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Epilepsy Surgery Outcomes: Quality of Life and Seizure Control
Original Articles
Epilepsy Surgery Outcomes: Quality of Life and Seizure Control Mary L. Zupanc, MD*†, Elliane J. dos Santos Rubio, MD‡, Rhonda R. Werner, CNS†, Michael J. Schwabe, MD*†, Wade M. Mueller, MD†§, Sean M. Lew, MD†§, Charles J. Marcuccilli, MD, PhD*†, Sunila E. O’Connor, MD*†, Maria S. Chico, NP*, Kathy A. Eggener, NP*, and Kurt E. Hecox, MD, PhD*† A consecutive, retrospective analysis of seizure control and quality of life was performed among 83 pediatric patients undergoing epilepsy surgery at Children’s Hospital of Wisconsin. Seizure outcomes were generally favorable, with 68.7% class I outcomes; class II, 12%; and class III, 19.3%. Seizure freedom was highest among temporal lobectomies (84.2%) and hemispherectomies (76.2%). Outcomes among hemispherectomies were substantially superior to those of multilobar resections. Cortical dysplasia was associated with lower seizure freedom, at 57.5%. Among age groups, seizure-free outcomes in infants were lowest, at 50%. The lower infant seizure-free rate was likely attributable to frequency of multilobar resections and type of pathology (cortical dysplasia). Quality-of-life measures generally paralleled seizure outcomes. These results indicate that epilepsy surgery in children with intractable epilepsy can result in significant improvements in seizure control, quality of life, and development. Anticipated type of surgery, presumed location of epileptogenic site, absence of a defined lesion on magnetic resonance imaging scan of the brain, and patient’s age should not prevent surgical evaluations of children with intractable epilepsy. Ó 2010 by Elsevier Inc. All rights reserved. Zupanc ML, dos Santos Rubio EJ, Werner RR, Schwabe MJ, Mueller WM, Lew SM, Marcuccilli CJ, O’Connor SE, Chico MS, Eggener KA, Hecox KE. Epilepsy surgery outcomes: quality of life and seizure control. Pediatr Neurol 2010;42:12-20.
From the *Department of Neurology and §Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin; †Department of Neurology, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and ‡ Department of Pediatric Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
12 PEDIATRIC NEUROLOGY Vol. 42 No. 1
Introduction Epilepsy is one of the most prevalent chronic neurologic disorders, afflicting more than two million persons in the United States alone. Particularly frustrating is the inability to substantially decrease the percentage of patients resistant to all available antiepileptic medications, without producing unacceptable side effects. Depending on the sampling particulars and definitions used in the study, approximately 20-30% of patients are intractable to medical therapy [1]. One option available to this group of patients is surgical resection of the anatomic site responsible for generating the seizures. Although surgical outcomes are significantly better than the published likelihood of pharmacologic success after two to three antiepileptic drugs fail to produce seizure control, substantial hesitancy still precedes the initiation of surgical evaluation. This hesitancy is particularly strong for the pediatric population, where determinants of surgical outcomes are not welldocumented. We describe the outcomes of surgical intervention for intractable epilepsy in a group of pediatric patients, with emphasis on selection criteria for initiating surgical evaluations and a comprehensive look at patients’ quality of life. In previous reports, seizure freedom after epilepsy surgery in children varied between 59-80% [2-10]. Other studies, both pediatric and adult, assessed the contributions of different variables to patient outcomes. Jonas et al. reported that shorter seizure duration, level of seizure control before surgery, and good presurgical developmental quotients predict better postsurgical developmental outcomes in pediatric patients undergoing hemispherectomies [11].
Communications should be addressed to: Dr. Zupanc; Department of Neurology, Children’s Hospital of Wisconsin; 9000 W. Wisconsin Avenue; Children’s Hospital of Wisconsin Children’s Corporate Center, Suite C540; Milwaukee, WI 53201. E-mail: [email protected] Received April 2, 2009; accepted July 20, 2009.
Ó 2010 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2009.07.018 0887-8994/10/$—see front matter
Janszky et al. found that specific seizure types (secondarily generalized seizures and tonic seizures), older age, and longer seizure duration predict worse postsurgical outcomes after a temporal-lobe resection [12]. These and similar studies raise questions about which factors determine whether a referral and consequent surgical intervention will result in a favorable outcome. Several recent studies indicated that early surgical intervention not only results in seizure reduction but also improves quality of life (cognitive, behavioral, and social functioning), particularly with respect to behavioral and developmental ‘‘catch up,’’ in some patients [5,13,14]. Cognitive function studies generally report that intelligence and memory are not affected after temporal lobectomies in young children and adolescents [15-18]. However, Szabo´ et al. [19] found that a modest decline in verbal memory can occur with surgery, whereas Lendt et al. [20] reported improvements in language, attention, and memory that were not dependent on complete seizure control after epilepsy surgery. In retrospective studies, Keene et al. reported that seizure reduction resulted in improvements in overall quality of life in pediatric patients [21,22]. In addition, Mihara et al. reported that satisfaction with patient-family relationships improved after surgery in both children and adults, even when complete elimination of seizures does not occur [23]. A few studies suggest that the quality of life of both adult and pediatric patients does not improve despite better seizure control [24-27]. Smith et al. reported that cognitive, psychosocial, and family function in children did not improve after 1 year of seizure elimination [26]. Altshuler et al. reported that temporal lobectomies in adults can cause depression within a year after surgery [24]. A similar report by Reeves et al. stated that seizure-free outcomes failed to improve quality of life in adults [27]. In that study, the authors hypothesized that, after many years of the low selfesteem, poor peer relations, loss of independence, and academic failure caused by their disability with epilepsy, seizure reduction after epilepsy surgery did not result in gainful employment or improvement in depression. Malmgren et al. reported that, although seizure reduction led to an improvement in quality of life, it also led to an increase of anxiety in patients above 16 years of age [28]. These studies suggest that it is not safe to assume that seizure reduction implies an improvement in quality of life, and moreover, the determinants of quality of life may be complex, especially among adolescents and young adults. Methods Patients We retrospectively reviewed the charts of 83 consecutive pediatric patients who underwent epilepsy surgery between 2002 and 2005 at Children’s Hospital of Wisconsin. First, we examined the impact of surgery on seizure frequency, as a function of multiple clinical variables. We then reviewed the results of validated quality-of-life measures with
respect to seizure outcomes. Subsequently, we studied those patient features likely to determine whether surgery in a child would lead to a significant improvement in the patient’s life, as defined by a reduced seizure burden or ‘‘good’’ quality of life. In better identifying determinants of surgical outcomes, we hoped to improve our criteria for referring patients for surgical evaluation. Inclusion criteria comprised patients under age 18 years at time of surgery, who manifested medically intractable epilepsy (defined as failure to achieve seizure control after an adequate trial with two first-line antiepileptic medications), and who had undergone a preoperative evaluation, surgical intervention, and follow-up performed at Children’s Hospital of Wisconsin. We included two patients who did not meet our full criteria. Patient 60 had exceeded age 18 years at the time of surgical procedure. We included this patient because the surgical procedure had been recommended years earlier. Patient 77 was also included, although this patient did not undergo epilepsy surgery at Children’s Hospital of Wisconsin. However, the preoperative evaluation, recommendation for surgery, and follow-up were performed at Children’s Hospital of Wisconsin. To ensure that the epileptogenic zone was localized, we performed a preoperative evaluation consisting of: (1) clinical evaluation of seizure type and character, (2) continuous video-electroencephalogram monitoring, (3) a magnetic resonance imaging scan of the brain, (4) an interictal positron emission tomography scan, and (5) an ictal and interictal singleproton emission computerized tomography scan. If necessary, a Wada procedure was performed before surgery to localize speech and language, as well as memory, to the appropriate hemisphere. In some patients, invasive electroencephalogram monitoring was used to further localize the epileptogenic zone, particularly in patients who underwent multilobar or lobar resections. If preoperative data were lost or incompletely documented, or if postoperative follow-up was incomplete, patients were excluded from this review. We did not establish a minimum follow-up period, thus making the chart review comparable to our previous review, published in 2004 [29].
Data Collection Data extracted from charts included age at surgery; sex; age at seizure onset; epilepsy syndrome; seizure type and frequency; results of magnetic resonance imaging, video-electroencephalogram, ictal and interictal single-proton emission computerized tomography, and positron emission tomography; type of surgical procedure; date of surgical procedure; pathology; and postsurgical follow-up. Demographic characteristics are listed in Table 1.
Seizure Outcome Assessment Seizure outcomes were assessed through clinical visits and telephone contact. A seizure outcome was classified according to the classification system of Engel et al. [30]. Class I represents no seizures, auras only, or seizures with drug withdrawal only. Class II represents three or fewer seizures a year. Class III represents worthwhile improvement remaining, with more than three seizures per year. Class IV represents no worthwhile improvement after surgery.
Quality-of-Life Assessment All patients (or their caregivers) who were cognitively able to give consent, or complete a quality-of-life inventory, received questionnaires. Caregivers received a Quality of Life in Childhood Epilepsy inventory to complete. The Quality of Life in Childhood Epilepsy survey consists of a 91-item scale that assesses well-being, social activity, physical activity, cognitive functioning, behavioral functioning, general health, and overall quality of life within the previous 4 weeks. The scoring scale extends from 0-100, with the highest score reflecting excellent quality of life. Adolescents received a Quality of Life in Epilepsy for Adolescents inventory. It contains 48 items that assess epilepsy impact (scoring scale,
Zupanc et al: Quality of Life and Seizures in Children 13
Table 1. Demographic characteristics All Patients (n = 83) Age at surgery (in years, mean/S.D.) Onset of epilepsy (in years, mean/S.D.) Duration of epilepsy (in years, mean/S.D.) Follow-up after surgery (in years, mean/S.D.) Sex (male/female)
Mean ± S.D. 10.2 5.0 3.7 4.0 6.5 3.9 1.6 0.8
Range 0.75-21 birth to 16 0.3-18 0.3-3.5
35 48
Abbreviation: S.D. = Standard deviation
0-31), memory/concentration (scoring scale, 0-17), attitude toward epilepsy (scoring scale, 0-9), physical functioning (scoring scale, 0-9), stigma (scoring scale, 0-13), social support (scoring scale, 0-2), school behavior (scoring scale, 0-6), and perceptions of health (scoring scale, 0-12). The overall quality-of-life scoring scale ranges from 0-99, with the highest score reflecting excellent quality of life. Both of these surveys were validated in previous studies [31,32].
Data Analysis To analyze seizure outcomes, we converted seizure outcomes into dichotomous variables (seizure-free vs not seizure-free). To evaluate the association of seizure outcomes with other variables, we used c2 or Fisher’s exact tests. We used the independent t test and Mann-Whitney test to compare quality of life scores of Quality of Life in Childhood Epilepsy and Quality of Life in Epilepsy for Adolescents survey with seizure outcomes. In our statistical analysis, we grouped the several types of cortical dysplasias together. In addition, rather than analyzing the remaining diagnosed pathology into separate categories (which would have resulted in a very small number of cases per group), nondysplastic, discrete, welldefined lesions were placed in a single category, i.e., ‘‘all other pathologies.’’ Moreover, our corpus callosotomy group was too small for a statistical analysis. For the data analysis, P < 0.05 was considered significant. We used SPSS software, version 12.0 (SPSS, Inc., Chicago, IL), to analyze data.
(n = 10) or modified lateral (n = 11) [33,34]. The remainder of procedures consisted of temporal resections (n = 19) and corpus callosotomies (n = 4) (Table 2). Overall, temporal lobectomies had the highest rate of seizure-free outcomes (84%), followed closely by hemispherectomies (76%) (Table 2). Seizure-free outcomes were lower for focal resections, primarily because of the contribution of temporal-parietal-occipital resections. The outcomes of frontal resections matched those of hemispherectomies, and were only slightly lower than in temporal lobectomies. As expected, corpus callosotomies did not generally result in seizure freedom. Combining all groups, 68.7% of patients demonstrated seizure-free outcomes. If corpus callosotomies were excluded, 72% (57/79) demonstrated seizure-free outcomes. Twelve percent of the children (n = 10) had class II outcomes, and 19.3% of the children (n = 16) had class III seizure outcomes (Table 2). Seizure outcomes in terms of modified lateral hemispherectomies compared with Rasmussen functional hemispherectomies were 100% vs 50%, respectively. Seizure outcomes in modified lateral hemispherectomies compared with temporal-parietal-occipital resections were 100% vs 40%, respectively. Both reached statistical significance at the 0.01 level. Outcomes as a function of type of surgery were further divided according to age (Table 3). In general, the younger the patients, the lower the percentage of patients with a class I outcome. None of the differences reached statistical significance. Temporal-parietal-occipital resections contributed heavily to the lower class I outcome percentage in the youngest patient group.
Table 2. Seizure outcome by type of surgery
Results Type of Surgery
Demographics There were 83 patients in total, with a female predominance. The average age at surgery for this series was 10 years, but there was a large range of ages, from less than 1 year to 21 years, with a comparably wide range of durations of epilepsy (Table 1). Seizure Outcome by Surgical Type Surgical procedures consisted predominantly of extratemporal focal resections (n = 39). Temporal lobectomies (n = 19) were analyzed separately. Most focal resections, excluding temporal lobectomies, were located frontally (n = 17), followed by temporal-parietal-occipital resections (n = 10) and other focal resections (n = 12), i.e., occipital resections, parietal resections, or combinations. The hemispherectomies (n = 21) were either Rasmussen functional
14 PEDIATRIC NEUROLOGY Vol. 42 No. 1
I. Hemispherectomy (21) A. Standard functional (10) B. Modified functional (11) II. Extratemporal focal resection (39) A. Frontal resection (17) B. T-P-O resection (10) C. Other (12)* III. Temporal lobectomy (19) IV. Corpus callosotomy (4) Total (83)
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
16/21 (76.2%) 2/21 (9.5%) 3/21 (14.3%) 5/10 (50.0%) 2/10 (20.0%) 3/10 (30.0%) 11/11 (100%) 24/39 (61.5%) 4/39 (10.3%) 13/39 (33.3%) 13/17 (76.5%) 4/10 (40.0%) 7/12 (58.3%) 4/12 (33.3%) 16/19 (84.2%) 2/19 (10.5%) 1/ 4 (25.0%)
2/4 (50.0%)
4/17 (23.5%) 6/10 (60.0%) 1/12 (8.3%) 1/19 (5.3%) 1/4 (25.0%)
57/83 (68.7%) 10/83 (12.0%) 16/83 (19.3%)
* Parietal, occipital, or combined resections. Abbreviation: T-P-O = Temporal-parietal-occipital resection
Table 3. Type of surgery per age group by seizure outcome
Type of Surgery per Age Group Birth to 5 years (18) A. Hemispherectomy (5) B. Extratemporal focal resection (11) C. Temporal lobectomy (2) D. Corpus callosotomy (0) Total 6-11 years (28) A. Hemispherectomy (8) B. Extratemporal focal resection (14) C. Temporal lobectomy (4) D. Corpus callosotomy (2) Total 12-21 years (37) A. Hemispherectomy (8) B. Extratemporal focal resection (14) C. Temporal lobectomy (13) D. Corpus callosotomy (2) Total
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
3/5 (60.0%) 5/11 (45.5%)
1/5 (20.0%) 1/11 (9.1%)
1/2 (50.0%)
1/5 (20.0%) 5/11 (45.5%) 1/2 (50.0%)
9/18 (50.0%)
2/18 (11.1%) 7/18 (38.9%)
6/8 (75.0%) 8/14 (57.1%)
1/8 (12.5%) 1/8 (12.5%) 2/14 (14.3%) 4/14 (28.6%)
Quality of Life
4/4 (100%) 1/2 (50.0%)
Seizure outcome by age of surgery revealed that infants and children under age 6 years demonstrated seizure-free outcomes of only 50%. Again, these results were significantly skewed by the number of temporal-parietal-occipital resections (40% seizure-free outcomes). Children between ages 6-11 years exhibited seizure-free outcomes of 67.9%, whereas 78.4% of adolescents (aged 12-18 years) were seizure-free (Table 3). The proportion of patients undergoing a hemispherectomy was similar across age groups (birth to age 5 years, 5/18 = 27.8%; ages 6-11 years, 8/28 = 28.6%; ages 12-21 years, 8/37 = 21.6%). The proportion of patients undergoing temporal lobectomies was higher in our older patients (birth to age 5 years, 2/18 = 11.1%; ages 6-11 years, 4/28 = 14.3%; ages 12-21 years, 13/37 = 35.1%), as listed in Table 3.
1/2 (50.0%)
19/28 (67.9%) 4/28 (14.3%) 5/28 (17.9%)
7/8 (87.5%) 11/14 (78.6%) 1/14 (7.1%)
1/8 (12.5%) 2/14 (14.3%)
11/13 (84.6%) 2/13 (15.4%) 1/2 (50.0%)
1/2 (50.0%)
29/37 (78.4%) 4/37 (10.8%) 4/37 (10.8%)
Seizure Outcome by Pathologic Diagnosis Pathologic diagnoses included 48.2% with cortical dysplasia (n = 40); 12% with mesial temporal sclerosis (n = 10); 9.6% with encephalomalacia (n = 8); 8.4% with a tumor (n = 7); 6.0% with tuberous sclerosis (n = 5); 4.8% with vascular disease (n = 4); 3.6% with Rasmussen’s encephalitis (n = 3) and 2.4% with Sturge-Weber syndrome (n = 2). Nearly 5% of resections were not viewed by a pathologist, because these procedures were corpus callosotomies without actual tissue resection (n = 4). Seizure outcomes by diagnosed pathology are listed in Table 4. Preoperative magnetic resonance imaging results were used to differentiate between lesional and nonlesional cases. The seizure-free outcomes of lesional cases (n = 67) were significantly higher than for nonlesional cases (n = 16), at 71.6% vs 56.3%. Comparisons of outcome according to pathology indicated that 57.5% were seizurefree in the cortical dysplasia category vs 76.7% seizurefree in the group with ‘‘all other pathologies.’’ The analysis of seizure outcome vs diagnosed pathology revealed seizure-free outcomes to be significantly (<0.008) less frequent in cortical dysplasias (57.5%) vs the remaining pathologic diagnoses (76.7%).
QUALITY OF LIFE IN CHILDHOOD EPILEPSY SURVEY Out of 83 Quality of Life in Childhood Epilepsy surveys distributed, 52 (62.7%) were completed. These results are given in Table 5. The response rate was 30.8% male vs 69.2% female. The mean age was 10.52 years. Types of surgery among patients who completed the survey generally paralleled the frequency of procedures in the total group, and were divided into hemispherectomies, 23.1% (n = 12); extratemporal focal resections, 57.7% (n = 30); temporal lobectomies, 17.3% (n = 9); and corpus callosotomies, 2% (n = 1). Extratemporal focal resections comprised frontal lobectomies, 43.3% (n = 13); temporalparietal-occipital resections, 23.3% (n = 7); and other focal extratemporal resections, 33.3% (n = 10). Table 4. Seizure outcome by pathology
Disease/Disorder
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
I. Cortical dysplasia (40) 23/40 (57.5%) 6/40 (15.0%) 11/40 (27.5%) A. Hemispherectomy 4/7 (57.1%) 2/7 (28.6%) 1/7 (14.3%) (7) B. Cortical (33) 19/33 (57.6%) 4/33 (12.1%) 10/33 (30.3%) II. Tumor (7) 5/7 (71.4%) 1/7 (14.3%) 1/7 (14.3%) III. Vascular (4) 3/4 (75.0%) 1/4 (25.0%) IV. MTS (10) 10/10 (100%) V. Rasmussen’s 3/3 (100%) encephalitis (3) VI. Sturge-Weber 2/2 (100%) syndrome (2) VII. Tuberous 3/5 (60.0%) 1/5 (20.0%) 1/5 (20.0%) sclerosis (5) VIII. Encephalomalacia (8) 7/8 (87.5%) 1/8 (12.5%) IX. No pathology (4)* 1/4 (25.0%) 2/4 (50.0%) 1/4 (25.0%) Total (83) 57/83 (68.7%) 10/83 (12.0%) 16/83 (19.3%) * Corpus callosotomies. Abbreviation: MTS = Mesial temporal sclerosis
Zupanc et al: Quality of Life and Seizures in Children 15
Table 5. Quality of Life in Childhood Epilepsy score by type of surgery* Quality of Life in Childhood Epilepsy Items
Hemispherectomy (12), Mean ± S.D.
Frontal (13), Mean ± S.D.
T-P-O (7), Mean ± S.D.
Other (10), Mean ± S.D.
Temporal (9), Mean ± S.D.
C.C. (1), Mean
Physical restrictions Energy/fatigue Attention/concentration Memory Language Other cognitive functions Depression Anxiety Control/helplessness Self-esteem Social interaction Social activities Stigma Behavior General health Quality of life Overall quality of life
25.00 18.309 54.17 18.718 34.93 26.928 49.83 31.003 37.81 17.496 32.95 24.185 72.91 13.708 70.60 14.091 59.20 16.075 68.11 15.020 55.56 29.534 42.36 31.675 58.33 35.887 55.44 11.258 60.42 40.534 52.08 24.905 51.48 14.190
54.70 33.221 56.73 25.318 50.06 26.537 67.21 18.145 52.05 23.168 49.31 24.990 72.76 15.531 65.77 23.925 65.10 21.230 67.50 20.170 59.30 38.421 66.67 31.366 71.15 30.356 61.03 15.501 59.62 36.140 65.38 33.132 60.12 20.282
24.64 21.283 57.14 18.898 29.38 32.266 44.38 46.564 24.68 27.974 18.33 29.108 62.50 17.678 69.79 15.576 57.29 14.892 69.38 22.396 26.67 27.258 27.98 32.695 41.67 37.639 54.29 16.068 39.29 37.796 42.86 23.780 41.75 20.637
58.98 23.125 52.50 26.874 43.13 28.475 52.50 24.269 48.92 33.562 43.98 32.079 77.29 12.046 66.02 24.657 59.38 21.701 71.50 18.567 65.00 29.607 60.42 31.626 72.22 38.415 63.10 15.939 70.00 34.960 67.50 26.484 61.02 19.874
62.94 31.523 72.22 16.271 58.61 31.353 61.98 29.415 59.71 32.356 58.33 38.865 74.31 19.874 73.15 22.044 72.92 25.388 65.83 28.450 87.96 23.975 85.18 22.738 88.89 25.345 71.22 19.711 83.33 12.500 77.78 19.543 71.99 20.498
38.89 50.00 25.00 18.75 18.75 8.33 58.33 56.25 50.00 45.00 37.50 33.33 50.00 44.64 25.00 50.00 38.11
* Minimal score is 0; maximal score is 100. Abbreviations: C.C. = Corpus callosotomy Other = Other extratemporal focal resections, i.e., parietal, occipital, or combinations S.D. = Standard deviation T-P-O = Temporal-parietal-occipital
Of patients who completed the survey, 58.3% of patients with hemispherectomies demonstrated seizure-free outcomes. Most of these patients had undergone Rasmussen’s functional hemispherectomies. The extratemporal focal resection group demonstrated seizure-free outcomes at 60% (n = 18), subdivided into 76.9% seizure-free outcomes for frontal lobectomies (n = 10); 28.6% seizure-free outcomes for temporal-parietal-occipital resections (n = 2); and 60% for other extratemporal focal resections (n = 6). Most (88.9%) patients with temporal lobectomies demonstrated seizure-free outcomes (n = 8), and the single patient with a corpus callosotomy did not demonstrate a seizure-free outcome. Statistical analysis of the Quality of Life in Childhood Epilepsy survey (Table 6) demonstrated that physical activity, cognition, social activity, general health, quality of life, and overall quality of life were significantly better in children with seizure-free outcomes than in children who were not seizure-free. The subscale of well-being indicated that seizure-free children manifested significantly less depression, and felt significantly more in control. The subscale of social activity indicated that seizure-free children were significantly more socially active than children who were not seizure-free. However, well-being, anxiety, self-esteem, social interaction, stigma, and behavior did not reach statistical significance. QUALITY OF LIFE IN EPILEPSY FOR ADOLESCENTS SURVEY Twenty-six of 48 (54.2%) of the Quality of Life in Epilepsy
16 PEDIATRIC NEUROLOGY Vol. 42 No. 1
for Adolescents surveys were completed. Four completed surveys were excluded because parents acknowledged that they had assisted in completing the form. Analysis was performed on the remaining 22 surveys. Most surveys were from females (77.3%). The mean age was 15.3 years. Types of surgery among patients who completed the survey were divided into hemispherectomies, 13.6% (n = 3); extratemporal focal resections, 50% (n = 11); and temporal lobectomies, 36.4% (n = 8). Most (72.7%) extratemporal focal resections were frontal lobectomies (n = 8), and 27.3% were other focal resections (n = 3). There were no temporal-parietal-occipital resections or corpus callosotomies in the Quality of Life in Epilepsy for Adolescents group (Table 7). Of patients who completed the survey, the majority were seizure-free. All three hemispherectomies demonstrated seizure-free outcomes, and all underwent modified lateral hemispherectomies. The extratemporal focal resections demonstrated seizure-free outcomes of 81.8% (n = 9), subdivided by location, with 87.5% seizure-free outcomes for frontal lobectomies (n = 7), and 66.7% seizure-free outcomes for other extratemporal focal resections (n = 2). All temporal lobectomies (n = 8) demonstrated seizure-free outcomes. None of the individual items on the Quality of Life in Epilepsy for Adolescents demonstrated a significant difference between groups, presumably because of the small number of patients who were not seizure-free.
Table 6. Means compared according to t test for seizure-free vs not seizure-free by Quality of Life in Childhood Epilepsy categories Not SeizureFree
Seizure-Free Quality of Life in Childhood Epilepsy Items Physical activity Physical restrictions Energy/fatigue Cognition Attention/ concentration Memory Language Other cognitive functions Well-being Depression Anxiety Control/ helplessness Self-esteem Social activity Social interaction Social activities Stigma Behavior General health Quality of life Overall quality of life
N
Mean ± S.D.
N
Mean ± S.D.
P Value
33 32
58.9 24.6 58.5 27.9
19 19
27.0 14.0 23.3 18.2
0.0001 0.0001
33 33 33
63.3 21.9 56.9 23.6 56.2 24.8
19 18 18
48.7 19.4 23.7 24.1 20.9 21.1
0.020 0.0001 0.0001
30 33 33
64.4 24.0 54.4 24.8 54.7 26.3
11 14 14
33.3 26.8 23.6 22.1 12.2 18.7
0.001 0.0001 0.0001
33 33 31 33
70.3 15.5 77.3 12.5 70.0 20.2 67.1 21.3
19 19 17 17
61.2 15.7 63.6 17.0 65.7 20.5 54.3 14.9
NS 0.002 NS 0.033
33 33 33 33 32 33 33 33 33
69.1 19.3 69.6 28.6 65.4 33.9 70.3 29.4 73.4 32.3 62.5 17.0 80.3 25.6 72.0 25.6 66.0 17.7
14 19 17 19 18 17 19 19 19
64.9 22.2 45.5 28.2 52.5 33.3 34.4 30.5 56.9 37.2 57.6 14.0 32.6 28.7 43.4 21.8 42.6 15.9
NS 0.005 NS 0.0001 NS NS 0.0001 0.0001 0.0001
in mild, contralateral, lower-extremity paresis (4+/5). A small contralateral thalamic infarct occurred after a modified lateral hemispherectomy. This condition was attributed to an overaggressive use of suction drainage postoperatively. The patient made a complete recovery, and our technique was modified accordingly. The aggregate complication rate was 7.2%.
Discussion
Abbreviations: N = Number of patients evaluated NS = Not significant S.D. = Standard deviation
Generally, however, a number of the means were remarkably low in this group, despite the excellent results of surgery. More complete comment on possible differences between seizure-free and nonseizure-free populations will require larger groups (Table 8). Complications One patient required premature removal of subdural electrodes because of a subdural hematoma with symptomatic mass effect. He recovered completely, and underwent replacement of the electrodes and subsequent resection during the same hospitalization. Two wound infections occurred, both in patients undergoing intracranial monitoring with subdural electrodes. One of these patients required permanent removal of the bone flap and a subsequent cranioplasty. Both patients completely recovered. One patient manifested a small wound dehiscence without infection that was treated with primary closure. Two patients demonstrated small infarcts. One venous infarction occurred after a corpus callosotomy, resulting
Seizure Outcomes The proportion of seizure-free patients in this study (class I of Engel et al. [30]) is similar to that reported previously [2-6]. Previous studies indicated that seizure-free outcomes in young children and adolescents ranged between 59-80%, compared with an overall rate of 68.7% in this study. Seventy-two percent of our patients demonstrated seizurefree outcomes, if patients with corpus callosotomies were excluded. For the infants in our study, seizure-free outcomes were somewhat lower. Several reasons may account for this finding: (1) Several of these patients underwent palliative procedures. Surgery was conducted despite known bilateral epileptogenic foci. These patients exhibited multiple daily seizures with concomitant developmental regression. The most highly epileptogenic focus was removed. (2) Several patients underwent temporal-parietal-occipital resections, which demonstrated a particularly low success rate (40%). Temporal-parietal-occipital resections were performed in an attempt to spare the motor cortices of our patients. The resected tissue in patients with temporal-parietal-occipital resections demonstrated cortical dysplasias, whose margins were poorly delineated, particularly compared with magnetic resonance imaging findings. In retrospect, a hemispherectomy might have been a better choice of procedures, because it has demonstrated a high overall success rate, i.e., 100% with modified lateral hemispherectomies. (3) Most of the infants demonstrated cortical dysplasia as their pathology, again with poorly demarcated margins and lower surgical success rates, as reported previously. Modified lateral hemispherectomies provided superior seizure control (100% seizure-free) compared with Rasmussen functional hemispherectomies (50% seizurefree). Based on these results, we rarely perform temporalparietal-occipital resections, and prefer the modified lateral hemispherectomy technique for our functional hemispherectomies. The difference between hemispherectomy techniques, in this study, was larger than expected according to the literature [11,33]. The reasons for this finding are not clear. Hemispherectomies were evenly split among age groups.
Zupanc et al: Quality of Life and Seizures in Children 17
Table 7. Quality of Life in Epilepsy for Adolescents items by type of surgery
Quality of Life in Epilepsy for Adolescents Items (Total Score per Item)
Type of Surgery Frontal (8), Other (3), Range Range
Hemispherectomy (3), Range 9.2 27.1 8.5 14 0 6.3 5 8.7 1.6 2 5.6 6 0.6 6.8 8 11 54 69
Epilepsy impact (31) Memory/concentration (17) Physical function (9) Stigma (13) Social support (2) School behavior (6) Attitudes toward epilepsy (9) Health perception (12) Overall quality of life (99)
7.1 29.1 6.4 12.8 09 4.3 12.3 0.8 2 4.5 6 0 7.9 4 11 35.8 2.8
5.8 30.4 6.8 12.3 2.7 7.7 9.4 13 1.6 2 5.3 6 1.1 4.5 68 46.1 81.5
Temporal (8), Range 9.0 31 6 17 3.6 9 2.2 13 0.5 2 06 3.4 9 3 12 35.6 95
Abbreviation: Other = Other extra-temporal focal resections, i.e., parietal, occipital, or combinations
Temporal lobectomies were more common in our older adolescent patients, a finding consistent with other studies [2,17]. The temporal lobectomies performed in these patients, specifically in the oldest age group, demonstrated seizure-free outcomes in 84%. In all cases, the pathology of children with less-than-complete seizure freedom was cortical dysplasia. These results are somewhat better than those reported by Meyer et al., who demonstrated seizure-free outcomes between 60-80% [15] for temporal lobectomies. Seventy-seven percent of our patients with frontal lobectomies have enjoyed seizure-free outcomes. This figure is much higher than was reported in the literature. We have not fully analyzed our data, but all of our patients underwent aggressive resections, which included the supplementary motor cortex and mesial frontal tissue. Seizure-free outcomes for the cortical dysplasia group (n = 40) amounted to 57.5%, compared to 76.7% for the group with ‘‘all other pathologies.’’ This result is consistent with other studies, demonstrating that cortical dysplasias are likely widespread in the neocortex, and despite generous
resections, epilepsy surgery may not eliminate the entire epileptogenic network. Quality of Life Quantifying ‘‘quality of life’’ requires a reliable and valid scale. The Quality of Life in Childhood Epilepsy and Quality of Life in Epilepsy for Adolescents proved to be valid in previous studies of patients with epilepsy [31,32,35]. Overall, our results from the Quality of Life in Childhood Epilepsy survey demonstrated that patients with good seizure control achieve better quality of life. However, this was not the case with the Quality of Life in Epilepsy for Adolescents survey. In the adolescent survey, two seizurefree adolescents scored their overall quality of life as very low, with written comments describing their unhappiness. This finding was also reflected in their item scores regarding epilepsy impact, stigma, and attitudes toward epilepsy, which were much lower than in the remaining seizurefree group. In reviewing our data, these two adolescents demonstrated significant presurgical psychiatric disorders,
Table 8. Mann-Whitney test for comparison of two groups by Quality of Life in Epilepsy for Adolescents categories Seizure-Free
Not Seizure-Free
Quality of Life in Epilepsy for Adolescents Items
N
Mean ± S.D.
Median (Range)
N
Mean ± S.D.
Median (Range)
P Value
Epilepsy impact Memory/concentration Physical function Stigma Social support School behavior Attitudes toward epilepsy Health perceptions Overall quality of life
20 20 20 20 20 20 20 20 20
21.0 8.6 10.7 3.1 6.5 2.9 9.6 3.2 1.6 0.4 5.4 1.4 4.2 2.8 8.3 2.7 67.2 18.2
24.2 (6-31) 10.4 (6-17) 7.43 (0-9) 9.8 (2-13) 1.7 (1-2) 6.0 (0-6) 4.5 (0-9) 8.5 (3-12) 67.4 (36-95)
2 2 2 2 2 2 2 2 2
10.7 6.9 11.5 0.6 1.4 1.9 9.0 1.5 2.0 0 5.8 0.3 2.8 2.4 7.0 1.4 50.1 3.5
10.7 (6-16) 11.5 (11-12) 1.4 (0-3) 9.0 (8-10) 2.0 (2-2) 5.82 (6-6) 2.82 (1-5) 7.0 (6-8) 50.1 (48-53)
NS NS NS NS NS NS NS NS NS
Abbreviation: S.D. = Standard deviation
18 PEDIATRIC NEUROLOGY Vol. 42 No. 1
attributable to complex psychosocial issues and genetic factors (e.g., familial hereditary depression and bipolar disorder). These two adolescents may have skewed our data in a negative direction, rendering the overall quality-of-life score insignificant. An alternative hypothesis states that by the time of adolescence, the consequences of intractable epilepsy have taken a significant psychosocial toll, and one that is not easily corrected by epilepsy surgery alone. The nonseizure-free group was too small for valid statistical analysis and comparison. Although the Quality of Life in Childhood Epilepsy survey revealed that better quality of life is parallel to a good seizure outcome, we encountered major limitations in the use of this survey during our study. The items in this survey compared participants with children of their own age, over the previous 4 weeks, rather than comparing improvement before vs after epilepsy surgery in an individual child. This probably resulted in lower overall scores that did not mirror the improvement evident in the majority of our patients. The majority of our children demonstrated other neurologic, physical, and developmental disabilities, in addition to their epilepsy. This happenstance resulted in difficulties in our analysis of quality of life, and contributed to lower scores. Some parents wrote comments to confirm this hypothesis. For example, one parent stated that the child had significantly improved after surgery in all items addressed in the survey, specifically in behavior, i.e., ‘‘X’s behavior has improved 110%.’’ The overall score for this specific child was 68.3, with a score of 67.9 for behavior. Another parent stated, ‘‘Although X’s social interaction is not age appropriate, it is a world away from before surgery.’’ Before surgery, X had never attempted to interact or engage with peers. The parent also stated that the child was nonverbal before surgery, but after surgery, began talking. The overall quality-of-life score for this child was 61.60, with social interaction and cognition scores of 25 and 55.9, respectively. An epilepsy-surgery inventory specifically for children, which would assess quality of life presurgery and postsurgery, might provide additional insights. An adult epilepsy-surgery inventory is available, but no version exists for children [36]. Although we cannot statistically compare the two different surveys, we observed that some parents of adolescents gave their children lower quality-of-life scores than the adolescents gave themselves. For example, one adolescent scored 81.5 on overall quality of life; however, the parent assessed an overall quality-of-life score of 50.5. Lower scoring by parents may be explained on the basis of high expectations after successful epilepsy surgery. This trend is probably not isolated to the adolescent age group, and may be the case for the remaining age groups. The use of a quality-of-life survey is still considered a very subjective research technique. The subjectivity may increase when parents assess the quality of life of their children. This subjectivity might be reduced if we were to develop a qualityof-life survey capable of allowing children of all different
ages and cognitive levels to complete the form. Consideration should be given to developing surveys that include pictures and verbal questions. A Quality of Life in Childhood Epilepsy survey is being developed in which children assess their own quality of life [35]. Conclusions In conclusion, our results are promising, and are consistent with other studies. The success rate for all types of surgery, age groups, and forms of pathology were substantially higher than those cited for continued trials of antiepileptic medications. In this regard, we agree with Engel et al. that the low rate of referral is not entirely rational from the perspective of outcomes [30]. None of the clinical variables examined in this study should prevent a child from being evaluated as a surgical candidate. In addition, it is reasonable to assume that seizure-free outcomes with epilepsy surgery will improve even further as we intervene earlier and use increasingly sophisticated techniques to identify the epileptogenic zone. An earlier age of intervention is pertinent, with respect to both seizure control and developmental outcomes. Animal-model evidence is emerging that epilepsy in the developing brain inflicts potentially more devastating consequences, with the development of permanent, aberrant, excitatory neural circuitry. The quality-of-life measures for the Quality of Life in Childhood Epilepsy survey mirrored seizure-free outcomes. Specifically, the better the seizure control outcome, the greater the improvement in quality of life. This finding was not the case for the Quality of Life in Epilepsy for Adolescents survey. As stated previously, the data from the Quality of Life in Epilepsy for Adolescents survey may have been affected by two adolescents with psychiatric disorders who were seizure-free after epilepsy surgery, but who continued to demonstrate significant psychiatric issues and who scored themselves very low on the survey. In addition, adolescents may have had to endure years of epilepsy, with its significant effects on cognition, academic performance, self-esteem, and depression. Here, perhaps, is one of the most potent arguments for early intervention, before the psychosocial consequences of epilepsy take hold. Although quality-of-life surveys have their limitations, they remain reasonable tools with which to evaluate the impact of epilepsy and epilepsy surgery on our patients and their families. We hope to use quality-of-life surveys before and after epilepsy surgery in a larger study group, to validate our hypothesis that successful epilepsy surgery in children produces significant improvements in development and quality of life. In conclusion, the results of this study argue that epilepsy surgery in children with intractable epilepsy results in significant improvement in seizure control, quality of life, and development. Neither the anticipated type of surgery, presumed location of the epileptogenic site, absence of
Zupanc et al: Quality of Life and Seizures in Children 19
a defined lesion on magnetic resonance imaging scan of the brain, nor age of the patient should prevent the surgical evaluation of children with intractable epilepsy. We thank Jingnan N. Mao, MS, for assistance with statistical analyses, and the parents and children who participated in this study. We also thank Stichting Bekker-la Bastide Fonds and Stichting A.A. van Beek Funds for their generosity, which in part made it possible for E.J.d.S.R. to contribute to this study. Lastly, we thank Willem F.M Arts, MD, for his support. We have read this journal’s position on issues involved in ethical publication, and affirm that this report is consistent with those guidelines.
References [1] Hauser WA. The natural history of seizures. In: Wyllie E, editor. The treatment of epilepsy: Principles and practice. 4th ed. Philadelphia: Lea & Febiger, 2005:117-25. [2] Wyllie E, Comair YG, Kotagal P, Bulacio J, Bingaman W, Ruggieri P. Seizure outcome after epilepsy surgery in children and adolescents. Ann Neurol 1998;44:740-8. [3] Paolicchi JM, Jayakar P, Dean P, et al. Predictors of outcome in pediatric epilepsy surgery. Neurology 2000;54:642-7. [4] Chugani HT, Shewmon DA, Shields WD, et al. Surgery for intractable infantile spasms: Neuroimaging perspectives. Epilepsia 1993; 34:764-71. [5] Wyllie E, Comair YG, Kotagal P, Raja S, Ruggieri P. Epilepsy surgery in infants. Epilepsia 1996;37:625-37. [6] Duchowny M, Jayakar P, Resnick T, et al. Epilepsy surgery in the first three years of life. Epilepsia 1998;39:737-43. [7] Hader WJ, Mackay M, Otsubo H, et al. Cortical dysplastic lesions in children with intractable epilepsy: Role of complete resection. J Neurosurg 2004;100(Suppl. 2):110-7. [8] Kloss S, Pieper T, Pannek H, Holthausen H, Tuxhorn I. Epilepsy surgery in children with focal cortical dysplasia (FCD): Results of longterm seizure outcome. Neuropediatrics 2002;33:21-6. [9] Hamiwka L, Jayakar P, Resnick T, et al. Surgery for epilepsy due to cortical malformations: Ten-year follow-up. Epilepsia 2005;46:556-60. [10] Terra-Bustamante VC, Fernandes RM, Inuzuka LM, et al. Surgically amenable epilepsies in children and adolescents: Clinical, imaging, electrophysiological, and post-surgical outcome data. Childs Nerv Syst 2005;21:546-51. [11] Jonas R, Nguyen BS, Hu B, et al. Cerebral hemispherectomy: Hospital course, seizure, developmental, language, and motor outcomes. Neurology 2004;62:1712-21. [12] Janszky J, Janszky I, Schulz R, et al. Temporal lobe epilepsy with hippocampal sclerosis: Predictors for long-term surgical outcome. Brain 2005;128:395-404. [13] Asarnow RF, LoPresti C, Guthrie D, et al. Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms. Dev Med Child Neurol 1997;39:430-40. [14] Bourgeois M, Sainte-Rose C, Lellouch-Tubiana A, et al. Surgery of epilepsy associated with focal lesions in childhood. J Neurosurg 1999; 90:833-42. [15] Meyer FB, Marsch WR, Laws ER Jr, Sharbrough FW. Temporal lobectomy in children with epilepsy. J Neurosurg 1986;64:371-6. [16] Gilliam F, Wyllie E, Kashden J, et al. Epilepsy surgery outcome: Comprehensive assessment in children. Neurology 1997;48:1368-74.
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[17] Westerveld M, Sass KJ, Chelune GL, et al. Temporal lobectomy in children: Cognitive outcome. J Neurosurg 2000;92:24-30. [18] Gleissner U, Sassen R, Lendt M, Clusmann H, Elger CE, Helmstaedter C. Pre- and post-operative verbal memory in pediatric patients with temporal lobe epilepsy. Epilepsy Res 2002;51:287-96. [19] Szabo´ CA, Wyllie E, Stanford LD, et al. Neuropsychological effect of temporal lobe resection in preadolescent children with epilepsy. Epilepsia 1998;39:814-9. [20] Lendt M, Gleissner U, Helmstaedter C, Sassen R, Clusmann H, Elger CE. Neuropsychological outcome in children after frontal lobe epilepsy surgery. Epilepsy Behav 2002;3:51-9. [21] Keene DL, Higgins MJ, Ventureyra EC. Outcome and life prospects after surgical management of medically intractable epilepsy in patients under 18 years of age. Childs Nerv Syst 1997;13:530-5. [22] Keene DL, Loy-English I, Ventureya EC. Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence. Childs Nerv Syst 1998;14:362-5. [23] Mihara T, Inoue Y, Watanabe Y, et al. Improvement in quality-of-life following resective surgery for temporal lobe epilepsy: Results of patient and family assessments. Jpn J Psychiatry Neurol 1994;48: 221-9. [24] Altshuler L, Rausch R, Delrahim S, Kay J, Crandall P. Temporal lobe epilepsy, temporal lobectomy, and major depression. J Neuropsychiatry Clin Neurosci 1999;11:436-43. [25] Mizrahi EM, Kellaway P, Grossman RG, et al. Anterior temporal lobectomy and medically refractory temporal lobe epilepsy of childhood. Epilepsia 1990;31:302-12. [26] Smith ML, Elliott IM, Lach L. Cognitive, psychosocial, and family function one year after pediatric epilepsy surgery. Epilepsia 2004;45: 650-60. [27] Reeves AL, So EL, Evans RW, et al. Factors associated with work outcome after anterior temporal lobectomy for intractable epilepsy Epilepsia 1997;38:689-95. [28] Malmgren K, Sullivan M, Ekstedt G, Kullberg G, Kumlien E. Health-related quality of life after epilepsy surgery: A Swedish multicenter study. Epilepsia 1997;38:830-8. [29] Zupanc ML, Schwabe MJ, Mueller W, Eggener K, Chico M. Pediatric epilepsy surgery—Experience of Children’s Hospital of Wisconsin—Milwaukee, Wisconsin. Epilepsia 2004;45:170-1. [30] Engel JJ, Van Ness PC, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel JJ, editor. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:609-21. [31] Cramer JA, Westbrook LE, Devinsky O, Perrine K, Glassman MB, Camfield C. Development of the quality of life in epilepsy inventory for adolescents: The Qolie-AD-48. Epilepsia 1999;40: 1114-21. [32] Sabaz M, Cairns DR, Lawson JA, Nheu N, Bleasel AF, Bye AM. Validation of a new quality of life measure for children with epilepsy. Epilepsia 2000;41:765-74. [33] Cook SW, Nguyen ST, Hu B, et al. Cerebral hemispherectomy in pediatric patients with epilepsy: Comparison of three techniques by pathological substrate in 115 patients. J Neurosurg Pediatr 2004;100:125-41. [34] Rasmussen T. Hemispherectomy for seizures revisited. Can J Neurol Sci 1983;10:71-8. [35] Cowan J, Baker GA. A review of subjective impact for use with children and adolescents with epilepsy. Qual Life Res 2004;13:1435-43. [36] Vickrey BG. A procedure for developing a quality of life measure for epilepsy surgery patients. Epilepsia 1993;34(Suppl.):S22-7.
Epilepsy Surgery Outcomes: Quality of Life and Seizure Control Mary L. Zupanc, MD*†, Elliane J. dos Santos Rubio, MD‡, Rhonda R. Werner, CNS†, Michael J. Schwabe, MD*†, Wade M. Mueller, MD†§, Sean M. Lew, MD†§, Charles J. Marcuccilli, MD, PhD*†, Sunila E. O’Connor, MD*†, Maria S. Chico, NP*, Kathy A. Eggener, NP*, and Kurt E. Hecox, MD, PhD*† A consecutive, retrospective analysis of seizure control and quality of life was performed among 83 pediatric patients undergoing epilepsy surgery at Children’s Hospital of Wisconsin. Seizure outcomes were generally favorable, with 68.7% class I outcomes; class II, 12%; and class III, 19.3%. Seizure freedom was highest among temporal lobectomies (84.2%) and hemispherectomies (76.2%). Outcomes among hemispherectomies were substantially superior to those of multilobar resections. Cortical dysplasia was associated with lower seizure freedom, at 57.5%. Among age groups, seizure-free outcomes in infants were lowest, at 50%. The lower infant seizure-free rate was likely attributable to frequency of multilobar resections and type of pathology (cortical dysplasia). Quality-of-life measures generally paralleled seizure outcomes. These results indicate that epilepsy surgery in children with intractable epilepsy can result in significant improvements in seizure control, quality of life, and development. Anticipated type of surgery, presumed location of epileptogenic site, absence of a defined lesion on magnetic resonance imaging scan of the brain, and patient’s age should not prevent surgical evaluations of children with intractable epilepsy. Ó 2010 by Elsevier Inc. All rights reserved. Zupanc ML, dos Santos Rubio EJ, Werner RR, Schwabe MJ, Mueller WM, Lew SM, Marcuccilli CJ, O’Connor SE, Chico MS, Eggener KA, Hecox KE. Epilepsy surgery outcomes: quality of life and seizure control. Pediatr Neurol 2010;42:12-20.
From the *Department of Neurology and §Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin; †Department of Neurology, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and ‡ Department of Pediatric Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
12 PEDIATRIC NEUROLOGY Vol. 42 No. 1
Introduction Epilepsy is one of the most prevalent chronic neurologic disorders, afflicting more than two million persons in the United States alone. Particularly frustrating is the inability to substantially decrease the percentage of patients resistant to all available antiepileptic medications, without producing unacceptable side effects. Depending on the sampling particulars and definitions used in the study, approximately 20-30% of patients are intractable to medical therapy [1]. One option available to this group of patients is surgical resection of the anatomic site responsible for generating the seizures. Although surgical outcomes are significantly better than the published likelihood of pharmacologic success after two to three antiepileptic drugs fail to produce seizure control, substantial hesitancy still precedes the initiation of surgical evaluation. This hesitancy is particularly strong for the pediatric population, where determinants of surgical outcomes are not welldocumented. We describe the outcomes of surgical intervention for intractable epilepsy in a group of pediatric patients, with emphasis on selection criteria for initiating surgical evaluations and a comprehensive look at patients’ quality of life. In previous reports, seizure freedom after epilepsy surgery in children varied between 59-80% [2-10]. Other studies, both pediatric and adult, assessed the contributions of different variables to patient outcomes. Jonas et al. reported that shorter seizure duration, level of seizure control before surgery, and good presurgical developmental quotients predict better postsurgical developmental outcomes in pediatric patients undergoing hemispherectomies [11].
Communications should be addressed to: Dr. Zupanc; Department of Neurology, Children’s Hospital of Wisconsin; 9000 W. Wisconsin Avenue; Children’s Hospital of Wisconsin Children’s Corporate Center, Suite C540; Milwaukee, WI 53201. E-mail: [email protected] Received April 2, 2009; accepted July 20, 2009.
Ó 2010 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2009.07.018 0887-8994/10/$—see front matter
Janszky et al. found that specific seizure types (secondarily generalized seizures and tonic seizures), older age, and longer seizure duration predict worse postsurgical outcomes after a temporal-lobe resection [12]. These and similar studies raise questions about which factors determine whether a referral and consequent surgical intervention will result in a favorable outcome. Several recent studies indicated that early surgical intervention not only results in seizure reduction but also improves quality of life (cognitive, behavioral, and social functioning), particularly with respect to behavioral and developmental ‘‘catch up,’’ in some patients [5,13,14]. Cognitive function studies generally report that intelligence and memory are not affected after temporal lobectomies in young children and adolescents [15-18]. However, Szabo´ et al. [19] found that a modest decline in verbal memory can occur with surgery, whereas Lendt et al. [20] reported improvements in language, attention, and memory that were not dependent on complete seizure control after epilepsy surgery. In retrospective studies, Keene et al. reported that seizure reduction resulted in improvements in overall quality of life in pediatric patients [21,22]. In addition, Mihara et al. reported that satisfaction with patient-family relationships improved after surgery in both children and adults, even when complete elimination of seizures does not occur [23]. A few studies suggest that the quality of life of both adult and pediatric patients does not improve despite better seizure control [24-27]. Smith et al. reported that cognitive, psychosocial, and family function in children did not improve after 1 year of seizure elimination [26]. Altshuler et al. reported that temporal lobectomies in adults can cause depression within a year after surgery [24]. A similar report by Reeves et al. stated that seizure-free outcomes failed to improve quality of life in adults [27]. In that study, the authors hypothesized that, after many years of the low selfesteem, poor peer relations, loss of independence, and academic failure caused by their disability with epilepsy, seizure reduction after epilepsy surgery did not result in gainful employment or improvement in depression. Malmgren et al. reported that, although seizure reduction led to an improvement in quality of life, it also led to an increase of anxiety in patients above 16 years of age [28]. These studies suggest that it is not safe to assume that seizure reduction implies an improvement in quality of life, and moreover, the determinants of quality of life may be complex, especially among adolescents and young adults. Methods Patients We retrospectively reviewed the charts of 83 consecutive pediatric patients who underwent epilepsy surgery between 2002 and 2005 at Children’s Hospital of Wisconsin. First, we examined the impact of surgery on seizure frequency, as a function of multiple clinical variables. We then reviewed the results of validated quality-of-life measures with
respect to seizure outcomes. Subsequently, we studied those patient features likely to determine whether surgery in a child would lead to a significant improvement in the patient’s life, as defined by a reduced seizure burden or ‘‘good’’ quality of life. In better identifying determinants of surgical outcomes, we hoped to improve our criteria for referring patients for surgical evaluation. Inclusion criteria comprised patients under age 18 years at time of surgery, who manifested medically intractable epilepsy (defined as failure to achieve seizure control after an adequate trial with two first-line antiepileptic medications), and who had undergone a preoperative evaluation, surgical intervention, and follow-up performed at Children’s Hospital of Wisconsin. We included two patients who did not meet our full criteria. Patient 60 had exceeded age 18 years at the time of surgical procedure. We included this patient because the surgical procedure had been recommended years earlier. Patient 77 was also included, although this patient did not undergo epilepsy surgery at Children’s Hospital of Wisconsin. However, the preoperative evaluation, recommendation for surgery, and follow-up were performed at Children’s Hospital of Wisconsin. To ensure that the epileptogenic zone was localized, we performed a preoperative evaluation consisting of: (1) clinical evaluation of seizure type and character, (2) continuous video-electroencephalogram monitoring, (3) a magnetic resonance imaging scan of the brain, (4) an interictal positron emission tomography scan, and (5) an ictal and interictal singleproton emission computerized tomography scan. If necessary, a Wada procedure was performed before surgery to localize speech and language, as well as memory, to the appropriate hemisphere. In some patients, invasive electroencephalogram monitoring was used to further localize the epileptogenic zone, particularly in patients who underwent multilobar or lobar resections. If preoperative data were lost or incompletely documented, or if postoperative follow-up was incomplete, patients were excluded from this review. We did not establish a minimum follow-up period, thus making the chart review comparable to our previous review, published in 2004 [29].
Data Collection Data extracted from charts included age at surgery; sex; age at seizure onset; epilepsy syndrome; seizure type and frequency; results of magnetic resonance imaging, video-electroencephalogram, ictal and interictal single-proton emission computerized tomography, and positron emission tomography; type of surgical procedure; date of surgical procedure; pathology; and postsurgical follow-up. Demographic characteristics are listed in Table 1.
Seizure Outcome Assessment Seizure outcomes were assessed through clinical visits and telephone contact. A seizure outcome was classified according to the classification system of Engel et al. [30]. Class I represents no seizures, auras only, or seizures with drug withdrawal only. Class II represents three or fewer seizures a year. Class III represents worthwhile improvement remaining, with more than three seizures per year. Class IV represents no worthwhile improvement after surgery.
Quality-of-Life Assessment All patients (or their caregivers) who were cognitively able to give consent, or complete a quality-of-life inventory, received questionnaires. Caregivers received a Quality of Life in Childhood Epilepsy inventory to complete. The Quality of Life in Childhood Epilepsy survey consists of a 91-item scale that assesses well-being, social activity, physical activity, cognitive functioning, behavioral functioning, general health, and overall quality of life within the previous 4 weeks. The scoring scale extends from 0-100, with the highest score reflecting excellent quality of life. Adolescents received a Quality of Life in Epilepsy for Adolescents inventory. It contains 48 items that assess epilepsy impact (scoring scale,
Zupanc et al: Quality of Life and Seizures in Children 13
Table 1. Demographic characteristics All Patients (n = 83) Age at surgery (in years, mean/S.D.) Onset of epilepsy (in years, mean/S.D.) Duration of epilepsy (in years, mean/S.D.) Follow-up after surgery (in years, mean/S.D.) Sex (male/female)
Mean ± S.D. 10.2 5.0 3.7 4.0 6.5 3.9 1.6 0.8
Range 0.75-21 birth to 16 0.3-18 0.3-3.5
35 48
Abbreviation: S.D. = Standard deviation
0-31), memory/concentration (scoring scale, 0-17), attitude toward epilepsy (scoring scale, 0-9), physical functioning (scoring scale, 0-9), stigma (scoring scale, 0-13), social support (scoring scale, 0-2), school behavior (scoring scale, 0-6), and perceptions of health (scoring scale, 0-12). The overall quality-of-life scoring scale ranges from 0-99, with the highest score reflecting excellent quality of life. Both of these surveys were validated in previous studies [31,32].
Data Analysis To analyze seizure outcomes, we converted seizure outcomes into dichotomous variables (seizure-free vs not seizure-free). To evaluate the association of seizure outcomes with other variables, we used c2 or Fisher’s exact tests. We used the independent t test and Mann-Whitney test to compare quality of life scores of Quality of Life in Childhood Epilepsy and Quality of Life in Epilepsy for Adolescents survey with seizure outcomes. In our statistical analysis, we grouped the several types of cortical dysplasias together. In addition, rather than analyzing the remaining diagnosed pathology into separate categories (which would have resulted in a very small number of cases per group), nondysplastic, discrete, welldefined lesions were placed in a single category, i.e., ‘‘all other pathologies.’’ Moreover, our corpus callosotomy group was too small for a statistical analysis. For the data analysis, P < 0.05 was considered significant. We used SPSS software, version 12.0 (SPSS, Inc., Chicago, IL), to analyze data.
(n = 10) or modified lateral (n = 11) [33,34]. The remainder of procedures consisted of temporal resections (n = 19) and corpus callosotomies (n = 4) (Table 2). Overall, temporal lobectomies had the highest rate of seizure-free outcomes (84%), followed closely by hemispherectomies (76%) (Table 2). Seizure-free outcomes were lower for focal resections, primarily because of the contribution of temporal-parietal-occipital resections. The outcomes of frontal resections matched those of hemispherectomies, and were only slightly lower than in temporal lobectomies. As expected, corpus callosotomies did not generally result in seizure freedom. Combining all groups, 68.7% of patients demonstrated seizure-free outcomes. If corpus callosotomies were excluded, 72% (57/79) demonstrated seizure-free outcomes. Twelve percent of the children (n = 10) had class II outcomes, and 19.3% of the children (n = 16) had class III seizure outcomes (Table 2). Seizure outcomes in terms of modified lateral hemispherectomies compared with Rasmussen functional hemispherectomies were 100% vs 50%, respectively. Seizure outcomes in modified lateral hemispherectomies compared with temporal-parietal-occipital resections were 100% vs 40%, respectively. Both reached statistical significance at the 0.01 level. Outcomes as a function of type of surgery were further divided according to age (Table 3). In general, the younger the patients, the lower the percentage of patients with a class I outcome. None of the differences reached statistical significance. Temporal-parietal-occipital resections contributed heavily to the lower class I outcome percentage in the youngest patient group.
Table 2. Seizure outcome by type of surgery
Results Type of Surgery
Demographics There were 83 patients in total, with a female predominance. The average age at surgery for this series was 10 years, but there was a large range of ages, from less than 1 year to 21 years, with a comparably wide range of durations of epilepsy (Table 1). Seizure Outcome by Surgical Type Surgical procedures consisted predominantly of extratemporal focal resections (n = 39). Temporal lobectomies (n = 19) were analyzed separately. Most focal resections, excluding temporal lobectomies, were located frontally (n = 17), followed by temporal-parietal-occipital resections (n = 10) and other focal resections (n = 12), i.e., occipital resections, parietal resections, or combinations. The hemispherectomies (n = 21) were either Rasmussen functional
14 PEDIATRIC NEUROLOGY Vol. 42 No. 1
I. Hemispherectomy (21) A. Standard functional (10) B. Modified functional (11) II. Extratemporal focal resection (39) A. Frontal resection (17) B. T-P-O resection (10) C. Other (12)* III. Temporal lobectomy (19) IV. Corpus callosotomy (4) Total (83)
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
16/21 (76.2%) 2/21 (9.5%) 3/21 (14.3%) 5/10 (50.0%) 2/10 (20.0%) 3/10 (30.0%) 11/11 (100%) 24/39 (61.5%) 4/39 (10.3%) 13/39 (33.3%) 13/17 (76.5%) 4/10 (40.0%) 7/12 (58.3%) 4/12 (33.3%) 16/19 (84.2%) 2/19 (10.5%) 1/ 4 (25.0%)
2/4 (50.0%)
4/17 (23.5%) 6/10 (60.0%) 1/12 (8.3%) 1/19 (5.3%) 1/4 (25.0%)
57/83 (68.7%) 10/83 (12.0%) 16/83 (19.3%)
* Parietal, occipital, or combined resections. Abbreviation: T-P-O = Temporal-parietal-occipital resection
Table 3. Type of surgery per age group by seizure outcome
Type of Surgery per Age Group Birth to 5 years (18) A. Hemispherectomy (5) B. Extratemporal focal resection (11) C. Temporal lobectomy (2) D. Corpus callosotomy (0) Total 6-11 years (28) A. Hemispherectomy (8) B. Extratemporal focal resection (14) C. Temporal lobectomy (4) D. Corpus callosotomy (2) Total 12-21 years (37) A. Hemispherectomy (8) B. Extratemporal focal resection (14) C. Temporal lobectomy (13) D. Corpus callosotomy (2) Total
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
3/5 (60.0%) 5/11 (45.5%)
1/5 (20.0%) 1/11 (9.1%)
1/2 (50.0%)
1/5 (20.0%) 5/11 (45.5%) 1/2 (50.0%)
9/18 (50.0%)
2/18 (11.1%) 7/18 (38.9%)
6/8 (75.0%) 8/14 (57.1%)
1/8 (12.5%) 1/8 (12.5%) 2/14 (14.3%) 4/14 (28.6%)
Quality of Life
4/4 (100%) 1/2 (50.0%)
Seizure outcome by age of surgery revealed that infants and children under age 6 years demonstrated seizure-free outcomes of only 50%. Again, these results were significantly skewed by the number of temporal-parietal-occipital resections (40% seizure-free outcomes). Children between ages 6-11 years exhibited seizure-free outcomes of 67.9%, whereas 78.4% of adolescents (aged 12-18 years) were seizure-free (Table 3). The proportion of patients undergoing a hemispherectomy was similar across age groups (birth to age 5 years, 5/18 = 27.8%; ages 6-11 years, 8/28 = 28.6%; ages 12-21 years, 8/37 = 21.6%). The proportion of patients undergoing temporal lobectomies was higher in our older patients (birth to age 5 years, 2/18 = 11.1%; ages 6-11 years, 4/28 = 14.3%; ages 12-21 years, 13/37 = 35.1%), as listed in Table 3.
1/2 (50.0%)
19/28 (67.9%) 4/28 (14.3%) 5/28 (17.9%)
7/8 (87.5%) 11/14 (78.6%) 1/14 (7.1%)
1/8 (12.5%) 2/14 (14.3%)
11/13 (84.6%) 2/13 (15.4%) 1/2 (50.0%)
1/2 (50.0%)
29/37 (78.4%) 4/37 (10.8%) 4/37 (10.8%)
Seizure Outcome by Pathologic Diagnosis Pathologic diagnoses included 48.2% with cortical dysplasia (n = 40); 12% with mesial temporal sclerosis (n = 10); 9.6% with encephalomalacia (n = 8); 8.4% with a tumor (n = 7); 6.0% with tuberous sclerosis (n = 5); 4.8% with vascular disease (n = 4); 3.6% with Rasmussen’s encephalitis (n = 3) and 2.4% with Sturge-Weber syndrome (n = 2). Nearly 5% of resections were not viewed by a pathologist, because these procedures were corpus callosotomies without actual tissue resection (n = 4). Seizure outcomes by diagnosed pathology are listed in Table 4. Preoperative magnetic resonance imaging results were used to differentiate between lesional and nonlesional cases. The seizure-free outcomes of lesional cases (n = 67) were significantly higher than for nonlesional cases (n = 16), at 71.6% vs 56.3%. Comparisons of outcome according to pathology indicated that 57.5% were seizurefree in the cortical dysplasia category vs 76.7% seizurefree in the group with ‘‘all other pathologies.’’ The analysis of seizure outcome vs diagnosed pathology revealed seizure-free outcomes to be significantly (<0.008) less frequent in cortical dysplasias (57.5%) vs the remaining pathologic diagnoses (76.7%).
QUALITY OF LIFE IN CHILDHOOD EPILEPSY SURVEY Out of 83 Quality of Life in Childhood Epilepsy surveys distributed, 52 (62.7%) were completed. These results are given in Table 5. The response rate was 30.8% male vs 69.2% female. The mean age was 10.52 years. Types of surgery among patients who completed the survey generally paralleled the frequency of procedures in the total group, and were divided into hemispherectomies, 23.1% (n = 12); extratemporal focal resections, 57.7% (n = 30); temporal lobectomies, 17.3% (n = 9); and corpus callosotomies, 2% (n = 1). Extratemporal focal resections comprised frontal lobectomies, 43.3% (n = 13); temporalparietal-occipital resections, 23.3% (n = 7); and other focal extratemporal resections, 33.3% (n = 10). Table 4. Seizure outcome by pathology
Disease/Disorder
Class I, n (%)
Seizure Outcome Class II, Class III, n (%) n (%)
I. Cortical dysplasia (40) 23/40 (57.5%) 6/40 (15.0%) 11/40 (27.5%) A. Hemispherectomy 4/7 (57.1%) 2/7 (28.6%) 1/7 (14.3%) (7) B. Cortical (33) 19/33 (57.6%) 4/33 (12.1%) 10/33 (30.3%) II. Tumor (7) 5/7 (71.4%) 1/7 (14.3%) 1/7 (14.3%) III. Vascular (4) 3/4 (75.0%) 1/4 (25.0%) IV. MTS (10) 10/10 (100%) V. Rasmussen’s 3/3 (100%) encephalitis (3) VI. Sturge-Weber 2/2 (100%) syndrome (2) VII. Tuberous 3/5 (60.0%) 1/5 (20.0%) 1/5 (20.0%) sclerosis (5) VIII. Encephalomalacia (8) 7/8 (87.5%) 1/8 (12.5%) IX. No pathology (4)* 1/4 (25.0%) 2/4 (50.0%) 1/4 (25.0%) Total (83) 57/83 (68.7%) 10/83 (12.0%) 16/83 (19.3%) * Corpus callosotomies. Abbreviation: MTS = Mesial temporal sclerosis
Zupanc et al: Quality of Life and Seizures in Children 15
Table 5. Quality of Life in Childhood Epilepsy score by type of surgery* Quality of Life in Childhood Epilepsy Items
Hemispherectomy (12), Mean ± S.D.
Frontal (13), Mean ± S.D.
T-P-O (7), Mean ± S.D.
Other (10), Mean ± S.D.
Temporal (9), Mean ± S.D.
C.C. (1), Mean
Physical restrictions Energy/fatigue Attention/concentration Memory Language Other cognitive functions Depression Anxiety Control/helplessness Self-esteem Social interaction Social activities Stigma Behavior General health Quality of life Overall quality of life
25.00 18.309 54.17 18.718 34.93 26.928 49.83 31.003 37.81 17.496 32.95 24.185 72.91 13.708 70.60 14.091 59.20 16.075 68.11 15.020 55.56 29.534 42.36 31.675 58.33 35.887 55.44 11.258 60.42 40.534 52.08 24.905 51.48 14.190
54.70 33.221 56.73 25.318 50.06 26.537 67.21 18.145 52.05 23.168 49.31 24.990 72.76 15.531 65.77 23.925 65.10 21.230 67.50 20.170 59.30 38.421 66.67 31.366 71.15 30.356 61.03 15.501 59.62 36.140 65.38 33.132 60.12 20.282
24.64 21.283 57.14 18.898 29.38 32.266 44.38 46.564 24.68 27.974 18.33 29.108 62.50 17.678 69.79 15.576 57.29 14.892 69.38 22.396 26.67 27.258 27.98 32.695 41.67 37.639 54.29 16.068 39.29 37.796 42.86 23.780 41.75 20.637
58.98 23.125 52.50 26.874 43.13 28.475 52.50 24.269 48.92 33.562 43.98 32.079 77.29 12.046 66.02 24.657 59.38 21.701 71.50 18.567 65.00 29.607 60.42 31.626 72.22 38.415 63.10 15.939 70.00 34.960 67.50 26.484 61.02 19.874
62.94 31.523 72.22 16.271 58.61 31.353 61.98 29.415 59.71 32.356 58.33 38.865 74.31 19.874 73.15 22.044 72.92 25.388 65.83 28.450 87.96 23.975 85.18 22.738 88.89 25.345 71.22 19.711 83.33 12.500 77.78 19.543 71.99 20.498
38.89 50.00 25.00 18.75 18.75 8.33 58.33 56.25 50.00 45.00 37.50 33.33 50.00 44.64 25.00 50.00 38.11
* Minimal score is 0; maximal score is 100. Abbreviations: C.C. = Corpus callosotomy Other = Other extratemporal focal resections, i.e., parietal, occipital, or combinations S.D. = Standard deviation T-P-O = Temporal-parietal-occipital
Of patients who completed the survey, 58.3% of patients with hemispherectomies demonstrated seizure-free outcomes. Most of these patients had undergone Rasmussen’s functional hemispherectomies. The extratemporal focal resection group demonstrated seizure-free outcomes at 60% (n = 18), subdivided into 76.9% seizure-free outcomes for frontal lobectomies (n = 10); 28.6% seizure-free outcomes for temporal-parietal-occipital resections (n = 2); and 60% for other extratemporal focal resections (n = 6). Most (88.9%) patients with temporal lobectomies demonstrated seizure-free outcomes (n = 8), and the single patient with a corpus callosotomy did not demonstrate a seizure-free outcome. Statistical analysis of the Quality of Life in Childhood Epilepsy survey (Table 6) demonstrated that physical activity, cognition, social activity, general health, quality of life, and overall quality of life were significantly better in children with seizure-free outcomes than in children who were not seizure-free. The subscale of well-being indicated that seizure-free children manifested significantly less depression, and felt significantly more in control. The subscale of social activity indicated that seizure-free children were significantly more socially active than children who were not seizure-free. However, well-being, anxiety, self-esteem, social interaction, stigma, and behavior did not reach statistical significance. QUALITY OF LIFE IN EPILEPSY FOR ADOLESCENTS SURVEY Twenty-six of 48 (54.2%) of the Quality of Life in Epilepsy
16 PEDIATRIC NEUROLOGY Vol. 42 No. 1
for Adolescents surveys were completed. Four completed surveys were excluded because parents acknowledged that they had assisted in completing the form. Analysis was performed on the remaining 22 surveys. Most surveys were from females (77.3%). The mean age was 15.3 years. Types of surgery among patients who completed the survey were divided into hemispherectomies, 13.6% (n = 3); extratemporal focal resections, 50% (n = 11); and temporal lobectomies, 36.4% (n = 8). Most (72.7%) extratemporal focal resections were frontal lobectomies (n = 8), and 27.3% were other focal resections (n = 3). There were no temporal-parietal-occipital resections or corpus callosotomies in the Quality of Life in Epilepsy for Adolescents group (Table 7). Of patients who completed the survey, the majority were seizure-free. All three hemispherectomies demonstrated seizure-free outcomes, and all underwent modified lateral hemispherectomies. The extratemporal focal resections demonstrated seizure-free outcomes of 81.8% (n = 9), subdivided by location, with 87.5% seizure-free outcomes for frontal lobectomies (n = 7), and 66.7% seizure-free outcomes for other extratemporal focal resections (n = 2). All temporal lobectomies (n = 8) demonstrated seizure-free outcomes. None of the individual items on the Quality of Life in Epilepsy for Adolescents demonstrated a significant difference between groups, presumably because of the small number of patients who were not seizure-free.
Table 6. Means compared according to t test for seizure-free vs not seizure-free by Quality of Life in Childhood Epilepsy categories Not SeizureFree
Seizure-Free Quality of Life in Childhood Epilepsy Items Physical activity Physical restrictions Energy/fatigue Cognition Attention/ concentration Memory Language Other cognitive functions Well-being Depression Anxiety Control/ helplessness Self-esteem Social activity Social interaction Social activities Stigma Behavior General health Quality of life Overall quality of life
N
Mean ± S.D.
N
Mean ± S.D.
P Value
33 32
58.9 24.6 58.5 27.9
19 19
27.0 14.0 23.3 18.2
0.0001 0.0001
33 33 33
63.3 21.9 56.9 23.6 56.2 24.8
19 18 18
48.7 19.4 23.7 24.1 20.9 21.1
0.020 0.0001 0.0001
30 33 33
64.4 24.0 54.4 24.8 54.7 26.3
11 14 14
33.3 26.8 23.6 22.1 12.2 18.7
0.001 0.0001 0.0001
33 33 31 33
70.3 15.5 77.3 12.5 70.0 20.2 67.1 21.3
19 19 17 17
61.2 15.7 63.6 17.0 65.7 20.5 54.3 14.9
NS 0.002 NS 0.033
33 33 33 33 32 33 33 33 33
69.1 19.3 69.6 28.6 65.4 33.9 70.3 29.4 73.4 32.3 62.5 17.0 80.3 25.6 72.0 25.6 66.0 17.7
14 19 17 19 18 17 19 19 19
64.9 22.2 45.5 28.2 52.5 33.3 34.4 30.5 56.9 37.2 57.6 14.0 32.6 28.7 43.4 21.8 42.6 15.9
NS 0.005 NS 0.0001 NS NS 0.0001 0.0001 0.0001
in mild, contralateral, lower-extremity paresis (4+/5). A small contralateral thalamic infarct occurred after a modified lateral hemispherectomy. This condition was attributed to an overaggressive use of suction drainage postoperatively. The patient made a complete recovery, and our technique was modified accordingly. The aggregate complication rate was 7.2%.
Discussion
Abbreviations: N = Number of patients evaluated NS = Not significant S.D. = Standard deviation
Generally, however, a number of the means were remarkably low in this group, despite the excellent results of surgery. More complete comment on possible differences between seizure-free and nonseizure-free populations will require larger groups (Table 8). Complications One patient required premature removal of subdural electrodes because of a subdural hematoma with symptomatic mass effect. He recovered completely, and underwent replacement of the electrodes and subsequent resection during the same hospitalization. Two wound infections occurred, both in patients undergoing intracranial monitoring with subdural electrodes. One of these patients required permanent removal of the bone flap and a subsequent cranioplasty. Both patients completely recovered. One patient manifested a small wound dehiscence without infection that was treated with primary closure. Two patients demonstrated small infarcts. One venous infarction occurred after a corpus callosotomy, resulting
Seizure Outcomes The proportion of seizure-free patients in this study (class I of Engel et al. [30]) is similar to that reported previously [2-6]. Previous studies indicated that seizure-free outcomes in young children and adolescents ranged between 59-80%, compared with an overall rate of 68.7% in this study. Seventy-two percent of our patients demonstrated seizurefree outcomes, if patients with corpus callosotomies were excluded. For the infants in our study, seizure-free outcomes were somewhat lower. Several reasons may account for this finding: (1) Several of these patients underwent palliative procedures. Surgery was conducted despite known bilateral epileptogenic foci. These patients exhibited multiple daily seizures with concomitant developmental regression. The most highly epileptogenic focus was removed. (2) Several patients underwent temporal-parietal-occipital resections, which demonstrated a particularly low success rate (40%). Temporal-parietal-occipital resections were performed in an attempt to spare the motor cortices of our patients. The resected tissue in patients with temporal-parietal-occipital resections demonstrated cortical dysplasias, whose margins were poorly delineated, particularly compared with magnetic resonance imaging findings. In retrospect, a hemispherectomy might have been a better choice of procedures, because it has demonstrated a high overall success rate, i.e., 100% with modified lateral hemispherectomies. (3) Most of the infants demonstrated cortical dysplasia as their pathology, again with poorly demarcated margins and lower surgical success rates, as reported previously. Modified lateral hemispherectomies provided superior seizure control (100% seizure-free) compared with Rasmussen functional hemispherectomies (50% seizurefree). Based on these results, we rarely perform temporalparietal-occipital resections, and prefer the modified lateral hemispherectomy technique for our functional hemispherectomies. The difference between hemispherectomy techniques, in this study, was larger than expected according to the literature [11,33]. The reasons for this finding are not clear. Hemispherectomies were evenly split among age groups.
Zupanc et al: Quality of Life and Seizures in Children 17
Table 7. Quality of Life in Epilepsy for Adolescents items by type of surgery
Quality of Life in Epilepsy for Adolescents Items (Total Score per Item)
Type of Surgery Frontal (8), Other (3), Range Range
Hemispherectomy (3), Range 9.2 27.1 8.5 14 0 6.3 5 8.7 1.6 2 5.6 6 0.6 6.8 8 11 54 69
Epilepsy impact (31) Memory/concentration (17) Physical function (9) Stigma (13) Social support (2) School behavior (6) Attitudes toward epilepsy (9) Health perception (12) Overall quality of life (99)
7.1 29.1 6.4 12.8 09 4.3 12.3 0.8 2 4.5 6 0 7.9 4 11 35.8 2.8
5.8 30.4 6.8 12.3 2.7 7.7 9.4 13 1.6 2 5.3 6 1.1 4.5 68 46.1 81.5
Temporal (8), Range 9.0 31 6 17 3.6 9 2.2 13 0.5 2 06 3.4 9 3 12 35.6 95
Abbreviation: Other = Other extra-temporal focal resections, i.e., parietal, occipital, or combinations
Temporal lobectomies were more common in our older adolescent patients, a finding consistent with other studies [2,17]. The temporal lobectomies performed in these patients, specifically in the oldest age group, demonstrated seizure-free outcomes in 84%. In all cases, the pathology of children with less-than-complete seizure freedom was cortical dysplasia. These results are somewhat better than those reported by Meyer et al., who demonstrated seizure-free outcomes between 60-80% [15] for temporal lobectomies. Seventy-seven percent of our patients with frontal lobectomies have enjoyed seizure-free outcomes. This figure is much higher than was reported in the literature. We have not fully analyzed our data, but all of our patients underwent aggressive resections, which included the supplementary motor cortex and mesial frontal tissue. Seizure-free outcomes for the cortical dysplasia group (n = 40) amounted to 57.5%, compared to 76.7% for the group with ‘‘all other pathologies.’’ This result is consistent with other studies, demonstrating that cortical dysplasias are likely widespread in the neocortex, and despite generous
resections, epilepsy surgery may not eliminate the entire epileptogenic network. Quality of Life Quantifying ‘‘quality of life’’ requires a reliable and valid scale. The Quality of Life in Childhood Epilepsy and Quality of Life in Epilepsy for Adolescents proved to be valid in previous studies of patients with epilepsy [31,32,35]. Overall, our results from the Quality of Life in Childhood Epilepsy survey demonstrated that patients with good seizure control achieve better quality of life. However, this was not the case with the Quality of Life in Epilepsy for Adolescents survey. In the adolescent survey, two seizurefree adolescents scored their overall quality of life as very low, with written comments describing their unhappiness. This finding was also reflected in their item scores regarding epilepsy impact, stigma, and attitudes toward epilepsy, which were much lower than in the remaining seizurefree group. In reviewing our data, these two adolescents demonstrated significant presurgical psychiatric disorders,
Table 8. Mann-Whitney test for comparison of two groups by Quality of Life in Epilepsy for Adolescents categories Seizure-Free
Not Seizure-Free
Quality of Life in Epilepsy for Adolescents Items
N
Mean ± S.D.
Median (Range)
N
Mean ± S.D.
Median (Range)
P Value
Epilepsy impact Memory/concentration Physical function Stigma Social support School behavior Attitudes toward epilepsy Health perceptions Overall quality of life
20 20 20 20 20 20 20 20 20
21.0 8.6 10.7 3.1 6.5 2.9 9.6 3.2 1.6 0.4 5.4 1.4 4.2 2.8 8.3 2.7 67.2 18.2
24.2 (6-31) 10.4 (6-17) 7.43 (0-9) 9.8 (2-13) 1.7 (1-2) 6.0 (0-6) 4.5 (0-9) 8.5 (3-12) 67.4 (36-95)
2 2 2 2 2 2 2 2 2
10.7 6.9 11.5 0.6 1.4 1.9 9.0 1.5 2.0 0 5.8 0.3 2.8 2.4 7.0 1.4 50.1 3.5
10.7 (6-16) 11.5 (11-12) 1.4 (0-3) 9.0 (8-10) 2.0 (2-2) 5.82 (6-6) 2.82 (1-5) 7.0 (6-8) 50.1 (48-53)
NS NS NS NS NS NS NS NS NS
Abbreviation: S.D. = Standard deviation
18 PEDIATRIC NEUROLOGY Vol. 42 No. 1
attributable to complex psychosocial issues and genetic factors (e.g., familial hereditary depression and bipolar disorder). These two adolescents may have skewed our data in a negative direction, rendering the overall quality-of-life score insignificant. An alternative hypothesis states that by the time of adolescence, the consequences of intractable epilepsy have taken a significant psychosocial toll, and one that is not easily corrected by epilepsy surgery alone. The nonseizure-free group was too small for valid statistical analysis and comparison. Although the Quality of Life in Childhood Epilepsy survey revealed that better quality of life is parallel to a good seizure outcome, we encountered major limitations in the use of this survey during our study. The items in this survey compared participants with children of their own age, over the previous 4 weeks, rather than comparing improvement before vs after epilepsy surgery in an individual child. This probably resulted in lower overall scores that did not mirror the improvement evident in the majority of our patients. The majority of our children demonstrated other neurologic, physical, and developmental disabilities, in addition to their epilepsy. This happenstance resulted in difficulties in our analysis of quality of life, and contributed to lower scores. Some parents wrote comments to confirm this hypothesis. For example, one parent stated that the child had significantly improved after surgery in all items addressed in the survey, specifically in behavior, i.e., ‘‘X’s behavior has improved 110%.’’ The overall score for this specific child was 68.3, with a score of 67.9 for behavior. Another parent stated, ‘‘Although X’s social interaction is not age appropriate, it is a world away from before surgery.’’ Before surgery, X had never attempted to interact or engage with peers. The parent also stated that the child was nonverbal before surgery, but after surgery, began talking. The overall quality-of-life score for this child was 61.60, with social interaction and cognition scores of 25 and 55.9, respectively. An epilepsy-surgery inventory specifically for children, which would assess quality of life presurgery and postsurgery, might provide additional insights. An adult epilepsy-surgery inventory is available, but no version exists for children [36]. Although we cannot statistically compare the two different surveys, we observed that some parents of adolescents gave their children lower quality-of-life scores than the adolescents gave themselves. For example, one adolescent scored 81.5 on overall quality of life; however, the parent assessed an overall quality-of-life score of 50.5. Lower scoring by parents may be explained on the basis of high expectations after successful epilepsy surgery. This trend is probably not isolated to the adolescent age group, and may be the case for the remaining age groups. The use of a quality-of-life survey is still considered a very subjective research technique. The subjectivity may increase when parents assess the quality of life of their children. This subjectivity might be reduced if we were to develop a qualityof-life survey capable of allowing children of all different
ages and cognitive levels to complete the form. Consideration should be given to developing surveys that include pictures and verbal questions. A Quality of Life in Childhood Epilepsy survey is being developed in which children assess their own quality of life [35]. Conclusions In conclusion, our results are promising, and are consistent with other studies. The success rate for all types of surgery, age groups, and forms of pathology were substantially higher than those cited for continued trials of antiepileptic medications. In this regard, we agree with Engel et al. that the low rate of referral is not entirely rational from the perspective of outcomes [30]. None of the clinical variables examined in this study should prevent a child from being evaluated as a surgical candidate. In addition, it is reasonable to assume that seizure-free outcomes with epilepsy surgery will improve even further as we intervene earlier and use increasingly sophisticated techniques to identify the epileptogenic zone. An earlier age of intervention is pertinent, with respect to both seizure control and developmental outcomes. Animal-model evidence is emerging that epilepsy in the developing brain inflicts potentially more devastating consequences, with the development of permanent, aberrant, excitatory neural circuitry. The quality-of-life measures for the Quality of Life in Childhood Epilepsy survey mirrored seizure-free outcomes. Specifically, the better the seizure control outcome, the greater the improvement in quality of life. This finding was not the case for the Quality of Life in Epilepsy for Adolescents survey. As stated previously, the data from the Quality of Life in Epilepsy for Adolescents survey may have been affected by two adolescents with psychiatric disorders who were seizure-free after epilepsy surgery, but who continued to demonstrate significant psychiatric issues and who scored themselves very low on the survey. In addition, adolescents may have had to endure years of epilepsy, with its significant effects on cognition, academic performance, self-esteem, and depression. Here, perhaps, is one of the most potent arguments for early intervention, before the psychosocial consequences of epilepsy take hold. Although quality-of-life surveys have their limitations, they remain reasonable tools with which to evaluate the impact of epilepsy and epilepsy surgery on our patients and their families. We hope to use quality-of-life surveys before and after epilepsy surgery in a larger study group, to validate our hypothesis that successful epilepsy surgery in children produces significant improvements in development and quality of life. In conclusion, the results of this study argue that epilepsy surgery in children with intractable epilepsy results in significant improvement in seizure control, quality of life, and development. Neither the anticipated type of surgery, presumed location of the epileptogenic site, absence of
Zupanc et al: Quality of Life and Seizures in Children 19
a defined lesion on magnetic resonance imaging scan of the brain, nor age of the patient should prevent the surgical evaluation of children with intractable epilepsy. We thank Jingnan N. Mao, MS, for assistance with statistical analyses, and the parents and children who participated in this study. We also thank Stichting Bekker-la Bastide Fonds and Stichting A.A. van Beek Funds for their generosity, which in part made it possible for E.J.d.S.R. to contribute to this study. Lastly, we thank Willem F.M Arts, MD, for his support. We have read this journal’s position on issues involved in ethical publication, and affirm that this report is consistent with those guidelines.
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