) neurological impairment, assessed by the National Institutes of Health Stroke Scale (NIHSS) score [27], with a higher score indicating increased functional impairment; (2) dependence, assessed by the Barthel Activities of Daily Living Index (Barthel Index) [28, 29], where a score of 0 indicates complete dependence and a score of 20 independence; (3) cognitive impairment, by using the Mini Mental State Examination (MMSE) [30], where a low score indicates cognitive impairment; (4) outcome after severe brain injury, assessed by the Glasgow Outcome Scale (GOS)
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[31], ranging from 1 (death) to 5 (low disability); (5) mental health, evaluated with the Hospital Anxiety and Depression (HAD) scale [32], where a HAD-A (anxiety) or HAD-D (depression) subscores of 8–10 points was considered as a possible case of anxiety or depression, and a subscore C11 points as a definite case [32], and (6) QoL, assessed by the Short Form-36 (SF-36) [33]. The baseline SF-36 scores were calculated for the eight subscales physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), mental health (MH) and the two summary scales physical component summary (PCS), and mental component summary (MCS). Each subscale in SF36 is scored from 0 to 100, with high scores representing good function. The data were compared with the U.S. general population scores from 1998 (with a normal score defined as 50 points). These subscales are indicated PF-US norm, RP-US norm, BP-US norm, GH-US norm, VT-US norm, SF-US norm, RE-US norm, and MH-US norm, and reflect the outcome in our patients compared with the normal U.S. general population score of 50 points. For scoring of the SF-36, we used QualityMetric Health OutcomesTM Scoring Software 2.0 (QualityMetric Incorporated, Lincoln, USA). Finally, all patients were asked the following question: ‘‘Knowing your outcome after the probable life-saving decompressive craniectomy procedure, would you retrospectively consent to the treatment you have received’’? Answer options were ‘‘yes’’, ‘‘no’’, or ‘‘do not know’’. Ethical Considerations The study was approved by the Regional Committee for Medical and Health Research Ethics and the data protection official for research. The patients or their closest relatives were contacted by JS by phone and informed about the study. All agreed to receive an informational letter about the trial, and all but one accepted participation. Written consent was given by the patients, close relatives, or legal guardians. Surgical Procedure Decompressive Craniectomy A standard frontotemporoparietal craniectomy was performed, whereupon the dura mater was opened in a stellate fashion. A dura substitute (Neuro-PatchÒ Aesculap AG, Am Aesculap-Platz, 78532 Tuttlingen) was then placed over the cerebral cortex, and the opened dura repositioned over the substitute. No patients underwent resection of brain tissue. During the later years, a second dura substitute was positioned between the dura and the temporal muscle
in order to facilitate surgical dissection of the temporal muscle during cranioplasty. The subcutis and cutis were closed separately. A subcutaneous drainage (AbdovacTM Wellspect HealthCare, PO Box 14, SE-43121, Mo¨lndal, Sweden) and an intracranial pressure sensor (Johnson & Johnson Plaza, New Brunswick, NJ 08933) were placed to ease the postoperative intensive care monitoring. Connective tissue and blood were removed from the bone flap before it was cleansed in sterile H2O2 and NaCl 9 mg/ml. The flap was thereafter dried with sterile gauze, packed in two layers of sterile instrument pouch (3M Health Care 9097 St. Paul, MN 55144-1000, USA), and placed in an ultra-freezer (Forma Scientific Inc. SA mod. 925, 401 Mill Creek Rd, Marietta, OH 45750) at -86 °C. Statistical Analysis Categorical variables are presented as absolute values and percentages. Continuous normally distributed data are presented as mean and standard deviation (SD). Betweengroup differences were determined by v2 statistics or Fischer exact test, as appropriate, and unpaired 2-sample t test. Time intervals and mRS score are presented as medians and interquartile ranges (IQR), and between-group differences were analyzed by Mann–Whitney U test. The between-group difference in good outcome is presented as odds ratio (OR) with 95 % confidence interval (CI), adjusted for age and NIHSS score on admission with multivariable regression analysis. A p value < 0.05 was used as a level of significance. All statistical analyses were performed using SPSS 18.0.
Results Patient Cohort From May 1998 to October 2010, a total of 45 patients (58 % male) with MMCAI were operated with decompressive craniectomy. Their mean age (SD) was 48.1 (11.6) years (range 19–74 years). The mean age of females was 48.8 (11.4) years (range 21–74 years), and of males 47.5 (12.0) years (range 19–66 years). The median time from stroke onset to decompressive craniectomy was 46.7 h (IQR 30.7–72.7). The left hemisphere was affected in 17 patients (38 %). Information about the patient being rightor left-handed before stroke onset was available in 43 patients. The speech-dominant side was affected in 19 patients (42 %), and the non-dominant side in 24 patients (53 %). Information about the territory affected was available in 44 patients; in one patient, the radiological diagnosis could not be used with certainty to determine the affected territory. The middle cerebral artery (MCA) was
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Neurocrit Care Table 1 Patient demographics at stroke onset
Table 2 Outcome at follow-up in the speech-dominant and nondominant side groups
Dominant side (N = 13)
Non-dominant side p (N = 13) value
Age, mean (SD)
42.2 (13.7)
50.4 (7.4)
0.07
Male n (%)
10 (77)
8 (62)
0.56
mRS score, median (IQR) 3 (2–4)
4 (3–4)
0.34
0.76
mRS score B 3 n (%)
6 (46)
6 (46)
0.65
0.28
NIHSS score, mean (SD) GOS score, mean (SD)
10.3 (7.0) 3.8 (0.7)
8.9 (2.7) 3.3 (0.6)
0.51 0.10
GOS score B 3 n (%)
5 (39)
10 (77)
0.06
Barthel index, mean (SD)
16.2 (5.0)
13.1 (4.8)
0.12
HAD-A score, mean (SD) 5.0 (4.6)
7.3 (5.8)
0.30
HAD-D score, mean (SD) 5.0 (5.2)
5.9 (3.9)
0.62
MMSE score, mean (SD)
26.5 (2.7)
0.40
Premorbid mRS score, 1.0 (2.5) mean (SD) NIHSS on admission, 15.8 (5.5) mean (SD) Timea in hours, median (IQR)
0.7 (2.5) 13.7 (4.0)
46.7 (30.7–72.7) 51.7 (38.0–79.1)
0.34
Territory n (%) MCA
10 (77)
11 (85)
MCA + ACA
2 (15)
2 (15)
MCA + PCA
1 (8)
0
0.86
b
Comorbidity n (%) Cancerc
0
2 (15)
Hypertension
2 (15)
3 (23)
0.31 0.30
Heart disease
3 (23)
1 (8)
0.50
Previous stroke or TIAd
2 (15)
1 (8)
0.96
Diabetes
1 (8)
2 (15)
0.54
Depression
1 (8)
1 (8)
ACA indicates anterior cerebral artery, MCA middle cerebral artery, mRS modified Rankin Scale, PCA posterior cerebral artery, TIA transient ischemic attack a Time from stroke onset to decompressive craniectomy b
Prior to stroke
c
Known prior to craniectomy and considered stable disease: one patient with breast cancer, and one with testicular cancer d
Without sequelae
affected in 32 patients (71 %), MCA and the anterior cerebral artery (ACA) in 10 patients (22 %), and MCA and the posterior cerebral artery (PCA) in two patients (4 %). Surviving Patients Eligible for Follow-up Fourteen patients (31 %) died during primary hospitalization at a median of 7 days after decompressive surgery (range 3–44 days), while two patients (4 %) died during the follow-up time period. A 74-year-old woman died after 510 days for unknown reasons, and a 47-year-old woman after 1,921 days from burn injuries at a nursing home. Two out of the 29 surviving patients were not eligible for follow-up. A tourist who had her bone flap replaced 24 days after stroke onset was repatriated soon thereafter and lost to follow-up. The other patient refused to participate in the study. In one patient with right-sided infarction, information about speech involvement pre- and postoperatively was unavailable. He was, therefore, excluded from further analyses.
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Dominant Non-dominant p value side (N = 13) side (N = 13)
25.0 (5.1)
GOS Glasgow Outcome Scale, HAD-A Hospital Anxiety and Depression scale—anxiety subscore, HAD-D Hospital Anxiety and Depression scale—depression subscore, mRS modified Rankin Scale, MMSE Mini Mental State Examination, NIHSS National Institutes of Health Stroke Scale
The remaining 26 patients were followed for a median of 66 months (IQR 32–93). The speech-dominant (dominant side group) and non-dominant hemisphere (nondominant side group) was affected in 13 patients each. The patients’ demographics and NIHSS score at admission are presented in Table 1. All patients included in the present study had their cryopreserved bone flaps replaced after a median of 105 days (IQR 81–123). Nineteen of the 26 surviving patients eligible for follow-up (73 %) were married or living in cohabitation prior to stroke, and 20 patients (77 %) were working full time. At follow-up, 13 (50 %) were still married, but none of the patients had resumed to their previous work. Only one patient was in a facilitated, reduced work situation. Outcome At follow-up, patients in the speech-dominant and nondominant side group had a median mRS score (IQR) of 3.0 (2–4) vs. 4 (3–4), respectively (p = 0.34). We found no statistical or clinical difference regarding NIHSS score [mean (SD): 10.3 (7.0) vs. 8.9 (2.7), p = 0.51], GOS score [mean (SD): 3.8 (0.7) vs. 3.3 (0.6), p = 0.10], Barthel Index [mean (SD): 16.2 (5.0) vs. 13.1 (4.8), p = 0.12], HAD-A score [mean (SD): 5.0 (4.5) vs. 7.3 (5.8), p = 0.30], and HAD-D score [mean (SD): 5.0 (5.2) vs. 5.9 (3.9), p = 0.62] (Table 2). Six out of 13 patients in each group had a good outcome at follow-up [OR (95 % CI): 1.00 (0.21–4.67), p = 1.00]. Still, after adjustment for age and NIHSS score on admission, there was no statistical or clinical difference between the groups [OR (95 % CI): 0.75 (0.13–4.18), p = 0.74].
Neurocrit Care Table 3 Quality of life at follow-up assessed by Short Form-36 Dominant side Non-dominant side p value (N = 11) (N = 13) PF, mean (SD)
53.2 (41.7)
22.7 (21.4)
PF-US norma, mean (SD)
37.5 (17.5)
24.7 (9.0)
RP, mean (SD)
38.6 (46.6)
69.2 (25.3)
RP-US norma, mean (SD) 38.9 (13.2)
47.5 (7.2)
BP, mean (SD)
59.4 (27.3)
43.2 (32.5)
BP-US norma, mean (SD) 45.3 (11.7)
38.4 (13.9)
GH, mean (SD)
71.3 (26.6)
59.5 (27.1)
GH-US norma, mean (SD) 50.5 (12.5)
45.0 (12.7)
VT, mean (SD)
63.2 (24.9)
44.4 (22.9)
VT-US norma, mean (SD) 52.9 (11.8)
44.0 (10.8)
SF, mean (SD)
68.2 (33.7)
73.1 (31.0)
SF-US norma, mean (SD)
43.3 (14.6)
45.4 (13.5)
RE, mean (SD)
36.4 (50.5)
43.6 (39.4)
RE-US norma, mean (SD) 35.2 (15.9)
37.5 (12.5)
MH, mean (SD)
77.1 (22.4)
66.2 (26.5)
MH-US norma, mean (SD) 51.1 (12.7)
44.9 (15.0)
Table 4 Functional outcome related to time from stroke onset to surgery and age mRS score B 3 mRS score > 3 p (N = 12) (N = 14) value
0.12 0.12
Time to surgery in hours, 58 (34–80) median (IQR)
49 (32–62)
0.71
Age < 50 n (%)
6 (43)
0.70
7 (58)
0.19
mRS indicates modified Rankin Scale
0.25
Age and Time
0.11
The age [mean (SD)] of the patients in the speech-dominant and non-dominant side group was 42.2 (13.7) and 50.4 (7.4) years (p = 0.07), and the time from stroke onset to surgery [median (IQR)] was 46.7 (30.7–72.7) and 51.7 (38.0–79.1) h (p = 0.34), respectively. There was no difference in the proportion of those younger or older than 50 years having a good functional outcome (mRS score B 3) at follow-up (p = 0.70), or the time from stroke onset to surgery in patients with mRS score B 3 versus mRS score > 3 (p = 0.71) (Table 4).
0.82 0.73 0.23
PCS, mean (SD)
42.2 (8.0)
36.9 (8.4)
0.08
MCS, mean (SD)
47.7 (6.7)
46.8 (9.1)
0.87
BP bodily pain, GH general health, MCS mental component summary, MH mental health, PCS physical component summary, PF physical functioning, RE role-emotional, RP role-physical, SF social functioning, VT vitality
Discussion
a
Data compared to U.S. general population in 1998 where 50 points were set as the normal score
Twenty-four patients were able to complete the SF-36 questionnaire. We found no statistical or clinical difference between patients with speech-dominant and non-dominant side MMCAI regarding any of the eight subscales or the two summary scales (Table 3). Patients with speech-dominant side MMCAI performed similar to the general U.S. population scores from 1998 (with a normal score defined as 50 points) in the categories general health [mean (SD) 50.5 (12.5)], vitality [52.9 (11.8)], and mental health [51.1 (12.7)] (Table 3). At follow-up, 77 % of patients with non-dominant side infarction suffered from hemispatial neglect. Two patients (19 and 23 years) with global aphasia regained almost normal speech function, and two (21 and 41 years) were able to speak understandable sentences at follow-up. Knowing their outcome, 10 patients (77 %) with speechdominant and 12 (92 %) with non-dominant side infarction would retrospectively consent to the treatment they received (p = 0.12). Three patients in the dominant side group were uncertain whether they would consent to treatment retrospectively; one patient in the non-dominant side group would not consent.
The present study could not confirm the hypothesis that surgery on speech-dominant side MMCAI results in less favorable outcome at follow-up. No statistical or clinical differences were found between patients with speechdominant and non-dominant side MMCAI regarding our primary outcome measure, the mRS score, or any of the secondary outcome measures. The groups were balanced regarding demographics, comorbidity, and affected territory of the brain. Retrospect agreement to treatment with craniectomy was high in both groups in corroboration with earlier studies [15, 34]. Aphasia The controversy whether to perform decompressive craniectomy on patients with speech-dominant side infarction emerges from the assumption that aphasia with the loss of ability to communicate results in poor outcome [22]. Some previous studies have excluded patients with speech-dominant side infarction [21–24]. A significant improvement in aphasic symptoms over time has, however, been observed among patients with MMCAI in the speech-dominant hemisphere operated with decompressive craniectomy [6, 35, 36]. In the present study, the NIHSS aphasia subscore was used to evaluate the degree of speech impairment. We observed that two out of 13 patients (19 and 23 years) with speech-dominant side infarction and global aphasia had
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regained almost normal speech function, and an additional two patients (21 and 41 years) were able to speak understandable sentences at follow-up. This corresponds well with the results of Kastrau and colleagues, who found a more pronounced improvement of the aphasic syndrome in young age [35]. Cortical language activation in stroke patients recovering from aphasia studied on functional MRI has shown that language activity significantly increases in the right hemisphere [37]. However, age was not significantly correlated to improvement. Others have found that the right-hemisphere shift seems to be an ineffective attempt of the brain to improve speech function after speech-dominant side infarction, and that improvement of the post-stroke dominant side language patterns gives the best language function recovery [38]. Mood Disorders and Neglect Although most patients with speech-dominant side infarction in the present study remained aphasic, they achieved a similar functional outcome and were not more dependent than patients with infarction in the non-dominant hemisphere. The admission NIHSS scores were higher in the speech-dominant side group which we believe may be explained by the fact that seven out of 42 possible points of the scale are directly related to measurement of language compared with only two points related to neglect. Thus, a probable explanation for our results could be that hemispatial neglect, most often seen when the non-dominant side is affected, may be as disabling as aphasia [39, 40]. The HAMLET investigators found that 78 % of patients randomized to surgery suffered from depression at 1-year follow-up [15]. Several authors have studied whether depression and mood disorders are related to the hemisphere affected. While Carson and colleagues found no support for the hypothesis that the risk of depression after stroke is dependent on the location of the brain lesion [41], others have found that patients with infarctions in the non-dominant hemisphere were at high risk of depression and severe cognitive impairment [42, 43]. Lesions in the non-dominant hemisphere affect verbal and non-verbal memory as well as learning [44, 45] which may result in problems with emotional processing [46–49], and are associated with affective disorders [50]. However, our study did not reveal statistical or clinical differences in the level of anxiety and depression between patients in the speech-dominant and non-dominant side group. Quality of Life Patients with speech-dominant side MMCAI scored as high on physical function, vitality, general, and mental health,
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and had no more bodily pain than patients in the nondominant side group. Social function was equal in the two groups. Interestingly, patients with speech-dominant side MMCAI considered themselves as ‘‘normal’’ regarding general health, vitality, and mental health when compared to the U.S. general population scores with a score of 50 set as normal. Our pooled data on the SF-36 summary scores PCS and MCS were similar to the findings in the HAMLET trial [15].
Age and Timing of Surgery Age is the strongest predictor of mortality and poor functional outcome in patients with MMCAI [11]. All the European randomized controlled trials DECIMAL [12], DESTINY [13], and HAMLET [14, 15] included only patients 60, but their definition of dominant and non-dominant hemisphere was related to the side affected, and not to speech involvement. Thus, there are unanswered questions about when to intervene surgically in MMCAI, and especially concerning the benefit of surgery on speech-dominant versus non-dominant side [55]. The recently published DESTINY-S trial concluded that there is little consensus among physicians regarding therapeutic management and what constitutes acceptable outcome in patients with MMCAI [56]. In 48 % of the respondents, the decision on treatment strategy actually was influenced by the hemisphere affected [56]. Limitations The present study is a retrospective observational cohort study. The retrospective analysis may have suffered from anticipated deficiencies related to loss of patient information. A single follow-up within a large time interval may also have influenced our results. Somewhat younger patients with speech-dominant side MMCAI and the relatively small sample size preclude firm conclusions about our results. Age may have influenced the decision-making whether to operate patients with speech-dominant side MMCAI, based on the notion that they achieve a less favorable outcome compared to patients with non-dominant side infarction. The SF-36 results of our patients with aphasia should be interpreted with caution, as there is some uncertainty about the understanding and processing of the questionnaire in aphasic patients.
Conclusions The main results of the present study were that decompressive craniectomy in patients with speech-dominant side MMCAI compared with non-dominant side MMCAI does not result in poorer functional outcome, QoL, or mental health. The similar clinical outcome may be explained by the typical non-dominant side sequelae neglect that may be
as disabling for the patient as aphasia. Knowing their outcome, most patients in both groups retrospectively consented to the treatment they received. Based on these data, the side affected does not influence suitability for decompressive craniectomy after MMCAI. Acknowledgments foundation.
Gidske and Peter Jacob Sørensens research
Conflict of interest of interest.
The authors declare that they have no conflict
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