Uncovered primary seizure foci in Lennox–Gastaut syndrome after corpus callosotomy

doi:10.1016/j.braindev.2010.11.005

Brain and Development

Volume 33, Issue 8, September 2011, Pages 672-677

https://doi.org/10.1016/j.braindev.2010.11.005 Get rights and content

Abstract

Purpose

Corpus callosotomy (CC) is a palliative surgical procedure to control atonic, tonic, or generalized tonic–clonic seizure in Lennox–Gastaut syndrome (LGS). Here, we report patients with LGS who underwent resective surgery, following CC better delineating the presumed seizure foci localized in one hemisphere.

Methods

We retrospectively reviewed seven patients with LGS who underwent CC and subsequent cortical resection. The median follow-up duration after lobectomy was 20 months (range, 15–54 months) and three patients had follow-up periods over 24 months. The findings of video electroencephalography (EEG) monitoring, structural and functional neuroimagings were compared between pre- and post-CC.

Results

Four patients had Engel class I and one patient had Engel class II outcomes following cortical resection; post-CC, compared to pre-CC, showed better localized ictal/interictal epileptiform discharges in the unilateral frontal area in two patients, in the unilateral parieto-temporo-occipital areas in one patient and in the unilateral fronto-temporal areas in the remaining two patients. Two patients had Engel Class III outcome following cortical resection; post-CC EEG continued to show multifocal epileptiform discharges but predominantly arising from a unilateral frontal area. Following CC, positron emission tomography showed localized glucose hypometabolism of which location was concordant with post-CC EEG abnormalities in all patient. Similarly, ictal/interictal single photon emission computed tomography also showed localized abnormalities concordant with post-CC EEG abnormalities in five of the six patients. Pathological assessment revealed cortical dysplasia in six patients, whereas no pathological abnormality was found in the remaining patient, who obtained Engel Class I outcome following cortical resection.

Conclusion

CC could change EEG findings, glucose metabolisms and cerebral blood flows, and it is sometimes helpful in delineating the primary seizure focus in patients with LGS.

Introduction

Lennox–Gastaut syndrome (LGS) is described as an epileptic syndrome with intractable, multiple seizure types including tonic, atonic, myoclonic and atypical absence seizures. Its interictal electroencephalography (EEG) pattern is characterized by generalized slow sharp wave discharges (GSSW) and generalized paroxysmal fast activities (GPFA) [1], [2]. Sometimes, LGS has shown symptomatic generalized epileptic encephalopathy with primary seizure foci in which it would be possible to do potential resection by the multimodal approach [1], [2], [3], [4], [5].

Corpus callosotomy (CC) is a palliative surgical procedure used to control intractable seizure, especially atonic, tonic, or generalized tonic–clonic seizure and also improves the quality of life [6], [7], [8]. CC disrupts the pathway that connects homologous cortical areas of cerebral hemisphere and disconnects epileptogenic discharges that propagate from one hemisphere to the other. It not only interrupts the generalization of focal epileptogenic discharges and suppresses the duration, frequency and amplitude of seizure, but also allows patients to decrease intake of antiepileptic drugs [9], [10], [11], [12]. Some authors have observed gratifying results, such that generalized bilaterally synchronous spikes in interictal EEG might change into unilateral or asymmetric focal discharges after the procedure [13], [14], [15], [16].

Section snippets

Methods

39 patients with LGS had undergone CC to control the seizures as palliative goals from January 2004 to December 2008. All patients had suffered from medically-intractable seizures. Prior to CC, EEG showed GSSW or GPFA and no conclusive evidence of unilateral seizure foci was obtained following the phase-I assessment including EEG or neuroimaging. Fortunately, all patients had no serious surgical complication although two patients showed a transient ataxia for about 1 month and another one

Results

Among 39 patients who had undergone CC, seven patients were able to undergo the second operation for the control of seizures because of being identified primary seizure foci after CC. Four patients were classified as having cryptogenic infantile spasms and three patients as symptomatic infantile spasms had normal development prior to seizure onset. All patients progressed to develop LGS which represented various type of seizure. Two patients had pathologic handedness associated with the primary

Discussion

Our observations found that callosotomy sometimes happened to make EEG convert to focal evidence of epileptic discharges in some patients with secondary epileptic encephalopathy who had primary epileptogenic foci. These finding could support the fact that corpus callosum might play a role in interhemispheric spread and generation of cortical discharges and contribute to pathway for bilateral synchrony [21], [22]. Callosotomy could not only disrupt bilateral synchrony of generalization and

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Cited by (29)

Corpus Callosotomy in the Modern Era: Origins, Efficacy, Technical Variations, Complications, and Indications
2022, World Neurosurgery
Citation Excerpt :
After corpus callosotomy, 17.4% and 8.7% of patients were seizure free at 1 year and 5 years follow-up, respectively; the greatest improvement in seizure frequency was seen for tonic, tonic-clonic, and atypical absence seizures and the least improvement for myoclonic seizures.103 Corpus callosotomy may offer an additional benefit for this syndrome by altering the preoperative EEG or fluorodeoxyglucose-PET imaging patterns and uncovering underlying focal lesions that can subsequently be removed, leading to seizure freedom.104 Although ≤25% of the LGS population may show focal abnormalities on EEG, an even higher percentage might be considered for potentially curative focal resections after corpus callosotomy.105
Corpus callosotomy is among the oldest surgeries performed for drug-resistant epilepsy. Since it was first performed in 1940, numerous studies have assessed its outcomes in various patient populations in addition to describing different extents of sectioning and emerging technologies (i.e., endoscopic, laser interstitial thermal therapy, and radiosurgery). To capture the current state and offer a reappraisal, we comprehensively review the origins of corpus callosotomy, efficacy for various seizure types, technical variations, complications, and indications and compare the procedure with vagus nerve stimulation therapy, which has similar indications. We consider corpus callosotomy to be a safe and efficacious procedure, which should be considered by clinicians when appropriate. Furthermore, it can play an important role in treating patients with drug-resistant epilepsy when appropriate in low-to-middle-income countries where resources are limited.
Epilepsy Surgery is a Viable Treatment for Lennox Gastaut Syndrome
2021, Seminars in Pediatric Neurology
Lennox Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy with onset in childhood characterized by multiple seizure types and characteristic electroencephalogram findings. The majority of patients develop drug resistant epilepsy, defined as failure of 2 appropriate anti-seizure medications used at adequate doses. Epilepsy surgery can reduce seizure burden, in some cases leading to seizure freedom, and improve neuro-developmental outcomes and quality of life. Epilepsy surgery should be considered for all patients with drug resistant LGS. Herein, we review current surgical treatment options for patients with LGS, both definitive and palliative, including: focal cortical resection, vagus nerve stimulation and corpus callosotomy. Newer neuromodulation techniques will be explored, as well as the concept of LGS as a secondary network disorder.
Challenges in managing epilepsy associated with focal cortical dysplasia in children
2018, Epilepsy Research
Focal cortical dysplasia (FCD) is the most common cause of intractable focal epilepsy in children, in whom seizures are most commonly pharmacoresistant from onset. This review summarizes the current understandings of the epidemiology, natural history, and the proposed mechanisms of epileptogenisis in FCD. Advances in neuroimaging techniques have enhanced the recognition of this pathology, which can be subtle. Illustrative neurophysiology and imaging examples are provided to help the clinicians identify diagnostic evidence of suspected FCD. Given the refractory course to pharmacologic management, alternative options such as ketogenic diet, resective surgery or neuromodulation can be considered. Recognition of FCD pathology in children with early onset epilepsy should prompt timely evaluations for resective surgery, which may render a significant number of patients seizure-free and improve neurocognitive outcome.
Predictive role of brain connectivity for resective surgery in Lennox–Gastaut syndrome
2016, Clinical Neurophysiology
Citation Excerpt :
Therefore, these discharges may provide a clue of the underlying brain pathologies, such as cortical dysplasia. Corpus callosotomy reveals PEAs by disrupting GSWs, and it can induce changes in electrical activity, blood flow, and metabolism in the lesion (Ono et al., 2009; Lin and Kwan, 2012; Hur et al., 2011). A previous study suggested that bilateral cortical epileptogenesis could exist with asymmetrical susceptibility, although callosal compound action potentials exhibited no difference in conduction time between an altered and an unaltered group after corpus callosotomy (Ono et al., 2002).
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.
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).
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.
Causal connectivity methods showed good concordance with hidden epileptogenic areas, and its concordance was associated with the prognosis of surgical outcome.
This study provides evidence that causal connectivity methods can be helpful in deciding which type of surgery will be suitable for an LGS patient.
The causal epileptic network identifies the primary epileptogenic zone in Lennox-Gastaut syndrome
2015, Seizure
Citation Excerpt :
Lennox–Gastaut syndrome (LGS) is one of the most intractable epilepsies and is characterized by multiple types of seizures, electroencephalographic (EEG) characteristics, such as generalized slow sharp and wave discharges and generalized paroxysmal fast activities, and progressive mental retardation. Generalized sharp and wave discharges (GSW) with bilateral synchronization in a secondary generalized epileptic encephalopathy, such as LGS, can originate from the primary epileptogenic zone through the transcallosal pathway [1–3]. Although resective surgery of the primary epileptogenic zone results in a seizure-free surgical outcome in 59.2% of patients, the GSW often fail to reveal the primary epileptogenic zone if they are not accompanied by the types of focal EEG features that have been described in previous studies [2,3].
Lennox–Gastaut syndrome (LGS) can be successfully treated by resective surgery in patients with a primary epileptogenic zone. This study aimed to identify the primary epileptogenic zone based on the causal epileptic network using direct directed transfer function (dDTF) analysis.
We reviewed the dDTF findings for generalized sharp and wave discharges (GSW) from the preoperative electroencephalography (EEG) of 12 LGS patients (group A) with unilateral focal pathology who were successfully treated with resective surgery. These findings were compared with preoperative dDTF findings for the GSW from 15 LGS patients with bilateral non-resectable pathology (group B) who exhibited persistent bilateral independent diffuse sharp and wave discharges, even after corpus callosotomy.
The dDTF analysis of the GSW revealed concordant findings of localization or lateralization with the primary epileptogenic zone in 83.3% (10/12 cases) of group A patients and bilateral or multifocal localization in 93.3% (14/15) of group B patients (p < 0.01). The regions identified by dDTF analysis were included in the resected areas of all patients in group A, and complete matches of the resected areas without other foci were observed in 7 patients (58.3%) in group A. The region of GSW most frequently identified by dDTF analysis was the frontal area, which was identified in 91.7% (11/12) of group A and in 100% of group B, while extra-frontal areas were identified in 36.1% and 24.5% of groups A and B, respectively.
The dDTF analysis of GSW could provide additional information to identify resective surgery candidates for patients with LGS.
Bilateral intracranial EEG with corpus callosotomy may uncover seizure focus in Nonlocalizing focal epilepsy
2015, Seizure
To evaluate the value of a new multi-stage surgical procedure using bilateral intracranial electroencephalogram (iEEG) prior and post complete corpus callosotomy (CC) for epileptogenic focus localization.
Thirty patients with drug-resistant epilepsy underwent bilateral iEEG monitoring to localize epileptogenic focus for surgical treatment. Among them, bisynchronous epileptogenic activities were found in 9 pediatric patients. These 9 patients then received complete CC and continued bilateral iEEG monitoring for further seizure localization. Final surgical treatment decisions were made based on the bilateral iEEG findings post complete CC. The entire multi-stage procedure was performed during the same hospital stay. We retrospectively studied the data from the 9 patients.
Seizure onset was lateralized in 3 patients who later received functional hemispherectomy. In another 4 patients, seizure onset was localized, resulting in resective surgery. Bilateral multiple subpial transection was performed on 1 patient with identified bilateral independent seizure onset. One patient did not have seizures following complete CC leading to removal of electrodes without any further resection. Subsequent follow-up showed favorable outcome in all patients: seizure-free in 7, more than 90% reduction in 2. None of the patients experienced surgery related complications during the procedure and follow-up period.
The multi-stage surgical procedure utilizing iEEG monitoring with CC is a viable option for select patients with catastrophic non-localizing epilepsy. Further study is necessary to find the optimal selection criteria for use of this novel approach.

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¹: These authors contributed equally to this work.

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Original articleUncovered primary seizure foci in Lennox–Gastaut syndrome after corpus callosotomy

Abstract

Purpose

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Brain Dev

Brain Dev

Epilepsy Res

Seizure

Clin Neurophysiol

Epilepsy Res

The Lennox–Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography

Ann Neurol

Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic patients for surgical treatment

Ann Neurol

Cerebral glucose metabolism in the Lennox–Gastaut syndrome

Ann Neurol

Response of multiple seizure types to corpus callosum section

Epilepsia

Callosotomy for epilepsy after west syndrome

Epilepsia

Corpus callosotomy for intractable seizures in the pediatric age group

Arch Neurol

Original article
Uncovered primary seizure foci in Lennox–Gastaut syndrome after corpus callosotomy

The Lennox–Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[¹⁸F]fluoro-d-glucose positron emission tomography