Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

[Current Position of Callosotomy].

Callosotomy is widely used today as a treatment option for medically refractory epilepsy in patients with generalized or unknown-onset seizures. Other surgical indications include bilaterally distributed, most often synchronous, epileptiform discharges on EEG and some epilepsy syndromes, including Lennox-Gastaut syndrome and infantile spasms/West syndrome. Patients with drop attacks, mainly caused by epileptic spasms or atonic seizures, are most likely to benefit from this procedure. A more favorable seizure outcome was observed after a one-stage total callosal section in pediatric patients. For older children and adults, anterior callosotomy should initially be applied, and staged complete sections should be considered if the seizure outcome is insufficient. In terms of complications, most surgically associated brain and vascular injuries are avoidable in this era of microsurgery, and some less invasive newer methods, including endoscopic and stereotactic methods, are being explored. Disconnection syndrome is an unavoidable condition. However, it is usually transient in most cases and does not outweigh the improvement in symptoms of epilepsy in most patients, particularly in children who have compensatory functions or plasticity of the developing brain.

Evolución clínica, cognitiva y calidad de vida posquirúrgica en un caso con síndrome de Lennox Gastaut / Clinical and Cognitive Evolution and Postoperative Quality of Life in a Case with Lennox Gastaut Syndrome

Introducción: El síndrome de Lennox Gastaut se considera una encefalopatía epiléptica. Las anomalías epileptiformes en este síndrome contribuyen a la discapacidad intelectual gradual, a las comorbilidades psiquiátricas y alteraciones conductuales. En la práctica clínica aparecen atipicidades del síndrome, con focalización funcional cuyo tratamiento constituye un desafío. Objetivo: Describir la evolución clínica, cognitiva y calidad de vida en un caso con síndrome de Lennox Gastaut antes, y después del tratamiento quirúrgico. Presentación del caso: Paciente masculino de 16 años con síndrome de Lennox Gastaut. Se revisó la historia clínica y se tomaron en consideración, los resultados del video-electroencefalograma, de la resonancia magnética nuclear y de la tomografía computarizada por emisión de fotón único. Se evaluó, además, el proceder quirúrgico, la evaluación clínica y neuropsicológica. Se realizó una descripción cualitativa de la evolución del paciente a los 6 meses y al año de la intervención quirúrgica. Conclusiones: el paciente con síndrome de Lennox Gastaut presentó una evolución favorable después del tratamiento quirúrgico, lo cual se reflejó en una disminución en la frecuencia de las crisis. mejoría cognitiva, conductual y mejor calidad de vida(AU)

Introduction: Lennox Gastaut syndrome is considered an epileptic encephalopathy. Epileptiform abnormalities in this syndrome contribute to gradual intellectual disability, psychiatric comorbidities and behavioral disturbances. In clinical practice, atypicalities of the syndrome appear with functional focalization whose treatment constitutes a challenge. Objective: To describe the clinical and cognitive evolution and quality of life in a case with Lennox Gastaut syndrome before and after surgical treatment. Case presentation: A 16-year-old male patient with Lennox Gastaut syndrome. The clinical history was reviewed and the results of the video-electroencephalogram, nuclear magnetic resonance and single photon emission computed tomography were taken into consideration. The surgical procedure, clinical and neuropsychological evaluation were also evaluated. A qualitative description of the patient's evolution past 6 months and one year after surgery was prepared. Conclusions: the patient with Lennox Gastaut syndrome has a favorable evolution after surgical treatment, which is reflected in a decrease in seizure frequency, cognitive and behavioral improvement and better quality of life(AU)

Efficacy and safety of corpus callosotomy versus vagus nerve stimulation as long-term adjunctive therapies in children with Lennox-Gastaut syndrome: Experience of a tertiary care center.

OBJECTIVES: To compare the efficacy and safety of corpus callosotomy versus vagus nerve stimulation (VNS) as long-term adjunctive therapies in children with Lennox-Gastaut syndrome. METHODS: This retrospective study was conducted in King Fahad Medical City between 2010 and 2019. The authors identified and followed 9 patients with Lennox-Gastaut syndrome (LGS) who underwent corpus callosotomy or VNS implantation for at least 12 months; seizure frequency and major complications were monitored. Five patients with a mean age of 10.8±1.3 years had corpus callosotomy, and 4 patients with a mean age of 13.8±3.9 years were implanted with VNS stimulators. RESULTS: Reduction in seizure frequency was achieved in all 5 patients who underwent corpus callosotomy, with greater than 75% seizure reduction in more than 50% in one, and greater than 25% in 2 respectively. However, in those implanted with VNS, 2 (50%) patients achieved a reduction in seizure frequency of greater than 75% and 2 (50%) greater than 25%, respectively. No significant difference was observed between the 2 treatment groups. One patient who underwent corpus callosotomy suffered cerebrospinal fluid leakage, and swallowing difficulties in one patient who underwent VNS. CONCLUSION: Both corpus callosotomy and VNS are safe and effective as adjunctive treatments for LGS patients.

Endoscopic Total Corpus Callosotomy and Pan Commissurotomy for Lennox-Gastaut Syndrome.

Background: Corpus callosotomy (CC) is a major disconnection procedure that functionally isolates the cerebral hemispheres, thereby interrupting the spread of epileptic activity from one hemisphere to the other. It is extremely useful in children suffering from non-localized drug refractory epilepsy, especially drop attacks. The technique has evolved from microscopic to minimally invasive endoscopic surgery. The extent of callosotomy also varies based on the institutional practices ranging from anterior 1/3rd to total corpus callosotomies (TCC). The performance of TCC in conjunction with anterior, posterior, and hippocampal commissurotomies was described for the first time by the senior author from our institution. Objective: To describe the technique of performing endoscopic total corpus callosotomy, and pan commissurotomy using the interhemispheric corridor. Methods: A seven-year-old right-handed male child with seizure onset at the age of six months presented with three types of semiologies consisting of myoclonic jerks, frequent head drops and tonic posturing involving right upper and lower limbs with secondary generalization. Results: Video electroencephalography (VEEG) revealed diffuse slowing of the background, and slow spike and wave pattern. Generalized paroxysmal fast activity (GPFA) was noted in the VEEG, suggestive of LGS. MRI brain revealed bilateral parieto-occipital gliosis and gross brain atrophy. Ictal SPECT localized to left temporo-occipital area, while magnetoencephalography revealed bilateral temporal localization. Patient underwent TCC with pancommissurotomy. The patient was seizure-free (ILAE Class 3) at one-year follow up with no drop attacks, and significant reduction noted in other seizure types. Conclusion: Endoscopic corpus callosotomy and pan commissurotomy using the interhemispheric corridor is an elegant and minimally invasive technique best suited for appropriately selected children with refractory epilepsy.

Efficacy and safety of corpus callosotomy and ketogenic diet in children with Lennox Gastaut syndrome: a systematic review and meta-analysis.

BACKGROUND: Both corpus callosotomy (CC) and the ketogenic diet (KD) are commonly used in patients with Lennox Gastaut syndrome (LGS), as a significant proportion of these patients develop pharmacoresistant epilepsy. But no systematic review has yet compared the efficacy and safety of these two measures. METHODS: We conducted a systematic search on various databases to collating all available literature until 30th November 2020 with a primary objective to compare the efficacy of KD and CC in terms of the proportion of patients with complete seizure freedom, at least 75% and 50% reduction in seizure frequency at various time points after the institution of these modalities. We also attempted to compare the proportion and nature of adverse effects, impact on EEG, cognition, and behavior with these modalities. We only included original articles enrolling at least 10 patients with CC or KD for quantitative synthesis to determine a pooled estimate. We used a fixed or random effects model, depending on the degree of heterogeneity. RESULTS: We selected 23 and 7 articles describing the efficacy of CC and KD in 436 and 185 LGS patients out of 217 search items, but none of the studies compared directly these two entities. The indirect comparison between the pooled estimate of all patients with individual modalities revealed more patients with CC had seizure freedom, at least 75% and 50% reduction in seizure frequency (p=0.0001, 0.01, and 0.04 respectively). The proportion of patients with adverse effects was also higher for CC patients (p=0.01), although the proportion with serious adverse effects was not significantly different between the two modalities. Patients selected for CC were older, had higher seizure burden, more lag time after the onset of seizures, and received more number of antiseizure medications previously. Due to the availability of limited data, a firm conclusion could not be determined regarding the effect on EEG, cognition, and behavior with CC and KD. CONCLUSION: CC is more efficacious than KD in reducing seizure frequency in patients with LGS, although it has relatively more adverse effects during the immediate perioperative period.

The role of surgery in the management of Lennox-Gastaut syndrome: A systematic review and meta-analysis of the clinical evidence.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood onset epilepsy in which patients require multiple medications and may be candidates for palliative surgical intervention. In this meta-analysis, we sought to evaluate the impact of palliative vagus nerve stimulation (VNS), corpus callosotomy (CC), and resective surgery (RS) by analyzing their impact on seizure control, antiepileptic drug (AED) usage, quality of life (QOL), behavior, cognition, prognostic factors, and complications. A systematic search of PubMed MEDLINE, Scopus, and Cochrane Database of Systematic Reviews was performed to find articles that met the following criteria: (1) prospective/retrospective study with original data, (2) at least one LGS surgery patient aged less than 18 years, and (3) information on seizure frequency reduction (measured as percentage, Engel class, or qualitative comment). Seizures were analyzed quantitatively in a meta-analysis of proportions and a random-effects model, whereas other outcomes were analyzed qualitatively. Forty studies with 892 LGS patients met the selection criteria, with 19 reporting on CC, 17 on VNS, four on RS, two on RS + CC, one on CC + VNS, and one on deep brain stimulation. CC seizure reduction rate was 74.1% (95% confidence interval [CI] = 64.5%-83.7%), and VNS was 54.6% (95% CI = 42.9%-66.3%), which was significantly different (p < .001). RS seizure reduction was 88.9% (95% CI = 66.1%-99.7%). Many VNS patients reported alertness improvements, and most had no major complications. VNS was most effective for atonic/tonic seizures; higher stimulation settings correlated with better outcomes. CC patients reported moderate cognitive and QOL improvements; disconnection syndrome, transient weakness, and respiratory complications were noted. Greater callosotomy extent correlated with better outcomes. AED usage most often did not change after surgery. RS showed considerable QOL improvements for patients with localized seizure foci. In the reported literature, CC appeared to be more effective than VNS for seizure reduction. VNS may provide a similar or higher level of QOL improvement with lower aggregate risk of complications. Patient selection, anatomy, and seizure type will inform decision-making.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome.

OBJECTIVE: We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. METHODS: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. RESULTS: GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5-0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3 Hz) frequency band. For alpha (8-12 Hz) and beta (13-30 Hz) frequencies, PTE was greatest 1-0.5 seconds before GPFA onset. SIGNIFICANCE: Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG-functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

Stereotactic laser anterior corpus callosotomy for Lennox-Gastaut syndrome.

OBJECTIVE: Corpus callosotomy is an effective palliative treatment for drug-resistant Lennox-Gastaut syndrome (LGS). Laser interstitial thermal therapy has been increasingly used in the treatment of epilepsy. Here, we assess the safety and effectiveness of minimally invasive stereotactic laser anterior corpus callosotomy (SLACC) for drop attacks in LGS. METHODS: We reviewed sequential cases of patients with medically intractable LGS who underwent SLACC using a two-cannula technique between November 2014 and July 2019. Pre- and postoperative magnetic resonance imaging was used to measure the anteroposterior length of callosal ablation (contrast-enhancing lesion) and estimated disconnection (gap in tract projections on diffusion tensor imaging). Patients were followed longitudinally to assess clinical outcomes. RESULTS: Ten patients were included in this study. The median age was 33 (range = 11-52) years, median duration of epilepsy was 26 (range = 10-49) years, and median duration of postoperative follow-up was 19 (range = 6-40) months. In the anteroposterior direction, 53 ± 7% (mean ± SD) of the corpus callosum was ablated and 62 ± 19% of the corpus callosum was estimated to be disconnected. Six (60%) of 10 patients achieved >80% seizure reduction, two (20%) of whom became seizure-free. Eight (80%) patients had >80% reduction in drop attacks, five (50%) of whom became free of drop attacks. Three patients subsequently underwent laser posterior callosotomy with further improvement in drop attacks and/or overall seizure frequency. One patient had an asymptomatic intracerebral hemorrhage along the cannula tract. One patient developed significant aggression after becoming seizure-free. SIGNIFICANCE: Seizure outcomes following SLACC were comparable to previously reported outcomes of open callosotomy, with reasonable safety profile. SLACC appears to be an effective alternative to open anterior corpus callosotomy with minimal postoperative discomfort and a short recovery period.

Dexmedetomidine for Electrocorticography in Patients With Lennox-Gastaut Syndrome Presenting for Epilepsy Surgery: A Case Report.

We report the anesthetic management of 2 patients with Lennox-Gastaut syndrome presenting for respective epilepsy surgery with intraoperative electrocorticography. Electrocorticography is a useful tool to guide the localization of the epileptogenic focus for surgical resection in epilepsy surgery. Drug interactions, proconvulsant or anticonvulsant activity of the anesthetics, and anesthetic influence on intraoperative electrocorticography are the primary concerns to be addressed in these patients. We observed that dexmedetomidine-based anesthesia facilitates intraoperative electrocorticography monitoring. Dexmedetomidine, by decreasing the requirements of other anesthetic agents, offers better recovery profile and pain relief with minimal respiratory depression in patients undergoing disconnective epilepsy surgeries.

Interstitial Stereotactic Laser Anterior Corpus Callosotomy: A Report of 2 Cases with Operative Technique and Effectiveness.

BACKGROUND AND IMPORTANCE: Corpus callosotomy is an effective palliative treatment for medically intractable Lennox-Gastaut syndrome (LGS) that disrupts the interhemispheric synchronization of epileptiform discharges. However, traditional open corpus callosotomy carries a significant risk of surgical complications associated with craniotomy and a parafalcine approach to the corpus callosum. Here, we report 2 cases of anterior corpus callosotomy using MRI-guided stereotactic laser interstitial thermal therapy (LITT) as a minimally invasive technique for mitigating the risks of craniotomy while achieving favorable outcomes. CLINICAL PRESENTATION: Two patients with medically intractable LGS underwent stereotactic laser anterior corpus callosotomy using a 2 laser-fiber approach. Ablation of 70%-80% of the corpus callosum was confirmed by postoperative MRI diffusion tensor imaging and volumetric analysis. Marked reduction of epileptiform activity was observed in both patients during postoperative video-EEG studies as compared to preoperative video-EEG studies. Freedom from disabling seizures including drop attacks was achieved in 1 patient for 18 mo, and more than a 90% reduction of disabling seizures was achieved in the other patient for 7 mo with cognitive improvement and without surgical complications. CONCLUSION: These early data demonstrate the technical feasibility, safety, and favorable outcomes of MRI-guided stereotactic laser anterior corpus callosotomy in patients with LGS, making it a potentially safe and effective alternative to traditional open corpus callosotomy and other stereotactic methods including radiofrequency ablation and radiosurgery due to the ability to monitor the ablation in real time with MRI.

Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut Syndrome.

OBJECTIVE: We aimed to evaluate the long-term outcome of resective epilepsy surgery in patients with Lennox-Gastaut syndrome (LGS). METHODS: 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 a minimum period of 2 years. RESULTS: 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 seizure 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 seizures, 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 and social competence than did patients with persistent seizures at the second (2-3 years after surgery) and third (4-6 years after surgery) follow-ups, as indicated by social quotients (P < .05). CONCLUSIONS: 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.

Anterior two-thirds corpus callosotomy via stereotactic laser ablation.

Anterior two-thirds corpus callosotomy is a common palliative surgical intervention most commonly employed in patients with atonic or drop seizures. Recently, stereotactic laser ablation of the corpus callosum without a craniotomy has shown promise in achieving similar outcomes with fewer side effects and shorter hospitalizations. The authors demonstrate ablation of the anterior two-thirds corpus callosum in a patient with Lennox-Gastaut syndrome and drug-resistant drop seizures. Technical nuances of laser ablation with 3 laser fibers are described. Postoperatively, the patient showed a significant reduction in seizure frequency and severity over a 9-month follow-up period. The video can be found here: https://youtu.be/3-mMq5-PLiM .

Changes in functional brain network topology after successful and unsuccessful corpus callosotomy for Lennox-Gastaut Syndrome.

Corpus callosotomy (CC) is an effective palliative surgical treatment for patients with Lennox-Gastaut Syndrome (LGS). However, research on the long-term functional effects of CC is sparse. We aimed to investigate these effects and their associated clinical conditions over the two years after CC. Long-term clinical EEG recordings of 30 patients with LGS who had good and bad seizure outcome after CC were collected and retrospectively studied. It was found that CC caused brain network 'hubs' to shift from paramedian to lateral regions in the good-recovery group, which reorganized the brain network into a more homogeneous state. We also found increased local clustering coefficients in patients with bad outcomes and decreases, implying enhanced network integration, in patients with good outcomes. The small worldness of brain networks in patients with good outcomes increased in the two years after CC, whereas it decreased in patients with bad outcomes. The covariation of small-worldness with the rate of reduction in seizure frequency suggests that this can be used as an indicator of CC outcome. Local and global network changes during the long-term state might be associated with the postoperative recovery process and could serve as indicators for CC outcome and long-term LGS recovery.

Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome.

We previously observed that adults with Lennox-Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small-world network organization and node-wise strength; and (2) seed-based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG-fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small-world organization, stronger connectivity in subcortical structures, and greater within-network integration/between-network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible.

Spectral characteristics of intracranial electroencephalographic activity in patients with Lennox-Gastaut syndrome.

OBJECTIVE: The purpose of the current study was to characterize the frequency profiles of epileptogenic regions, independent of visible epileptiform discharges, in intracranial EEG (iEEG) recordings of Lennox-Gastaut syndrome (LGS) patients. METHODS: We selected eight LGS patients who underwent resective surgery in the absence of definite neuroimaging findings. We calculated the absolute and relative band powers of continuous spike-free iEEG data and compared the characteristics of the resected and remaining regions. RESULTS: For absolute band powers, there was a trend for higher absolute gamma band power in the remaining brain section. We also found that the absolute delta power in the resected area was higher than that in the remaining area. However, this trend was not statistically different in all patients. For relative band powers, we found decreased relative band power in the beta and gamma band ranges within the areas defined by the surgical margins. Delta, theta, and alpha relative band power differences between the resected and remaining areas were inconsistent between the subjects. CONCLUSIONS: Our results showed systematic relative beta and gamma band power variation in the resected areas of LGS patients.

Endoscopic posterior interhemispheric complete corpus callosotomy.

Traditionally corpus callosotomy is done through a craniotomy centered at the coronal suture, with the aid of a microscope. This involves dissecting through the interhemispheric fissure below the falx to reach the corpus callosum. The authors describe a posterior interhemispheric approach to complete corpus callosotomy with an endoscope, which bypasses the need to perform interhemispheric dissection because the falx is generally close to the corpus callosum in this region.

Resective surgery combined with corpus callosotomy for children with non-focal lesional Lennox-Gastaut syndrome.

BACKGROUND: The first prospective trial for resective surgery combined with corpus callosotomy (CCT) was performed to investigate the outcomes of the combined surgery in children with Lennox-Gastaut syndrome (LGS) without focal lesion on brain MRI. METHODS: This study enrolled 68 children with LGS and without focal lesion on brain MRI, of which 25 received medicine (medicine group) and 43 underwent surgery (surgery group), including 20 with exclusively resective surgery (exclusively resection subgroup) and 23 with resective surgery combined with CCT (combined CCT subgroup). All patients were followed for 3-5 years. RESULTS: Significant differences in seizure control were observed between the medicine group and the exclusively resection subgroup and combined CCT subgroup at the 1-year, 3-year, and 5-year follow-ups. There was a trend that the children with resection combined with CCT had better seizure control than those with exclusively resection at the three follow-ups, but this could not be verified by the statistical method used. Furthermore, significant differences were not observed in seizure control between children with different MRI findings, age at surgery, or pathology in the surgery group. The percentage of long-term seizure-free did not remain as high as the percentage of early stage seizure-free at 1-year follow-up. However, the children with combined CCT surgery demonstrated more postoperative improvement than the children with resective surgery alone based on the mean QOL score (10.78 vs. 5.75, p = 0.0152) and full-scale IQ (7.91 vs. 4.55, p = 0.0446). CONCLUSIONS: Resective surgery combined with CCT can provide favorable seizure control and obvious improvements in QOL and IQ in children with LGS. This combined approach can be performed in carefully selected LGS children without focal lesions and can localize the epileptogenic zone following a comprehensive preoperative evaluation.

Predictive role of brain connectivity for resective surgery in Lennox-Gastaut syndrome.

OBJECTIVE: Callosotomy can reveal hidden primary epileptogenic areas in Lennox-Gastaut syndrome (LGS). We studied the significance of causal connectivity for identifying hidden epileptogenic areas in preoperative electroencephalography (EEG) and for making a decision regarding resective surgery. METHODS: We enrolled 18 LGS patients who underwent corpus callosotomy. Eight patients with unilateral epileptogenicity on post-callosotomy EEG underwent resective surgery (group A). Ten patients with independent bilateral epileptogenicity did not undergo resective surgery (group B). We analyzed generalized epileptiform discharges on pre-callosotomy EEG via direct directed transfer function (dDTF) and partial directed coherence (PDC). RESULTS: All regions exhibiting unilaterality in group A and bilaterality identified by dDTF or PDC in group B were concordant with the lateralization of the irritative zone on post-callosotomy EEG and with the localization of the resective areas, except for one patient in group A. The regions identified by dDTF exhibited high concordance rates with the resective areas in patients with good outcomes. CONCLUSIONS: Causal connectivity methods showed good concordance with hidden epileptogenic areas, and its concordance was associated with the prognosis of surgical outcome. SIGNIFICANCE: This study provides evidence that causal connectivity methods can be helpful in deciding which type of surgery will be suitable for an LGS patient.

Combined surgical intervention with vagus nerve stimulation following corpus callosotomy in patients with Lennox-Gastaut syndrome.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a drug-resistant pediatric epilepsy characterized by multiple seizure types, including drop attacks (DAs). Palliative procedures such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate seizure control in LGS patients who are not candidates for resective surgery. We evaluated the efficacy of the combination of these two procedures for LGS-related seizures. METHOD: Ten patients with LGS (age 3-30 years at VNS implantation) underwent CC and subsequent VNS. We evaluated surgical outcomes, particularly with respect to the efficacy of VNS on seizure reduction rates for different residual seizure types after CC. We compared clinical parameters, including sex, age, seizure duration, history, MRI findings, extent of CC, number of antiepileptic drugs, and neuropsychological states, between VNS responders and non-responders to predict satisfactory seizure outcomes with respect to residual seizures after CC. FINDINGS: VNS was effective for residual seizures regardless of seizure type (except for DAs) after CC in patients with LGS. Six of ten (60%) patients had a satisfactory seizure outcome (≥50% seizure reduction) for all residual seizure types after VNS. Two of ten (20%) patients were seizure-free at 12 months post-VNS. Even those patients that were non-responders, with respect to all seizures including DAs, after prior CC showed favorable responses to subsequent VNS. Compared to VNS, excellent seizure outcomes for DAs were achieved after CC in seven of nine (77.8%) patients with DAs. Among the clinical parameters, only conversation ability before VNS was significantly different between responders and non-responders (p = 0.033). CONCLUSION: Combined VNS and prior CC produced satisfactory seizure outcomes in LGS patients with different seizure types, including DAs. Even non-responders to prior CC responded to subsequent VNS for residual seizures, except for DAs. There is a greater likelihood that these procedures may be more feasible in patients who possess conversation ability prior to VNS.