Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study.

Background: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a 'cold-spot' and a 'sweet-spot', which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. Objective: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. Methods: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. Results: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. Conclusion: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy.

The Role of Magnetoencephalography and Single-Photon Emission Computed Tomography in Evaluation of Children With Drug-Resistant Epilepsy.

Surgery holds the best outcomes for drug-resistant epilepsy in children, making localization of a seizure focus essential. However, there is limited research on the contribution of magnetoencephalography and single-photon emission computed tomography (SPECT) to the presurgical evaluation of lesional and nonlesional pediatric patients. This study proposed to evaluate the concordance of SPECT and magnetoencephalography (MEG) to scalp electroencephalography (EEG) to determine their effective contribution to the presurgical evaluation. On review, MEG and SPECT studies for 28 drug-resistant epilepsy cases were completed at Children's Hospital of Pittsburgh from May 2012 to August 2018. Although not reaching statistical significance, MEG had increased lobar concordance with EEG compared with SPECT (68% vs 46%). MEG or SPECT results effectively provided localization data leading to 6 surgical evaluations and 3 resections with outcomes of Engel class I or II at 12 months. This study suggests MEG and SPECT provide valuable localizing information for presurgical epilepsy evaluation of children with drug-resistant epilepsy.