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Theses

Control of epileptic seizures by the basal ganglia: clinical and experimental approaches

Abstract : As about one third of epileptic patients are resistant to antiepileptic drugs, and only 30% of them are candidates for resective surgery, it exists a great demand for the development of alternative surgical therapies. It has been shown in animal studies, that the basal ganglia and especially the substantia nigra (SN) are involved in the control of epilepsy. Clinical evidence, using either electrophysiological or imaging approaches, also supports the involvement of the basal ganglia in some epileptic syndromes. The influence of seizure spread into the basal ganglia in patients with focal epilepsies was investigated on the rate of secondary generalization. We showed that activation of the basal ganglia was associated with an inhibitory effect on seizure propagation, when seizures spread into the frontal lobe. The elucidation of inhibitory mechanisms in epilepsy may open a new approach for therapeutic strategies such as electrical deep brain stimulation. First open case series, investigating deep brain stimulation of the basal ganglia to suppress epileptic seizures, showed encouraging results in some patients. However, more preclinical studies are mandatory to investigate the optimal stimulation parameters. The aim of our experimental approach was to determine the optimal stimulation parameters to control spontaneous seizures in a genetic model of absence epilepsy in the rat. In this model, the optimal parameters of single substantia nigra pars reticulata (SNr) stimulation were determined as bilateral, bipolar, monophasic, 60 Hz frequency and 60 µs pulse width. When these parameters were used for repeated stimulations, no long-term suppression and even increase of the number of seizures was observed. A delay of at least 60 sec was necessary between stimulations to be fully effective. Although single high-frequency stimulation of the SNr can be used to suppress ongoing seizures, repeated stimulation are ineffective and could even aggravate seizures, thus supporting the need of closed-loop stimulation procedures to chronically suppress seizures in therapeutical applications. Such an adaptative device would be effective only when detectable changes heralds the seizure onset. In a genetic model of absence epilepsy such changes in the EEG-coherence between the left and right SNr could be identified. Such changes might be used as an hallmark for adaptative procedures like triggered single stimulation to avoid the occurrence of the presumed seizures. To date it remains unknown, if such changes in coherence between left and right SNr, are specific to the model of GAERS and if such changes occur also in other animal models or humans with different epileptic syndromes. Accumulating evidences support that epilepsy is not a pathology restricted to the cortex as a seizure generator, but that subcortical structures are also involved, which might open new therapeutic options for patients who are pharmacoresistant and no candidates for a resective surgical treatment.
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https://tel.archives-ouvertes.fr/tel-00413972
Contributor : Deransart Colin <>
Submitted on : Monday, September 7, 2009 - 2:56:42 PM
Last modification on : Friday, November 6, 2020 - 4:11:49 AM
Long-term archiving on: : Saturday, November 26, 2016 - 12:46:17 PM

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  • HAL Id : tel-00413972, version 1

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Feddersen Berend. Control of epileptic seizures by the basal ganglia: clinical and experimental approaches. Neurons and Cognition [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2009. English. ⟨tel-00413972⟩

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