TY - JOUR
T1 - Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy
AU - Koubeissi, Mohamad Z.
AU - Joshi, Sweta
AU - Eid, Alexandra
AU - Emami, Mehrdad
AU - Jaafar, Nadim
AU - Syed, Tanvir
AU - Foreman, Perry J.
AU - Sheth, Anumeha
AU - Amdur, Richard
AU - Bou Nasif, Mei
AU - Puente, Antonio N.
AU - Aly, Radwa
AU - Chen, Hai
AU - Becker, Andrew
AU - Gholipour, Taha
AU - Makke, Yamane
AU - Elmashad, Ahmed
AU - Gagnon, Linda
AU - Durand, Dominique M.
AU - Gaillard, William D.
AU - Shields, Donald C.
N1 - Funding Information:
Funding: The current research was done through a start-up fund from George Washington University to MZK, a grant from the Coulter Foundation to DMD and MZK, and a device grant from Medtronic to MZK.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/5
Y1 - 2022/5
N2 - Objective: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. Methods: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. Results: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ± 2.67 (median 3.0 [IQR 1–4.0]) during stimulation-off blocks, compared with 0.96 ± 1.23 (median 1.0 [IQR 0–1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. Significance: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.
AB - Objective: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. Methods: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. Results: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ± 2.67 (median 3.0 [IQR 1–4.0]) during stimulation-off blocks, compared with 0.96 ± 1.23 (median 1.0 [IQR 0–1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. Significance: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.
KW - Deep brain stimulation
KW - Dorsal hippocampal commissure
KW - Fornix
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U2 - 10.1016/j.yebeh.2022.108667
DO - 10.1016/j.yebeh.2022.108667
M3 - Article
C2 - 35344808
AN - SCOPUS:85127004049
SN - 1525-5050
VL - 130
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
M1 - 108667
ER -