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.

Laser Ablation Therapy for Pediatric Patients with Intracranial Lesions in Eloquent Areas.

BACKGROUND: Laser interstitial thermal therapy (LITT) is an alternative, less-invasive, and, in some circumstances, effective treatment for patients with intracranial pathology including epilepsy and some tumors. For intracranial lesions in eloquent areas, resection by conventional craniotomy proves often to be a challenge, including in the care of pediatric patients. Herein, we reviewed our experience with magnetic resonance imaging (MRI)-guided LITT as treatment for pediatric patients with intracranial lesions in eloquent areas and evaluate neurologic function and clinical outcomes. METHODS: We retrospectively reviewed consecutive patients with intracranial lesions in eloquent speech and motor areas who underwent MRI-guided LITT. Clinical evaluation, including neurologic function and neuropsychological testing, was conducted according to clinical considerations. MRI pre- and postoperative imaging was reviewed to compare the change of lesion size. RESULTS: Five pediatric patients received MRI-guided LITT of intracranial lesions in eloquent cortex. One patient experienced complications secondary to MRI-guided LITT, but neither was discharged with a neurologic deficit. CONCLUSIONS: For intracranial lesions in the eloquent cortex, conventional craniotomy with surgical resection is a challenge for neurosurgeons, especially pediatric patients. MRI-guided LITT provides a less-invasive and potentially effective option for treatment in the management of pediatric epilepsy and tumors.

Stereotactic laser ablation for hypothalamic and deep intraventricular lesions.

OBJECTIVE Laser ablation is a novel, minimally invasive procedure that utilizes MRI-guided thermal energy to treat epileptogenic and other brain lesions. In addition to treatment of mesial temporal lobe epilepsy, laser ablation is increasingly being used to target deep or inoperable lesions, including hypothalamic hamartoma (HH), subependymal giant cell astrocytoma (SEGA), and exophytic intrinsic hypothalamic/third ventricular tumors. The authors reviewed their early institutional experience with these patients to characterize clinical outcomes in patients undergoing this procedure. METHODS A retrospective cohort (n = 12) of patients undergoing laser ablation at a single institution was identified, and clinical and radiographic records were reviewed. RESULTS Laser ablation was successfully performed in all patients. No permanent neurological or endocrine complications occurred; 2 (17%) patients developed acute obstructive hydrocephalus or shunt malfunction following treatment. Laser ablation of HH resulted in seizure freedom (Engel Class I) in 67%, with the remaining patients having a clinically significant reduction in seizure frequency of greater than 90% compared with preoperative baseline (Engel Class IIB). Treatment of SEGAs resulted in durable clinical and radiographic tumor control in 2 of 3 cases, with one patient receiving adjuvant everolimus and the other receiving no additional therapy. Palliative ablation of hypothalamic/third ventricular tumors resulted in partial tumor control in 1 of 3 patients. CONCLUSIONS Early experience suggests that laser ablation is a generally safe, durable, and effective treatment for patients harboring HHs. It also appears effective for local control of SEGAs, especially in combination therapy with everolimus. Its use as a palliative treatment for intrinsic hypothalamic/deep intraventricular tumors was less successful and associated with a higher risk of serious complications. Additional experience and long-term follow-up will be beneficial in further characterizing the effectiveness and risk profile of laser ablation in treating these lesions in comparison with conventional resective surgery or stereotactic radiosurgery.

Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

IMPORTANCE: Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality. OBJECTIVE: To identify the underlying molecular cause of FCD, hemimegalencephaly, and diffuse megalencephaly. DESIGN, SETTING, AND PARTICIPANTS: Patients with FCD, hemimegalencephaly, or megalencephaly (mean age, 11.7 years; range, 2-32 years) were recruited from Pediatric Hospital A. Meyer, the University of Hong Kong, and Seattle Children's Research Institute from June 2012 to June 2014. Whole-exome sequencing (WES) was performed on 8 children with FCD or hemimegalencephaly using standard-depth (50-60X) sequencing in peripheral samples (blood, saliva, or skin) from the affected child and their parents and deep (150-180X) sequencing in affected brain tissue. Targeted sequencing and WES were used to screen 93 children with molecularly unexplained diffuse or focal brain overgrowth. Histopathologic and functional assays of phosphatidylinositol 3-kinase-AKT (serine/threonine kinase)-mammalian target of rapamycin (mTOR) pathway activity in resected brain tissue and cultured neurons were performed to validate mutations. MAIN OUTCOMES AND MEASURES: Whole-exome sequencing and targeted sequencing identified variants associated with this spectrum of developmental brain disorders. RESULTS: Low-level mosaic mutations of MTOR were identified in brain tissue in 4 children with FCD type 2a with alternative allele fractions ranging from 0.012 to 0.086. Intermediate-level mosaic mutation of MTOR (p.Thr1977Ile) was also identified in 3 unrelated children with diffuse megalencephaly and pigmentary mosaicism in skin. Finally, a constitutional de novo mutation of MTOR (p.Glu1799Lys) was identified in 3 unrelated children with diffuse megalencephaly and intellectual disability. Molecular and functional analysis in 2 children with FCD2a from whom multiple affected brain tissue samples were available revealed a mutation gradient with an epicenter in the most epileptogenic area. When expressed in cultured neurons, all MTOR mutations identified here drive constitutive activation of mTOR complex 1 and enlarged neuronal size. CONCLUSIONS AND RELEVANCE: In this study, mutations of MTOR were associated with a spectrum of brain overgrowth phenotypes extending from FCD type 2a to diffuse megalencephaly, distinguished by different mutations and levels of mosaicism. These mutations may be sufficient to cause cellular hypertrophy in cultured neurons and may provide a demonstration of the pattern of mosaicism in brain and substantiate the link between mosaic mutations of MTOR and pigmentary mosaicism in skin.

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.

Tissue localization during resective epilepsy surgery.

OBJECT: Imaging-guided surgery (IGS) systems are widely used in neurosurgical practice. During epilepsy surgery, the authors routinely use IGS landmarks to localize intracranial electrodes and/or specific brain regions. The authors have developed a technique to coregister these landmarks with pre- and postoperative scans and the Montreal Neurological Institute (MNI) standard space brain MRI to allow 1) localization and identification of tissue anatomy; and 2) identification of Brodmann areas (BAs) of the tissue resected during epilepsy surgery. Tracking tissue in this fashion allows for better correlation of patient outcome to clinical factors, functional neuroimaging findings, and pathological characteristics and molecular studies of resected tissue. METHODS: Tissue samples were collected in 21 patients. Coordinates from intraoperative tissue localization were downloaded from the IGS system and transformed into patient space, as defined by preoperative high-resolution T1-weighted MRI volume. Tissue landmarks in patient space were then transformed into MNI standard space for identification of the BAs of the tissue samples. RESULTS: Anatomical locations of resected tissue were identified from the intraoperative resection landmarks. The BAs were identified for 17 of the 21 patients. The remaining patients had abnormal brain anatomy that could not be meaningfully coregistered with the MNI standard brain without causing extensive distortion. CONCLUSIONS: This coregistration and landmark tracking technique allows localization of tissue that is resected from patients with epilepsy and identification of the BAs for each resected region. The ability to perform tissue localization allows investigators to relate preoperative, intraoperative, and postoperative functional and anatomical brain imaging to better understand patient outcomes, improve patient safety, and aid in research.

Epilepsy surgery after treatment of pediatric malignant brain tumors.

Epilepsy surgery is common in the face of benign brain tumors, but rarely for patients with a history of malignant brain tumors. Seizures are a common sequelae in survivors of malignant pediatric brain tumors. Medical management alone may not adequately treat epilepsy, including in this group. We report four cases of patients who previously underwent gross total resection, radiation therapy, and chemotherapy for successful treatment of malignant brain neoplasia, yet suffered from medically intractable seizures. All underwent surgery for treatment of epilepsy with extension of the original resection. Despite the aggressive primary treatment of the neoplasm, and the potential for diffuse cerebral insults, all benefited from focal surgical resection. Aggressive surgical management of intractable epilepsy can be considered in survivors of malignant brain tumors.

Multimodality localization of the sensorimotor cortex in pediatric patients undergoing epilepsy surgery.

OBJECT: The gold-standard method for determining cortical functional organization in the context of neurosurgical intervention is electrical cortical stimulation (ECS), which disrupts normal cortical function to evoke movement. This technique is imprecise, however, as motor responses are not limited to the precentral gyrus. Electrical cortical stimulation also can trigger seizures, is not always tolerated, and is often unsuccessful, especially in children. Alternatively, endogenous motor and sensory signals can be mapped by somatosensory evoked potentials (SSEPs), functional MRI (fMRI), and electrocorticography of high gamma (70-150 Hz) signal power, which reflect normal cortical function. The authors evaluated whether these 4 modalities of mapping sensorimotor function in children produce concurrent results. METHODS: The authors retrospectively examined the charts of all patients who underwent epilepsy surgery at Seattle Children's Hospital between July 20, 1999, and July 1, 2011, and they included all patients in whom the primary motor or somatosensory cortex was localized via 2 or more of the following tests: ECS, SSEP, fMRI, or high gamma electrocorticography (hgECoG). RESULTS: Inclusion criteria were met by 50 patients, whose mean age at operation was 10.6 years. The youngest patient who underwent hgECoG mapping was 2 years and 10 months old, which is younger than any patient reported on in the literature. The authors localized the putative sensorimotor cortex most often with hgECoG, followed by SSEP and fMRI; ECS was most likely to fail to localize the sensorimotor cortex. CONCLUSIONS: Electrical cortical stimulation, SSEP, fMRI, and hgECoG generally produced concordant localization of motor and sensory function in children. When attempting to localize the sensorimotor cortex in children, hgECoG was more likely to produce results, was faster, safer, and did not require cooperation. The hgECoG maps in pediatric patients are similar to those in adult patients published in the literature. The sensorimotor cortex can be mapped by hgECoG and fMRI in children younger than 3 years old to localize cortical function.

Is postresective intraoperative electrocorticography predictive of seizure outcomes in children?

OBJECT: Intraoperative electrocorticography (ECoG) is commonly used to guide the extent of resection, especially in lesion-associated intractable epilepsy. Interictal epileptiform discharges on postresective ECoG (post-ECoG) have been predictive of seizure recurrence in some studies, particularly in adults undergoing medial temporal lobectomy, frontal lesionectomy, or low-grade glioma resection. The predictive value of postresective discharges in pediatric epilepsy surgery has not been extensively studied. METHODS: The authors retrospectively examined the charts of all 52 pediatric patients who had undergone surgery with post-ECoG and had more than 1 year of follow-up between October 1, 2003, and October 1, 2009. RESULTS: Of the 52 pediatric patients, 37 patients showed residual discharges at the end of their resection and 73% of these patients were seizure free, whereas 15 patients had no residual discharges and 60% of them were seizure-free, which was not significantly different (p = 0.36, chi-square). CONCLUSIONS: Electrocorticography-guided surgery was associated with excellent postsurgical outcome. Although this sample size was too small to detect a subtle difference, absence of epileptiform discharges on post-ECoG does not appear to predict seizure freedom in all pediatric patients referred for epilepsy surgery. Future studies with larger study samples would be necessary to confirm this finding and determine whether post-ECoG may be useful in some subsets of pediatric epilepsy surgery candidates.

Freehand placement of depth electrodes using electromagnetic frameless stereotactic guidance.

The presurgical evaluation of patients with epilepsy often requires an intracranial study in which both subdural grid electrodes and depth electrodes are needed. Performing a craniotomy for grid placement with a stereotactic frame in place can be problematic, especially in young children, leading some surgeons to consider frameless stereotaxy for such surgery. The authors report on the use of a system that uses electromagnetic impulses to track the tip of the depth electrode. Ten pediatric patients with medically refractory focal lobar epilepsy required placement of both subdural grid and intraparenchymal depth electrodes to map seizure onset. Presurgical frameless stereotaxic targeting was performed using a commercially available electromagnetic image-guided system. Freehand depth electrode placement was then performed with intraoperative guidance using an electromagnetic system that provided imaging of the tip of the electrode, something that has not been possible using visually or sonically based systems. Accuracy of placement of depth electrodes within the deep structures of interest was confirmed postoperatively using CT and CT/MR imaging fusion. Depth electrodes were appropriately placed in all patients. Electromagnetic-tracking-based stereotactic targeting improves the accuracy of freehand placement of depth electrodes in patients with medically refractory epilepsy. The ability to track the electrode tip, rather than the electrode tail, is a major feature that enhances accuracy. Additional advantages of electromagnetic frameless guidance are discussed.

Functional MRI connectivity as a predictor of the surgical outcome of epilepsy.

PURPOSE: In planning epilepsy surgery, it is important to be able to assess the likelihood of success of surgery for each patient so that the possible risk and benefit can be properly considered. In this study, functional connectivity was investigated as a means for predicting surgical outcome from the preoperative functional magnetic resonance imaging (fMRI) of epilepsy patients. METHODS: Resting-state simultaneous electroencephalography (EEG)-fMRI data were collected from 18 patients with intractable epilepsy before surgery and from 14 healthy subjects. For each patient, EEG-spike correlated fMRI analysis was performed and an activation cluster that overlapped the most with the planned resection area for each patient was chosen as the seed for the functional connectivity analysis. After the functional connectivity maps were computed, laterality indices of functional connectivity were contrasted between patients who had seizures after surgeries (seizure-recurrence group) and those who did not have them for at least a year (seizure-free group). KEY FINDINGS: Patients in the seizure-recurrence group had less-lateralized functional connectivity than patients in the seizure-free group (t(16) = 2.3, after control subtracted and Fisher transformed, p < 0.05, two-tailed). SIGNIFICANCE: This study suggests the potential for using preoperative fMRI connectivity analysis as a predictive outcome measure. If confirmed by further research, a high laterality will be an important addition to the other predictors of better surgical outcome such as febrile seizures, mesial temporal sclerosis, tumors, abnormal MRI, and EEG/MRI concordance.

Positron emission tomography in Rasmussen's encephalitis.

This report presents unusual positron emission tomography findings in an 11-year-old male with Rasmussen's encephalitis. This patient underwent fluorine-18 fluorodeoxyglucose positron emission tomography to localize his ictal focus before surgical consideration. Positron emission tomography disclosed marked hypermetabolism in the left cerebral hemisphere and basal ganglia with subnormal right cerebral activity and crossed cerebellar diaschisis. The heterogeneous distribution of metabolism suggests a combination of areas in different stages of ictal and postictal involvement. The hypermetabolic region in the left hemisphere was larger in size and extent (now including the left frontoparietal lobe) than the sole hypermetabolic left temporal lobe on his positron emission tomography from 2 years ago. While this positron emission tomography pattern of progression appears most commonly in Rasmussen's encephalitis case studies, few serial reports exist. The complex positron emission tomography findings of this case emphasize the importance of knowing the history of recent seizures, seizure type, clinical status at time of injection, and electroencephalographic correlation before interpreting functional neuroimaging studies. Finally, positron emission tomography studies can help clarify whether patients with Rasmussen's encephalitis with dominant hemisphere involvement are appropriate candidates for surgery or not.

Aspartame: review of safety.

Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. These findings are reviewed here. The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.

Frontal lobe tumoral epilepsy: clinical, neurophysiologic features and predictors of surgical outcome.

PURPOSE: To review the clinical, neurophysiologic features and surgical outcomes in patients with frontal lobe tumors and chronic intractable seizures. METHODS: Medical records of patients with intractable epilepsy who underwent resection or stereotactic biopsy of frontal lobe tumor (confirmed by surgical pathology) seen between 1985 and 1999 at Yale University School of Medicine Epilepsy Center were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, use of anticonvulsants, extent of surgery, pathological diagnosis, and tumor recurrence. RESULTS: Thirty-seven patients were included. Mean age at seizure onset was 31.6 years, and at tumor diagnosis was 36.2 years. Mean duration between onset of seizures and tumor diagnosis was 6.1 years. Seventeen patients had auras. Seizure frequency averaged 7.6 seizures per week, with 58% of patients having more than one seizure type. All patients used anticonvulsants, with 90% eventually using polytherapy. All patients eventually underwent at least one surgical procedure. Only 13 (35.1%) patients were class I. Twelve (32.4%) patients were class II, seven (18.9%) class III, and five (13.5%) class IV. No statistically significant differences were seen between good and poor long-term seizure outcome in relation to specific tumor pathology, seizure types, or type of resection. CONCLUSIONS: Long-term surgical outcomes in tumoral frontal lobe epilepsy are more favorable than those in nontumoral intractable frontal lobe epilepsy (65% class I or II) and less favorable than those in other tumoral epilepsy (overall, 70% class I). Frontal location of intracranial neoplasm may predict a less favorable long-term epilepsy prognosis than tumoral epilepsy in general, an observation for which several explanations are proposed.