Long-term Outcome of Resective Joon Won Kang, MD, PhD,​a Soyong Eom, PhD,b​ William Hong, MD,​c Hye Eun Kwon, MD,​d SoyoungEpilepsy Park, MD,e​ Ara Ko, MD,​b,​f Hoon-Chul Kang, MD, in PhD,b,​ ​f JoonPatients Soo Lee, MD, PhD,b,​ ​f With g h b,f​ Lennox-GastautYoung-Mock Lee, MD, PhD,​ Dong Seok Kim, MD, PhD, Syndrome​ Heung Dong Kim, MD, PhD

OBJECTIVE: abstract

We aimed to evaluate the long-term outcome of resective surgery in METHODS: patients with Lennox-Gastaut syndrome (LGS). ’ We reviewed the case reports of 90 patients with LGS who had undergone resective surgery between 2003 and 2014 at the Severance Children s Hospital and managed them for RESULTS: a minimum period of 2 years. ± ± ± At the time of surgery, the patients were between 3.0 and 23.5 years old (mean ± – SD: 9.3 4.4). The time from onset to surgery ranged from 0.7 to 20.1 years (7.2 4.3). On postoperative follow-up for an average period of 6.1 2.2 years (range: 2.1 11.4 years), 45 patients (50.0%) had no , and 15 (16.7%) reported infrequent seizures. Seizure-free outcomes were achieved in 15 of the 21 (71.4%) hemispherectomies, 23 of the 51 (45.1%) multilobar resections, and 7 of the 18 (38.9%) single lobar resections. On high- resolution MRIs, 20 patients (22.2%) had negative findings, 8 of whom (40.0%) became seizure-free after resective surgery. Malformation of cortical development was the most common pathologic finding and was noted in 57 patients (63.3%). Seizure-free patients – – achieved better adaptive behavior andP social competence than did patients with persistent seizures at the second (2 3 years after surgery) and third (4 6 years after surgery) follow- CONCLUSIONS: ups, as indicated by social quotients ( < .05). Resective surgery is a viable option in some patients to treat seizures that are associated with LGS, with a high probability of seizure control and better adaptive function.

Departments of aPediatrics and Medical Science, Chungnam National University Hospital and College of WHAT’S KNOWN ON THIS SUBJECT: Approximately Medicine, Chungnam National University, Daejeon, Republic of Korea; bEpilepsy Research Institute, College one-half of the patients with Lennox-Gastaut of Medicine, fPediatric Epilepsy Clinics, Division of Pediatric Neurology, Department of Pediatrics, Severance syndrome are rendered seizure free with resective g h Children’s Hospital, Department of Pediatrics, Gangnam Severance Hospital, and Division of Pediatric , and they show better adaptive , Severance Hospital, Yonsei University, Seoul, Republic of Korea; cSection of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; function in serial follow-ups. d Department of Pediatrics, International St Mary’s Hospital and College of Medicine, Catholic Kwandong WHAT THIS STUDY ADDS: In patients with University, Incheon, Republic of Korea; and eDepartment of Pediatrics, Soon Chun Hyang University Hospital and College of Medicine, Soonchunhyang University, Bucheon, Republic of Korea seizure-free status, an improvement in profiles and a decrease in Dr J. Kang contributed to the analysis and interpretation of data, drafted the initial manuscript, the number of administered were and revised the manuscript; Dr Eom contributed to the analysis and interpretation of observed. Resective surgery can be a viable option psychological data and drafted the initial manuscript; Drs Hong, Kwon, and H. Kang contributed to treat patients with Lennox-Gastaut syndrome. to the acquisition and analysis of data; Drs Park and J. Lee contributed to the analysis of data; Drs Ko, Y. Lee, and Kim contributed to the acquisition of data; Dr Kim contributed to the study concept and design and the critical revision of the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. DOI: https://​doi.​org/​10.​1542/​peds.​2018-​0449 Accepted for publication Jul 6, 2018 To cite: Kang JW, Eom S, Hong W, et al. Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox- Gastaut Syndrome. Pediatrics. 2018;142(4):e20180449

Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 142, number 4, October 2018:e20180449 ARTICLE Clinical Characteristics, Diagnostic Workup, and Pathologic Lennox-Gastaut syndrome (LGS), onset of a seizure. Inclusion criteria Classification a severe childhood-onset epileptic for patients included the following: ≥ , can cause– (1) resective surgery because progressive cognitive1 decline3 and of refractoriness to 3 medical Data on individual patient history, behavioral problems. ‍‍ LGS has been management strategies, including clinical findings, findings in imaging regarded as refractory to medical AEDs and a ketogenic diet; (2) daily studies, seizure outcomes of surgery, treatment, including treatment with disabling seizures (generalized and developmental outcomes were ’ various new antiepileptic drugs tonic, tonic-clonic, or clonic), with collected. Seizure outcomes were (AEDs), altered diet, vagal generalized convulsions and/or assessed on the basis of caregivers stimulation,– palliative surgery (such myoclonic or atonic seizures mixed reports and seizure diaries at each as corpus callosotomy), and resective 2,4​ 10 with atypical absences or epileptic scheduled visit according to the Engel surgery ‍‍ ; experience with 14 spasms; (3) typical EEG features Epilepsy Surgery Outcome Scale. resective surgery is limited because – with GSSW and/or GPFA; and (4) of the small number of patients Presurgical evaluation included 11 13 cognitive decline after seizure onset. and short follow-up periods. ‍‍ long-term video EEG monitoring, We presumed focal abnormalities LGS exhibits diverse etiologies, high-resolution MRI with a to be present in patients who from genetic and/or metabolic to specific epilepsy protocol, structural causes with destructive had the following: (1) persistent 18-fluorodeoxyglucose positron lesions or cortical malformations. focal polymorphic slow waves, (2) emission tomography (18-FDGPET) Predominantly, LGS exhibits bilateral frequent focal rhythmic slow sharp scans, and interictal single-photon and diffuse epileptic foci; however, and waves, and/or (3) frequent focal emission computed tomography unilateral diffuse and localized interictal epileptiform discharges >3 (SPECT) according to feasibility. epileptic pathology are also observed. times those from the other side and/ The decision-making process for Patients with focal epileptogenic or areas of the brain in long-term performing the surgery is shown regions have been subjected to EEG recordings. We conducted visual in a flow diagram (Fig 1). There resective surgery, which seems– analyses of the long-term EEGs of were 27 patients with previous corpus callosotomy, 3 with corpus promising in terms of seizure11 13 and patients and focused on interictal developmental outcomes. ‍‍ focal abnormalities other than callosotomy after resective surgery, and 9 with We examined the case patients with generalized epileptiform discharges. (4 before and 5 after). With the LGS who had resective surgery to With the exception of generalized exception of those who underwent evaluate seizure and developmental epileptiform discharge, asymmetries corpus callosotomies and vagus nerve outcomes in a more extended that were quantitatively assessed stimulation, 10 underwent repeated follow-up period than in our previous >3 times in frequency were deemed 13 resective . Histopathologic study. to exhibit asymmetries when these examinations were completed METHODS focal abnormalities were localized in “ ” according to the International a certain area, and we decided to call Patients League Against Epilepsy and Palmini these features focal abnormalities. 15,16​ Seizureclassifications and Neurodevelopmental. ‍ We included patients of older age Outcomes with LGS who showed GSSW and/ We retrospectively reviewed the or GPFA in the course of disease medical records of 90 patients progression in serial EEGs, although with LGS who underwent resective Seizure outcome was assessed by ’ well-formed GSSW and/or GPFA was surgery from 2003 to 2014 at using Engel classification at the last absent at the time of surgery. The Severance Children s Hospital. follow-up visit after a minimum of LGS is characterized by the clinical exclusion criteria were as follows: 3 years, with a median duration of – triad of the following: (1) multiple (1) progressive, degenerative 7.6 years (interquartile range [IQR]; types of generalized seizures, neurologic disorders other than 5.7 10.9 years). In repeated surgery including generalized tonic, atonic, epileptic encephalopathy; (2) proven cases, seizure outcome was assessed and myoclonic seizures as well metabolic disorders, including as the outcome of the final seizure as atypical absences and spasms; mitochondrial cytopathy; (3) only after the last resective surgery. Global (2) generalized slow spike-and- nonmotor seizures or epileptic adaptive behavior functioning and wave (GSSW) discharges and/or spasms; and (4) electroclinical social competence skills, including generalized paroxysmal fast activities syndromes other than LGS. The communication, general self-help (GPFAs) on EEG; and (3) progressive clinical profiles of the patients are ability, locomotion, occupation, developmental regression after the shown in Table 1. self-direction, self-help eating and/ Downloaded from www.aappublications.org/news by guest on September 28, 2021 2 KANG et al TABLE 1 Patient Profiles Result patients, which was concordant Sex, n (%) with the resective areas (Table 1). Male 61 (67.8) Generalized epileptiform discharges, Female 29 (32.2) Onset of seizure, y, median (IQR) 1.0 (0.3–3.0) such as GSSWs and GPFAs, were Age at operation, y, median (IQR) 8.7 (6.0–11.8) observed in all patients. Focal Latent period, y, median (IQR) 6.2 (4.4–9.5) epileptiform discharges, such as Follow-up duration, y, median (IQR) 7.6 (5.7–10.9) localized paroxysmal fast activities, History of ISs, n (%) 26 (28.9) Seizure type, n (%) persistent focal sharp waves or Generalized tonic 90 (100.0) spikes, and focal rhythmic slow Other convulsive 69 (76.7) and sharp wave discharges, were Atonic 34 (37.8) observed in 77 patients (77.8%). Myoclonic 28 (31.1) The EEGs of all patients revealed Atypical absence 20 (22.2) generalized electrographic seizures, Focal 16 (17.8) Epileptic spasm 14 (15.6) and those of 22 patients (24.4%) EEG feature, n (%) revealed focal electrographic Abnormal background 90 (100.0) seizures. Persistent focal slowing 64 (63.1) Epileptiform discharges Malformations of cortical a Generalized epileptiform discharges 90 (100.0) development (MCDs) (36 patients; Focal epileptiform dischargesb 70 (77.8) 40.0%), including focal cortical Electrographic seizure Generalized seizure 90 (100.0) dysplasia (FCD), polymicrogyria, 22 (24.4) pachygyria, schizencephaly combined MRI finding, n (%) with heterotopia, and destructive Abnormal focal 70 (77.8) lesions (27 patients; 30.0%), were MCD 36 (40.0) commonly seen on MRIs. Of the 70 Destructive 27 (30.0) Tuberous sclerosis 3 (3.3) cases with abnormal MRI findings, 60 Otherc 4 (4.5) (85.7%; 66.6% of the 90 total cases) Abnormal nonfocal had unilateral focal abnormalities. Cortical atrophy 3 (3.3) 18-FDGPET scans were performed in Normal 17 (18.9) 81 patients; 56 patients (69.1%) had a GSSW discharges and GPFAs. decreased 18-fluorodeoxyglucose b Localized paroxysmal fast activities, persistent focal sharp and spike waves, and focal rhythmic slow sharp and wave discharges. uptake in the concordant hemisphere c Three dysembryoplastic neuroepithelial tumors and 1 arachnoid cyst in the right cerebellopontine angle. of the lesion. Interictal SPECT scanning was performed in 77 patients; 52 patients (67.5%) had – χ decreased blood perfusion in the or dressing, and socialization, were SPSS Statistics, IBM Corporation). “ ” – ’ t 2 concordant hemisphere of the lesion. evaluated at preoperation and 3 Mann Whitney tests, Pearson – We used the term concordant for times postoperation (<1 year, 2 3 tests, FisherP s exact tests, and tests the cases that had results that were years, and 4 6 years after surgery)17 were applied to the data to compare similar to those in the presurgical by using the Social Maturity Scale variables; < .05 was regarded as studies (EEG, MRI, positron emission in patients who had successful statisticallyStandard Protocol significant. Approvals, tomography, and SPECT). Twenty- follow-up evaluations. Registrations, and Patient Consents eight cases (31.1%) had concordant We also analyzed the relationship results in all of the investigations. between postoperative seizure Results that were concordant with The study was approved by the outcomes and preoperative clinical ’ 3 investigations were shown in 31 institutional review boards at data, including age at seizure onset, cases (34.4%), and results that were Severance Children s Hospital. age at the time of surgery, duration of concordant with 2 investigations RESULTS epilepsy before surgery, seizure type, were shown in 22 cases (24.4%). In presurgical MRI findings, and type of EEG, MRI, and Other Imaging Studies more than one-half of the cases, at Statisticalsurgery. Analyses Outcomeleast 3 test of results Surgery were concordant.

The EEGs of 90 patients revealed Statistical analysis was conducted slow and disorganized backgrounds Overall, 45 patients (50.0%) by using SPSS version 20.0 (IBM and persistent focal slowing in 64 achieved seizure-free status after Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 142, number 4, October 2018 3 FIGURE 1 Flow diagram of approaching patients with LGS for resective surgery. PET, positron emission tomography.

± resective surgery in the mean hemispherotomy group and 30 of posterior quadrantectomy (4 seizure follow-up period of 6.1 2.2 years theP 69 patients (43.5%) in the single- free; 66.7%), 4 underwent temporo- (Table 2). The MRIs of 20 patients and multilobar resection groups occipital lobectomy (4 seizure free; revealed no focal lesions, and of ( = .022) became seizure free (Engel 100.0%), 3 underwent parieto- these, 8 (40.0%) were seizure free class I). In the multilobar resection occipital lobectomy (2 seizure after surgery. Of the different types group, 9 case patients underwent free; 66.6%), 2 underwent of surgeries, hemispherotomy subtotal hemispherotomy (3 frontoparietal corticectomy (none resulted in the most favorable seizure free; 33.3%), 26 underwent were seizure free), and 1 underwent outcome in seizure control; 15 frontotemporal lobectomy (10 multiple tubectomy (none were of the 21 patients (71.4%) in the seizure free; 38.5%), 6 underwent seizure free). Downloaded from www.aappublications.org/news by guest on September 28, 2021 4 KANG et al TABLE 2 Outcome of Surgery by Engel Classification According to Surgery Type, Concordance, and Latent Period Class I, n (%) Class II, n (%) Class III, n Class IV, n (%) Total, n (%) were noted. There was no statistical (%) difference between the pathologic Surgery type (P < .05) findingsOutcomes and of surgery Adaptive outcomes. Behavior Functioning and Social Competence Hemispherotomy 15 (71.4) 1 (4.8) 2 (9.5) 3 (14.3) 21 (100.0) Lobar resection 30 (43.5) 7 (10.1) 5 (7.2) 27 (39.1) 69 (100.0) Single lobar 7 (38.9) 2 (11.1) 1 (5.6) 8 (44.4) 18 (100.0) a Multilobar 23 (45.1) 5 (9.8) 4 (7.8) 19 (37.3) 51 (100.0) The lead time from seizure onset to Concordance (P < .01) surgery was inversely correlated with >2 45 (55.6) 8 (9.9) 5 (6.2) 23 (28.3) 81 (100.0) All 16 (57.1) 5 (17.9) 0 (0.0) 7 (25.0) 28 (100.0) the presurgical adaptiveP function as 3 17 (54.8) 3 (9.7) 1 (3.2) 10 (32.3) 31 (100.0) a social quotient (SQ) when using the 2 12 (54.5) 0 (0.0) 4 (18.2) 6 (27.3) 22 (100.0) Social Maturity Scale ( = .037; Fig 1 0 (0.0) 0 (0.0) 2 (22.2) 7 (77.8) 9 (100.0) 2). The SQ level in the seizure-free Latent period (P > .05) group was significantly higher than Within 5 y 20 (62.5) 3 (9.4) 1 (3.1) 8 (25.0) 32 (100.0) – 5–10 y 16 (47.1) 3 (8.8) 1 (2.9) 14 (41.2) 34 (100.0) in the seizure-persistentP group at the >10 y 9 (37.5) 2 (8.3) 5 (20.8) 8 (33.3) 24 (100.0) second (short-term follow-up; 2 3 – Total 45 (50.0) 8 (8.9) 7 (7.8) 30 (33.3) 90 (100.0) years after surgery;P = .022) and Pearson χ2 and Fisher’s exact tests were used as appropriate. third (long-term follow-up; 4 6 years a Nine subtotal hemispherectomies, 26 frontotemporal lobectomies, 6 posterior quadrantectomies, 4 temporo-occipital after surgery; = .001) follow-up lobectomies, 3 parieto-occipital lobectomies, 2 frontoparietal cortisectomies, and 1 multiple tubectomy. evaluations after surgery (Fig 3). No significant differences were found at the baseline presurgical evaluation Of the 28 patients with localized (46.9%). Patients with a history of ISs and first follow-up evaluation after surgery (within 1 year after surgery). and concordant findings on EEG, had a higher seizure-free rate, although ± MRI, positron emission tomography, this was not statistically significant. Presurgical and postsurgical evaluation and SPECT, 16 (57.1%) achieved results for the SQ level (mean SD) By 2009, 44 case patients underwent ± seizure-free status. Of the 9 patients in the seizure-free versus seizure- surgery, and 46 underwent surgery ± with discordant findings, none persistent groups are as follows: 42.0 after 2010. In both periods, seizure- ± ± became seizure free. The patients 20.5 vs 36.3 22.2 in the presurgical free status was observed in 50% of ± ± with >2 concordant findings in the state, 44.0 22.9 vs 38.2 17.7 at the Pathologicthe cases. Findings first follow-up, 46.3 22.4 vs 31.6 presurgicalP studies were more likely ± ± to achieve seizure-free status after 19.3 at the second follow-up, and surgery ( = .003). Patients with focal 45.3 28.0 vs 22.3 16.0 at the third The pathology of the suspected follow-up. In patients with persistent MRI findings had a higher seizure-P free rate (52.9%) than those with lesions was examined in 80 seizures, the SQ was significantly reduced at the third follow-up nonfocal findings (40.0%; = .016). patients who underwent surgery; ± ± ± 10 patients were not examined Pcompared with the presurgical state An early latent period from seizure because of hemispherotomy. MCD (mean SD: 36.3 22.2 vs 22.3 16.0; onset to surgery revealed a tendencyP was the most common finding and = .002), whereas the SQ scores were of favorable surgery outcome but was was found in 57 patients (63.3%). maintainedNumbers of in AEDs seizure-free cases. not statistically significant ( = .113). FCD types I, II, and III (according to Twenty of 32 patients (62.5%) who the International League Against 15 – underwent surgery within 5 years Epilepsy classification ) were The number of AEDs was reduced from – P of seizure onset achieved seizure- noted in 6 (6.7%), 20 (22.2%), and 5.1 (range: 1 11) before surgery to 2.9 free status. Of 24 patients who had 4 (4.4%) patients, respectively; (range: 0 7) after surgery ( < .05). surgery after 10 yearsP from seizure mild MCD according16 to the Palmini In patients with seizure-free status, onset, only 9 (37.5%) were seizure classification was noted in 27 4.2 anticonvulsants were used before free after surgery ( = .056). Only patients (30.0%). Other findings were surgery and decreased to 1.6 after minor bleeding was observed in gliosis (12 cases), tuberous sclerosis surgery. In patients with persistent some cases during surgery without (3 cases), leukomalacia (3 cases), seizures, 5.9 AEDs were used before fatal complications. dysembryoplastic neuroepithelial surgery and decreased to 4.2 after There were 26 patients with a history tumor (1 case), and nonspecific surgery. In patients with Engel class of infantile spasms (ISs), and 15 of findings (4 cases). Of the 20 cases with IV, 6.4 AEDs were used before surgery these became seizure free (57.7%). MRI-negative results, FCD in 8 cases, but decreased to 4.4 after surgery. In Of the 64 patients with no history of MCD in 5 cases, gliosis in 4 cases, 45 patients with seizure-free status, 14 ISs, 30 achieved seizure-free status and nonspecific findings in 3 cases discontinued using AEDs. Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 142, number 4, October 2018 5 EEG Findings After Surgery

There was a difference between seizure-free patients and patients with persistent seizures with respect to the last postoperative EEG (Table 3). Focal slowing and GPFA were more common in seizure- free patients than in patients with persistent seizures, but there were no statistical differences. GSSW remained more common inP patients with persistent seizures (80%) and had statistical differences ( < .05). Focal epileptiform discharges were more frequently absent in seizure-freeP patients (70%), and this difference was statistically significant ( < .05). DISCUSSION

FIGURE 2 Correlation of the SQ and lead time from seizure onset to surgery (latent). The lead time from seizure LGS is 1 of the most severe forms1, of2​ onset to surgery was inversely correlated with the presurgical adaptive function as an SQ via the intractable childhood . ‍ In Vineland Social Maturity Scale (n = 83; P = .037). general, the remission of seizures with

anticonvulsants in the natural2,9,​ course18​ of LGS is known to be <10%. ‍ For patients with LGS with focal epileptic pathology, resective surgery has been regarded– as an important

management strategy11 13 for freedom from seizures. ‍ ‍ Our previous study of 27 cases revealed 59.3% of seizure-free ± outcomes with a mean duration of follow-up of 33.1 months (SD: 20.3 months). In this study, we observed long-term, seizure-free outcomes after resective surgery in patients with LGS at a 50.0% ± rate in 90 patients with a follow-up duration of 73.2 months (SD: 26.4 months). This long-term outcome with an extended follow-up duration in a large number of patients was comparable to the findings in our previous study, which revealed that FIGURE 3 a seizure-free outcome is expected Comparison of the serial SQ after resective surgery according to the surgery outcome. a The level of SQ in the seizure-free group was significantly higher than in the seizure-persistent group at the to be maintained for a prolonged b follow-up evaluations between 2 and 3 years after surgery (P = .022). The level of SQ in the seizure- period12 of time. In the study of Liu free group was significantly higher than in the seizure-persistent group at the follow-up evaluations et al,​ 7 of 18 patients with LGS between 4 and 6 years after surgery (P = .001). Adaptive function as an SQ was evaluated by using (38.9%) obtained seizure-free status the Vineland Social Maturity Scale. after resective surgery. This study involved observations for at least 1 year and up to 9 years. In a study by

Downloaded from www.aappublications.org/news by guest on September 28, 2021 6 KANG et al TABLE 3 Last EEG Findings After Surgery Seizure Free Seizures Persist Total P 24 patterns. GSSW disappeared more Focal slowing .274 frequently in seizure-free patients, None 19 (57.6) 14 (42.4) 33 (100.0) which is related to the prognosis of Persist 26 (45.6) 31 (54.4) 57 (100.0) GSSWs .011* seizures. This may render superior None 42 (56.0) 33 (44.0) 75 (100.0) cognitive abilities in seizure-free Persist 3 (20.0) 12 (80.0) 15 (100.0) patients rather than in patients GPFAs .134 with persistent seizures. Focal None 41 (53.2) 36 (46.8) 77 (100.0) epileptiform discharge still persisted Persist 4 (30.8) 9 (69.2) 13 (100.0) Focal epileptiform discharges .043* in 70 patients but was more often None 14 (70.0) 6 (30.0) 20 (100.0) absent in seizure-free patients. This Persist 31 (44.3) 39 (55.7) 70 (100.0) can also affect cognition. In addition, * P < .05. the number of AEDs that were taken after surgery was reduced, which can be thought of as a result of the 19 improvement of the EEG. Kang et al,​ 73.3% (22 of 30) of the findingsP in the investigations was patients with IS and FCD achieved related to better surgical prognosis LGS is accompanied by2 a characteristic seizure-free status after resective ( = .003). When all presurgical developmental delay. We found that surgery. IS and LGS are common investigations had the same a shorter latent period from seizure ; however, higher localization, 57.1% of the patients onset to surgery led to a better level of seizure-free rates were observed in became seizure free. In contrast, in adaptive behavioral functioning similar19 IS, probably because the study was case of discordant results, none of to that found in patients with ISs. restricted to IS patients with FCD. the 9 patients became seizure free. Thus, it could also be associated with Similarly, authors of other studies Patients with single- and multilobar better seizure outcomes; early surgery have also reported that higher after seizure onset was associated resection achieved significantly lower concordance rates correspond to seizure-free rates than those with 21,22​ with a favorable outcome of seizure better surgical outcome. ‍ Patients control in our study, although this was hemispherectomies. The seizure-free with focal MRI findings had a rate in those with hemispherotomy in not statistically significant. It would significantly higherP seizure-free rate be useful to study the effect of surgery LGS (71.4%) is higher20 than with other (52.9%) than those with nonfocal types of surgery. Our cases also had on the neurocognitive and motor findings (40.0%; = .016). The outcomes of patients. Unfortunately, better surgical outcomes with wider positivity of MRI lesion result is 1 of resection. Wider resection in epilepsy it was difficult to determine the IQ for the important23 factors for a successful most patients with mental retardation surgery is important for success of surgery. Along with the MRI results, the operation, which implicates that and LGS. Thus, adaptive function the localization of epileptic focus can was used as the outcome measure in the epileptogenic cortex is wider in be achieved with an 18-FDGPET scan distribution than what is estimated this study. Despite the small number or SPECT to increase the postsurgical of cases, there was a statistically in multimodal diagnostic studies. seizure-free rate. Resective surgery The seizure-free rate in multilobar significant difference in the level should be carefully considered of adaptive behavioral functioning resection was higher than in single- – in cases that are discordant from22, 23​ between the seizure-free and seizure- lobar resection, although there was multimodal diagnostic findings. – no statistical difference. An undefined persistent group at the within-2-to-3 epileptogenic zone should be a Changes in EEG results after surgery and 4-to-6 year follow-up. There was, concern for the surgery. are also notable. All the patients however, no significant improvement showed GSSW and/or GPFA in the in adaptive functioning between the Another prognostic factor that EEGs that were performed before presurgical evaluation and the first influences surgical outcome is surgery. In the last EEG performed year of follow-up in both the seizure- the degree of concordance in the after surgery, GSSW disappeared free and seizure-persistent groups. preoperative investigations, which in 75 cases, and GPFA disappeared Follow-up for a longer period, and in a include long-term video EEG in 77 cases. It can be expected that higher number of cases, is required to monitoring, MRI, 18-FDGPET, and abnormal epileptiform discharges determine long-term improvements SPECT. MRI scanning was performed will be resolved because of the in adaptive functioning. Although it in all patients, and 18-FDGPET and resection of the primary foci. This is difficult to reach an average range SPECT were performed in 81 and means that physicians should of adaptive functioning after surgery, 77 patients, respectively. A higher consider the surgical treatment effective surgery can preserve the degree of anatomic matching in the option despite generalized EEG baseline level in patients with LGS Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 142, number 4, October 2018 7 CONCLUSIONS ABBREVIATIONS (ie, without further deterioration), whereas a gradual improvement can be Early and intensive investigations 18-FDGPET: 18-fluorodeoxyglu - expected in the seizure-free patients. to determine underlying focal cose positron Thus, early surgery can lead to a better etiology are important for deciding emission prognosis in adaptive functioning surgical candidates, and careful tomography and help improve the quality25 of life of preoperative investigations can be AED: antiepileptic drug patients and their families. used to steer the course of LGS in FCD: focal cortical dysplasia There are some limitations of our patients toward seizure-free status GPFA: generalized paroxysmal study. There is no control group and better outcomes in adaptive fast activity without surgery with a 2-year functioning and social competence. GSSW: generalized slow follow-up; although a comparison Resective surgery should be spike-and-wave with this group is preferable, the actively used to treat patients with IQR: interquartile range caregivers, who did not undergo LGS with suspected focal epileptic IS: infantile spasm surgery, did not agree to undergo pathology. LGS: Lennox-Gastaut syndrome neurocognitive tests. The patient MCD: malformation of cortical cohort is also heterogeneous; in fact, ACKNOWLEDGMENT development the etiologies and age distribution SPECT: single-photon emission for patients with LGS is extremely computed tomography varied. The patient group would be We thank Dr In Sun Kwon for the SQ: social quotient extremely small if we had divided statistical analysis of the data in the patients according to etiology or age. article.

Address correspondence to Heung Dong Kim, MD, PhD, Division of Pediatric Neurology, Department of Pediatrics, Pediatric Epilepsy Clinic, Severance Children’s Hospital, Epilepsy Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Supported by the National Research Foundation of Korea (grant NRF-2012R1A2A2A01012608) funded by the Government of South Korea. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

REFERENCES 1. Arzimanoglou A, French J, Blume WT, 5. Carmant L, Whiting S. Lennox-Gastaut ketogenic diets and vagus nerve et al. Lennox-Gastaut syndrome: a syndrome: an update on treatment. stimulation. Epilepsia. 2014;55(suppl consensus approach on diagnosis, Can J Neurol Sci. 2012;39(6):702–711 4):29–33 assessment, management, and 6. Hancock EC, Cross HH. Treatment of 11. Douglass LM, Salpekar J. Surgical trial methodology. Lancet Neurol. Lennox-Gastaut syndrome. Cochrane options for patients with Lennox- 2009;8(1):82 93 – Database Syst Rev. 2009;(3):CD003277 Gastaut syndrome. Epilepsia. 2. Camfield PR. Definition and natural 2014;55(suppl 4):21 28 7. Michoulas A, Farrell K. Medical – history of Lennox-Gastaut syndrome. management of Lennox- 12. Liu SY, An N, Fang X, et al. Epilepsia. 2011;52(suppl 5):3 9 – Gastaut syndrome. CNS Drugs. Surgical treatment of patients 3. Archer JS, Warren AE, Jackson GD, 2010;24(5):363–374 with Lennox-Gastaut syndrome Abbott DF. Conceptualizing Lennox- phenotype. Scientific World Journal. 8. Cross JH. The ketogenic diet in Gastaut syndrome as a secondary 2012;2012:614263 the treatment of Lennox-Gastaut network epilepsy. Front Neurol. syndrome. Dev Med Child Neurol. 13. Lee YJ, Kang HC, Lee JS, et al. Resective 2014;5:225 2012;54(5):394–395 pediatric epilepsy surgery in Lennox- 4. Kwan P, Arzimanoglou A, Berg AT, Gastaut syndrome. Pediatrics. 9. Montouris GD. Rational approach to et al. Definition of drug resistant 2010;125(1). Available at: www.​pediatrics.​ treatment options for Lennox-Gastaut epilepsy: consensus proposal by org/cgi/​ content/​ full/​ 125/​ 1/​ e58​ syndrome. Epilepsia. 2011;52(suppl the ad hoc Task Force of the ILAE 5):10 20 14. Engel J Jr. Epilepsy surgery. Curr Opin Commission on Therapeutic Strategies – Neurol. 1994;7(2):140 147 [published correction appears in 10. Kossoff EH, Shields WD. – Epilepsia. 2010;51(9):1922]. Epilepsia. Nonpharmacologic care for patients 15. Blümcke I, Thom M, Aronica E, et al. 2010;51(6):1069–1077 with Lennox-Gastaut syndrome: The clinicopathologic spectrum of

Downloaded from www.aappublications.org/news by guest on September 28, 2021 8 KANG et al focal cortical dysplasias: a consensus pharmacologic treatment options 22. Seo JH, Holland K, Rose D, et al. classification proposed by an ad hoc for Lennox-Gastaut syndrome Multimodality imaging in the Task Force of the ILAE Diagnostic [published correction appears in surgical treatment of children with Methods Commission. Epilepsia. Epilepsia. 2015;56(6):984]. Epilepsia. nonlesional epilepsy. Neurology. 2011;52(1):158–174 2014;55(suppl 4):10–20 2011;76(1):41–48 16. Palmini A, Najm I, Avanzini G, et al. 19. Kang JW, Rhie SK, Yu R, et al. Seizure 23. Arya R, Leach JL, Horn PS, et al. Clinical Terminology and classification of outcome of infantile spasms with factors predict surgical outcomes in the cortical dysplasias. Neurology. focal cortical dysplasia. Brain Dev. pediatric MRI-negative drug-resistant 2004;62(6, suppl 3):S2–S8 2013;35(8):816–820 epilepsy. Seizure. 2016;41:56–61 17. Gould J. The use of the Vineland Social 20. Griessenauer CJ, Salam S, Hendrix P, 24. Wyllie E, Lachhwani DK, Gupta A, et al. Maturity Scale, the Merrill-Palmer et al. for treatment Successful surgery for epilepsy Scale of mental tests (non-verbal of refractory epilepsy in the pediatric due to early brain lesions despite items) and the Reynell Developmental age group: a systematic review. generalized EEG findings. Neurology. Language Scales with children in J Neurosurg Pediatr. 2015;15(1):34–44 2007;69(4):389–397 contact with the services for severe 21. Pittau F, Grouiller F, Spinelli L, Seeck 25. Perry MS, Duchowny M. Surgical mental retardation. J Ment Defic Res. M, Michel CM, Vulliemoz S. The role versus medical treatment for 1977;21(3):213–226 of functional in pre- refractory epilepsy: outcomes 18. Montouris GD, Wheless JW, Glauser surgical epilepsy evaluation. Front beyond seizure control. Epilepsia. TA. The efficacy and tolerability of Neurol. 2014;5:31 2013;54(12):2060–2070

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Downloaded from www.aappublications.org/news by guest on September 28, 2021 Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut Syndrome Joon Won Kang, Soyong Eom, William Hong, Hye Eun Kwon, Soyoung Park, Ara Ko, Hoon-Chul Kang, Joon Soo Lee, Young-Mock Lee, Dong Seok Kim and Heung Dong Kim Pediatrics 2018;142; DOI: 10.1542/peds.2018-0449 originally published online September 7, 2018;

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