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Effect of subthalamic nucleus stimulation on penicillin induced focal motor seizures in primate
S Prabhu1, S Chabardès2, A Sherdil1
1Univ Grenoble Alpes, GIN, F-38000 Grenoble, France; INSERM, U836, F-38000 Grenoble, France.
Background:
Drug-resistant motor epilepsies are particularly incapacitating for the patients. In a primate model of focal motor seizures induced by intracortical injection of penicillin, we recently showed that seizures propagated from the motor cortex towards the basal ganglia.
Objective:
Using the same animal model here, we hypothesized that disruption of subthalamic nucleus (STN) activity by chronic high frequency stimulation (HFS) could modify pathological excessive cortical synchronisation occurring during focal motor seizures, and therefore could reduce seizure activity.
Methods:
Two monkeys were chronically implanted with one electrode positioned into the STN. In each experiment, seizures were induced during 6 hours by injecting penicillin into the motor cortex. During stimulation sessions, HFS-STN was applied at the beginning of penicillin injection.
Results:
Our results indicate that HFS-STN improved focal motor seizures by delaying the occurrence of the first seizure, by decreasing the number of seizures by 47% and therefore the total time spent seizing by 53% compared to control. These results argue for a therapeutic use of HFS-STN in motor seizures because they were obtained in a very severe primate model of motor status similar to that seen in human. Furthermore, HFS-STN was much more efficient than direct cortical HFS of the epileptic focus, which we already tested in the same primate model.
Conclusions:
The present study suggests that HFS-STN could be used as an experimental therapy when other therapeutic strategies are not possible or have failed in humans suffering from motor epilepsy but the present study still warrants controlled studies in humans.
Insights
High-frequency stimulation of the subthalamic nucleus (HFS-STN) effectively reduced motor seizures in a primate model. This approach delayed seizure onset, decreased seizure frequency by 47%, and reduced seizure duration by 53%.
Area of Science:
- Neuroscience
- Epileptology
- Neurosurgery
Background:
- Drug-resistant motor epilepsies present significant patient challenges.
- A primate model of focal motor seizures was established via intracortical penicillin injection.
- Seizures were previously shown to propagate from motor cortex to basal ganglia.
Purpose of the Study:
- To investigate if disrupting subthalamic nucleus (STN) activity with chronic high-frequency stimulation (HFS) could alter pathological cortical synchronization during focal motor seizures.
- To determine if HFS-STN could reduce overall seizure activity in a primate model.
Main Methods:
- Two primates underwent chronic implantation of electrodes into the STN.
- Focal motor seizures were induced over 6-hour periods by injecting penicillin into the motor cortex.
- HFS-STN was administered at the onset of penicillin injection during stimulation sessions.
Main Results:
- HFS-STN significantly improved focal motor seizure outcomes.
- The occurrence of the first seizure was delayed.
- Seizure number decreased by 47% and total seizure time by 53% compared to controls.
- HFS-STN demonstrated greater efficacy than direct cortical HFS.
Conclusions:
- HFS-STN shows promise as an experimental therapy for motor epilepsy, particularly when other treatments fail or are not feasible.
- The findings in this severe primate model suggest potential clinical applicability in humans.
- Further controlled studies in humans are warranted to validate these experimental findings.
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