BACKGROUND: A number of epilepsy syndromes are characterized by sleep-activated epileptiform discharges, however drivers of this process are not well understood. Previous research has found that thalamic injury in early life may increase the odds of sleep-activated spikes. Benign childhood epilepsy with centrotemporal spikes (BECTS) is among the most common pediatric-onset epilepsy syndromes, characterized by sleep-potentiated spike activity, a focal sensorimotor seizure semiology, and deficits in language, attention, and behavioral functioning. Though ictal and interictal electro-clinical activity resolves during mid-adolescence, adverse psychosocial outcomes may persist. Previous findings from monozygotic twin and neuroimaging studies suggest a multifactorial pattern of disease and raise suspicion for structural changes in thalamocortical connectivity focal to the seizure onset zone, though this has not been explored.
OBJECTIVE: This research aims to (1) assess white matter differences in focal thalamocortical connectivity between BECTS cases and healthy controls using validated probabilistic tractography methods, (2) assess the association between spike burden and white matter connectivity focal to the seizure onset zone, and (3) evaluate longitudinal changes in thalamocortical connectivity across four cases.
METHODS: 42 subjects ages 6-15 years were recruited between November 2015 and February 2018, including 23 BECTS cases and 19 healthy controls. Subjects underwent 3 Tesla structural and diffusion-weighted magnetic resonance imaging (2mm x 2mm x 2mm) with 64 gradient directions (b-value=2000) and 72 electrode sleep-deprived electroencephalographic (EEG) recordings. Seed and target regions of interest (ROIs) were created within each hemisphere using the Desikan-Killiany atlas, with the thalamus set as a seed ROI, and SOZ cortex and non-SOZ (NSOZ) cortex as target ROIs. Probabilistic tractography was executed using PROBTRACKX2 with 500 streamlines per seed voxel, 0.5 millimeter steps, and a curvature threshold of 0.2. All streamlines reaching the target ROI were summed and normalized by seed voxel count. Results for BECTS and healthy controls were plotted by age. The slope of thalamocortical connectivity versus age was computed for each group and compared between groups using nonparametric bootstrap analysis. Additionally, the association between SOZ connectivity and spike burden was assessed in a subgroup analysis using a linear regression model, controlling for age.
RESULTS: A significant difference in the developmental trajectory of thalamocortical connectivity to the SOZ in BECTS cases compared to healthy controls was found (p=0.014), where the increase in connectivity with age observed in healthy controls was not present in BECTS children. These results did not extend to NSOZ thalamocortical connections (p=0.192). Longitudinal results support these observations, where all BECTS cases who underwent repeat imaging (N=4) showed a decrease in thalamocortical connectivity to the SOZ over the follow-up period. No relationship was found between thalamocortical connectivity and spike burden (p=0.840).
CONCLUSIONS: These findings suggest that children with BECTS show subtle alterations in thalamocortical white matter development focal to the seizure onset zone. Thalamocortical connectivity to the SOZ does not appear to directly mediate non-REM sleep spike potentiation in BECTS. Limitations of this study include the potential for selection bias and limited power to detect sample differences. Additional research is needed to further characterize thalamocortical network changes and electrographic and neuropsychological correlates.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/33036 |
| Date | 25 October 2018 |
| Creators | Thorn, Emily |
| Contributors | Chu, Catherine J., Douglass, Laurie M. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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