Clinical outcomes of pediatric hemispherectomy following unsuccessful subhemispheric resection for refractory epilepsy: a case review study.

OBJECTIVE: Epilepsy surgery remains one of the most underutilized procedures in epilepsy despite its proven superiority to other available therapies. This underutilization is greater in patients in whom initial surgery fails. This case series examined the clinical characteristics, reasons for initial surgery failure, and outcomes in a cohort of patients who underwent hemispherectomy following unsuccessful smaller resections for intractable epilepsy (subhemispheric group [SHG]) and compared them to those of a cohort of patients who underwent hemispherectomy as the first surgery (hemispheric group [HG]). The objective of this paper was to determine the clinical characteristics of patients in whom a small, subhemispheric resection failed, who went on to become seizure free after undergoing a hemispherectomy. METHODS: Patients who underwent hemispherectomy at Seattle Children's Hospital between 1996 and 2020 were identified. Inclusion criteria for SHG were as follows: 1) patients ≤ 18 years of age at the time of hemispheric surgery; 2) initial subhemispheric epilepsy surgery that did not produce seizure freedom; 3) hemispherectomy or hemispherotomy after the subhemispheric surgery; and 4) follow-up for at least 12 months after hemispheric surgery. Data collected included the following: patient demographics; seizure etiology; comorbidities; prior neurosurgeries; neurophysiological studies; imaging studies; and surgical details-plus surgical, seizure, and functional outcomes. Seizure etiology was classified as follows: 1) developmental, 2) acquired, or 3) progressive. The authors compared SHG to HG in terms of demographics, seizure etiology, and seizure and neuropsychological outcomes. RESULTS: There were 14 patients in the SHG and 51 patients in the HG. All patients in the SHG had Engel class IV scores after their initial resective surgery. Overall, 86% (n = 12) of the patients in the SHG had good posthemispherectomy seizure outcomes (Engel class I or II). All patients in the SHG who had progressive etiology (n = 3) had favorable seizure outcomes, with eventual hemispherectomy (1 each with Engel classes I, II, and III). Engel classifications posthemispherectomy between the groups were similar. There were no statistical differences in postsurgical Vineland Adaptive Behavior Scales Adaptive Behavior Composite scores or postsurgical full-scale IQ scores between groups when accounting for presurgical scores. CONCLUSIONS: Hemispherectomy as a repeat surgery after unsuccessful subhemispheric epilepsy surgery has a favorable seizure outcome, with stable or improved intelligence and adaptive functioning. Findings in these patients are similar to those in patients who had hemispherectomy as their first surgery. This can be explained by the relatively small number of patients in the SHG and the higher likelihood of hemispheric surgeries to resect or disconnect the entire epileptogenic lesion compared to smaller resections.

Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries.

OBJECTIVE: The goal of epilepsy surgery is both seizure cessation and maximal preservation of function. In temporal lobe (TL) cases, the lack of functional MRI (fMRI) tasks that effectively activate mesial temporal structures hampers preoperative memory risk assessment, especially in children. This study evaluated pediatric TL surgery outcome optimization associated with tailored resection informed by an fMRI memory task. METHODS: The authors identified focal onset TL epilepsy patients with 1) TL resections; 2) viable fMRI memory scans; and 3) pre- and postoperative neuropsychological (NP) evaluations. They retrospectively evaluated preoperative fMRI memory scans, available Wada tests, pre- and postoperative NP scores, postoperative MRI scans, and postoperative Engel class outcomes. To assess fMRI memory task outcome prediction, the authors 1) overlaid preoperative fMRI activation onto postoperative structural images; 2) classified patients as having "overlap" or "no overlap" of activation and resection cavities; and 3) compared these findings with memory improvement, stability, or decline, based on Reliable Change Index calculations. RESULTS: Twenty patients met the inclusion criteria. At a median of 2.1 postoperative years, 16 patients had Engel class IA outcomes and 1 each had Engel class IB, ID, IIA, and IID outcomes. Functional MRI activation was linked to NP memory outcome in 19 of 20 cases (95%). Otherwise, heterogeneity characterized the cohort. CONCLUSIONS: Functional MRI memory task activation effectively predicted individual NP outcomes in the context of tailored TL resections. Patients had excellent seizure and overall good NP outcomes. This small study adds to extant literature indicating that pediatric TL epilepsy does not represent a single clinical syndrome. Findings support individualized surgical intervention using fMRI memory activation to help guide this precision medicine approach.

A clinically applicable functional MRI memory paradigm for use with pediatric patients.

OBJECTIVE: Clinically employable functional MRI (fMRI) memory paradigms are not yet established for pediatric patient epilepsy surgery workups. Seeking to establish such a paradigm, we evaluated the effectiveness of memory fMRI tasks we developed by quantifying individual activation in a clinical pediatric setting, analyzing patterns of activation relative to the side of temporal lobe (TL) pathology, and comparing fMRI and Wada test results. METHODS: We retrospectively identified 72 patients aged 6.7-20.9 years with pathology (seizure focus and/or tumor) limited to the TL who had attempted memory and language fMRI tasks over a 9-year period as part of presurgical workups. Memory fMRI tasks required visualization of autobiographical memories in a block design alternating with covert counting. Language fMRI protocols involved verb and sentence generation. Scans were both qualitatively interpreted and quantitatively assessed for blood oxygenation level dependent (BOLD) signal change using region of interest (ROI) masks. We calculated the percentage of successfully scanned individual cases, compared 2 memory task activation masks in cases with left versus right TL pathology, and compared fMRI with Wada tests when available. Patients who had viable fMRI and Wada tests had generally concordant results. RESULTS: Of the 72 cases, 60 (83%), aged 7.6-20.9 years, successfully performed the memory fMRI tasks and 12 (17%) failed. Eleven of 12 unsuccessful scans were due to motion and/or inability to perform the tasks, and the success of a twelfth was indeterminate due to orthodontic metal artifact. Seven of the successful 60 cases had distorted anatomy that precluded employing predetermined masks for quantitative analysis. Successful fMRI memory studies showed bilateral mesial temporal activation and quantitatively demonstrated: (1) left activation (L-ACT) less than right activation (R-ACT) in cases with left temporal lobe (L-TL) pathology, (2) nonsignificant R-ACT less than L-ACT in cases with right temporal lobe (R-TL) pathology, and (3) lower L-ACT plus R-ACT activation for cases with L-TL versus R-TL pathology. Patients who had viable fMRI and Wada tests had generally concordant results. SIGNIFICANCE: This study demonstrates evidence of an fMRI memory task paradigm that elicits reliable activation at the individual level and can generally be accomplished in clinically involved pediatric patients. This autobiographical memory paradigm showed activation in mesial TL structures, and cases with left compared to right TL pathology showed differences in activation consistent with extant literature in TL epilepsy. Further studies will be required to assess outcome prediction.

Awake Mapping of the Auditory Cortex during Tumor Resection in an Aspiring Musical Performer: A Case Report.

INTRODUCTION: Preoperative functional MRI (fMRI) and intraoperative awake cortical mapping are established strategies to identify and preserve critical language structures during neurosurgery. There is growing appreciation for the need to similarly identify and preserve eloquent tissue critical for music production. CASE REPORT: A 19-year-old female musician, with a 3- to 4-year history of events concerning for musicogenic seizures, was found to have a right posterior temporal tumor, concerning for a low-grade glial neoplasm. Preoperative fMRI assessing passive and active musical tasks localized areas of activation directly adjacent to the tumor margin. Cortical stimulation during various musical tasks did not identify eloquent tissue near the surgical site. A gross total tumor resection was achieved without disruption of singing ability. At 9-month follow-up, the patient continued to have preserved musical ability with full resolution of seizures and without evidence of residual lesion or recurrence. CONCLUSION: A novel strategy for performing an awake craniotomy, incorporating preoperative fMRI data for music processing with intraoperative cortical stimulation, interpreted with the assistance of a musician expert and facilitated gross total resection of the patient's tumor without comprising her musical abilities.

Impact of epilepsy surgery on development of preschool children: identification of a cohort likely to benefit from early intervention.

OBJECT: Outcomes of focal resection in young children with early-onset epilepsy are varied in the literature due to study differences. In this paper, the authors sought to define the effect of focal resection in a small homogeneous sample of children who were otherwise cognitively intact, but who required early surgical treatment. Preservation of and age-appropriate development of intelligence following focal resection was hypothesized. METHODS: Cognitive outcome after focal resection was retrospectively reviewed for 15 cognitively intact children who were operated on at the ages of 2-6 years for lesion-related, early-onset epilepsy. Intelligence was tested prior to and after surgery. Effect sizes and confidence intervals for means and standard deviations were used to infer changes and differences in intelligence between 1) groups (pre vs post), 2) left versus right hemisphere resections, and 3) short versus long duration of seizures prior to resection. RESULTS: No group changes from baseline occurred in Full Scale, verbal, or nonverbal IQ. No change from baseline intelligence occurred in children who underwent left or right hemisphere surgery, including no group effect on verbal scores following surgery in the dominant hemisphere. Patients with seizure durations of less than 6 months prior to resection showed improvement from their presurgical baseline in contrast to those with seizure duration of greater than 6 months prior to surgery, particularly in Wechsler Full Scale IQ and nonverbal intelligence. CONCLUSIONS: This study suggests that surgical treatment of focal seizures in cognitively intact preschool children is likely to result in seizure remediation, antiepileptic drug discontinuation, and no significant decrement in intelligence. The latter finding is particularly significant in light of the longstanding concern associated with performing resections in the language-dominant hemisphere. Importantly, shorter seizure duration prior to resection can result in improved cognitive outcome, suggesting that surgery for this population should occur sooner to help improve intelligence outcomes.

Functional magnetic resonance imaging for presurgical evaluation of very young pediatric patients with epilepsy.

OBJECT: The authors describe their experience with functional MR (fMR) imaging in children as young as 5 years of age, or even younger in developmental age equivalent. Functional MR imaging can be useful for identifying eloquent cortex prior to surgical intervention. Most fMR imaging clinical work has been done in adults, and although children as young as 8 years of age have been included in larger clinical series, cases in younger children are rarely reported. METHODS: The authors reviewed presurgical fMR images in eight patients who were 8 years of age or younger, six of whom were 5 or 6 years of age. Each patient had undergone neuropsychological testing. Three patients functioned at a below-average level, with adaptive functioning age scores of 3 to 4 years. Self-paced finger tapping (with passive movement in one patient) and silent language tasks were used as activation tasks. The language task was modified for younger children, for whom the same (not novel) stimuli were used for extensive practice ahead of time and in the MR imaging unit. Patient preparation involved techniques such as having experienced staff present to work with patients and providing external management during imaging. Six of eight patients had extensive training and practice prior to the procedure. In the two youngest patients, this training included use of a mock MR unit. RESULTS: All cases yielded successful imaging. Finger tapping in all seven of the patients who could perform it demonstrated focal motor activation in the frontal-parietal region, with expected activation elsewhere, including in the cerebellum. Three of four patients had the expected verb generation task activations, with left-hemisphere dominance, including a 6-year-old child who functioned at the 3-year, 9-month level. The only child (an 8-year-old) who was not prepared prior to the imaging session for the verb generation task failed this task due to movement artifact. CONCLUSIONS: Despite the challenges of successfully using fMR imaging in very young and clinically involved patients, these studies can be performed successfully in children with a chronological age of 5 or 6 years and a developmental age as young as 3 or 4 years.

Use of dexmedetomidine in awake craniotomy in adolescents: report of two cases.

Awake craniotomy is a key tool in resection of lesions near critical functional regions, particularly the speech area. Craniotomy with an awake portion for mapping may be performed in carefully selected adolescents and preteenaged children. A number of different regimens may be used for sedation and anesthesia in these cases. We describe two adolescent patients in whom awake craniotomy was performed using an intravenous anesthesia technique with dexmedetomidine and without need for airway instrumentation.