Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy

Cristina V Torres Diaz,Marta Navas García,Dumitru Ciolac,Lorena Vega-Zelaya,Antonio Barbosa,Paloma Pulido Rivas,Gabriel González-Escamilla,Sergiu Groppa,Jesús Pastor,Rafael G Sola

doi:10.1007/s13311-021-01057-y

Abstract

Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2–11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation.

Highlights

Epilepsy is a very common chronic neurological disorder characterized by spontaneous recurrent seizures, presenting a high prevalence and leading to an enormous psychosocial burden for patients, families, caregivers, and health systems [1]
Our results show that the connectivity patterns of the CMDBS-modulated fiber tracts in generalized pharmacoresistant epilepsy are responsible for the reduction of seizure frequency and, improved clinical outcomes in these patients
Deep brain stimulation (DBS) efficacy relies on the connectivity of the CM to the brainstem and cerebellum, as well as to the sensorimotor and premotor cortices

Summary

Introduction

Epilepsy is a very common chronic neurological disorder characterized by spontaneous recurrent seizures, presenting a high prevalence and leading to an enormous psychosocial burden for patients, families, caregivers, and health systems [1]. The activation of the cortico-reticular (centromedian [CM] nucleus of the thalamus and parafascicular [Pf]) nuclei of the thalamus precede the activation of the anterior nucleus, suggesting that the CM-Pf complex as driving the generation, or early propagation of generalized seizures, while anterior nucleus activity supports its maintenance [4]. For other structures, such as the cerebellum and brainstem, despite the available evidence, their particular role is less clear. Its specific attribution for the therapeutic interventions in generalized pharmacoresistant epilepsy remains to be elucidated

Methods

Results

Discussion

Conclusion