Neuropsychological Phenotypes in Pediatric Temporal Lobe Epilepsy

Abstract

Objective: Adults with temporal lobe epilepsy (TLE) have been found to have a fairly characteristic pattern of neuropsychological performance, but there is considerably less research and more variability in findings with children. Because the cognitive domains included in most studies with children have been limited, the current study attempted to better characterize the cognitive phenotype of children with TLE using a broader neuropsychological battery. Methods: The study included 59 children with TLE (59% male) age 7 to 16 (M = 12.67; SD = 3.12) who underwent comprehensive neuropsychological evaluation. Patient results were grouped into cognitive domains (reasoning, language, visuoperceptual, verbal memory, executive function, and motor function) based upon their test performance. These factor scores were subjected to Ward’s hierarchical clustering method with squared Euclidean distance. Results: Cluster analysis revealed three distinct cognitive profiles: (1) normal functioning (20% of sample); (2) delayed verbal memory and motor weaknesses (61% of the sample); and (3) global impairment (19% of the sample). Cluster 3 had longer epilepsy duration and a higher incidence of hippocampal sclerosis (HS) compared to Cluster 1 (p < .05). There were no significant differences among the three cluster groups on demographic characteristics or remaining clinical characteristics. Conclusions: Children with TLE present with distinct cognitive phenotypes ranging from average performance to global impairment. Results partially support previous hypotheses highlighting the cumulative neurobiological burden on the developing brain in the context of chronic epilepsy and provide a preliminary framework for the cognitive domains most vulnerable to the TLE disease process.

Development and application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Initial results from a multi-center study of adults with temporal lobe epilepsy.

“…For these reasons, recent efforts have turned to identifying unique patterns of cognitive impairment, or cognitive phenotypes, and their associated disrupted networks within and across epilepsy syndromes. Studies in patients with focal epilepsy have typically identified three-to-four unique phenotypes that help to explain the heterogeneity observed at the group level (Baxendale & Thompson, 2020;Elverman et al, 2019;Hermann, et al, 2007;Hermann et al, 2020;Reyes et al, 2019Reyes et al, , 2020Rodríguez-Cruces et al, 2018;Schraegle et al, 2021). Furthermore, these unique phenotypes are characterized by distinct patterns of cortical thinning and subcortical atrophy (Dabbs et al, 2009), network disruption (Hermann et al, 2020;Kaestner et al, 2019;Reyes et al, 2019), risk for cognitive progression (Hermann et al, 2007), and risk for postsurgical decline (Baxendale & Thompson, 2020) that are not always apparent when patients are studied in aggregate.…”

Behavioral phenotypes of pediatric temporal lobe epilepsy

“…The present study utilized a similar statistical approach to previously published work examining behavioral phenotypes in children and adults with epilepsy. [26][27][28] Ward's hierarchical agglomerative clustering method was used with the nine BASC-2 clinical scales (Aim 1). 36 Squared Euclidean distance was used as the index of pairwise similarity -dissimilarity between participant profiles.…”

“…The test battery was comprehensive and included measures of intelligence, language, visuospatial, immediate verbal memory, delayed verbal memory, executive functioning, and motor dexterity. Cluster analysis identified seven cognitive factors (see Schraegle et al 27 for details) and served as the dependent variables.…”

“…The present study utilized a similar statistical approach to previously published work examining behavioral phenotypes in children and adults with epilepsy 26–28 36 .…”

“…8,19,20 An emerging approach in the epilepsy literature has been to empirically examine within-group variability to derive meaningful phenotypes of neurobehavioral status. 21 For instance, this approach has been used to identify a taxonomy of cognitive abnormalities in adult [22][23][24][25][26] and pediatric 27 TLE. These phenotypes typically range from (1) intact; (2) focal deficits predominantly in delayed verbal memory and language; and (3) generalized cognitive impairment.…”