Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome

Abstract

The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, especially when the removal is on the left side. Children may benefit most from surgery, because brain plasticity may facilitate post-surgical reorganization, and seizure cessation may promote cognitive development. However, the long-term impact of this intervention in children is not known. We examined memory function in 53 children (25 males, 28 females) who were evaluated for epilepsy surgery: 42 underwent unilateral temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11 were treated only pharmacologically. Average follow-up was 9 years (range 5-15). Post-surgical change in visual and verbal episodic memory, and semantic memory at follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were analysed to extract hippocampal and resection volumes, and evaluate post-surgical temporal lobe integrity. Language lateralization indices were derived from functional magnetic resonance imaging. There were no significant pre- to postoperative decrements in memory associated with surgery. In contrast, gains in verbal episodic memory were seen after right temporal lobe surgery, and visual episodic memory improved after left temporal lobe surgery, indicating a functional release in the unoperated temporal lobe after seizure reduction or cessation. Pre- to post-surgical change in memory function was not associated with any indices of brain structure derived from MRI. However, better verbal memory at follow-up was linked to greater post-surgical residual hippocampal volumes, most robustly in left surgical participants. Better semantic memory at follow-up was associated with smaller resection volumes and greater temporal pole integrity after left temporal surgery. Results were independent of post-surgical intellectual function and language lateralization. Our findings indicate post-surgical, hemisphere-dependent material-specific improvement in memory functions in the intact temporal lobe. However, outcome was linked to the anatomical integrity of the temporal lobe memory system, indicating that compensatory mechanisms are constrained by the amount of tissue which remains in the operated temporal lobe. Careful tailoring of resections for children undergoing epilepsy surgery may enhance long-term memory outcome.

Keywords: children; drug-resistant epilepsy; epilepsy surgery; hippocampus; memory.

Figure 1

Variability in surgical resection. (A) Overlay map of resections for surgical patients with DNT and hippocampal sclerosis (HS). Highest overlap of tissue removal is indicated in yellow. (B) MRI scans from four individual surgical participants preoperatively and at follow-up showing variability in resections even for the same lesion type (DNT or hippocampal sclerosis). Post-surgical resection volume and remaining ipsilesional hippocampal volumes for presented cases are as follows: Case 1: resection volume = 20.7 cm³, hippocampus = 2.4 cm³; Case 2: resection volume = 19.8 cm³, hippocampus = 0.6 cm³; Case 3: resection volume = 9.0 cm³, hippocampus = 1.1 cm³; Case 4: resection volume = 18.3 cm³, hippocampus = 0.7 cm³.

Figure 2

Memory function. Memory function from longitudinal (left) and cross-sectional analyses (right), presenting means and 95% confidence intervals (error bars) in left surgical, right surgical and non-surgical control groups. (A) Semantic memory function: IQ-derived semantic memory and BPVS-II. (B) Verbal episodic memory from WMS-R and The Doors and People Test. (C) Visual memory from WMS-R and The Doors and People Test. *Significant pre- to post-surgical changes (P < 0.05).

Figure 3

A diagrammatic overview of memory change before and after left temporal lobe surgery in children. Interpretation of our findings in the context of previous research: in dashed lines we present a schema of our findings in the non-surgical sample, and in solid lines findings from the surgical sample. Normal development is indicated with a dashed black line. Previous research from Helmstaedter and Elger (2009) showed an earlier and lower developmental peak of memory function for individuals with temporal lobe epilepsy, compared with their healthy peers. Gleissner et al. (2005) showed a short-lived decline in memory function at 3 months after temporal lobe surgery, resolving after just 1 year in children. Our findings indicate no differences in verbal memory outcome between children who undergo left temporal lobe surgery and those that do not, but indicate significant post-surgical improvements in visual memory function. Shading: Representation of the variability in the postoperative developmental trajectory of memory which may be optimized by tailoring of resections within the temporal lobe structures critical to declarative memory (brain image: showing in yellow the left temporal pole subserving semantic memory, and in red the left hippocampus subserving verbal episodic memory).