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Elysa Widjaja and Charles Raybaud

Intractable seizures can have a devastating effect on the development of a child. In children with intractable epilepsy that is refractory to medication, surgical treatment may be needed. Magnetic resonance imaging is an essential neuroimaging tool to assist in the identification of an epileptogenic substrate. The interpretation of MR images should be done in the context of clinical knowledge of the seizure symptomatology and electroencephalographic findings. Quantitative processing of structural MR data and advanced MR imaging such as diffusion tensor imaging and MR spectroscopy have the potential to identify subtle lesions that may otherwise have been missed. In addition to lesion localization, identification of eloquent cortex and white matter tracts are also an essential component of epilepsy surgery workup. Functional MR imaging maps the sensorimotor cortex and also lateralizes language. Diffusion tensor imaging tractography can be used to map the corticospinal tracts and the optic radiations. In addition to MR imaging, magnetoencephalography and nuclear medicine studies such as PET and SPECT scanning may be used to lateralize seizure focus when clinical, electrophysiological, and structural MR imaging findings are discordant.

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Mony Benifla, Francesco Sala, John Jane Jr., Hiroshi Otsubo, Ayako Ochi, James Drake, Shelly Weiss, Elizabeth Donner, Ayataka Fujimoto, Stephanie Holowka, Elysa Widjaja, O. Carter Snead III, Mary Lou Smith, Mandeep S. Tamber and James T. Rutka

Object

The authors undertook this study to review their experience with cortical resections in the rolandic region in children with intractable epilepsy.

Methods

The authors retrospectively reviewed the medical records obtained in 22 children with intractable epilepsy arising from the rolandic region. All patients underwent preoperative electroencephalography (EEG), MR imaging, prolonged video-EEG recordings, functional MR imaging, magnetoencephalography, and in some instances PET/SPECT studies. In 21 patients invasive subdural grid and depth electrode monitoring was performed. Resection of the epileptogenic zones in the rolandic region was undertaken in all cases. Seizure outcome was graded according to the Engel classification. Functional outcome was determined using validated outcome scores.

Results

There were 10 girls and 12 boys, whose mean age at seizure onset was 3.2 years. The mean age at surgery was 10 years. Seizure duration prior to surgery was a mean of 7.4 years. Nine patients had preoperative hemiparesis. Neuropsychological testing revealed impairment in some domains in 19 patients in whom evaluation was possible. Magnetic resonance imaging abnormalities were identified in 19 patients. Magnetoencephalography was performed in all patients and showed perirolandic spike clusters on the affected side in 20 patients. The mean duration of invasive monitoring was 4.2 days. The mean number of seizures during the period of invasive monitoring was 17. All patients underwent resection that involved primary motor and/or sensory cortex. The most common pathological entity encountered was cortical dysplasia, in 13 children. Immediately postoperatively, 20 patients had differing degrees of hemiparesis, from mild to severe. The hemiparesis improved in all affected patients by 3–6 months postoperatively. With a mean follow-up of 4.1 years (minimum 2 years), seizure outcome in 14 children (64%) was Engel Class I and seizure outcome in 4 (18%) was Engel Class II. In this series, seizure outcome following perirolandic resection was intimately related to the child's age at the time of surgery. By univariate logistic regression analysis, age at surgery was a statistically significant factor predicting seizure outcome (p < 0.024).

Conclusions

Resection of rolandic cortex for intractable epilepsy is possible with expected morbidity. Accurate mapping of regions of functional cortex and epileptogenic zones may lead to improved seizure outcome in children with intractable rolandic epilepsy. It is important to counsel patients and families preoperatively to prepare them for possible worsened functional outcome involving motor, sensory and/or language pathways.

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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.

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Michael J. Ellis, James T. Rutka, Abhaya V. Kulkarni, Peter B. Dirks and Elysa Widjaja

Arteriovenous malformations (AVMs) can lead to distortion or reorganization of functional brain anatomy, making localization of eloquent white matter tracts challenging. To improve the accuracy of corticospinal tract (CST) mapping, recent studies have examined the use of functional imaging techniques to help localize cortical motor activations and use these as seed points to reconstruct CSTs using diffusion-tensor imaging (DTI). The authors examined the role of pretreatment functionally guided DTI CST mapping in 3 children with ruptured AVMs. In 2 patients, magnetoencephalography motor activations were adjacent to the nidus and/or hemorrhagic cavity. However, in 1 child, functional MRI motor activations were detected in both hemispheres, suggestive of partial transfer of cortical motor function. In all children, quantitative analysis showed that fractional anisotropy values and fiber density indices were reduced in the CSTs of the hemisphere harboring the AVM compared with the unaffected side. In 2 children, CST caliber was slightly diminished, corresponding to no motor deficit in 1 patient and a temporary motor deficit in the other. In contrast, 1 child demonstrated marked reduction and displacement of the CSTs, correlating with severe motor deficit. Preoperative motor tractography data were loaded onto the intraoperative neuronavigation platform to guide complete resection of the AVM in 2 cases without permanent neurological deficits. These preliminary results confirm the feasibility of CST mapping in children with ruptured AVMs using functionally guided DTI tractography. Prospective studies are needed to assess the full value of this technique in the risk stratification, prognosis, and multimodality management of pediatric AVMs.

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Shobhan Vachhrajani, Sandrine de Ribaupierre, Hiroshi Otsubo, Ayako Ochi, Shelly K. Weiss, Elizabeth J. Donner, Elysa Widjaja, Elizabeth Kerr, Mary Lou Smith, James Drake, O. Carter Snead III and James T. Rutka

Object

Pediatric frontal lobe epilepsy (FLE) remains a challenging condition for neurosurgeons and epileptologists to manage. Postoperative seizure outcomes remain far inferior to those observed in temporal lobe epilepsies, possibly due to inherent difficulties in delineating and subsequently completely resecting responsible epileptogenic regions. In this study, the authors review their institutional experience with the surgical management of FLE and attempt to find predictors that may help to improve seizure outcome in this population.

Methods

All surgically treated cases of intractable FLE from 1990 to 2008 were reviewed. Demographic information, preoperative and intraoperative imaging and electrophysiological investigations, and follow-up seizure outcome were assessed. Inferential statistics were performed to look for potential predictors of seizure outcome.

Results

Forty patients (20 male, 20 female) underwent surgical management of FLE during the study period. Patients were an average of 5.6 years old at the time of FLE onset and 11.7 years at the time of surgery; patients were followed for a mean of 40.25 months. Most patients displayed typical FLE semiology. Twenty-eight patients had discrete lesions identified on MRI. Eight patients underwent 2 operations. Cortical dysplasia was the most common pathological diagnosis. Engel Class I outcome was obtained in 25 patients (62.5%), while Engel Class II outcome was observed in 5 patients (12.5%). No statistically significant predictors of outcome were found.

Conclusions

Control of FLE remains a challenging problem. Favorable seizure outcome, obtained in 62% of patients in this series, is still not as easily obtained in FLE as it is in temporal lobe epilepsy. While no statistically significant predictors of seizure outcome were revealed in this study, patients with FLE continue to require extensive workup and investigation to arrive at a logical and comprehensive neurosurgical treatment plan. Future studies with improved neuroimaging and advanced invasive monitoring strategies may well help define factors for success in this form of epilepsy that is difficult to control.

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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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Abhaya V. Kulkarni, Ruth Donnelly, Donald J. Mabbott and Elysa Widjaja

OBJECT

Larger-than-normal ventricles can persist in children following hydrocephalus treatment, even if they are asymptomatic and clinically well. This study aims to answer the following question: do large ventricles result in brain injuries that are detectable on diffusion tensor imaging (DTI) and/or in measurable neurocognitive deficits in children with stable, treated hydrocephalus that are not seen in children with small ventricles?

METHODS

For this prospective study, we recruited 23 children (age range 8–18 years) with hydrocephalus due to aqueductal stenosis or tectal glioma who were asymptomatic following hydrocephalus treatment that had been performed at least 2 years earlier. All patients underwent detailed DTI and a full battery of neuropsychological tests. Correlation analysis was performed to assess the relationship between DTI parameters, neurocognitive tests, and ventricular size. The false-discovery rate method was used to adjust for multiple comparisons.

RESULTS

The median age of these 23 children at the time of assessment was 15.0 years (interquartile range [IQR] 12.1–17.6 years), and the median age at the first hydrocephalus treatment was 5.8 years (IQR 2.2 months–12.8 years). At the time of assessment, 17 children had undergone endoscopic third ventriculostomy and 6 children had received a shunt. After adjusting for multiple comparisons, there were no significant correlations between any neurocognitive test and ventricular volume, any DTI parameter and ventricular volume, or any DTI parameter and neurocognitive test.

CONCLUSIONS

Our data do not show an association between large ventricular size and additional white matter injury or worse neurocognitive deficits in asymptomatic children with stable, treated hydrocephalus caused by a discrete blockage of the cerebral aqueduct. Further investigations using larger patient samples are needed to validate these results.

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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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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.