Pediatric Temporal Lobe Epilepsy Research Articles

Verbal episodic memory in children undergoing temporal lobe epilepsy surgery: a one-year follow-up study.

Verbal episodic memory (VEM) is often unimpaired in children with focal epilepsy undergoing left temporal lobe resections, unlike what we might expect in the adult brain. The latter findings suggest that epileptiform activity in early life disrupts memory system lateralization, leading to the development of bilateral memory representation. The present study aims to analyze whether the laterality of epilepsy is a major predictor for post-operative VEM prognosis in pediatric temporal lobe epilepsy (TLE) surgery. This research also pretends to provide evidence about the relationship of VEM performance with other relevant demographical and clinical factors such as sex, age at onset of seizures, age at surgery and duration of epilepsy, as well as to study the impact of presurgical VEM performance on postsurgical outcomes. Pre-operative and one-year follow-up post-operative word-list recall scores from 25 children who underwent TLE surgery (left-sided, n = 11; right-sided, n = 14) were extracted from the Hospital Sant Joan de Deu database and were retrospectively analyzed. No significant presurgical intergroup differences were found when comparing VEM scores by laterality of epilepsy (p > 0.5). Looking at the left TLE group, a high negative correlation was found between the onset age and the pre-operative long-term free recall score (rho = -0.72, p = 0.01). No significant pre- to post-operative intragroup changes were found regarding VEM performance, regardless of epilepsy laterality (left TLE group, p > 0.56; right TLE group, p > 0.12). The laterality of epilepsy does not show to be a significant factor in and of itself regarding presurgical VEM outcome and its prognosis one year after surgery, thus supporting the bilateral memory representation hypothesis. Furthermore, a younger age at onset of seizures seems to be related with a better pre-operative VEM performance, likely due to a more efficient reorganization of memory system induced by a greater brain plasticity at lower ages; however, this relationship has been only reported for the left-sided epilepsies in our sample.

The osteoplastic flap for pediatric temporal lobe epilepsy treatment: step-by-step guide and technical nuances.

The osteoplastic flap is an under-utilized craniotomy approach in pediatric temporal lobe epilepsy treatment. By preserving the myofascial attachment of the temporalis muscle, the flap is allowed the remain vascularized while subdural and intracranial electrodes are in place. The process in which the flap is made and handled throughout this process can be complicated. We herein detail our surgical technique for the osteoplastic flap in the setting of pediatric temporal lobe epilepsy treatment, and highlight the surgical nuances specific to our 2-stage protocol in treating pediatric temporal lobe epilepsy.

Concordance of functional MRI memory task and resting-state functional MRI connectivity used in surgical planning for pediatric temporal lobe epilepsy.

Assessing memory is often critical in surgical evaluation, although difficult to assess in young children and in patients with variable task abilities. While obtaining interpretable data from task-based functional MRI (fMRI) measures is common in compliant and awake patients, it is not known whether functional connectivity MRI (fcMRI) data show equivalent results. If this were the case, it would have substantial clinical and research generalizability. To evaluate this possibility, the authors evaluated the concordance between fMRI and fcMRI data collected in a presurgical epilepsy cohort. Task-based fMRI data for autobiographical memory tasks and resting-state fcMRI data were collected in patients with epilepsy evaluated at Seattle Children's Hospital between 2010 and 2017. To assess memory-related activation and laterality, signal change in task-based measures was computed as a percentage of the average blood oxygen level-dependent signal over the defined regions of interest. An fcMRI data analysis was performed using 1000 Functional Connectomes Project scripts based on Analysis of Functional NeuroImages and FSL (Functional Magnetic Resonance Imaging of the Brain Software Library) software packages. Lateralization indices (LIs) were estimated for activation and connectivity measures. The concordance between these two measures was evaluated using correlation and regression analysis. In this epilepsy cohort studied, the authors observed concordance between fMRI activation and fcMRI connectivity, with an LI regression coefficient of 0.470 (R2 = 0.221, p = 0.00076). Previously published studies have demonstrated fMRI and fcMRI overlap between measures of vision, attention, and language. In the authors' clinical sample, task-based measures of memory and analogous resting-state mapping were similarly linked in pattern and strength. These results support the use of fcMRI methods as a proxy for task-based memory performance in presurgical patients, perhaps including those who are more limited in their behavioral compliance. Future investigations to extend these results will be helpful to explore how the magnitudes of effect are associated with neuropsychological performance and postsurgical behavioral changes.

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

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. 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. 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. 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.

Global network alterations of the cognitive phenotypes in pediatric temporal lobe epilepsy

ObjectiveAn emerging literature suggests that the neuropsychological sequelae of pediatric temporal lobe epilepsy (TLE) are characterized by a continuum of cognitive phenotypes that range in type and severity. The goal of the present investigation was to better characterize the neuropsychological networks that underlie these phenotypes. MethodsThe study included 59 patients with TLE who were empirically categorized into three cognitive phenotypes (normal, focal, and generalized impairment). Nine neuropsychological measures representing multiple cognitive domains (i.e., reasoning, language, visouperception, memory, and executive function) were examined by graph theory to characterize the global network properties of the cognitive phenotypes. ResultsAcross the cognitive phenotype groups (i.e., normal, focal, generalized impaired) the following findings emerged: (1) the adjacency matrices demonstrated different patterns of association between cognitive measures within the neuropsychological network; (2) global measures including global efficiency (GE) and average clustering coefficient (aCC) showed a stepwise increase across the range of impaired pediatric TLE phenotypes; however, modularity (M) demonstrated the opposite pattern. ImpressionsCognitive networks in pediatric TLE demonstrate stepwise perturbation in underlying neuropsychological networks. Graph theory offers a novel approach to examine cognitive abnormalities in pediatric TLE that may be applied to other pediatric epilepsies.

Simultaneously Acquired MRI Arterial Spin-Labeling and Interictal FDG-PET Improves Diagnosis of Pediatric Temporal Lobe Epilepsy.

Interictal FDG-PET scans are a routine diagnostic technique for the identification of epileptogenic foci in the presurgical work-up of medically refractory pediatric epilepsy. With the advent of PET/MR imaging, it has become possible to simultaneously acquire FDG-PET and arterial spin-labeling perfusion data. The objective of this study was to evaluate whether the incorporation of arterial spin-labeling data with interictal FDG-PET could improve the diagnostic performance metrics of FDG-PET for identification of epileptogenic foci. Forty-five pediatric patients with a mean age of 10.8 years were retrospectively included in this study. These patients all underwent PET/MR imaging to diagnose suspected focal epilepsy. When compared to interpretations of interictal FDG findings alone, FDG combined with arterial spin-labeling findings resulted in significantly decreased sensitivity (0.64 versus 0.52, P = .02), significantly increased specificity (0.50 versus 0.75, P = .04), and an increased positive predictive value (0.59 versus 0.75). The decreased sensitivity was found to be primarily driven by patients with extratemporal lobe epilepsy, as a subgroup analysis showed decreased sensitivity for patients with extratemporal epilepsy (0.52 versus 0.38, P = .04), but not for temporal epilepsy (0.83 versus 0.75, P = .16). Additionally, substantial agreement between focal FDG hypometabolism and arterial spin-labeling hypoperfusion was demonstrated with the Cohen κ (0.70, P < .01). These findings suggest that simultaneously acquired interictal FDG-PET and arterial spin-labeling data can improve the diagnosis of epileptogenic foci, especially in the setting of temporal lobe epilepsy where they improve specificity and positive predictive value, with preservation of sensitivity.

Behavioral phenotypes of pediatric temporal lobe epilepsy.

A broad spectrum of emotional-behavioral problems have been reported in pediatric temporal lobe epilepsy (TLE), but with considerable variability in their presence and nature of expression, which hampers precise identification and treatment. The present study aimed to empirically identify latent patterns or behavioral phenotypes and their correlates. Data included parental ratings of emotional-behavioral status on the Behavior Assessment System for Children, 2nd Edition (BASC-2) of 81 children (mean age=11.79, standard deviation [SD]=3.93) with TLE. The nine clinical subscales were subjected to unsupervised machine learning to identify behavioral subgroups. To explore concurrent validity and the underlying composition of the identified clusters, we examined demographic factors, seizure characteristics, psychosocial factors, neuropsychological performance, psychiatric status, and health-related quality of life (HRQoL). Three behavioral phenotypes were identified, which included no behavioral concerns (Cluster 1, 43% of sample), externalizing problems (Cluster 2, 41% of sample), and internalizing problems (Cluster 3, 16% of sample). Behavioral phenotypes were characterized by important differences across clinical seizure variables, psychosocial/familial factors, everyday executive functioning, and HRQoL. Cluster 2 was associated with younger child age, lower maternal education, and higher rate of single-parent households. Cluster 3 was associated with older age at epilepsy onset and higher rates of hippocampal sclerosis and parental psychiatric history. Both Cluster 2 and 3 demonstrated elevated family stress. Concurrent validity was demonstrated through the association of psychiatric (i.e., rate of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) disorders and psychotropic medication) and parent-rated HRQoL variables. Youth with TLE present with three distinct behavioral phenotypes that correspond with important clinical and sociodemographic markers. The current findings demonstrate the variability of behavioral presentations in youth with TLE and provide a preliminary framework for screening and targeting intervention to enhance support for youth with TLE and their families.

Neuroimaging in pediatric temporal lobe epilepsy: Does neuroimaging accurately predict pathology and surgical outcome?

Temporal lobe epilepsy (TLE) in children is considered different from that in adults. As such, characterizing the structural lesions present in pediatric patients with TLE and their association with long-term seizure control is important. Here, we aimed to assess the concordance between preoperative imaging and postoperative histopathological diagnoses and their associations with seizure outcomes in pediatric patients with TLE undergoing temporal lobe surgery.We retrospectively reviewed the charts of pediatric patients with TLE who underwent surgical treatment between 1988 and 2020 as a part of the Comprehensive Epilepsy Program at the University of Alberta. Demographic, age at seizure onset, age at surgery, preoperative electroencephalography (EEG), long-term video EEG, imaging (magnetic resonance imaging [MRI] and computed tomography), neuropathology, and long-term seizure outcome data were acquired and analyzed.One hundred and seventeen patients underwent surgery for refractory TLE; the preoperative MRI diagnosis was concordant with the histopathological diagnosis in 76 % of cases. Tumors were identified with high accuracy (91 %). Mesial temporal sclerosis (MTS) was strongly associated with an excellent outcome after surgery (94 %). Patients with normal imaging results or non-specific pathologies were more likely to experience poor seizure outcomes after surgery (50 %).The radiological identification of lesions was associated with good long-term seizure outcomes, whereas normal MRI results were associated with significantly poorer long-term seizure outcomes. An accurate preoperative MRI is essential to epilepsy surgery since it impacts all stages of management; these results will thereafter help inform practitioners’ efforts to predict seizure outcome.

Quantitative Meta-Analyses: Lateralization of Memory Functions Before and After Surgery in Children with Temporal Lobe Epilepsy.

Memory deficits in children with epilepsy have been reported in some but not all studies assessing the effects of side of seizures and resection from the temporal lobe on cognitive performance. This meta-analysis provides a quantitative systematic review of previous studies on this issue. A critical review and meta-analysis of the literature on memory performance in children with Temporal Lobe Epilepsy (TLE) was conducted. Search identified 25 studies, 13 of which compared children with TLE to healthy age-matched controls and 12 of which compared children with TLE before and after surgery. Heterogeneity of the comparisons of children with TLE to healthy controls impeded drawing definitive conclusions. However, in 55% of the studies, verbal memory in children with left TLE (LTLE) was impaired as compared to healthy controls. Verbal memory performance slightly declines after pediatric LTLE surgery, but nonverbal memory tasks are not affected. By contrast, verbal memory performance is not affected by pediatric right TLE (RTLE) surgery. The findings suggest that side of the epileptogenic zone and resection from the temporal lobe affect verbal memory in children with LTLE. Right resection seems to be safe with respect to verbal memory performance.

Executive function and depressed mood are independently disruptive to health-related quality of life in pediatric temporal lobe epilepsy

ObjectiveYouth with temporal lobe epilepsy (TLE) are at increased risk of depressive features and diminished health-related quality of life (HRQOL). To assist in the development of future behavioral interventions for youth with TLE, the current study explored potential pathways by which executive functioning (EF) and depressive features impinge upon HRQOL in the context of psychosocial and seizure-specific factors. MethodsData included parental ratings on the Behavior Assessment System for Children (BASC-2), Behavior Rating Inventory of Executive Function (BRIEF), and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaires for 82 children (Age = 11.99, SD = 3.80) with TLE. Observed path analysis was used to simultaneously investigate the determinants of HRQOL in pediatric TLE. Indirect effects were evaluated with bootstrap analyses. ResultsBoth executive dysfunction and depressive features were negatively linked to child HRQOL, and, furthermore, EF and HRQOL were indirectly connected by depressive features. In addition, depressive features were linked to lower EF, current antiepileptic drug (AED) regimen, and the presence of hippocampal sclerosis. Diminished EF was linked to parental psychiatric history and family stress; EF mediated the relationship of parental psychiatric history and family stress on both depressive features and diminished HRQOL. Finally, a more complicated AED regimen and higher HRQOL were indirectly connected by depressive features. ConclusionThis study underscores the importance of child depressive features and EF along with environmental and epilepsy-specific factors on HRQOL in pediatric TLE.

Abnormalities of Cortical Thickness in Pediatric Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common intractable seizure type of pediatric epilepsy, with alterations in the cortex across the whole brain. The aim of this study is to investigate the abnormalities of cortical thickness in pediatric MTLE-HS. Subjects were recruited from Shenzhen Children's Hospital between September 2015 and December 2016. MTLE was confirmed by the experienced neurological physician based on International League Against Epilepsy (ILAE) diagnosis criteria, and structural magnetic resonance imaging (MRI) was performed at 3T for quantitative assessment of cortical thickness. A general linear model with age and gender as covariates was used to examine the vertex-wise differences in cortical thickness between 1) left MTLE-HS (LMTLE-HS) and healthy controls (HC), and 2) right MTLE-HS (RMTLE-HS) and HC. The family-wise error corrected significance threshold was set at P < 0.05. Through a combination of probability and cluster-size thresholding, cluster-wise P values were obtained for the resulting clusters. 13 LMTLE-HS, 6 RMTLE-HS, and 20 age-matched HC were finally enrolled in the study. No significant difference in the mean age (LMTLE-HS vs. HC, p=0.57; RMTLE-HS vs. HC, p=0.39) and gender ratio (LMTLE-HS vs. HC, p=0.24; RMTLE-HS vs. HC, p=0.72) was found between MTLE-HS and HC. In LMTLE-HS, cortical thickness was found significantly decreased in the ipsilateral caudal middle frontal gyrus (p=0.012) and increased in the contralateral inferior temporal gyrus (p=0.020). In RMTLE-HS, cortical thickness significantly decreased in the ipsilateral posterior parietal lobe (superior, p<0.001 and inferior parietal gyrus, p=0.03), the anterior parietal lobe (postcentral gyrus, p=0.006), the posterior frontal lobe (precentral gyrus, p=0.04 and the lateral occipital gyrus, p<0.001), and the contralateral lateral occipital gyrus, middle frontal (p<0.0001) and superior frontal gyrus (p<0.001), and pericalcarine cortex (p=0.020). We detected significant cortical abnormalities in pediatric MTLE-HS patients compared with HC. These cortical abnormalities could be explained by specific pathogenesis in MTLE-HS, and may finally contribute to understanding the intrinsic mechanism of MTLE-HS.

A Functional MRI Paradigm Suitable for Language and Memory Mapping in Pediatric Temporal Lobe Epilepsy.

Functional Magnetic Resonance Imaging (fMRI) is a technique frequently used to determine the territories of eloquent tissue that serve critical functions, such as language. This can be particularly useful as part of the pre-surgical assessment for temporal lobe epilepsy (TLE) in order to predict cognitive outcome and guide surgical decision-making. Whereas language fMRI is widely used, memory fMRI is less frequently employed in adult TLE, and lacking in childhood TLE. We have developed a combined language/memory fMRI paradigm that is suitable for children, to provide clinically useful information for surgical planning in pediatric TLE. We evaluated this paradigm in 28 healthy children, aged 8 to 18 years. The advantages of this paradigm are: (a) it examines the functional mapping of language and memory networks within one scanning session, (b) provides assessment of both memory encoding- and retrieval-related neural networks, (c) examines recall-based retrieval to engage hippocampal involvement compared to recognition-based retrieval, and (d) provides overt verbal responses to monitor in-scanner memory performance. This novel fMRI paradigm was designed for language and memory mapping in pediatric TLE and could provide clinically useful information for surgical planning. Finally, parallel versions of the paradigm allow the comparison of brain activations pre- and post-surgical intervention.

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

There is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy. Children who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates. One hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2-8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis. A lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

Default mode network deactivation in pediatric temporal lobe epilepsy: Relationship to a working memory task and executive function tests

ObjectivesChildren with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. There is limited evidence of different functional network alterations associated with this clinical executive dysfunction. This study investigates working memory deficits in children with TLE by assessing deactivation of the default mode network (DMN) on functional Magnetic Resonance Imaging (fMRI) and the relationship of DMN deactivation with fMRI behavioral findings and neuropsychological test performance. Experimental designfMRI was conducted on 15 children with TLE and 15 healthy controls (age: 8–16 years) while performing the N-back task in order to assess deactivation of the DMN. N-back accuracy, N-back reaction time, and neuropsychological tests of executive function (Delis–Kaplan Executive Function System [D-KEFS] Color-Word Interference and Card Sort tests) were also assessed. Principal observationsDuring the N-back task, children with TLE exhibited significantly less deactivation of the DMN, primarily in the precuneus/posterior cingulate cortex compared with controls. These alterations significantly correlated with N-back behavioral findings and D-KEFS results. ConclusionsChildren with TLE exhibit executive dysfunction which correlates with DMN alterations. These findings suggest that the level of deactivation of specific functional networks may contribute to cognitive impairment in children with TLE. The findings also indicate that children with TLE have network alterations in extratemporal lobe brain regions.

Executive dysfunction is associated with an altered executive control network in pediatric temporal lobe epilepsy

ObjectivesChildren with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. However, there is limited evidence of neural network alterations associated with this clinical executive dysfunction. The objective of this study was to characterize working memory deficits in children with TLE via activation of the executive control network on functional magnetic resonance imaging (fMRI) and determine the relationships to fMRI behavioral findings and traditional neuropsychological tests. Experimental designFunctional magnetic resonance imaging was conducted on 17 children with TLE and 18 healthy control participants (age 8–16 years) while they performed the N-back task in order to assess activation of the executive control network. N-back accuracy, N-back reaction time, and traditional neuropsychological tests (Delis–Kaplan Executive Function System [D-KEFS] color–word interference and card-sort test) were also assessed. Principal observationsChildren with TLE exhibited executive dysfunction on D-KEFS testing, reduced N-back accuracy, and increased N-back reaction time compared with healthy controls; D-KEFS and N-back behavioral findings were significantly correlated. Children with TLE also exhibited significant reduction in activation of the frontal lobe within the executive control network compared to healthy controls. These alterations were significantly correlated with N-back behavioral findings and D-KEFS testing. ConclusionsChildren with TLE exhibit executive dysfunction, which correlates with executive control network alterations. This lends validity to the theory that the executive control network contributes to working memory function. The findings also indicate that children with TLE have network alterations in nontemporal brain regions.

Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy.

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the initial operation was significantly more likely following ATL (47/61, 77%) than SelAH (8/18, 44%; p = 0.017, Fisher's exact test). There was no statistically significant difference in the proportion of patients with postoperative neuropsychological deficits following SelAH (8/18, 44%) or ATL (21/61, 34%). However, reoperation was significantly more likely following SelAH (8/18, 44%) than after ATL (7/61, 11%; p = 0.004) and was more likely to result in Engel I outcome for ATL after failed SelAH (7/8, 88%) than for posterior extension after failed ATL (1/7, 14%; p = 0.01). Reoperation was well tolerated without significant neuropsychological deterioration. Ultimately, including 15 reoperations, 58 of 79 (73%) patients were free from disabling seizures at the most recent follow-up. CONCLUSIONS SelAH among pediatric patients with medically refractory unilateral TLE yields significantly worse rates of seizure control compared with ATL. Reoperation is significantly more likely following SelAH, is not associated with incremental neuropsychological deterioration, and frequently results in freedom from disabling seizures. These results are significant in that they argue against using SelAH for pediatric TLE surgery.

Changes in resting-state connectivity in pediatric temporal lobe epilepsy.

OBJECTIVE Functional connectivity magnetic resonance imaging (fcMRI) is a form of fMRI that allows for analysis of blood oxygen level-dependent signal changes within a task-free, resting paradigm. This technique has been shown to have efficacy in evaluating network connectivity changes with epilepsy. Presurgical data from patients with unilateral temporal lobe epilepsy were evaluated using the fcMRI technique to define connectivity changes within and between the diseased and healthy temporal lobes using a within-subjects design. METHODS Using presurgical fcMRI data from pediatric patients with unilateral temporal lobe epilepsy, the authors performed seed-based analyses within the diseased and healthy temporal lobes. Connectivity within and between temporal lobe seeds was measured and compared. RESULTS In the cohort studied, local ipsilateral temporal lobe connectivity was significantly increased on the diseased side compared to the healthy temporal lobe. Connectivity of the diseased side to the healthy side, on the other hand, was significantly reduced when compared to connectivity of the healthy side to the diseased temporal lobe. A statistically significant regression was observed when comparing the changes in local ipsilateral temporal lobe connectivity to the changes in inter-temporal lobe connectivity. A statistically significant difference was also noted in ipsilateral connectivity changes between patients with and those without mesial temporal sclerosis. CONCLUSIONS Using fcMRI, significant changes in ipsilateral temporal lobe and inter-temporal lobe connectivity can be appreciated in unilateral temporal lobe epilepsy. Furthermore, fcMRI may have a role in the presurgical evaluation of patients with intractable temporal lobe epilepsy.

Thalamocortical Connections and Executive Function in Pediatric Temporal and Frontal Lobe Epilepsy.

Largely accepted in the literature is the role the interconnections between the thalamus and cortex play in generalized epilepsy. However, thalamocortical involvement is less understood in focal epilepsy in terms of the effect of seizures on thalamocortical circuitry in the developing brain and subsequent cognitive outcome. We investigated thalamocortical pathway microstructure in pediatric frontal lobe epilepsy and temporal lobe epilepsy and examined the associations between pathway microstructure and measures of executive function. We examined thalamocortical connections in 24 children with frontal lobe epilepsy, 17 patients with temporal lobe epilepsy, and 25 healthy children using DTI. We investigated several executive function measures in patients and controls, which were distilled into latent executive function components to compare among groups, and the associations between measures of thalamocortical microstructure and executive function. We found no differences in thalamocortical pathway microstructure between the groups, but aspects of executive function (mental flexibility/inhibition/shifting) were impaired in the frontal lobe epilepsy group compared with controls. In patients with frontal lobe epilepsy, younger age at seizure onset and a greater number of antiepileptic drugs were associated with DTI indices indicative of damaged/less developed thalamocortical pathways. In patients with temporal lobe epilepsy, poorer performance on all measures of executive function was associated with DTI indices reflective of damaged/less developed pathways. Our results give insight into vulnerable neural networks in pediatric focal epilepsy and suggest thalamocortical pathway damage as a potential mechanism of executive function impairment in temporal lobe epilepsy but not frontal lobe epilepsy. Identifying structure-function relations can help inform how we measure functional and cognitive/behavioral outcomes in these populations.

P.015 Mesial Temporal Sclerosis is a rare occurrence in Intractable Pediatric Temporal Lobe Epilepsies

Background: Temporal lobe epilepsy (TLE) accounts for approximately 20% of pediatric epilepsy cases. Of those, many are considered medically intractable and require surgical interventions. In this study, we hypothesized that mesial temporal sclerosis (MTS) was less common in patients who had undergone surgery for intractable pediatric TLE than in adult series. We further hypothesized that there was a radiological and pathological discordance in identifying the cause of pediatric TLE. Methods: We retrospectively reviewed the charts of pediatric patients with TLE who had undergone surgical treatments as part of the University of Alberta’s Comprehensive Epilepsy Program between 1988 and 2018. Along with preoperative magnetic resonance imaging (MRI) reports, post-surgical pathology results and seizure outcomes were studied Results: Of the 83 pediatric patients who had undergone temporal lobe epilepsy surgery, 28% had tumors, 22% had dual pathologies, 18% had MTS, 11% had focal cortical dysplasia, and 22% had other pathologies. In addition, for 36% of these patients, discordance between their pre-surgical MRI reports and post-surgical pathology reports were found. Conclusions: This was one of the largest retrospective cohort studies of pediatric patients who had undergone surgery for intractable TLE. This study showed that tumors, and not MTS, were the most common pathology in surgical pediatric TLE.