Postdoctoral researcher Brigham and Women's hospital, Harvard Medical School, Boston
This abstract is a recipient of the Grass Foundation Young Investigator Award This abstract will be presented during the Translational Research/Genetics Platform poster session This abstract has been invited to present during the Investigators Workshop Platform poster session
Rationale: Treatment of drug-resistant focal epilepsy has traditionally focused on the epileptogenic zone. However, epilepsy is a disease of brain networks and the large-scale brain networks involved in the cause and control of epilepsy in humans remain largely unknown. Methods: We studied 1,153 brain lesions, including four lesion types (stroke, tumor, penetrating head trauma, and tubers) associated with structural epilepsy (28%, n=324) or not (72%, n=829), which were shared by collaborators around the world. Lesion locations were mapped to a common brain atlas and the network of brain regions functionally connected to each lesion location was computed using the human connectome (Fox 2018, NEJM). Connections associated with structural epilepsy were identified. We investigated the relevance of these connections in MRI-negative epilepsy using stereo-EEG data (2692 recording sites, n=23) and their therapeutic relevance using data from patients who received thalamic deep brain stimulation for drug-resistant epilepsy (n=30). Results: Lesions causing structural epilepsy map to a specific brain circuit defined by connectivity to the cerebellum, substantia nigra reticulata and globus pallidus internus (fwe p < 0.0001). Using a rigorous leave-one-lesion-type out cross-validation, damage to this circuit was significantly associated with the risk of epilepsy (p < 0.0001, relative risk 2.79 [CI: 1.81 – 3.11]). Connectivity to this same circuit was associated with seizure-onset zones in MRI-negative epilepsy (fwe p < 0.01) and with therapeutic response to thalamic deep brain stimulation (fwe p < 0.01). Conclusions: Lesions causing structural epilepsy map to a specific brain circuit, that may have prognostic value in predicting the risk for epilepsy after a brain lesion, and therapeutic value as a neuromodulation target for patients with drug-resistant epilepsy.
References Fox, M. D. (2018). Mapping Symptoms to Brain Networks with the Human Connectome. The New England Journal of Medicine, 379(23), 2237–2245. Funding: Please list any funding that was received in support of this abstract.: This research project did not receive any specific funding.
