It is important to correctly diagnose medically intractable epilepsy in children and to identify those children whose medically refractory, localization-related seizures may be surgically remediable as soon as possible to optimize the surgical outcome. In this paper the authors review the definition of medically intractable seizures and discuss the various causes and risk factors for this disorder in children. They also outline the presurgical diagnostic evaluation process for pharmacologically intractable epilepsy in children who may be candidates for surgical treatment of localization-related seizures. The treatment of children with medically intractable epilepsy is both challenging and rewarding. Surgery has the potential of altering the natural history of epilepsy by improving or eliminating seizures in carefully selected patients.
Pharmacologically intractable epilepsy in children: diagnosis and preoperative evaluation
Cristina Go and O. Carter Snead III
Surgical outcomes in children with bottom-of-sulcus dysplasia and drug-resistant epilepsy: a retrospective cohort study
Puneet Jain, Ayako Ochi, Carter McInnis, Hiroshi Otsubo, O. Carter Snead III, George M. Ibrahim, Elizabeth Donner, and Elysa Widjaja
Bottom-of-sulcus dysplasia (BOSD) is challenging to identify radiologically. The aim of this study was to explore seizure outcomes after resective surgery or MR-guided laser interstitial thermal therapy (MRgLITT) in children with BOSD.
Children with radiologically defined BOSD who underwent resective surgery or MRgLITT, with at least 1 year of follow-up were included. Clinical, radiological, neurophysiological, and histological data were extracted from medical records. Invasive video EEG (IVEEG) was used to evaluate the ictal onset zone or motor/language mapping, wherever appropriate. Histology of MRI-visible BOSD, including the overlying and adjacent cortex, was also evaluated.
Forty-one children with BOSD underwent surgical treatment. The lesion was initially overlooked on MRI in 20 patients (48.8%). Of 34 patients who underwent IVEEG and who had available ictal data, the ictal onset zone extended beyond the MRI-visible BOSD in 23 patients (67.6%). Surgical treatment included lesionectomy (24 patients), extended lesionectomy (12 patients), lobectomy (1 patient), and ablation of BOSD (4 patients). The pathology in 37 patients who underwent resection showed focal cortical dysplasia type IIB and type IIA in 21 (53.8%) and 16 patients (41%), respectively. Seizure freedom was achieved in 32 patients (78.1%) after a mean follow-up of 4.3 years.
Seizure outcomes after resective surgery or MRgLITT in children with BOSD were generally favorable. The authors found that the neurophysiological abnormality and pathology often extended beyond the MRI-visible BOSD.
Reoperation after failed resective epilepsy surgery in children
Osama Muthaffar, Klajdi Puka, Luc Rubinger, Cristina Go, O. Carter Snead III, James T. Rutka, and Elysa Widjaja
Although epilepsy surgery is an effective treatment option, at least 20%–40% of patients can continue to experience uncontrolled seizures resulting from incomplete resection of the lesion, epileptogenic zone, or secondary epileptogenesis. Reoperation could eliminate or improve seizures. Authors of this study evaluated outcomes following reoperation in a pediatric population.
A retrospective single-center analysis of all patients who had undergone resective epilepsy surgery in the period from 2001 to 2013 was performed. After excluding children who had repeat hemispherotomy, there were 24 children who had undergone a second surgery and 2 children who had undergone a third surgery. All patients underwent MRI and video electroencephalography (VEEG) and 21 underwent magnetoencephalography (MEG) prior to reoperation.
The mean age at the first and second surgery was 7.66 (SD 4.11) and 10.67 (SD 4.02) years, respectively. The time between operations ranged from 0.03 to 9 years. At reoperation, 8 patients underwent extended cortical resection; 8, lobectomy; 5, lesionectomy; and 3, functional hemispherotomy. One year after reoperation, 58% of the children were completely seizure free (International League Against Epilepsy [ILAE] Class 1) and 75% had a reduction in seizures (ILAE Classes 1–4). Patients with MEG clustered dipoles were more likely to be seizure free than to have persistent seizures (71% vs 40%, p = 0.08).
Reoperation in children with recurrent seizures after the first epilepsy surgery could result in favorable seizure outcomes. Those with residual lesion after the first surgery should undergo complete resection of the lesion to improve seizure outcome. In addition to MRI and VEEG, MEG should be considered as part of the reevaluation prior to reoperation.
Computerized brain-surface voltage topographic mapping for localization of intracranial spikes from electrocorticography
Hiroshi Otsubo, Atsushi Shirasawa, Shiro Chitoku, James T. Rutka, Scott B. Wilson, and O. Carter Snead III
✓ The purpose of this paper is to describe the use of computerized brain-surface voltage topographic mapping to localize and identify epileptic discharges recorded on electrocorticographic (ECoG) studies in which a subdural grid was used during intracranial video electroencephalographic (IVEEG) monitoring. The authors studied 12 children who underwent surgery for intractable extrahippocampal epilepsy. Cortical surfaces and subdural grid electrodes were photographed during the initial surgery to create an electrode map that could be superimposed onto a picture of the brain surface. Spikes were selected from ictal discharges recorded at the beginning of clinically confirmed seizures and from interictal discharges seen on ECoG studies during IVEEG recording. A computer program was used to calculate the sequential amplitude of the spikes by using squared interpolation, and they were then superimposed onto the electrode map. Interictal discharges and high-amplitude spike complexes at seizure onset were plotted on the map. This mapping procedure depicted the ictal zone in nine patients and the interictal zone in 12, and proved to be an accurate and useful source of information for planning corrective surgery.
Steal phenomenon in Sturge-Weber syndrome imitating an ictal electroencephalography change in the contralateral hemisphere: report of 2 cases
Chusak Limotai, Cristina Y. Go, Shiro Baba, Kazuo Okanari, Ayako Ochi, James T. Rutka, O. Carter Snead III, and Hiroshi Otsubo
Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they develop seizures and the seizures prove medically refractory. The authors report on 2 infants (15 and 19 months old) with SWS who underwent scalp video electroencephalography (EEG) and subsequent functional hemispherotomy for intractable partial motor seizures due to extensive left hemispheric angiomatosis. They presented with similar interictal and ictal EEG findings. Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the contralateral hemisphere before the build-up of ictal EEG changes on the lesional hemisphere. The patients became seizure free after hemispherotomy. The ictal contralateral slow waves were not a sign of an ictal hemisphere and may indicate prominent ischemic changes resulting from a steal phenomenon of hemispheric angiomatosis during seizure.
Inequities in access to pediatric epilepsy surgery: a bioethical framework
George M. Ibrahim, Benjamin W. Barry, Aria Fallah, O. Carter Snead III, James M. Drake, James T. Rutka, and Mark Bernstein
Epilepsy is a common childhood condition associated with a considerable medical and psychosocial burden. Children in whom medical treatment fails to reduce seizure burden represent an especially vulnerable patient population because prolonged, uncontrolled seizures are associated with poor developmental and neurocognitive outcomes. Surgical treatment in the form of cortical resection, functional disconnection, or neuromodulation may alleviate or significantly reduce the disease burden for a subset of these patients. However, there remains a dichotomy between the perceived benefits of surgery and the implementation of surgical strategies in the management of medically intractable epilepsy. The current paper presents an analysis of the bioethical implications of existing inequities in access to pediatric epilepsy surgery that result from inconsistent referral practices and discrepant evaluation techniques. The authors provide a basic bioethical framework composed of 5 primary expectations to inform public, institutional, and personal policies toward the provision of epilepsy surgery to afflicted children.
Cortical dysplastic lesions in children with intractable epilepsy: role of complete resection
Walter J. Hader, Mark Mackay, Hiroshi Otsubo, Shiro Chitoku, Shelly Weiss, Lawrence Becker, O. Carter Snead III, and James T. Rutka
Object. The authors conducted a study to determine seizure-related outcomes in a group of pediatric patients with pathologically proven focal cortical dysplasia (FCD) treated by focal cortical resections and multiple subpial transections (MSTs).
Methods. The authors performed a retrospective review of pediatric patients in whom surgery was conducted to treat medically refractory epilepsy secondary to cortical dysplasia between April 1989 and January 2001. Diagnostic studies included preoperative scalp electroencephalography (EEG), magnetic resonance (MR) imaging, positron emission tomography (PET), and magnetoencephalography (MEG). Intraoperative electrocorticography (ECoG) or extraoperative subdural grid EEG monitoring was performed in all patients. Seizure outcome was classified using the Engel scheme. The authors analyzed nine data points and compared these with seizure outcome, including seizure semiology, MR imaging, PET and MEG data, as well as location of resection, intracranial video-EEG findings, MSTs, postresection ECoG data, and histological findings.
The authors analyzed data obtained in 39 children in whom the follow-up interval after epilepsy surgery was at least 18 months. Patients had suffered epilepsy for a mean of 7.7 years prior to surgical intervention and their mean age at treatment was 9.6 years (range 2 months–18 years). A good seizure-related outcome was demonstrated in 28 patients (72%), including 21 (54%) who were free of seizures (Engel Class I) and seven (18%) in whom seizures were rare (Engel Class II). In 11 patients seizure-related outcome was less favorable, including six (15%) with worthwhile improvement involving some seizures (Engel Class III) and five (13%) with no postoperative seizure improvement (Engel Class IV). There was no significant correlation between seizure outcome and data related to seizure characteristics, MR imaging, PET scanning, MEG, location of resection, intracranial video-EEG, postresection ECoG, and histological findings. Eight (50%) of 16 patients who underwent MSTs in addition to incomplete resection of FCD experienced a good outcome (Engel Class I and II). Twenty (87%) of 23 patients in whom resection of FCD was complete and in whom MSTs were not performed experienced a good seizure outcome (p < 0.05).
Conclusions. Complete resection of FCD results in good seizure outcome in a majority of children. When conducted in conjunction with incomplete cortical resection, MSTs do not improve seizure outcome in patients with FCD. Focal cortical dysplasia located outside of eloquent cortex and complete excision of the lesion are the most important predictors of seizure outcome.
Complications of invasive subdural grid monitoring in children with epilepsy
Çagatay Önal, Hiroshi Otsubo, Takashi Araki, Shiro Chitoku, Ayako Ochi, Shelly Weiss, William Logan, Irene Elliott, O. Carter Snead III, and James T. Rutka
Object. This study was performed to evaluate the complications of invasive subdural grid monitoring during epilepsy surgery in children.
Methods. The authors retrospectively reviewed the records of 35 consecutive children with intractable localization-related epilepsy who underwent invasive video electroencephalography (EEG) with subdural grid electrodes at The Hospital for Sick Children between 1996 and 2001. After subdural grid monitoring and identification of the epileptic regions, cortical excisions and/or multiple subpial transections (MSTs) were performed. Complications after these procedures were then categorized as either surgical or neurological.
There were 17 male and 18 female patients whose mean age was 11.7 years. The duration of epilepsy before surgery ranged from 2 to 17 years (mean 8.3 years). Fifteen children (43%) had previously undergone surgical procedures for epilepsy. The number of electrodes on the grids ranged from 40 to 117 (mean 95). During invasive video EEG, cerebrospinal fluid leaks occurred in seven patients. Also, cerebral edema (five patients), subdural hematoma (five patients), and intracerebral hematoma (three patients) were observed on postprocedural imaging studies but did not require surgical intervention. Hypertrophic scars on the scalp were observed in nine patients. There were three infections, including one case of osteomyelitis and two superficial wound infections. Blood loss and the amounts of subsequent transfusions correlated directly with the size and number of electrodes on the grids (p < 0.001). Twenty-eight children derived significant benefit from cortical resections and MSTs, with a more than 50% reduction of seizures and a mean follow-up period of 30 months.
Conclusions. The results of this study indicate that carefully selected pediatric patients with intractable epilepsy can benefit from subdural invasive monitoring procedures that entail definite but acceptable risks.
Magnetoencephalography helps delineate the extent of the epileptogenic zone for surgical planning in children with intractable epilepsy due to porencephalic cyst/encephalomalacia
Odeya Bennett-Back, Ayako Ochi, Elysa Widjaja, Shohei Nambu, Akio Kamiya, Cristina Go, Sylvester Chuang, James T. Rutka, James Drake, O. Carter Snead III, and Hiroshi Otsubo
Porencephalic cyst/encephalomalacia (PC/E) is a brain lesion caused by ischemic insult or hemorrhage. The authors evaluated magnetoencephalography (MEG) spike sources (MEGSS) to localize the epileptogenic zone in children with intractable epilepsy secondary to PC/E.
The authors retrospectively studied 13 children with intractable epilepsy secondary to PC/E (5 girls and 8 boys, age range 1.8–15 years), who underwent prolonged scalp video-electroencephalography (EEG), MRI, and MEG. Interictal MEGSS locations were compared with the ictal and interictal zones as determined from scalp video-EEG.
Magnetic resonance imaging showed PC/E in extratemporal lobes in 3 patients, within the temporal lobe in 2 patients, and in both temporal and extratemporal lobes in 8 patients. Magnetoencephalographic spike sources were asymmetrically clustered at the margin of PC/E in all 13 patients. One cluster of MEGSS was observed in 11 patients, 2 clusters in 1 patient, and 3 clusters in 1 patient. Ictal EEG discharges were lateralized and concordant with MEGSS in 8 patients (62%). Interictal EEG discharges were lateralized and concordant with MEGSS hemisphere in 9 patients (69%). Seven patients underwent lesionectomy in addition to MEGSS clusterectomy with (2 patients) and without (5 patients) intracranial video-EEG. Temporal lobectomy was performed in 1 patient and hemispherectomy in another. Eight of 9 patients achieved seizure freedom following surgery.
Magnetoencephalography delineated the extent of the epileptogenic zone adjacent to PC/E in patients with intractable epilepsy. Complete resection of the MEGSS cluster along with PC/E can provide favorable seizure outcomes.
Magnetoencephalography-guided resection of epileptogenic foci in children
Gregory W. Albert, George M. Ibrahim, Hiroshi Otsubo, Ayako Ochi, Cristina Y. Go, O. Carter Snead III, James M. Drake, and James T. Rutka
Resective surgery is increasingly used in the management of pediatric epilepsy. Frequently, invasive monitoring with subdural electrodes is required to adequately map the epileptogenic focus. The risks of invasive monitoring include the need for 2 operations, infection, and CSF leak. The aim of this study was to evaluate the feasibility and outcomes of resective epilepsy surgery guided by magnetoencephalography (MEG) in children who would have otherwise been candidates for electrode implantation.
The authors reviewed the records of patients undergoing resective epilepsy surgery at the Hospital for Sick Children between 2001 and 2010. They identified cases in which resections were based on MEG data and no intracranial recordings were performed. Each patient's chart was reviewed for presentation, MRI findings, MEG findings, surgical procedure, pathology, and surgical outcome.
Sixteen patients qualified for the study. All patients had localized spike clusters on MEG and most had abnormal findings on MRI. Resection was carried out in each case based on the MEG data linked to neuronavigation and supplemented with intraoperative neuromonitoring. Overall, 62.5% of patients were seizure free following surgery, and 20% of patients experienced an improvement in seizures without attaining seizure freedom. In 2 cases, additional surgery was performed subsequently with intracranial monitoring in attempts to obtain seizure control.
MEG is a viable alternative to invasive monitoring with intracranial electrodes for planning of resective surgery in carefully selected pediatric patients with localization-related epilepsy. Good candidates for this approach include patients who have a well-delineated, localized spike cluster on MEG that is concordant with findings of other preoperative evaluations and patients with prior brain pathologies that make the implantation of subdural and depth electrodes somewhat problematic.