Acute Seizure Control Efficacy of Multi-Site Closed-Loop Stimulation in a Temporal Lobe Seizure Model

• Published in: IEEE transactions on neural systems and rehabilitation engineering 2019-03, Vol.27 (3), p.419-428
• Main Authors: Zheng, Yongte, Jiang, Zifan, Ping, An, Zhang, Fang, Zhu, Junming, Wang, Yueming, Zhu, Wentao, Xu, Kedi
• Format: Article
• Language: English
• Subjects: Acute Disease; acute seizure model; Algorithms; Animals; Brain modeling; CA1 Region, Hippocampal; CA3 Region, Hippocampal; closed-loop; Convulsions & seizures; Cortex (motor); Cortex (temporal); Customization; Deep Brain Stimulation - methods; Effectiveness; Electric Stimulation; Electrical stimulation; Electrical stimuli; Epilepsy; Epilepsy, Generalized - physiopathology; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - therapy; Excitatory Amino Acid Agonists; Hemispheric laterality; Hippocampus; Kainic Acid; Male; Models, Neurological; Modulation; Multi-site; neurostimulator; Rats; Rats, Sprague-Dawley; Recording; Seizing; seizure detection; seizure suppression; Seizures; Seizures - chemically induced; Seizures - therapy; Status Epilepticus - physiopathology; Stimulation; Temporal lobe; temporal lobe seizure; Thalamus
• ISSN: 1534-4320; 1558-0210
• DOI: 10.1109/TNSRE.2019.2894746

The closed-loop electrical stimulation is emerging as a promising neural modulation therapy for refractory epilepsy. However, the efficacy of electrical stimulation is less than optimal and the mechanism of seizure control is still unclear. In this paper, we evaluated the acute seizure control efficacy of the multi-site closed-loop stimulation (MSCLS) in a rodent model with a custom designed closed-loop neurostimulator. A total of 18 rats were injected with kainic-acid in CA3 of the left hippocampus to induce acute temporal lobe seizures. Instead of single target stimulation, four target sites in left hemisphere including CA1 and CA3 of the hippocampus, sub-thalamic nucleus, and M1 region of the motor cortex were selected for both recording and stimulation. A low-cost efficient multi-site seizure detection algorithm was implemented in the neurostimulator for MSCLS. With MSCLS treatment, the rats without status-epilepsy (SE) significantly reduced the seizure duration and the number of generalized seizures in each site. When considering the rats developed SE, the MSCLS could also alleviate the seizure severity, but had little effect on the seizure duration and seizure number. In conclusion, although the efficacy of MSCLS was still limited by the stimulation sites, stimulation parameters, and seizure model chosen in this paper, the MSCLS itself would be a promising direction for the refractory seizure treatment.