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ARTICLE

Developmental Outcome After Epilepsy Surgery

in Infancy

Tobias Loddenkemper, MDa, Katherine D. Holland, MD, PhDb, Lisa D. Stanford, PhDc, Prakash Kotagal, MDa, William Bingaman, MDd,

Elaine Wyllie, MDa

Departments ofaPediatric Neurology anddPediatric Neurosurgery, Cleveland Clinic, Cleveland, Ohio;bDivision of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio;cDepartment of Psychiatry, University of Illinois College of Medicine, Chicago, Illinois

The authors have indicated they have no financial relationships relevant to this article to disclose.

ABSTRACT

OBJECTIVES.Our goals were to determine the effect of epilepsy surgery in infants (⬍3 years of age) on development and describe factors associated with postoperative developmental outcome.

METHODS.We identified 50 infants among 251 consecutive pediatric patients (⬍18

years old) undergoing epilepsy surgery. Charts were reviewed for clinical data and neurodevelopmental testing with the Bayley Scales of Infant Development. A developmental quotient was calculated to compare scores of children at different ages.

RESULTS.Complete data were available on 24 of 50 infants. Surgeries included 14

hemispherectomies and 10 focal resections. Seventeen patients became seizure free; 5 patients had⬎90% seizure reduction, 1 had⬎50% seizure reduction, and 1 had no change. The developmental quotient indicated modest postoperative improvement of mental age. The preoperative and postoperative development quotients correlated well. Younger infants had a higher increase in developmental quotient after surgery. Patients with epileptic spasms were younger and had a lower developmental quotient at presentation, but increase in developmental quotient was higher in this subgroup.

CONCLUSIONS.After surgery, seizure frequency and developmental quotient

im-proved. Developmental status before surgery predicted developmental function after surgery. Patients who were operated on at younger age and with epileptic spasms showed the largest increase in developmental quotient after surgery.

www.pediatrics.org/cgi/doi/10.1542/ peds.2006-2530

doi:10.1542/peds.2006-2530

Drs Loddenkemper and Holland contributed equally to this work. Key Words

epilepsy surgery, infants, development Abbreviations

AED— antiepileptic drug MCD—malformation of cortical development

DQ— developmental quotient

Accepted for publication Jan 11, 2007 Address correspondence to Tobias Loddenkemper, MD, Department of Pediatric Neurology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195-5245. E-mail: loddent@ ccf.org

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E

PILEPSY SURGERY ISthe standard of care for patients with medically intractable focal epilepsy. However, little is known about the impact of epilepsy surgery on development in infants. Decision making about the tim-ing of surgery remains difficult: early surgery may be indicated to prevent recurrent seizures and their devas-tating effect on development.1 This, however, implies

the risk of unnecessary resection and loss of developing brain tissue in cases where potential medical seizure control may be reached as the brain matures.

Relatively few studies and case reports on surgical and developmental outcome after epilepsy surgery are avail-able in children ⬍3 years old.2,3 Two-year postsurgical

developmental outcomes were assessed in 24 children with medically intractable infantile spasms who under-went epilepsy surgery. Significant developmental im-provement was noted 2 years after surgery. Develop-mental outcome after surgery was best for patients who received surgery at a younger age and who had the best presurgical developmental scores.2

Our aim was to determine the effect of epilepsy sur-gery in infants (⬍3 years of age) on development and to describe factors associated with postoperative develop-mental outcome. The study reports a 12-year experience with infancy epilepsy surgery at the Cleveland Clinic from 1989 to 2001.

METHODS

We identified 50 infants ⬍3 years old among 251 con-secutive pediatric patients (⬍18 years old) undergoing epilepsy surgery at our center between 1989 and 2001. All patients were assessed by a standard protocol includ-ing clinical, neuroradiological, neurophysiological, neu-ropsychiatric, and developmental teams. Each infant was evaluated by using video electroencephalogram monitoring, MRI, and cognitive and developmental as-sessments. Seizures were classified according to the semiological seizure classification.4 The data were

dis-cussed in a multidisciplinary presurgical meeting. Me-dian follow-up duration after surgery was 6 months. Seizure outcome was assessed by using 4 categories of a modified Engel scale: seizure free,⬎90% seizure reduc-tion,⬎50% seizure reduction, and no change in seizure frequency.

Charts were reviewed retrospectively for preoperative and postoperative seizure frequency, neuropsychologi-cal testing with the Bayley Sneuropsychologi-cales of Infant Development, antiepileptic drugs (AEDs), surgery type, and pathology. The Bayley Scales of Infant Development (1969)5 was

used with all patients before 1994, at which time the Bayley Scales of Infant Development, second edition,6

was initiated when it became available at our clinic. A developmental quotient (DQ; ratio of the Bayley mental age divided by the subject’s biological age⫻100) was calculated to compare scores of children at different ages. For example, an infant was tested at 12 months’

biological age. Neuropsychological testing revealed a Bayley mental age of 6 months. The DQ was 6/12⫻100

⫽ 50. Fisher’s exact test, Mann-Whitney U Wilcoxon test, and Spearman’s correlation coefficient were used for statistics. SPSS 10.0 (SPSS Inc, Chicago, IL) was used to calculate statistics.

RESULTS

Twenty-four patients (18 boys) with complete data and formal neurodevelopmental evaluation were identified among 50 consecutive patients⬍3 years of age at sur-gery. Twenty-six patients were excluded because of in-complete neuropsychological data or different preoper-ative and postoperative neuropsychological tests. Median age at preoperative assessment was 12 months (range: 3.3–33.1 months), median age at surgery was 14 months (range: 3–34 months), and postoperative evalu-ation was at 24 months (range: 10 –53 months), a me-dian of 6 months (range: 4 – 42 months) after surgery. Median duration between preoperative testing and sur-gery was 45.5 days (minimum: 1 day; maximum: 408 days) and 195.5 days (minimum: 128 days; maximum: 1259 days) between surgery and postoperative assess-ment.

Surgeries (13 right, 11 left) included 14 hemispherec-tomies and 10 focal resections (3 frontal, 3 frontoparie-tal, 2 pariefrontoparie-tal, 1 parieto-occipifrontoparie-tal, and 1 occipital). Pathol-ogy consisted of malformation of cortical development (19 patients, 7 with hemimegalencephaly), malforma-tion of cortical development combined with ganglio-glioma (2 patients), Sturge-Weber syndrome (2 pa-tients), and tuberous sclerosis (1 patient).

Patients presented with a median of 2 different semi-ological seizure types (range: 1– 4). Seizure semiology included tonic seizures (15), clonic seizures (15), epilep-tic spasms (11), eye versive seizures (7), hypomotor seizures (5), and myoclonic seizures (3).

Seizure frequency and number of AEDs decreased after surgery. Before surgery, the patients had a median of 15 seizures per day (range: 0.2–120) and were taking a median of 3 AEDs (range: 0 –5). After surgery, seizure frequency decreased to a median of 0 (range: 0 –15;P

.001), and the number of AEDs was reduced to a median of 1 (range: 1–3;P⬍.001). Seventeen patients became seizure free; 5 patients had ⬎90% seizure reduction (with 0.03– 6.00 seizures per day [median: 0.3]), 1 had

⬎50% seizure reduction, and 1 had no change. Median developmental mental age according to the Bayley scale was 3 months (mean: 5.83) before surgery and 9 months (mean: 11.94) after surgery. The DQ was below average (⬍100) before and after surgery in all infants. There was a modest postoperative improvement of mental age. It increased from a preoperative median of 37 (range: 0 –92) to 49 (range: 2–92) after surgery (P

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1). All 7 infants with no measurable mental develop-ment (develop-mental age⬍1 month on the Bayley scale) before surgery made progress after surgery.

The development of all infants in the study was below that of the average infant (DQ⫽100). Only 2 patients were developmentally within the reference range (DQ⬎ 80) before and 3 were within the reference range after surgery. Before surgery, developmental delay (DQ⬍70) was present in 22 of 24 children (Table 1). After surgery the number of delayed infants decreased to 18. How-ever, this change was not statistically significant (P

.125, McNemar test). An increase in the number of patients with borderline functioning (DQ⫽70 – 80) ac-counted for this improvement (0 patients before and 4 after surgery). Profound developmental delay (DQ⬍50) was seen in 13 (54%) of 24 infants postoperatively.

Whereas a higher DQ before surgery was correlated with a higher DQ after surgery (correlation coefficient: 0.67; P ⬍ .001), infants with a preoperative DQ ⬎50 were more likely to experience a reduction in DQ (6 of 8) than those with a DQ ⬍50 (1 of 16; P ⫽ .01). Al-though the DQ declined in 7 infants, none of these infants experienced a loss of skills after surgery.

Younger age at the time of surgery was correlated with improvement in the DQ (correlation coefficient: 0.72;P⬍.001). However, surgery did not affect devel-opmental outcome in infants⬎12 months of age at time of surgery. The DQ increased after surgery in 10 of the 11 children who had surgery younger than 12 months of age (Fig 2). However, it increased in only 6 of 13 who were older than 12 months of age at the time of surgery (P⬍.05).

Analysis of seizure semiology revealed that patients with epileptic spasms presented for preoperative assess-ment and for surgery at a younger age than patients without epileptic spasms. Median age at presentation in

patients with epileptic spasms was 4.2 months and in patients without epileptic spasms was 6.1 months (P

.01). Median age at surgery in patients with epileptic spasms was 6.1 months and in patients without epileptic spasms was 19.9 months (P⬍.01). Preoperative DQ in infants with epileptic spasms was lower (median: 23) than in infants without epileptic spasms (median: 54;P

⬍ .01). Change in DQ and improvement was more prominent in the subgroup of infants with epileptic spasms (Fig 3;P⬍.01). When analyzed separately, only the group of infants with epileptic spasms had a signifi-cant improvement in DQ after surgery. There was no difference in the time interval from presurgical assess-ment to surgery among patients with or without epilep-tic spasms. Other semiological features were not related to developmental outcome.

Other factors that were not associated with develop-ment before or after surgery included preoperative and postoperative seizure frequency, postoperative seizure freedom, and change in number of AEDs, side of sur-gery, type of resection, or pathology.

CASE ILLUSTRATIONS

Two cases may illustrate the wide spectrum of develop-ment in our patient series.

Case 1 (Patient 4)

This patient had seizures since the age of 1 month pre-senting with right-eye deviation and bilateral eye blink-ing occurrblink-ing up to 40 times per day despite treatment with phenobarbital, phenytoin, carbamazepine, and clonazepam. Baseline evaluation at 3.1 months’ biolog-ical age revealed a mental Bayley Scales developmental age of 1 month (DQ⫽1/3.1 ⫻100⫽32%). Based on video electroencephalogram, MRI, and fluorodeoxyglu-cose positron emission tomographic scan data, the pa-tient underwent right parietal resection. Pathology re-vealed malformation of cortical development. The patient became seizure free and was only maintained on phenobarbital after 6 months. Neuropsychological reas-sessment at 9.83 months after surgery revealed a devel-opmental age of 9 months (DQ ⫽ 92%) The patient caught up, and development at repeat assessment was comparable to a normal infant.

Case 2 (Patient 8)

Left-arm clonic seizures started at the age of 4 months old. The patient continued to have 5 seizures per day despite phenobarbital and carbamazepine. Examination revealed left hemiparesis, left hemianopia, and a port wine stain over the right hemicranium. Baseline neuro-psychological assessment at 19.27 months’ biological age revealed a Bayley Scale mental age equivalent of 11 months (DQ⫽57%). Based on video electroencephalo-gram, MRI, and FDG-positron emission tomography

FIGURE 1

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data, the patient underwent right functional hemi-spherectomy and became seizure free. Carbamazepine was discontinued. The patient underwent repeat neuro-psychological assessment at 27.03 months’ biological age, revealing a Bayley Scales mental age equivalent of 14 months (DQ⫽52%). Development progressed by 3 months between the first and the second assessment, but not at a normal rate.

DISCUSSION

We present the first study with formal preoperative and postoperative neuropsychological testing limited to in-fants⬍36 months of age at the time of epilepsy surgery. All infants (79% with malformation of cortical develop-ment) had below average development (DQ ⬍ 100) before and after surgery. After surgery, 71% of infants were seizure free, and 92% of patients had at least 90% seizure reduction on reduced AEDs. The median DQ

TABLE 1 Developmental Outcome in 24 Infants After Epilepsy Surgery

ID Gender Age at Surgery,

mo

Type of Surgery Pathology Seizures per Day AEDs DQ, %

Before After Before After Before After

1 M 4 L frontoparietal MCD 6.0 2.0 2 2 50 80

2 M 25 R hemispherectomy HEMI 100.0 6.0 3 3 58 65

3 M 3 L hemispherectomy MCD 15.0 0.0 3 1 0 50

4 M 3 R parietal MCD⫹ 40.0 0.0 4 1 32 92

5 M 21 R hemispherectomy SWS 5.0 0.0 2 1 57 52

6 M 9 L hemispherectomy HEMI 5.0 0.0 3 1 0 21

7 M 18 R hemispherectomy HEMI 14.0 0.2 5 2 0 2

8 M 20 R hemispherectomy MCD 3.0 0.3 5 2 43 35

9 M 34 L parietal MCD 6.0 0.0 2 1 54 48

10 F 14 L parietal MCD 43.0 0.0 3 2 35 70

11 M 20 R hemispherectomy HEMI 0.2 0.0 3 2 39 47

12 F 26 R hemispherectomy SWS 2.0 0.0 1 1 66 60

13 F 6 R hemispherectomy MCD 20.0 0.0 3 2 0 26

14 M 20 L frontoparietal MCD 100.0 6.0 3 1 92 83

15 F 23 L frontal TS 10.0 ⬍0.1 2 2 56 58

16 M 13 R hemispherectomy MCD 8.0 0.0 4 2 23 40

17 M 14 L frontal MCD⫹ 3.0 0.0 3 1 45 65

18 F 9 L hemispherectomy HEMI 20.0 0.0 3 1 0 40

19 M 6 R hemispherectomy MCD 40.0 0.0 3 1 34 71

20 M 10 L frontoparietal MCD 30.0 0.0 3 1 54 36

21 F 29 L frontal MCD 30.0 0.0 4 1 87 86

22 M 11 R parietal-occipital MCD 6.0 0.0 4 1 9 34

23 M 11 R hemispherectomy HEMI 15.0 15.0 1 2 0 15

24 M 5 L hemispherectomy HEMI 120.0 0.25 2 1 0 40

M indicates male; F, female; L, left; R, right; MCD, malformation of cortical development without hemimegalencephaly; HEMI, hemimegalencephaly; MCD⫹, MCD with ganglioglioma; SWS, Sturge-Weber syndrome; TS, tuberous sclerosis.

FIGURE 2

Effect of age at the time of surgery on developmental outcome. An increase of the DQ after surgery was most prominent in patients having operations at⬍12 months of age.

FIGURE 3

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improved after surgery for the group, individual DQs improved for 71% of infants, and postoperative DQ de-clined in only 7 children. Mental age increased after surgery in every case. Developmental status before sur-gery predicted developmental function after sursur-gery. As-sessment of DQ change in relation to age at surgery will require a refined study design. In our series, patients operated on at a younger age and with epileptic spasms showed the largest increase in DQ after surgery.

Seizure frequency and number of AEDs after surgery decreased significantly in all infants. Seventeen of 24 in-fants became seizure free. This result confirms a study by Chugani et al.7 that reported seizure freedom or at least

90% seizure frequency reduction in 18 of 23 patients who had focal cortical resections or hemispherectomy between the ages of 5 months to 3.7 years. Our study also reflects previous results from our center that reported 9 of 12 infants with only rare or no epileptic seizures after epilepsy surgery between the ages of 3 and 29 months of age.8In

addition, the results from our study (71% seizure freedom) also match the seizure freedom rates of extratemporal re-sections in older children9–11and 67% with seizure freedom

or auras in a survey of 2464 patients (adults and children) operated on at 38 different epilepsy centers between 1995 and 1999.12

Discontinuation of AEDs after epilepsy surgery has been described in adults13and in children,14but no

stud-ies with focus on children⬍3 years of age are available. We were able to show that, for the first time, epilepsy surgery in infancy reduces AED treatment. Because sei-zure frequency reduction and AED reduction both oc-curred after epilepsy surgery, we are not able to deter-mine whether developmental improvement was related to decreased seizure frequency or AED reduction. It is likely that frequent seizures, as well as the sedating effect of the AEDs, both impair cognitive development.

Previous case reports on developmental outcome after epilepsy surgery suggested that early epilepsy surgery in infants with catastrophic epilepsy may allow the resump-tion of developmental progression during critical stages of brain development and maturation.7,8Mental development

tends to progress in the majority of infants after epilepsy surgery, in particular in those with initially no measurable development. In addition, a statistically significant increase occurs in developmental levels at an average age of 21 months after surgery compared with presurgical results.2

These authors also compared the developmental outcome of their study with all other previously reported infants receiving medical treatment for infantile spasms and found that the developmental outcome in their surgical group was equal and sometimes superior to children treated with either corticotropin or valproic acid.2Although overall

de-velopment remains severely impaired, in our series only a short period of follow-up could be included. Some patients may continue to lose ground and develop at a slower pace, whereas others may actually continue to cross percentiles

and continue to catch up. Many infants develop at a faster rate or pick up development but remain abnormal. Mean-ingful changes may be seen in all infants that develop at a faster rate than their preoperative baseline.

Preoperative and postoperative neurodevelopmental testing in infants ⬍3 years of age undergoing epilepsy surgery is an important tool to predict postsurgical men-tal outcome and helps to determine the ideal time for resective epilepsy surgery based on presurgical develop-mental baseline. Developdevelop-mental outcome was best in children who received epilepsy surgery at a younger age and who had the best baseline assessments before epi-lepsy surgery.2One hypothesis that explains the better

presurgical test results in children who undergo surgery when they are⬍1 year of age is that there is less time for seizures to influence development. Early treatment and seizure control seem to be key to improved developmen-tal outcome. This has also been confirmed by a recent study on long-term cognitive outcomes of a cohort of children with infantile spasms of unknown etiology that were treated with high-dose corticotropin.15Twenty-two

infants were treated within 1 month of onset of infantile spasms and 15 after 1 to 6 months. All 22 infants of the early treatment group, but only 40% in the late treat-ment group, had normal cognitive outcome. In addition, infants with only minimal mental retardation at presen-tation were more likely to have a normal cognitive out-come between the ages of 6 to 21 years of age.15

Seizure semiology may correlate with outcome after epilepsy surgery. Recent work on the developmental out-comes after epilepsy surgery that also included older chil-dren at the time of surgery suggested that postoperative DQ calculated based on the Vineland Adaptive Behavior Scale was better in patients with epilepsy of shorter duration and earlier surgical intervention.16 In this series, infants were

classified based on medically refractory spasms, success-fully treated spasms, and no epileptic spasms. Interestingly, age at surgery was older with fewer documented spasms.16

This correlates with our results that showed more spasms in the patients that underwent early operative interven-tion. Epileptic spasms present earlier and, therefore, may just be an indicator for severe developmental delay at the time of presentation and early recognition and treatment of epilepsy. It remains unclear whether epileptic spasms are a separate risk factor or whether the analysis of patients with spasms may be confounded by the early time of presenta-tion and surgery.

Pathologic findings in our group may have influenced our data. The most prominent pathologic diagnosis in our group consisted of malformation of cortical develop-ment, which was shown to predispose for less improve-ment in language and intelligence scores on follow-up after hemispherectomy in a series of older children (age at hemispherectomy ranged from 4 months to 20 years).17Two patients with Sturge-Weber syndrome did

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de-spite seizure freedom in our series. A previous case series describes the IQ after hemispherectomy in a case series of patients with Sturge-Weber syndrome on develop-ment.18Five of 6 patients had a favorable outcome with

intelligence quotients ⬎80%, with follow-up ranging from 1 to 13 years. The sixth patient was the only patient in this series who did not undergo hemispherectomy during the first year of life, and this patient was the only one that had no improvement in his IQ.18These results

correspond to our experience that children undergoing epilepsy surgery during the first year of life may have a better developmental outcome (Fig 2).

A limitation of our series is the lack of an appropriate control group. To compare presurgical and postsurgical development in our series, we had to use the hypothetical construct of the DQ to compare presurgical and postsurgi-cal development. The retrospective study approach led to variable intervals between preoperative and postoperative testing, selection bias because of data acquisition at a ter-tiary epilepsy center with referral bias and ascertainment bias, as well as limitations of the applied test scales. In addition, neuropsychological data were incomplete in half of the initially included 50 cases. Although our patients were highly selected, it seems unlikely that they were selected to have favorable outcome, because infants were only selected for surgical intervention after they had failed several antiepileptic medications.

CONCLUSIONS

We present the first study, to our knowledge, with for-mal preoperative and postoperative neurodevelopmen-tal testing limited to infants⬍36 months old at the time of epilepsy surgery. The median DQ improved after sur-gery for the group overall, and individual DQs improved for 71% of infants. Developmental status before surgery predicted developmental function after surgery. Assess-ment of DQ change in relation to age at surgery and seizure semiology will require a refined prospective study design comparing surgical and medical treatment of seizures in infants.

REFERENCES

1. Elger CE, Helmstaedter C, Kurthen M. Chronic epilepsy and cognition.Lancet Neurol.2004;3:663– 672

2. Asarnow RF, LoPresti C, Guthrie D, et al. Developmental out-comes in children receiving resection surgery for.Dev Med Child Neurol.1997;39:430 – 440

3. Daniel RT, Meagher-Villemure K, Roulet E, Villemure JG. Sur-gical treatment of temporoparietooccipital cortical dysplasia in infants: report of two cases.Epilepsia.2004;45:872– 876 4. Luders H, Acharya J, Baumgartner C, et al. Semiological

sei-zure classification.Epilepsia.1998;39:1006 –1013

5. Bayley N.Bayley Scales of Infant Development: Birth to Two Years. New York, NY: Psychological Corporation; 1969

6. Bayley N.Bayley Scales of Infant Development. 2nd ed. San An-tonio, TX: Psychological Corporation; 1993

7. Chugani HT, Shewmon DA, Shields WD, et al. Surgery for intractable infantile spasms: neuroimaging perspectives. Epilep-sia.1993;34:764 –771

8. Wyllie E, Comair YG, Kotagal P, Raja S, Ruggieri P. Epilepsy surgery in infants.Epilepsia.1996;37:625– 637

9. Gilliam F, Wyllie E, Kashden J, et al. Epilepsy surgery outcome: comprehensive assessment in children. Neurology. 1997;48: 1368 –1374

10. Sinclair DB, Aronyk KE, Snyder TJ, et al. Pediatric epilepsy surgery at the University of Alberta: 1988 –2000.Pediatr Neurol.

2003;29:302–311

11. 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 –748

12. Lu¨ders HO. Protocols and outcome statistics from epilepsy sur-gery centers. In: Lu¨ders HO, Comair YG, eds.Epilepsy Surgery. Philadelphia, PA: Lippincott Williams & Wilkins; 2001: 973–977

13. Schiller Y, Cascino GD, So EL, Marsh WR. Discontinuation of antiepileptic drugs after successful epilepsy surgery.Neurology.

2000;54:346 –349

14. Lachhwani DK, Wyllie E, Loddenkemper T, Holland K, Kotagal P, Bingaman W. Discontinuation of antiepileptic medications following epilepsy surgery in childhood and adolescence [ab-stract].Neurology2003;60(suppl 1):A259

15. Kivity S, Lerman P, Ariel R, Danziger Y, Mimouni M, Shinnar S. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocor-ticotropic hormone.Epilepsia.2004;45:255–262

16. Jonas R, Asarnow RF, LoPresti C, et al. Surgery for symptom-atic infant-onset epileptic encephalopathy with and without infantile spasms.Neurology.2005;64:746 –750

17. Pulsifer MB, Brandt J, Salorio CF, Vining EP, Carson BS, Free-man JM. The cognitive outcome of hemispherectomy in 71 children.Epilepsia.2004;45:243–254

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DOI: 10.1542/peds.2006-2530

2007;119;930

Pediatrics

William Bingaman and Elaine Wyllie

Tobias Loddenkemper, Katherine D. Holland, Lisa D. Stanford, Prakash Kotagal,

Developmental Outcome After Epilepsy Surgery in Infancy

Services

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DOI: 10.1542/peds.2006-2530

2007;119;930

Pediatrics

William Bingaman and Elaine Wyllie

Tobias Loddenkemper, Katherine D. Holland, Lisa D. Stanford, Prakash Kotagal,

Developmental Outcome After Epilepsy Surgery in Infancy

http://pediatrics.aappublications.org/content/119/5/930

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