Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Abstract

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. βFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. βFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

Keywords: IQ; academic attainment; epilepsy surgery; neuropsychology; paediatric; trajectories.

Figure 1

Preoperative changes in neuropsychological performance. (A) Cross-sectional trajectories in FSIQ across different aetiologies. A single preoperative assessment was included for each patient. If patients had more than one preoperative assessment, the assessment closest to surgery was chosen. Linear modelling was fitted to all data-points (dashed line); shaded area represents the 95% confidence interval. (B) Longitudinal trajectories in FSIQ across different aetiologies. Only patients with two or more preoperative assessments were included in the visualization. All preoperative assessments were included for each patient. Linear modelling was fitted to all data-points (dotted line); shaded area represents the 95% confidence interval. One patient, diagnosed with a tumour, had an FSIQ score available prior to epilepsy onset. (C) Individual change in preoperative FSIQ. The distribution of change scores is represented using a density plot. The change score for each patient was computed by subtracting the first preoperative score for the patient from their last preoperative score. The median change score is displayed with a dashed purple line. Only patients with two or more preoperative assessments were included in the visualization (patients with unknown aetiology were also included). See Supplementary Fig. 1 for verbal IQ, performance IQ, working memory, processing speed, reading, spelling and numeracy. FCD = focal cortical dysplasia; FSIQ = full-scale IQ; MCD = malformation of cortical development; MTS = mesial temporal sclerosis.

Figure 2

Postoperative changes in neuropsychological performance. (A) Longitudinal trajectories in FSIQ in seizure-free (green) versus not seizure-free (orange) patients. Only patients with two or more postoperative assessments were included. All postoperative assessments were included for each patient. Linear modelling was fitted to all data-points, according to seizure outcome (dashed green line for patients who were seizure free and dashed orange line for patients who were not seizure free); shaded areas represent the 95% confidence intervals. (B) Individual change in postoperative FSIQ in seizure-free (green) versus not seizure-free (orange) patients. The distribution of change scores is represented using a density plot. The change score for each patient was computed by subtracting the first postoperative score for the patient from their last postoperative score. The median change scores are displayed with a green dashed line (in seizure-free patients) and with an orange dashed line (in not seizure-free patients). Only patients with two or more postoperative assessments were included in the visualization. See Supplementary Fig. 3 for verbal IQ, performance IQ, working memory, processing speed, reading, spelling and numeracy. FSIQ = full-scale IQ.

Figure 3

Pre- to postoperative changes in neuropsychological performance. (A) Pre- and postoperative trajectories in FSIQ in seizure-free (green) versus not seizure-free (orange) patients. All patients were included in the visualization, irrespective of whether they had one or multiple pre- and/or postoperative assessments. If patients had multiple pre- and/or postoperative assessments, all assessments were included for each patient. Generalized additive modelling was fitted to all data-points, according to seizure outcome (solid green line for patients who were seizure free and solid orange line for patients who were not seizure free); shaded areas represent the 95% confidence intervals. (B) Pre- and postoperative trajectories in FSIQ in seizure-free patients who were still receiving or weaning ASMs (yellow) versus no longer receiving ASMs (light green). Grey points represent FSIQ in the preoperative period and FSIQ for patients who did not become seizure free postoperatively. All patients were included in the visualization, irrespective of whether they had one or multiple pre- and/or postoperative assessments. If patients had multiple pre- and/or postoperative assessments, all assessments were included for each patient. Generalized additive modelling was fitted to all data-points, according to postoperative ASM status (solid yellow line for patients who were still receiving or weaning ASMs and solid light green line for patients who were no longer receiving ASMs); shaded areas represent the 95% confidence intervals. See Supplementary Fig. 4 for verbal IQ, performance IQ, working memory, processing speed, reading, spelling and numeracy. ASM = antiseizure medication; FSIQ = full-scale IQ.

Figure 4

Overview of study findings. Based on our findings, we propose the following schematic model to capture the impact of epilepsy surgery on neuropsychological trajectories in children with drug-resistant focal epilepsy. Prior to epilepsy surgery, children with epilepsy fall increasingly behind their typically developing peers, resulting in them displaying a decline in IQ (standard) scores. Children who are rendered seizure free after surgery display a ‘catching-up’ effect, which allows them to attain a cognitive level that is comparable to that of their typically developing peers without epilepsy. Children who are not seizure free after surgery do not display this same ‘catching-up’ effect and have lower IQ scores already prior to surgery. The blue line (of typically developing children) shows the mean of a normative sample and corresponds to an IQ score of 100 at each data-point.