Hemispherectomy for treatment of refractory epilepsy in the pediatric age group: a systematic review

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OBJECT

Evidence in support of hemispherectomy stems from a multitude of retrospective studies illustrating individual institutions' experience. A systematic review of this topic, however, is lacking in the literature.

METHODS

A systematic review of hemispherectomy for the treatment of refractory epilepsy available up to October 2013 was performed using the following inclusion criteria: reports of a total of 10 or more patients in the pediatric age group (≤ 20 years) undergoing hemispherectomy, seizure outcome reported after a minimum follow-up of 1 year after the initial procedure, and description of the type of hemispherectomy. Only the most recent paper from institutions that published multiple papers with overlapping study periods was included. Two reviewers independently applied the inclusion criteria and extracted all the data.

RESULTS

Twenty-nine studies with a total of 1161 patients met the inclusion criteria. Seizure outcome was available for 1102 patients, and the overall rate of seizure freedom at the last follow-up was 73.4%. Sixteen studies (55.2%) exclusively reported seizure outcomes of a single type of hemispherectomy. There was no statistically significant difference in seizure outcome and type of hemispherectomy (p = 0.737). Underlying etiology was reported for 85.4% of patients with documented seizure outcome, and the overall distribution of acquired, developmental, and progressive etiologies was 30.5%, 40.7%, and 28.8%, respectively. Acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001). Twenty of the 29 studies (69%) reported complications. The overall rate of hydrocephalus requiring CSF diversion was 14%. Mortality within 30 days was 2.2% and was not statistically different between types of hemispherectomy (p = 0.787).

CONCLUSIONS

Hemispherectomy is highly effective for treating refractory epilepsy in the pediatric age group, particularly for acquired and progressive etiologies. While the type of hemispherectomy does not have any influence on seizure outcome, hemispherotomy procedures are associated with a more favorable complication profile.

OBJECT

Evidence in support of hemispherectomy stems from a multitude of retrospective studies illustrating individual institutions' experience. A systematic review of this topic, however, is lacking in the literature.

METHODS

A systematic review of hemispherectomy for the treatment of refractory epilepsy available up to October 2013 was performed using the following inclusion criteria: reports of a total of 10 or more patients in the pediatric age group (≤ 20 years) undergoing hemispherectomy, seizure outcome reported after a minimum follow-up of 1 year after the initial procedure, and description of the type of hemispherectomy. Only the most recent paper from institutions that published multiple papers with overlapping study periods was included. Two reviewers independently applied the inclusion criteria and extracted all the data.

RESULTS

Twenty-nine studies with a total of 1161 patients met the inclusion criteria. Seizure outcome was available for 1102 patients, and the overall rate of seizure freedom at the last follow-up was 73.4%. Sixteen studies (55.2%) exclusively reported seizure outcomes of a single type of hemispherectomy. There was no statistically significant difference in seizure outcome and type of hemispherectomy (p = 0.737). Underlying etiology was reported for 85.4% of patients with documented seizure outcome, and the overall distribution of acquired, developmental, and progressive etiologies was 30.5%, 40.7%, and 28.8%, respectively. Acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001). Twenty of the 29 studies (69%) reported complications. The overall rate of hydrocephalus requiring CSF diversion was 14%. Mortality within 30 days was 2.2% and was not statistically different between types of hemispherectomy (p = 0.787).

CONCLUSIONS

Hemispherectomy is highly effective for treating refractory epilepsy in the pediatric age group, particularly for acquired and progressive etiologies. While the type of hemispherectomy does not have any influence on seizure outcome, hemispherotomy procedures are associated with a more favorable complication profile.

Hemispherectomy for the treatment of refractory epilepsy was first performed in the first half of the 20th century.20 Anatomical hemispherectomy, the resection of an entire hemisphere frequently done in the 1950s and 1960s that was associated with high complication rates from hydrocephalus and superficial cerebral hemosiderosis, has been replaced with less invasive procedures that accomplish a functional equivalent by disconnection of the epileptogenic cortex of one hemisphere from the contralateral hemisphere and deeper brain structures or removal of the epileptogenic cortex. These procedures are associated with comparable seizure control rates but a lower incidence of the aforementioned complications. This transition began with the development of functional hemispherectomy28 and hemidecortication16 in the 1970s and 1980s and evolved in the 1990s with the introduction of several different approaches, collectively referred to as hemispherotomy. These procedures were developed almost simultaneously, rely mostly on disconnection, and require only minimal brain resection.10,30,33,44 Conditions amenable to these procedures are characterized by diffuse damage to one hemisphere resulting in medically resistant epilepsy and are frequently grouped into acquired (e.g., perinatal cerebral infarction or intracranial hemorrhage, hemiconvulsion-hemiplegia-epilepsy syndrome, and other sequelae of brain trauma and infection), developmental (e.g., cortical dysplasia, hemimegalencephaly, and migration disorders), and progressive (e.g., Rasmussen's encephalitis and Sturge-Weber syndrome) etiologies.11,27,41 The aim of this study was to systematically review the literature on hemispherectomy with emphasis on seizure outcome stratified by type of hemispherectomy and underlying etiology.

Methods

A PubMed search was performed, of the literature until October 2013, with the search terms “hemispherectomy” and “outcome” limited to papers written in the English language with a focus on the pediatric age group. Additionally, papers retrieved from the references listed in the papers found in the PubMed search were also evaluated. Two reviewers independently applied the following inclusion criteria: reports of a total of 10 or more patients in the pediatric age group (≤ 20 years) undergoing hemispherectomy, seizure outcome reported after a minimum followup of 1 year after the initial procedure, and description of the type of hemispherectomy. To account only once for each patient, only the most recent paper from institutions that published multiple papers with overlapping study periods was included. Studies reporting outcome after repeat hemispherectomy with failure of the initial procedure were excluded. Studies were categorized by the type of hemispherectomy (Fig. 1) into anatomical hemispherectomy, functional hemispherectomy (Fig. 1B),6,28 hemispherotomy including trans- and perisylvian (Fig. 1C)30,31,33,44 and vertical parasagittal techniques (Fig. 1D),9 and hemidecortication.16 Indications for hemispherectomy were grouped into acquired, developmental, and progressive etiologies. Two reviewers independently extracted all the data and resolved any disagreements through discussions. Descriptive and statistical analyses were performed using commercially available software (version 21, SPSS, IBM). A comparison of groups of 3 or more studies was conducted using ANOVA and Fisher's least significant difference post hoc analysis, where appropriate. This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.24

FIG. 1.
FIG. 1.

Schematic drawings of the types of hemispherectomy illustrated by the senior author (P.A.W.). A: Coronal view of the brain at the level of mammillary bodies. B. Functional hemispherectomy (Rasmussen). C: Trans- and perisylvian technique (Villemure, Mascott, and Schramm). D: Vertical parasagittal technique (Delalande). Copyright Peter Winkler. Published with permission. Figure is available in color online only.

Results

Descriptive Analysis

The literature search yielded 186 references, of which 85 (45.7%) were excluded based on the abstract. One hundred one potentially eligible studies underwent a full-text review, and 29 studies (15.6%) met the inclusion criteria and constituted the data set. The search strategy is outlined in detail in Fig. 2. Two reviewers independently performed assessment at each step. All 29 studies identified were retrospective in nature. The cumulative number of patients from all 29 studies was 1161. The number of patients per study ranged from 10 to 186. All 29 studies reported seizure outcome, and 21 (72.4%) reported complete Engel scores.13 One study used the International League Against Epilepsy classification.32 Seizure outcome was available for 1102 patients, and the overall rate of seizure freedom at last follow-up was 73.4%. Of the 29 studies, 16 (55.2%) exclusively reported seizure outcomes of a single type of hemispherectomy. Eight studies (27.6%) reported only hemispherotomy results, while 6 (20.1%) and 2 (6.9%) studies reported results of functional and anatomical hemispherectomy, respectively. No study exclusively studied hemidecortication. The underlying etiology was reported for 85.4% of patients with documented seizure outcome. The overall distribution of acquired, developmental, and progressive etiologies was 30.5%, 40.7%, and 28.8%, respectively (Table 1).

FIG. 2.
FIG. 2.

Outline of search strategy.

TABLE 1

Studies included in the systematic review

Authors & YearStudy PeriodInstitutionJournalOutcome AssessmentNo. of PtsNo. of Pts w/ Sz Outcome InformationMortalityNo. of Patients (%)
No.No. Sz Free (%)30 Daysw/in FUAcquiredDevelopmentalProgressive
Anatomical hemispherectomy
 Beardsworth & Adams, 19881979–NRRadcliffe InfirmaryBr J NeurosurgSz, yes/no10107 (70)00
 Davies et al., 19931950–1971University of MinnesotaJ NeurosurgSz, yes/no10104 (40)022 (20)1 (10)
Functional hemispherectomy
 Smith et al., 19911976–1988Montreal Neurological Institute & HospitalNeurologySz, yes/no201915 (79)10
 Duchowny et al., 19981979–1996Miami Children's HospitalEpilepsiaEngel14129 (75)111 (7)10 (71)2 (14)
 Sugimoto et al., 19991991–1996Hospital for Sick ChildrenEpilepsiaEngel11118 (73)002 (18)4 (36)5 (45)
 Shimizu & Maehara, 2000341983–1998Tokyo Metropolitan Neurological HospitalEpilepsiaEngel24188 (44)002 (8)18 (75)
 Aaberg et al., 20121995–2004Oslo University HospitalActa PaediatrEngel10109 (90)00
 Villarejo-Ortega et al., 20132001–2009Hospital Infantil Universitario Niño JesúsChilds Nerv SystEngel171710 (59)009 (53)5 (29)3 (18)
Hemispherotomy
 Villemure & Daniel, 2006NRChristian Medical College, Centre Hospitalier Universitaire VaudoisChilds Nerv SystEngel433734 (92)1017 (40)5 (12)12 (28)
 Delalande et al., 20071990–2000Fondation OphtalmologiqueNeurosurgeryEngel787557 (76)3016 (21)28 (36)31 (40)
 Marras et al., 20102000–2007Carlo Besta Neurological InstituteEpilepsy ResEngel13138 (62)002 (15)5 (38)6 (46)
 Thomas et al., 20102005–2009Christian Medical CollegeChilds Nerv SystEngel161615 (94)002 (13)12 (75)
 Dagar et al., 20112000–2011All India Institute of Medical SciencesPediatr NeurosurgEngel353530 (86)00
 Torres et al., 20112002–2007Hospital for Sick ChildrenJ Neurosurg PediatrEngel131310 (77)007 (54)6 (46)
 Ramantani et al., 20132002–2011University Hospital FreiburgEpilepsiaEngel525243 (83)0024 (46)22 (42)6 (12)
 van der Kolk et al., 20131996–2007Wilhelmina Children's HospitalEpilepsy ResEngel353530 (86)0013 (37)13 (37)9 (26)
Hemidecortication
 Kossoff et al., 2003*1975–2001Johns Hopkins UniversityNeurologySz, yes/no11110568 (65)3216 (14)33 (30)51 (46)
Mixed surgery type
 Carmant et al., 19951963–1992Boston Children's HospitalElectroencephalogr Clin NeurophysiolEngel12128 (67)006 (50)3 (25)3 (25)
 Villemure et al., 2003NRLausanne University HospitalEpileptic DisordEngel12118 (73)1011 (92)
 Devlin et al., 20031991–1997Great Ormond Street HospitalBrainEngel333317 (52)007 (21)16 (48)6 (18)
 Cook et al., 20041986–2002University of California, Los AngelesJ Neurosurg PediatrSz, yes/no11510379 (77)2027 (23)55 (48)21 (18)
 Basheer et al., 20071993–2004British Columbia's Children's HospitalEpilepsiaEngel242419 (79)007 (29)7 (29)10 (42)
 Terra-Bustamante et al., 20071996–2005Ribeirão Preto, BrazilChilds Nerv SystEngel393821 (55)129 (23)14 (36)
 Lettori et al., 20081980–2003Università Cattolica del Sacro CuoreSeizureEngel191914 (74)002 (11)13 (68)4 (21)
 Limbrick et al., 20091995–2008University of Washington, St. LouisJ Neurosurg PediatrEngel494938 (78)0013 (27)16 (33)8 (16)
 Caraballo et al., 20111990–2010Hospital Nacional de Pediatria, Buenos AiresChilds Nerv SystEngel454533 (73)0118 (40)14 (31)
 Schramm et al., 20121990–2009Bonn University Medical CenterActa NeurochirILAE969278 (85)1242 (44)20 (21)19 (20)
 Yu et al., 20122001–2009Capital Medical UniversitySeizureSz, yes/no191817 (94)10
 Moosa et al., 20131997–2009Cleveland ClinicNeurologySz, yes/no186170112 (66)0079 (42)63 (34)28 (15)
Overall11611102809 (73.4)1510287 (30.5)383 (40.7)271 (28.8)

FU = follow-up; ILAE = International League Against Epilepsy; NR = not reported; pt = patient; Sz = seizure.

Two of 111 patients did not undergo hemidecortication.

Seizure Outcome, Type of Hemispherectomy, and Underlying Etiology

In addition to the 16 studies that reported solely one type of hemispherectomy, another 6 studies2,6,11,21,32,38 from the mixed study pool provided detailed enough information allowing for extraction of seizure outcome as a function of the type of hemispherectomy. One additional study was analyzed as if all patients had hemidecortication since the vast majority (98%) of patients in this study underwent hemidecortication.19 Thus, seizure outcome was available for 406 (56.7%), 132 (18.4%), 61 (8.5%), and 117 (16.3%) patients who underwent hemispherotomy, functional hemispherectomy, anatomical hemispherectomy, and hemidecortication, respectively. The seizure-free rate was highest for anatomical hemispherectomy and lowest for hemidecortication without any statistically significant differences between types of hemispherectomy (p = 0.737) (Table 2; Fig. 3).

TABLE 2

Seizure outcome and type of hemispherectomy*

Type of Hemispherectomy & StudyNo. of StudiesNo. of PtsSz-Free Rate (%)
Mean ± SD95% CI
Hemispherotomy1040676.0 ± 16.769.4–82.6
 Cook 2004, Villemure 2006, Basheer 2007, Delalande 2007, Terra-Bustamante 2007, Marras 2010, Torres 2011, Schramm 2012, van der Kolk 2013, Ramantani 2013
Functional hemispherectomy713271.9 ± 26.758.1–85.6
 Duchowny 1998, Sugimoto 1999, Shimizu 2000,34 Devlin 2003, Cook 2004, Lettori 2008, Villarejo-Ortega 2013
Anatomical hemispherectomy46180.7 ± 21.063.1–98.2
 Davies 1993, Devlin 2003, Cook 2004, Lettori 2008
Hemidecortication311771.2 ± 20.953.8–88.7
 Kossof 2003, Basheer 2007, Lettori 2008

There was no statistically significant difference in seizure outcome and type of hemispherectomy (p = 0.737).

FIG. 3.
FIG. 3.

Seizure-free rates and type of hemispherectomy (p = 0.737).

Information on underlying etiology was available from 17 studies with a total of 667 patients. Of these patients, 211 (31.6%) had acquired, 269 (40.3%) developmental, and 187 (28%) progressive etiologies. The mean seizure-free rates for acquired, progressive, and developmental etiologies were 82.4%, 82.8%, and 61.4%, respectively. Both acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001). There was, however, no difference in seizure-free rates between acquired and progressive etiologies (p = 0.945) (Table 3; Fig. 4).

TABLE 3

Seizure outcome and underlying etiology*

Underlying Etiology & StudyNo. of StudiesNo. of PtsSz-Free Rate (%)
Mean ± SD95% CI
Acquired1521182.4 ± 15.974.7–90.0
 Davies 1993, Duchowny 1998, Sugimoto 1999, Devlin 2003, Kossof 2003, Cook 2004, Villemure 2006, Basheer 2007, Delalande 2007, Lettori 2008, Marras 2010, Schramm 2012, Ramantani 2013, van der Kolk 2013, Villarejo-Ortega 2013
Developmental1626961.4 ± 20.852.2–70.7
 Duchowny 1998, Sugimoto 1999, Devlin 2003, Kossof 2003, Cook 2004, Villemure 2006, Basheer 2007, Delalande 2007, Terra-Bustamante 2007, Lettori 2008, Marras 2010, Torres 2011, Schramm 2012, Ramanti 2013, van der Kolk 2013, Villarejo-Ortega 2013
Progressive1618782.8 ± 17.574.3–91.2
 Duchowny 1998, Sugimoto 1999, Devlin 2003, Kossof 2003, Cook 2004, Villemure 2006, Basheer 2007, Delalande 2007, Terra-Bustamante 2007, Lettori 2008, Marras 2010, Torres 2011, Schramm 2012, Ramantani 2013, van der Kolk 2013, Villarejo-Ortega 2013

Acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001).

FIG. 4.
FIG. 4.

Seizure-free rates and underlying etiology. Post hoc analysis using Fisher's least significant difference. ***p < 0.001.

A comparison of seizure outcome for different etiologies dependent on the type of hemispherectomy was feasible for hemispherotomy and functional hemispherectomy only. For anatomical hemispherectomy and hemidecortication there were fewer than 3 studies each, thereby precluding them from inclusion in the analysis. There was no difference in seizure-free rates for the 3 etiologies between hemispherectomy and functional hemispherectomy. While developmental etiologies had the lowest rates of seizure freedom, seizure-free rates among patients undergoing functional hemispherectomy were significantly higher in those who suffered from an acquired or progressive etiology in contrast to those suffering from a developmental etiology (p < 0.05). Seizure-free rates in patients undergoing hemispherotomy for a developmental etiology did not significantly differ from seizure-free rates for acquired (p = 0.063) or progressive (p = 0.106) etiology (Table 4; Fig. 5).

TABLE 4

Seizure outcome, type of hemispherectomy, and underlying etiology*

Variables & StudyNo. of StudiesNo. of PtsSz-Free Rate (%)
Mean ± SD95% CI
Hemispherotomy
 Acquired814083.3 ± 11.573.7–92.9
  Cook 2004, Villemure 2006, Delalande 2007, Basheer 2007, Marras 2010, Schramm 2012, Ramantani 2013, van der Kolk 2013
 Developmental1015266.1 ± 15.854.8–77.4
  Cook 2004, Villemure 2006, Delalande 2007, Terra-Bustamante 2007, Basheer 2007, Marras 2010, Torres 2011, Schramm 2012, Ramantani 2013, van der Kolk 2013
 Progressive99380.5 ± 17.766.9–94.1
  Cook 2004, Villemure 2006, Delalande 2007, Terra-Bustamante 2007, Marras 2010, Torres 2011, Schramm 2012, Ramantani 2013, van der Kolk 2013
Functional hemispherectomy
 Acquired63282.8 ± 21.160.6–104.9
  Duchowny 1998, Sugimoto 1999, Devlin 2003, Cook 2004, Lettori 2008, Villarejo-Ortega 2013
 Developmental65053.9 ± 29.622.8–85.0
  Duchowny 1998, Sugimoto 1999, Devlin 2003, Cook 2004, Lettori 2008, Villarejo-Ortega 2013
 Progressive52380.3 ± 21.154.1–106.4
  Duchowny 1998, Sugimoto 1999, Devlin 2003, Cook 2004, Villarejo-Ortega 2013

p = 0.048.

FIG. 5.
FIG. 5.

Seizure-free rates, underlying etiology, and type of hemispherectomy. Post hoc analysis using Fisher's least significant difference. *p < 0.05. ns = not significant.

Hydrocephalus, Complications, and Mortality

Twenty of the 29 studies (69%) reported complications. Data from 20 studies (69%) that reported postoperative CSF diversion rates revealed a cumulative overall shunt rate of 14% following hemispherectomy. Fifteen studies (52%) provided detailed enough information to compare shunt rates for hemispherotomy, functional hemispherectomy, and anatomical hemispherectomy. For hemidecortication there were fewer than 3 studies, thus precluding them from inclusion in the analysis. Anatomical hemispherectomy was associated with a significantly higher shunt rate than functional hemispherectomy (p < 0.05) and hemispherotomy (p < 0.01). One of the 4 studies in the anatomical hemispherectomy group had a shunt rate of 78%,6 which was considerably higher than the shunt rate in the other 3 studies. The study, however, was included because it contributed 37 patients and was the single largest contributor to this group (54.4%) (Table 5; Fig. 6).

TABLE 5

Shunted hydrocephalus and type of hemispherectomy*

Type of Hemispherectomy & StudyNo. of StudiesNo. of PtsShunt Rate (%)
Mean ± SD95% CI
Hemispherotomy93888.3 ± 7.92.2 to 14.4
 Cook 2004, Villemure 2006, Delalande 2007, Terra-Bustamante 2007, Marras 2010, Dagar 2011, Torres 2011, Schramm 2012, Ramantani 2013
Functional hemispherectomy610512.9 ± 8.24.3 to 21.4
 Duchowny 1998, Shimizu 2000,34 Cook 2004, Lettori 2008, Schramm 2012, Villarejo-Ortega 2013
Anatomical hemispherectomy46836.4 ± 29.3−10.3 to 83.1
 Beardsworth & Adams 1988, Davies 1993, Cook 2004, Lettori 2008

p = 0.017.

FIG. 6.
FIG. 6.

Shunted hydrocephalus rates and type of hemispherectomy. Post hoc analysis using Fisher's least significant difference. *p < 0.05; **p < 0.01.

The rate of wound complications requiring surgical revision was 2%. The rate for other surgical complications, such as epidural, subdural, or intraparenchymal hemorrhages, and intracranial abscesses, was 3.5%. The rate of nonsurgical, medical complications was 10.6% and included, but was not limited to, meningitis, ventriculitis, venous thrombosis, and others. Neurological deficits affecting motor and sensory function or visual fields are expected following hemispherectomy and were not considered complications. The need for additional epilepsy surgery was reported in 18 studies with a cumulative rate of 4.5%. Complications other than hydrocephalus were all reported inconsistently, thereby not allowing for further statistical analysis.

The overall mortality was 2.2% (25 patients), with 15 patients (1.3%) dying within 30 days after surgery. Fifteen studies (52%) provided detailed enough information to compare mortality rates for hemispherotomy, functional hemispherectomy, and anatomical hemispherectomy. For hemidecortication there were fewer than 3 studies, thus precluding them from inclusion in the analysis. There were no significant differences between mortality rates from the 3 types of hemispherectomy (p = 0.787) (Table 6; Fig. 7).

TABLE 6

Mortality and type of hemispherectomy*

Type of HemispherectomyNo. of StudiesNo. of PtsMortality Rate (%)
Mean ± SD95% CI
Hemispherotomy93881.1 ± 1.6−0.2 to 2.3
 Cook 2004, Villemure 2006, Delalande 2007, Terra-Bustamante 2007, Marras 2010, Dagar 2011, Torres 2011, Schramm 2012, Ramantani 2013
Functional hemispherectomy61052.4 ± 5.8−3.7 to 8.5
 Duchowny 1998, Shimizu 2000,34 Cook 2004, Lettori 2008, Schramm 2012, Villarejo-Ortega 2013
Anatomic hemispherectomy4681.4 ± 2.7−2.9 to 5.7
 Beardsworth & Adams 1988, Davies 1993, Cook 2004, Lettori 2008

Mortality within 30 days was not statistically different between types of hemispherectomy (p = 0.787).

FIG. 7.
FIG. 7.

Mortality rates and type of hemispherectomy (p = 0.787).

Discussion

Hemispherectomy refers to a group of surgical interventions for treatment-refractory epilepsy that is due to a diffusely damaged hemisphere. The evidence supporting this procedure is largely based on a multitude of retrospective studies illustrating individual institutions' experience with a few notable exceptions. One such important study is a retrospective multicenter study led by Holthausen et al. that gathered information concerning hemispherectomy from 333 patients at 11 participating centers.15 However, more than a decade has passed since Holthausen and colleagues' report was published, significant advances have been made, and many centers have subsequently reported their experience. Therefore, the aim of this study was to systematically review the literature available on hemispherectomy with emphasis on seizure outcome stratified by type of hemispherectomy and underlying etiologies.

Seizure Outcome, Type of Procedure, and Underlying Etiology

Twenty-nine studies comprising 1161 patients were identified and met inclusion criteria. The overall rate of seizure freedom was 73.4%, which is slightly higher than the rate of seizure freedom found by Holthausen et al.15 and comparable to other large, more recent series.6,9,19,25,27,32,43 Long-term sustainability of seizure freedom is absolutely critical to justify surgery for epilepsy, which is an irreversible intervention. Long-term seizure-free rates (≥ 5 years) following surgery for temporal lobe epilepsy are comparable to those reported in shorter-term studies. The rates of seizure freedom after surgery for extratemporal epilepsy, however, decline over time.14,37,46 Existing evidence shows that the benefit of hemispherectomy is maintained over time and seizure-free rates drop only slightly in the long term.26,37 For the purpose of this review, only studies with at least 1 year of follow-up were considered in an attempt to compensate for the initial decrease in seizure-free rates after hemispherectomy.17 Insufficient data on long-term outcome were available to perform any meaningful statistical analysis. Also, to account only once for each patient, only the most recent paper from institutions that published multiple papers with overlapping study periods was considered. This predominantly affected institutions that published a sequential series of papers on outcomes.

There was no significant difference in the rate of seizure freedom between different types of hemispherectomy in this study, which is plausible as they all follow the same underlying principle. Holthausen et al., however, found that hemispherotomy is superior to anatomical and functional hemispherectomies as well as hemidecortication.15 However, other studies did not make such an observation.6,32

The underlying etiology warranting hemispherectomy is by contrast an important determinant for seizure outcome. To assess this effect, indications for hemispherectomy were grouped similarly to those in prior studies into acquired, developmental, and progressive etiologies.11,27,41 Patients suffering from acquired and progressive conditions generally do better than patients with developmental disorders,11,18,19,21 and this observation is supported by the findings of the present study. Due to the small number of available studies for anatomical hemispherectomy and hemidecortication, seizure outcome for different etiologies dependent on the type of hemispherectomy was only feasible for hemispherotomy and functional hemispherectomy. The highest rate of seizure freedom was achieved with hemispherotomy and functional hemispherectomy for acquired lesions (83.3% and 82.8% seizure free, respectively). Functional hemispherectomy of developmental conditions was least successful (53.9% seizure free). The lower success rate for developmental etiologies was statistically significant for functional hemispherectomy but not for hemispherotomy. A higher hemispherectomy failure rate for developmental etiologies has been associated with epileptogenesis in the contralateral hemisphere and higher rates of incomplete disconnection, particularly in hemimegalencephaly.15 In the present study, the influence of epileptiform discharges over the normal hemisphere could not be assessed as these data were inconsistently reported.

Hydrocephalus, Complications, and Mortality

The most common complication reported was hydrocephalus requiring CSF diversion with an overall rate across all studies of 14%. Anatomical hemispherectomy resulted in the highest rate of shunted hydrocephalus with rates for functional hemispherectomy and hemispherotomy comparable and significantly lower. Shunt rates of 8%–23% have been previously reported and seem to be directly proportional to the amount of brain tissue removed.29 Approximately 5% of patients underwent additional epilepsy surgery, most commonly for completion of incomplete disconnection. Incomplete disconnection has been reported as a cause of persistent seizures in up to 30% of patients who do not become seizure free after the initial intervention.29 The overall number of patients requiring additional epilepsy surgery found in the present study appears somewhat low. This may, however, be explained by the greater experience high-volume centers that published their outcomes have with these procedures. Mortality was generally low at 2% and was similar for all types of hemispherectomy.29

Limitations

The categorization of studies based on the type of hemispherectomy applied here presents a challenge as there are surgical modifications and nuances that may go beyond these basic categories that are not accounted for. Multiple variations of functional hemispherectomy have been reported.6,28 Hemispherotomy is a collective term encompassing trans- and perisylvian30,31,33,44 as well as vertical parasagittal techniques.9 However, to accumulate numbers large enough to perform any meaningful statistical analysis, a common denominator has to be agreed upon.

Conclusions

Hemispherectomy is highly effective for the treatment of refractory epilepsy in the pediatric age group, particularly for acquired and progressive etiologies. While the type of hemispherectomy does not have any influence on seizure outcome, hemispherotomy procedures are associated with a more favorable complication profile. Developmental etiologies have worse outcomes than acquired or progressive etiologies regardless of hemispherectomy technique.

Author Contributions

Conception and design: Griessenauer, Blount, Winkler. Acquisition of data: Griessenauer, Salam, Hendrix, Patel. Analysis and interpretation of data: Griessenauer, Salam, Hendrix, Patel. Drafting the article: Griessenauer. Critically revising the article: Griessenauer, Hendrix, Tubbs, Blount, Winkler. Reviewed submitted version of manuscript: Griessenauer, Tubbs, Blount, Winkler. Approved the final version of the manuscript on behalf of all authors: Griessenauer. Statistical analysis: Griessenauer, Hendrix. Administrative/technical/material support: Griessenauer, Tubbs. Study supervision: Griessenauer, Blount, Winkler.

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    • Export Citation
  • 9

    Delalande OBulteau CDellatolas GFohlen MJalin CBuret V: Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children. Neurosurgery 60:2 Suppl 1ONS19ONS322007

    • Search Google Scholar
    • Export Citation
  • 10

    Delalande OPinard JMBasdevant CGauthe MPlouin PDulac O: Hemispherotomy: a new procedure for central disconnection. Epilepsia 33:Suppl 3991001992

    • Search Google Scholar
    • Export Citation
  • 11

    Devlin AMCross JHHarkness WChong WKHarding BVargha-Khadem F: Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain 126:5565662003

    • Search Google Scholar
    • Export Citation
  • 12

    Duchowny MJayakar PResnick THarvey ASAlvarez LDean P: Epilepsy surgery in the first three years of life. Epilepsia 39:7377431998

    • Search Google Scholar
    • Export Citation
  • 13

    Engel J JrVan Ness PCRasmussen TBOjemann LMOutcome with respect to epileptic seizures. Engel J Jr: Surgical Treatment of the Epilepsies ed 2New YorkRaven Press1993. 609621

    • Search Google Scholar
    • Export Citation
  • 14

    Engel J JrWiebe SFrench JSperling MWilliamson PSpencer D: Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60:5385472003

    • Search Google Scholar
    • Export Citation
  • 15

    Holthausen HMay TWAdams CTAndermann FComair YDelalande OSeizures post hemispherectomy. Tuxhorn IHolthausen HBoenigk H: Paediatric Epilepsy Syndromes and Their Surgical Treatment LondonJohn Libbey1997. 749773

    • Search Google Scholar
    • Export Citation
  • 16

    Ignelzi RJBucy PC: Cerebral hemidecortication in the treatment of infantile cerebral hemiatrophy. J Nerv Ment Dis 147:14301968

  • 17

    Jonas RNguyen SHu BAsarnow RFLoPresti CCurtiss S: Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology 62:171217212004

    • Search Google Scholar
    • Export Citation
  • 18

    Kossoff EHBuck CFreeman JM: Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide. Neurology 59:173517382002

  • 19

    Kossoff EHVining EPPillas DJPyzik PLAvellino AMCarson BS: Hemispherectomy for intractable unihemispheric epilepsy etiology vs outcome. Neurology 61:8878902003

    • Search Google Scholar
    • Export Citation
  • 20

    Krynauw RA: Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry 13:2432671950

  • 21

    Lettori DBattaglia DSacco AVeredice CChieffo DMassimi L: Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up. Seizure 17:49632008

    • Search Google Scholar
    • Export Citation
  • 22

    Limbrick DDNarayan PPowers AKOjemann JGPark TSBertrand M: Hemispherotomy: efficacy and analysis of seizure recurrence. Clinical article. J Neurosurg Pediatr 4:3233322009

    • Search Google Scholar
    • Export Citation
  • 23

    Marras CEGranata TFranzini AFreri EVillani FCasazza M: Hemispherotomy and functional hemispherectomy: indications and outcome. Epilepsy Res 89:1041122010

    • Search Google Scholar
    • Export Citation
  • 24

    Moher DLiberati ATetzlaff JAltman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e10000972009

    • Search Google Scholar
    • Export Citation
  • 25

    Moosa ANGupta AJehi LMarashly ACosmo GLachhwani D: Longitudinal seizure outcome and prognostic predictors after hemispherectomy in 170 children. Neurology 80:2532602013

    • Search Google Scholar
    • Export Citation
  • 26

    Pulsifer MBBrandt JSalorio CFVining EPCarson BSFreeman JM: The cognitive outcome of hemispherectomy in 71 children. Epilepsia 45:2432542004

    • Search Google Scholar
    • Export Citation
  • 27

    Ramantani GKadish NEBrandt AStrobl KStathi AWiegand G: Seizure control and developmental trajectories after hemispherotomy for refractory epilepsy in childhood and adolescence. Epilepsia 54:104610552013

    • Search Google Scholar
    • Export Citation
  • 28

    Rasmussen T: Hemispherectomy for seizures revisited. Can J Neurol Sci 10:71781983

  • 29

    Schramm JHemispheric disconnection procedures. Winn HR: Youmans Neurological Surgery ed 6PhiladelphiaElsevier/Saunders2011. 1:796806

    • Search Google Scholar
    • Export Citation
  • 30

    Schramm JBehrens EEntzian W: Hemispherical deafferentation: an alternative to functional hemispherectomy. Neurosurgery 36:5095161995

    • Search Google Scholar
    • Export Citation
  • 31

    Schramm JKral TClusmann H: Transsylvian keyhole functional hemispherectomy. Neurosurgery 49:8919012001

  • 32

    Schramm JKuczaty SSassen RElger CEvon Lehe M: Pediatric functional hemispherectomy: outcome in 92 patients. Acta Neurochir (Wien) 154:201720282012

    • Search Google Scholar
    • Export Citation
  • 33

    Shimizu HMaehara T: Modification of peri-insular hemispherotomy and surgical results. Neurosurgery 47:3673732000

  • 34

    Shimizu HMaehara T: Neuronal disconnection for the surgical treatment of pediatric epilepsy. Epilepsia 41:Suppl 928302000

  • 35

    Smith SJAndermann FVillemure JGRasmussen TBQuesney LF: Functional hemispherectomy: EEG findings, spiking from isolated brain postoperatively, and prediction of outcome. Neurology 41:179017941991

    • Search Google Scholar
    • Export Citation
  • 36

    Sugimoto TOtsubo HHwang PAHoffman HJJay VSnead OC III: Outcome of epilepsy surgery in the first three years of life. Epilepsia 40:5605651999

    • Search Google Scholar
    • Export Citation
  • 37

    Téllez-Zenteno JFDhar RWiebe S: Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 128:118811982005

    • Search Google Scholar
    • Export Citation
  • 38

    Terra-Bustamante VCInuzuka LMFernandes RMEscorsi-Rosset SWichert-Ana LAlexandre V Jr: Outcome of hemispheric surgeries for refractory epilepsy in pediatric patients. Childs Nerv Syst 23:3213262007

    • Search Google Scholar
    • Export Citation
  • 39

    Thomas SGDaniel RTChacko AGThomas MRussell PS: Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy. Childs Nerv Syst 26:106710732010

    • Search Google Scholar
    • Export Citation
  • 40

    Torres CVFallah AIbrahim GMCheshier SOtsubo HOchi A: The role of magnetoencephalography in children undergoing hemispherectomy. Clinical article. J Neurosurg Pediatr 8:5755832011

    • Search Google Scholar
    • Export Citation
  • 41

    van der Kolk NMBoshuisen Kvan Empelen RKoudijs SMStaudt Mvan Rijen PC: Etiology-specific differences in motor function after hemispherectomy. Epilepsy Res 103:2212302013

    • Search Google Scholar
    • Export Citation
  • 42

    Villarejo-Ortega FGarcía-Fernández MFournier-Del Castillo CFabregate-Fuente MÁlvarez-Linera JDe Prada-Vicente I: Seizure and developmental outcomes after hemispherectomy in children and adolescents with intractable epilepsy. Childs Nerv Syst 29:4754882013

    • Search Google Scholar
    • Export Citation
  • 43

    Villemure JGDaniel RT: Peri-insular hemispherotomy in paediatric epilepsy. Childs Nerv Syst 22:9679812006

  • 44

    Villemure JGMascott CR: Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery 37:9759811995

  • 45

    Villemure JGMeagher-Villemure KMontes JLFarmer JPBroggi G: Disconnective hemispherectomy for hemispheric dysplasia. Epileptic Disord 5:Suppl 2S125S1302003

    • Search Google Scholar
    • Export Citation
  • 46

    Wiebe SBlume WTGirvin JPEliasziw M: A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 345:3113182001

    • Search Google Scholar
    • Export Citation
  • 47

    Yu TZhang GKohrman MHWang YCai LShu W: A retrospective study comparing preoperative evaluations and postoperative outcomes in paediatric and adult patients undergoing surgical resection for refractory epilepsy. Seizure 21:4444492012

    • Search Google Scholar
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Information

Correspondence Christoph J. Griessenauer, 1530 3rd Ave. S, Birmingham, AL, 35294. email: cgriessenauer@uabmc.edu.

INCLUDE WHEN CITING Published online November 7, 2014; DOI: 10.3171/2014.10.PEDS14155.

DISCLOSURE The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Schematic drawings of the types of hemispherectomy illustrated by the senior author (P.A.W.). A: Coronal view of the brain at the level of mammillary bodies. B. Functional hemispherectomy (Rasmussen). C: Trans- and perisylvian technique (Villemure, Mascott, and Schramm). D: Vertical parasagittal technique (Delalande). Copyright Peter Winkler. Published with permission. Figure is available in color online only.

  • View in gallery

    Outline of search strategy.

  • View in gallery

    Seizure-free rates and type of hemispherectomy (p = 0.737).

  • View in gallery

    Seizure-free rates and underlying etiology. Post hoc analysis using Fisher's least significant difference. ***p < 0.001.

  • View in gallery

    Seizure-free rates, underlying etiology, and type of hemispherectomy. Post hoc analysis using Fisher's least significant difference. *p < 0.05. ns = not significant.

  • View in gallery

    Shunted hydrocephalus rates and type of hemispherectomy. Post hoc analysis using Fisher's least significant difference. *p < 0.05; **p < 0.01.

  • View in gallery

    Mortality rates and type of hemispherectomy (p = 0.787).

References

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    Basheer SNConnolly MBLautzenhiser ASherman EMHendson GSteinbok P: Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function. Epilepsia 48:1331402007

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    Caraballo RBartuluchi MCersósimo RSoraru APomata H: Hemispherectomy in pediatric patients with epilepsy: a study of 45 cases with special emphasis on epileptic syndromes. Childs Nerv Syst 27:213121362011

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    Carmant LKramer URiviello JJHelmers SLMikati MAMadsen JR: EEG prior to hemispherectomy: correlation with outcome and pathology. Electroencephalogr Clin Neurophysiol 94:2652701995

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    Cook SWNguyen STHu BYudovin SShields WDVinters HV: Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients. J Neurosurg 100:2 Suppl Pediatrics1251412004

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    Dagar AChandra PSChaudhary KAvnish CBal CSGaikwad S: Epilepsy surgery in a pediatric population: a retrospective study of 129 children from a tertiary care hospital in a developing country along with assessment of quality of life. Pediatr Neurosurg 47:1861932011

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    Davies KGMaxwell REFrench LA: Hemispherectomy for intractable seizures: long-term results in 17 patients followed for up to 38 years. J Neurosurg 78:7337401993

    • Search Google Scholar
    • Export Citation
  • 9

    Delalande OBulteau CDellatolas GFohlen MJalin CBuret V: Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children. Neurosurgery 60:2 Suppl 1ONS19ONS322007

    • Search Google Scholar
    • Export Citation
  • 10

    Delalande OPinard JMBasdevant CGauthe MPlouin PDulac O: Hemispherotomy: a new procedure for central disconnection. Epilepsia 33:Suppl 3991001992

    • Search Google Scholar
    • Export Citation
  • 11

    Devlin AMCross JHHarkness WChong WKHarding BVargha-Khadem F: Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain 126:5565662003

    • Search Google Scholar
    • Export Citation
  • 12

    Duchowny MJayakar PResnick THarvey ASAlvarez LDean P: Epilepsy surgery in the first three years of life. Epilepsia 39:7377431998

    • Search Google Scholar
    • Export Citation
  • 13

    Engel J JrVan Ness PCRasmussen TBOjemann LMOutcome with respect to epileptic seizures. Engel J Jr: Surgical Treatment of the Epilepsies ed 2New YorkRaven Press1993. 609621

    • Search Google Scholar
    • Export Citation
  • 14

    Engel J JrWiebe SFrench JSperling MWilliamson PSpencer D: Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60:5385472003

    • Search Google Scholar
    • Export Citation
  • 15

    Holthausen HMay TWAdams CTAndermann FComair YDelalande OSeizures post hemispherectomy. Tuxhorn IHolthausen HBoenigk H: Paediatric Epilepsy Syndromes and Their Surgical Treatment LondonJohn Libbey1997. 749773

    • Search Google Scholar
    • Export Citation
  • 16

    Ignelzi RJBucy PC: Cerebral hemidecortication in the treatment of infantile cerebral hemiatrophy. J Nerv Ment Dis 147:14301968

  • 17

    Jonas RNguyen SHu BAsarnow RFLoPresti CCurtiss S: Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology 62:171217212004

    • Search Google Scholar
    • Export Citation
  • 18

    Kossoff EHBuck CFreeman JM: Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide. Neurology 59:173517382002

  • 19

    Kossoff EHVining EPPillas DJPyzik PLAvellino AMCarson BS: Hemispherectomy for intractable unihemispheric epilepsy etiology vs outcome. Neurology 61:8878902003

    • Search Google Scholar
    • Export Citation
  • 20

    Krynauw RA: Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry 13:2432671950

  • 21

    Lettori DBattaglia DSacco AVeredice CChieffo DMassimi L: Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up. Seizure 17:49632008

    • Search Google Scholar
    • Export Citation
  • 22

    Limbrick DDNarayan PPowers AKOjemann JGPark TSBertrand M: Hemispherotomy: efficacy and analysis of seizure recurrence. Clinical article. J Neurosurg Pediatr 4:3233322009

    • Search Google Scholar
    • Export Citation
  • 23

    Marras CEGranata TFranzini AFreri EVillani FCasazza M: Hemispherotomy and functional hemispherectomy: indications and outcome. Epilepsy Res 89:1041122010

    • Search Google Scholar
    • Export Citation
  • 24

    Moher DLiberati ATetzlaff JAltman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e10000972009

    • Search Google Scholar
    • Export Citation
  • 25

    Moosa ANGupta AJehi LMarashly ACosmo GLachhwani D: Longitudinal seizure outcome and prognostic predictors after hemispherectomy in 170 children. Neurology 80:2532602013

    • Search Google Scholar
    • Export Citation
  • 26

    Pulsifer MBBrandt JSalorio CFVining EPCarson BSFreeman JM: The cognitive outcome of hemispherectomy in 71 children. Epilepsia 45:2432542004

    • Search Google Scholar
    • Export Citation
  • 27

    Ramantani GKadish NEBrandt AStrobl KStathi AWiegand G: Seizure control and developmental trajectories after hemispherotomy for refractory epilepsy in childhood and adolescence. Epilepsia 54:104610552013

    • Search Google Scholar
    • Export Citation
  • 28

    Rasmussen T: Hemispherectomy for seizures revisited. Can J Neurol Sci 10:71781983

  • 29

    Schramm JHemispheric disconnection procedures. Winn HR: Youmans Neurological Surgery ed 6PhiladelphiaElsevier/Saunders2011. 1:796806

    • Search Google Scholar
    • Export Citation
  • 30

    Schramm JBehrens EEntzian W: Hemispherical deafferentation: an alternative to functional hemispherectomy. Neurosurgery 36:5095161995

    • Search Google Scholar
    • Export Citation
  • 31

    Schramm JKral TClusmann H: Transsylvian keyhole functional hemispherectomy. Neurosurgery 49:8919012001

  • 32

    Schramm JKuczaty SSassen RElger CEvon Lehe M: Pediatric functional hemispherectomy: outcome in 92 patients. Acta Neurochir (Wien) 154:201720282012

    • Search Google Scholar
    • Export Citation
  • 33

    Shimizu HMaehara T: Modification of peri-insular hemispherotomy and surgical results. Neurosurgery 47:3673732000

  • 34

    Shimizu HMaehara T: Neuronal disconnection for the surgical treatment of pediatric epilepsy. Epilepsia 41:Suppl 928302000

  • 35

    Smith SJAndermann FVillemure JGRasmussen TBQuesney LF: Functional hemispherectomy: EEG findings, spiking from isolated brain postoperatively, and prediction of outcome. Neurology 41:179017941991

    • Search Google Scholar
    • Export Citation
  • 36

    Sugimoto TOtsubo HHwang PAHoffman HJJay VSnead OC III: Outcome of epilepsy surgery in the first three years of life. Epilepsia 40:5605651999

    • Search Google Scholar
    • Export Citation
  • 37

    Téllez-Zenteno JFDhar RWiebe S: Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 128:118811982005

    • Search Google Scholar
    • Export Citation
  • 38

    Terra-Bustamante VCInuzuka LMFernandes RMEscorsi-Rosset SWichert-Ana LAlexandre V Jr: Outcome of hemispheric surgeries for refractory epilepsy in pediatric patients. Childs Nerv Syst 23:3213262007

    • Search Google Scholar
    • Export Citation
  • 39

    Thomas SGDaniel RTChacko AGThomas MRussell PS: Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy. Childs Nerv Syst 26:106710732010

    • Search Google Scholar
    • Export Citation
  • 40

    Torres CVFallah AIbrahim GMCheshier SOtsubo HOchi A: The role of magnetoencephalography in children undergoing hemispherectomy. Clinical article. J Neurosurg Pediatr 8:5755832011

    • Search Google Scholar
    • Export Citation
  • 41

    van der Kolk NMBoshuisen Kvan Empelen RKoudijs SMStaudt Mvan Rijen PC: Etiology-specific differences in motor function after hemispherectomy. Epilepsy Res 103:2212302013

    • Search Google Scholar
    • Export Citation
  • 42

    Villarejo-Ortega FGarcía-Fernández MFournier-Del Castillo CFabregate-Fuente MÁlvarez-Linera JDe Prada-Vicente I: Seizure and developmental outcomes after hemispherectomy in children and adolescents with intractable epilepsy. Childs Nerv Syst 29:4754882013

    • Search Google Scholar
    • Export Citation
  • 43

    Villemure JGDaniel RT: Peri-insular hemispherotomy in paediatric epilepsy. Childs Nerv Syst 22:9679812006

  • 44

    Villemure JGMascott CR: Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery 37:9759811995

  • 45

    Villemure JGMeagher-Villemure KMontes JLFarmer JPBroggi G: Disconnective hemispherectomy for hemispheric dysplasia. Epileptic Disord 5:Suppl 2S125S1302003

    • Search Google Scholar
    • Export Citation
  • 46

    Wiebe SBlume WTGirvin JPEliasziw M: A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 345:3113182001

    • Search Google Scholar
    • Export Citation
  • 47

    Yu TZhang GKohrman MHWang YCai LShu W: A retrospective study comparing preoperative evaluations and postoperative outcomes in paediatric and adult patients undergoing surgical resection for refractory epilepsy. Seizure 21:4444492012

    • Search Google Scholar
    • Export Citation

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