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Cristina Go and O. Carter Snead III

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.

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Zulma S. Tovar-Spinoza, Ayako Ochi, James T. Rutka, Cristina Go and Hiroshi Otsubo

Epilepsy surgery requires the precise localization of the epileptogenic zone and the anatomical localization of eloquent cortex so that these areas can be preserved during cortical resection. Magnetoencephalography (MEG) is a technique that maps interictal magnetic dipole sources onto MR imaging to produce a magnetic source image. Magneto-encephalographic spike sources can be used to localize the epileptogenic zone and be part of the workup of the patient for epilepsy surgery in conjunction with data derived from an analysis of seizure semiology, scalp video electroencephalography, PET, functional MR imaging, and neuropsychological testing. In addition, magnetoencephalographic spike sources can be linked to neuronavigation platforms for use in the neurosurgical field. Finally, paradigms have been developed so that MEG can be used to identify functional areas of the cerebral cortex including the somatosensory, motor, language, and visual evoked fields.

The authors review the basic principles of MEG and the utility of MEG for presurgical planning as well as intra-operative mapping and discuss future applications of MEG technology.

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Osama Muthaffar, Klajdi Puka, Luc Rubinger, Cristina Go, O. Carter Snead III, James T. Rutka and Elysa Widjaja

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

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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.

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Erin N. Kiehna, Elysa Widjaja, Stephanie Holowka, O. Carter Snead III, James Drake, Shelly K. Weiss, Ayako Ochi, Eric M. Thompson, Cristina Go, Hiroshi Otsubo, Elizabeth J. Donner and James T. Rutka

OBJECT

Hemispherectomy for unilateral, medically refractory epilepsy is associated with excellent long-term seizure control. However, for patients with recurrent seizures following disconnection, workup and investigation can be challenging, and surgical options may be limited. Few studies have examined the role of repeat hemispherotomy in these patients. The authors hypothesized that residual fiber connections between the hemispheres could be the underlying cause of recurrent epilepsy in these patients. Diffusion tensor imaging (DTI) was used to test this hypothesis, and to target residual connections at reoperation using neuronavigation.

METHODS

The authors identified 8 patients with recurrent seizures following hemispherectomy who underwent surgery between 1995 and 2012. Prolonged video electroencephalography recordings documented persistent seizures arising from the affected hemisphere. In all patients, DTI demonstrated residual white matter association fibers connecting the hemispheres. A repeat craniotomy and neuronavigation-guided targeted disconnection of these residual fibers was performed. Engel class was used to determine outcome after surgery at a minimum of 2 years of follow-up.

RESULTS

Two patients underwent initial hemidecortication and 6 had periinsular hemispherotomy as their first procedures at a median age of 9.7 months. Initial pathologies included hemimegalencephaly (n = 4), multilobar cortical dysplasia (n = 3), and Rasmussen's encephalitis (n = 1). The mean duration of seizure freedom for the group after the initial procedure was 32.5 months (range 6–77 months). In all patients, DTI showed limited but definite residual connections between the 2 hemispheres, primarily across the rostrum/genu of the corpus callosum. The median age at reoperation was 6.8 years (range 1.3–14 years). The average time taken for reoperation was 3 hours (range 1.8–4.3 hours), with a mean blood loss of 150 ml (range 50–250 ml). One patient required a blood transfusion. Five patients are seizure free, and the remaining 3 patients are Engel Class II, with a minimum follow-up of 24 months for the group.

CONCLUSIONS

Repeat hemispherotomy is an option for consideration in patients with recurrent intractable epilepsy following failed surgery for catastrophic epilepsy. In conjunction with other modalities to establish seizure onset zones, advanced MRI and DTI sequences may be of value in identifying patients with residual connectivity between the affected and unaffected hemispheres. Targeted disconnection of these residual areas of connectivity using neuronavigation may result in improved seizure outcomes, with minimal and acceptable morbidity.

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Gregory W. Albert, George M. Ibrahim, Hiroshi Otsubo, Ayako Ochi, Cristina Y. Go, O. Carter Snead III, James M. Drake and James T. Rutka

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Ying Meng, Mathew R. Voisin, Suganth Suppiah, Zamir Merali, Ali Moghaddamjou, Naif M. Alotaibi, Arbelle Manicat-Emo, Shelly Weiss, Cristina Go, Blathnaid McCoy, Elizabeth J. Donner and James T. Rutka

OBJECTIVE

Intracranial electroencephalography (iEEG) monitoring is an important method of identifying the seizure focus in patients with medically refractory epilepsy. While previous studies have demonstrated low rates of surgical complications, reported rates of surgical site infection (SSI) are highly variable. To date, no studies have specifically evaluated the patient or operative risk factors contributing to SSI. The goals of this study were to examine the rate of SSI after iEEG monitoring for epilepsy workup in pediatric patients and to determine the variables that might contribute to the development of SSI.

METHODS

A retrospective analysis of hospital charts at the Hospital for Sick Children was performed for all patients who had undergone iEEG monitoring between 2000 and 2016. Univariate and multivariate analyses were performed to look for statistically significant variables in relation to SSI.

RESULTS

Among 199 patients eligible for analysis, 8 (4.0%) developed SSIs within a period ranging from 21 to 51 days postoperatively. Univariate analysis yielded 4 factors related to SSI: number of people present in the operating room on electrode insertion (p = 0.02), length of insertion surgery (p = 0.04), previous operation at the same surgical site (p = 0.04), and number of depth electrodes inserted (p = 0.01). Multivariate analysis revealed that both the number of people present during the implant operation (OR 0.08, 95% CI 0.01–0.70) and the number of depth electrodes inserted (OR 3.52, 95% CI 1.44–8.59) independently contributed to SSI.

CONCLUSIONS

This is the largest case series and the first comprehensive review of both patient and operative risk factors in the development of SSI from iEEG monitoring in a pediatric population. The authors’ institution had a lower rate of infection than those in most other studies, which could be explained by their protocol of administering intravenous antibiotics perioperatively and post–implant removal antibiotics for 14 days. The authors found a correlation between SSI and the number of people present during the implant operation, as well as the number of depth electrodes; both may contribute to breaks in sterility.

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Eisha A. Christian, Elysa Widjaja, Ayako Ochi, Hiroshi Otsubo, Stephanie Holowka, Elizabeth Donner, Shelly K. Weiss, Cristina Go, James Drake, O. Carter Snead and James T. Rutka

OBJECTIVE

Small lesions at the depth of the sulcus, such as with bottom-of-sulcus focal cortical dysplasia, are not visible from the surface of the brain and can therefore be technically challenging to resect. In this technical note, the authors describe their method of using depth electrodes as landmarks for the subsequent resection of these exacting lesions.

METHODS

A retrospective review was performed on pediatric patients who had undergone invasive electroencephalography with depth electrodes that were subsequently used as guides for resection in the period between July 2015 and June 2017.

RESULTS

Ten patients (3–15 years old) met the criteria for this study. At the same time as invasive subdural grid and/or strip insertion, between 2 and 4 depth electrodes were placed using a hand-held frameless neuronavigation technique. Of the total 28 depth electrodes inserted, all were found within the targeted locations on postoperative imaging. There was 1 patient in whom an asymptomatic subarachnoid hemorrhage was demonstrated on postprocedural imaging. Depth electrodes aided in target identification in all 10 cases.

CONCLUSIONS

Depth electrodes placed at the time of invasive intracranial electrode implantation can be used to help localize, target, and resect primary zones of epileptogenesis caused by bottom-of-sulcus lesions.

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Ichiro Sugiyama, Katsumi Imai, Yu Yamaguchi, Ayako Ochi, Yoko Akizuki, Cristina Go, Tomoyuki Akiyama, O. Carter Snead III, James T. Rutka, James M. Drake, Elysa Widjaja, Sylvester H. Chuang, Doug Cheyne and Hiroshi Otsubo

Object

Magnetoencephalography (MEG) has been typically used to localize epileptic activity by modeling interictal activity as equivalent current dipoles (ECDs). Synthetic aperture magnetometry (SAM) is a recently developed adaptive spatial filtering algorithm for MEG that provides some advantages over the ECD approach. The SAM-kurtosis algorithm (also known as SAM[g2]) additionally provides automated temporal detection of spike sources by using excess kurtosis value (steepness of epileptic spike on virtual sensors). To evaluate the efficacy of the SAM(g2) method, the authors applied it to readings obtained in children with intractable epilepsy secondary to tuberous sclerosis complex (TSC), and compared them to localizations obtained with ECDs.

Methods

The authors studied 13 children with TSC (7 girls) whose ages ranged from 13 months to 16.3 years (mean 7.3 years). Video electroencephalography, MR imaging, and MEG studies were analyzed. A single ECD model was applied to localize ECD clusters. The SAM(g2) value was calculated at each SAM(g2) virtual voxel in the patient's MR imaging–defined brain volume. The authors defined the epileptic voxels of SAM(g2) (evSAM[g2]) as those with local peak kurtosis values higher than half of the maximum. A clustering of ECDs had to contain ≥ 6 ECDs within 1 cm of each other, and a grouping of evSAM(g2)s had to contain ≥ 3 evSAM(g2)s within 1 cm of each other. The authors then compared both ECD clusters and evSAM(g2) groups with the resection area and correlated these data with seizure outcome.

Results

Seizures started when patients were between 6 weeks and 8 years of age (median 6 months), and became intractable secondary to multiple tubers in all cases. Ictal onset on scalp video electroencephalography was lateralized in 8 patients (62%). The MEG studies showed multiple ECD clusters in 7 patients (54%). The SAM(g2) method showed multiple groups of epileptic voxels in 8 patients (62%). Colocalization of grouped evSAM(g2) with ECD clusters ranged from 20 to 100%, with a mean of 82%. Eight patients underwent resection of single (1 patient) and multiple (7 patients) lobes, with 6 patients achieving freedom from seizures. Of 8 patients who underwent surgery, in 7 the resection area covered ECD clusters and grouped evSAM(g2)s. In the remaining patient the resection area partially included the ECD cluster and grouped evSAM(g2)s. Six of the 7 patients became seizure free.

Conclusions

The combination of SAM(g2) and ECD analyses succeeded in localizing the complex epileptic zones in children with TSC who had intractable epilepsy secondary to multiple cortical tubers. For the subset of children with TSC who present with early-onset and nonlateralized seizures, MEG studies in which SAM(g2) and ECD are used might identify suitable candidates for resection to control seizures.