Increased Functional Connectivity During Epileptiform Discharges in Adult-Onset Mesial Temporal Lobe Epilepsy
Brian Jung1, Sebastian Hanna1, Lilit Mnatsakanyan1, Mona Sazgar1, Sumeet Vadera2, Richard Staba3, Jerome Engel3
1Neurology, 2Neurological Surgery, University of California, Irvine, 3Neurology, University of California, Los Angeles
Objective:

To evaluate differences in brain functional connectivity during epileptiform discharges between adult-onset and pediatric-onset MTLE.

Background:

Classical MTLE typically begins in childhood, characterized by unilateral hippocampal sclerosis with sparing of the CA2 region. Adult-onset MTLE is often marked by more diffuse hippocampal sclerosis affecting CA2 and contralateral involvement. Hyperphosphorylated tau deposition has been observed in adult MTLE, which also correlates with cognitive decline, suggesting a potential association with dementia.

Design/Methods:
Epileptiform discharges were manually identified from EEG recordings of nine adult-onset and six peds-onset MTLE patients. Each epileptiform discharge was segmented into five one-second epochs: baseline (-2 to -1 second), pre-spike (-1 to 0 second), spike (0 to +1 second), post-spike1 (+1 to +2 second), and post-spike2 (+2 to +3 second). Functional connectivity was analyzed using cross-correlation for each epoch and electrode pair. Inter-group and inter-epoch differences were evaluated with the Wilcoxon rank sum test and the False Discovery Rate method to account for multiple comparisons.
Results:

The peds-onset MTLE had a longer disease duration (P=0.03). Rates of bilateral independent temporal onset epilepsy (33.3% adult vs 50% peds), hippocampal sclerosis (55.5% adult vs 66.7% peds), and anterior temporal hypometabolism on PET (88.9% adult vs 83.3% peds) were similar. The age (P=0.93) and mean number of epileptiform discharges were comparable (P=0.93). 

Connectivity and node strengths increased from baseline to the spike epoch in both groups, then decreased post-spike, with post-spike2 levels lower than baseline. The adult-onset MTLE group showed increased degree and strength of connectivity in bilateral temporal and occipital lobes, and ipsilateral parietal lobe during the pre-spike (P<0.03). No significant inter-group differences were found in other epochs.
Conclusions:

Adult-onset MTLE may be functionally distinct from peds-onset MTLE. The more extensive synchronization of brain networks suggests that epileptiform discharges could have a wider impact in adult-onset MTLE, potentially contributing to the development of dementia-related phenotype.

10.1212/WNL.0000000000210796
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