Closed-loop Cortical Network Stimulation as treatment for refractory epilepsy originating from the primary motor cortex

Background: In epilepsy patients, cortical electrical stimulation is therapeutically applied in the seizure onset zone (SOZ) to reduce seizures. However, in patients with epilepsy arising from the primary motor cortex (M1), stimulation can result in undesired muscle contractions or loss of motor control. We postulate that seizure frequency reduction can also be obtained by cortical network stimulation in a site outside M1 with a connection to the SOZ in M1. Methods: Patients with electroclinical seizures suspected to arise from M1 were selected. SOZ was delineated during chronic intracranial EEG monitoring. Using Single Pulse Electrical Stimulation, the underlying effective corticocortical network was determined and a site for stimulation was selected that was connected to the SOZ. One subdural strip was implanted on top of the SOZ, and one on the stimulus location. A subcutaneous neurostimulator (Activa PC+S, Medtronic), capable of recording and closed-loop stimulation, was connected to both strips. Seizure data was collected for three to five months and used to optimize a seizure detection algorithm. After this, closed-loop cortical network stimulation was applied during seven to nine months. Results: In five subjects (two females, mean age 34 years, range: 21-51 years), a neurostimulation system was implanted. One subject was seizure free for 17 months post-implantation without applying any electrical stimulation. Two subjects were responders with a mean seizure frequency reduction of 73%. In two subjects, seizure frequency was reduced by on average 35%. Discussion: In this clinical trial with five subjects suffering from refractory epilepsy arising in M1, seizure frequency was reduced with electrical stimulation in all subjects. This is a proof of concept showing that closed-loop cortical network stimulation can reduce seizure frequency as equal to direct SOZ stimulation in non-primary motor epilepsy.