The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery.

OBJECTIVE: The aim of this study was to investigate the utility of three-dimensional electroencephalography source imaging (3D-ESI) with low-resolution electroencephalographic data in the pediatric noninvasive presurgical evaluation, and to compare the findings with positron emission tomography (PET) and ictal single-photon emission computed tomography (iSPECT). METHODS: We retrospectively selected 60 patients from a database of 594 patients who underwent excisional surgery for drug-resistant epilepsy. Patients were <18 years at time of surgery, had at least one presurgical volumetric brain magnetic resonance imaging (MRI), and at least 1 year of outcome data. 3D-ESI was performed with NeuroScan software CURRY V.7.0. For each patient the surgical resection was planned utilizing 3D-ESI as an adjunctive tool to supplement MRI and electrocorticographic data. Our analyses addressed three critical variables: pathology (focal cortical dysplasia vs. other pathologies), imaging (MRI negative vs. positive cases), and surgery (temporal resection vs. extratemporal and multilobar resections). We also compared the localizing utility and surgical outcome of 3D-ESI findings with PET, iSPECT, and the colocalized surgical resection. Statistical analyses were performed using the Statistical Package for the Social Sciences, Version 20. RESULTS: Mean age at surgery was 11.18 years (range 1-18 years). 3D-ESI showed a strong correlation with the surgical resection cavity (65.0%), particularly within the temporal lobe. 3D-ESI demonstrated better localization in MRI-negative cases (78.6%), which was not statistically significant. 3D-ESI also correlated with a superior surgical outcome profile compared to PET and iSPECT. SIGNIFICANCE: Our findings demonstrate that 3D-ESI data obtained with low-resolution electroencephalography achieves reasonably accurate noninvasive localization of epileptic spikes in pediatric focal epilepsy, especially in temporal lobe and MRI-negative cases, and is comparable to iSPECT and PET. Given its lesser expense and lack of radiation exposure, 3D-ESI is a useful and efficient tool for evaluating surgical candidacy in pediatric epilepsy surgery centers, particularly if PET and iSPECT are unavailable.

Atypical language representation in children with intractable temporal lobe epilepsy.

This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity.

Predictors of seizure-free outcome after epilepsy surgery for pediatric tuberous sclerosis complex.

PURPOSE: Variable predictors of postsurgical seizure outcome have been reported in children with tuberous sclerosis complex (TSC). We analyzed a large surgical series of pediatric TSC patients in order to identify prognostic factors crucial for selection of subjects for epilepsy surgery. METHODS: Thirty-three children with TSC who underwent excisional epilepsy surgery at Miami Children's Hospital were retrospectively reviewed. A total of 29 clinical, neuropsychological, electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical variables were analyzed and related to seizure outcomes. Univariate Barnard's exact test, Wilcoxon's rank-sum test, and multivariate statistical Cox's model were used to examine the significance of associations between the variables and seizure outcome. KEY FINDINGS: Eighteen patients (55%) have been seizure-free 2 years after (final) surgery; postoperative complications occurred in five subjects (15%). Complete removal of epileptogenic tissue detected by both MRI and intracranial EEG, regional scalp interictal EEG patterns, and agreement of interictal and ictal EEG localization were the most powerful predictors of seizure-free outcome. Other significant predictors included occurrence of regional scalp ictal EEG patterns, fewer brain regions affected by tubers, presence of preoperative hemiparesis, and one-stage surgery. Remaining factors such as age at seizure onset, incidence of infantile spasms or other seizure types, duration of epilepsy, seizure frequency, mental retardation, as well as types and extent of resections did not influence outcome. SIGNIFICANCE: Perioperative features rather than preoperative variables are the most important determinants of postsurgical seizure outcome in patients with TSC. Our findings may assist in the surgical management of these patients.

Low-grade focal cortical dysplasia is associated with prenatal and perinatal brain injury.

PURPOSE: Prenatal and perinatal adverse events are reported to have a pathogenetic role in focal cortical dysplasia (FCD). However, no data are available regarding the prevalence and significance of this association. A cohort of children with significant prenatal and perinatal brain injury and histologically proven mild malformations of cortical development (mMCD) or FCD was analyzed. METHODS: We retrospectively evaluated a surgical series of 200 patients with histologically confirmed mMCD/FCD. Combined historical and radiologic inclusion criteria were used to identify patients with prenatal and perinatal risk factors. Electroclinical, imaging, neuropsychological, surgical, histopathologic, and seizure outcome data were reviewed. RESULTS: Prenatal and perinatal insults including severe prematurity, asphyxia, bleeding, hydrocephalus, and stroke occurred in 12.5% of children with mMCD/FCD (n = 25). Their epilepsy was characterized by early seizure onset, high seizure frequency, and absence of seizure control. Patients with significant prenatal and perinatal risk factors had more abnormal neurologic findings, lower intelligence quotient (IQ) scores, and slower background EEG activity than mMCD/FCD subjects without prenatal or perinatal brain injury. MRI evidence of cortical malformations was identified in 74% of patients. Most patients underwent large multilobar resections or hemispherectomies; 54% were seizure-free 2 years after surgery. Histologically "milder" forms of cortical malformations (mMCD and FCD type I) were observed most commonly in our series. CONCLUSIONS: Surgically remediable low-grade cortical malformations may occur in children with significant prenatally and perinatally acquired encephalopathies and play an important role in the pathogenesis of their epilepsy. Presurgical detection of dysplastic cortex has important practical consequences for surgical planning.

Surgical management of pediatric patients with encephalopathy due to electrical status epilepticus during sleep (ESES).

ESES is a developmental epileptic disorder directly responsible for progressive encephalopathy and neurocognitive regression. The natural history, indications for surgical intervention, and predictors for favorable seizure and neuropsychological outcome remain unclear. We performed a retrospective review of children who underwent resective or disconnective surgery for ESES between January 2009 and July 2016 at a large tertiary pediatric center. Information on the patients' demographics, seizure semiology, radiographic and electrographic findings, and surgical management was collected. The primary outcome was seizure freedom at last follow-up visit, and secondary outcomes were neuropsychological improvement and electrographic ESES resolution. We identified 11 children who underwent surgery for ESES. The mean ages were 3.2 years for seizure onset, 7.1 years for formal ESES diagnosis, and 9.4 years for surgery. Seizure etiologies included cortical malformations (four patients), encephalomalacia and gliosis from prior hemorrhage or tumor resections (three patients), developmental porencephaly (one patient), and Rasmussen's encephalitis (one patient); the etiology was unknown in two children. Preoperatively, nine children had motor deficits, seven had speech and language delay, and three had visual field defects. All children had seizures and neuropsychological regression prior to surgical consideration. Focal cortical resections were performed in seven children, and hemispherectomies in four. Post-operatively, nine children experienced decreased seizure frequency, eight had neuropsychological improvement, and nine had resolution of electrographic ESES. Patients with poor surgical outcomes had more significant pre-operative comorbidities, in addition to bilateral ESES activity. In this case series, surgery for a carefully selected group of children with ESES is safe and feasible, yielding rates of seizure freedom and neuropsychological improvement that compare favorably with previous reports for antiepileptic drugs, benzodiazepines, and steroids. As we gain greater understanding into the management of ESES, surgery is an increasingly useful tool for patients with mild or moderate neurodevelopmental delay, focal epileptogenic foci, and hemi-ESES electrographic findings.

Different features of histopathological subtypes of pediatric focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most frequent pathological finding in pediatric epilepsy surgery patients. Several histopathological types of FCD are distinguished. The aim of the study was to define distinctive features of FCD subtypes. METHODS: We retrospectively reviewed clinical, electroencephalographic, magnetic resonance imaging, neuropsychological, and surgical variables, and seizure outcome data in 200 children. Cortical malformations were histopathologically confirmed in all patients, including mild malformation of cortical development type II (mMCD) in 36, FCD type Ia in 55, FCD type Ib in 39, FCD type IIa in 35, and FCD type IIb in 35 subjects. RESULTS: Perinatal risk factors were more frequent in mMCD/FCD type I than FCD type II. Children with FCD type IIb had more localized ictal electroencephalographic patterns and magnetic resonance imaging changes. Increased cortical thickness, abnormal gyral/sulcal patterns, gray/white matter junction blurring, and gray matter signal abnormality in fluid-attenuated inversion recovery and T2-weighted sequences occurred more often in FCD type II, were infrequent in FCD type I, and rare in mMCD. Lobar hypoplasia/atrophy was common in FCD type I. Hippocampal sclerosis was most frequent in FCD type I. Neuropsychological testing demonstrated no significant differences between the groups. There was a trend toward better surgical outcomes in FCD type II compared with FCD type I patients. INTERPRETATION: Different histopathological types of mMCD/FCD have distinct clinical and imaging characteristics. The ability to predict the subtype before surgery could influence surgical planning. Invasive electroencephalographic study should be considered when mMCD/FCD type I is expected based on noninvasive tests.

Nontask-Related Brain Lateralization Biomarkers in Children: The Asymmetry of Language Areas on Functional Connectivity Functional Magnetic Resonance Imaging.

In this work, we will test the hypothesis that the connectivity of language areas in normal children is asymmetric between the hemispheres. Intrahemispheric region of interest (ROI)-to-ROI connectivity was assessed in 40 normal right-handed children. Asymmetries were assessed (1) between the hemispheres (global language connectivity); (2) between Brodmann areas (BAs) pairs (pairwise connectivity); and (3) between two homotopic BA (Global BA connectivity). Sixteen BAs were selected: 6, 7, 9, 19, 21, 22, 37, 38, 39, 40, 41, 42, 44, 45, 46, and 47. T scores for connectivity of each BA pair were ascertained using the MATLAB toolbox CONN. Lateralization index (LI) scores based on T-values were obtained. Only LIs with 2SD above the mean were considered as significant. Comparisons between T-value groups (per side and per BA) were performed utilizing double-sided T-tests. Null hypothesis was rejected for p < 0.05. There was not a statistical difference between global left and right connectivity strength (p = 0.40). There was significant pairwise connectivity asymmetry for the following pairs: BA7-BA44 (LI = 0.662); BA21-BA42 (LI = -0.616); BA21-BA40 (LI = -0.595); BA38-BA44 (LI = 0.470); BA39-BA44 (LI = -0.903); and BA42-BA47 (LI = -0.445). Language-related brain connectivity asymmetries have been demonstrated in a group of children and young adolescents. Two pairs related to Broca's area were left dominant (BA44-BA38 and BA44-BA7) and four pairs right dominant (BA42-BA47, BA39-BA44, BA21-BA40, and BA21-BA42).

Are hypnosis and dissociation related? New evidence for a connection.

The authors revisit the question of the existence of a relationship between hypnotizability and dissociative capacity. In the present study, the State Scale of Dissociation (SSD) replaced the commonly employed Dissociative Experiences Scale (DES) as a measure of dissociation, due to the latter capturing primarily pathological aspects of dissociation. Relationships between the Harvard Scale of Hypnotic Susceptibility, Form A (HGSHS:A), the SSD, and the Phenomenology of Consciousness Inventory (PCI) were assessed in the context of hypnosis. Robust results were found when comparing pre- to post-SSD scores, suggesting heightened nonpathological forms of dissociation are indeed related to hypnotizability. The appropriateness of the DES and similar trait-based measures for evaluating hypnotic phenomena is discussed as well as the relationships between PCI and SSD subscales.

Early seizure onset and dysplastic lesion extent independently disrupt cognitive networks.

OBJECTIVE: To determine the most important factors influencing neuropsychological performance in children with intractable epilepsy due to focal cortical dysplasia and the nature of the interaction among significant variables. METHODS: Surgical patients with histologically verified focal cortical dysplasia were retrospectively evaluated to determine the impact of histopathology, extent of lobar involvement, hemispheric laterality, age at onset, and duration of epilepsy on cognitive functioning. A composite neuropsychological variable was obtained by transforming data from 5 major cognitive domains using principal components analysis. Multiple regression was used to examine the unique contributions of predictor variables on composite cognition and Full Scale IQ. Data were qualitatively evaluated for nonstatistical trends. RESULTS: Poor cognitive outcomes were associated with early age at onset of epilepsy (AOE) and widespread dysplastic involvement. Extent of dysplasia and AOE together accounted for 35% of Full Scale IQ variance, and 21% of composite cognitive performance. Each factor contributed independently to cognitive dysfunction. CONCLUSIONS: Early AOE disrupts critical periods of development and leads to poor cognitive outcome, but children with multilobar dysplasia are likely to have diminished cognitive skills regardless of AOE. Later AOE is not expected to mitigate deficits because of widespread pathology, nor would a localized lesion be likely to mollify the developmental deficits resulting from early AOE.

Atypical propositional language organization in prenatal and early-acquired temporal lobe lesions.

This study investigated differences in propositional language organization in children with developmental and acquired brain lesions. We evaluated 30 right-handed subjects with intractable epilepsy due to either focal cortical dysplasia or hippocampal sclerosis with neuropsychological testing and functional MRI prior to epilepsy surgery. Atypical activations were seen in both prenatal and early postnatal lesions, but the contribution of specific histopathological substrate was minimal. Atypical organization of both temporal and frontal language areas also correlated inversely with receptive vocabulary scores. The data demonstrated a greater propensity toward atypical activation patterns for receptive than expressive networks, particularly when lesions were located in the dominant temporal lobe. Atypical language organization was not correlated with seizure-related factors such as age at onset or duration of epilepsy. The patterns of atypical language activation support prior studies implicating proximity of pathology to eloquent cortex in the dominant hemisphere as the primary determinant of functional reorganization.