4.4 Article

Cortical responsive neurostimulation in a baboon with genetic generalized epilepsy

Journal

EPILEPSY & BEHAVIOR
Volume 120, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yebeh.2021.107973

Keywords

Responsive neurostimulation therapy; Genetic generalized epilepsy; Generalized tonic-clonic seizures; Baboon; Circadian rhythms

Funding

  1. [UT BRAIN - NNRI 365136]
  2. [P51 RR013986]
  3. [C06 RR013556]
  4. [C06 RR014578]
  5. [C06 RR015456]

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This study demonstrated the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with genetic generalized epilepsy (GGE), showing a 38% median reduction in generalized tonic-clonic seizures (GTCS) under treatment. The ictal patterns and circadian distribution of GTCS were also altered by the RNS therapy, shifting gradually from night to daytime.
Objective: To evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment. Methods: The baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified. Results: Twenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy. Significance: This case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon. (c) 2021 Elsevier Inc. All rights reserved.

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