Authors :
Presenting Author: Brian Lundstrom, MD, PhD – Mayo Clinic
Juan Luis Alcala-Zermeno, MD – Thomas Jefferson University; Julianna Ethridge, BS – Mayo Clinic; Nicholas Gregg, MD – Mayo Clinic; Kai Miller, MD, PhD – Mayo Clinic; Gamaleldin Osman, MBBCh – Mayo Clinic; Keith Starnes, MD – Mayo Clinic; Jamie Van Gompel, MD – Mayo Clinic; Gregory Worrell, MD, PhD – Mayo Clinic
Rationale:
Deep brain stimulation (DBS) systems can provide therapy with an infinite number stimulation parameter combinations including amplitude, frequency, pulse width, cycling and electrode configuration. Yet, stimulation parameters for anterior thalamic nuclei (ANT) DBS are largely restricted to those from the SANTE landmark trial,
1 which uses high frequency (145 Hz) stimulation. Not all patients respond to these parameters and there is little evidence regarding effective alternatives. Low frequency stimulation (LFS), defined as less than 100 Hz stimulation, can be beneficial, as suggested by cases series of fornix DBS,
2 RNS,
3 and neocortical chronic subthreshold stimulation (CSS).
4 We aim to prospectively compare the clinical efficacy of LFS in ANT DBS with HFS.
Methods:
Prospective, randomized, modified cross-over trial was used to examine two different sets of stimulation parameters in patients implanted with bilateral ANT-DBS. After implant, patients were randomized to either LFS (referential stimulation, 7 Hz, pulse width 200 μsec, cycling off) or HFS (referential stimulation, 145 Hz, pulse width 90 μsec , cycling 1 min on/5 min off). After three months, patients were then switched to the other parameter set (unless they were seizure free). The primary outcome was seizure frequency reduction (SFR). Secondary outcomes were change in seizure severity, life satisfaction and quality of sleep assessed using subjective 1-10 point scales.
Results:
Twelve patients (25% females) with a median baseline seizure frequency of 16.3 sz/mo (IQR 3.5-22.8) were included. Two patients did not switch parameter sets as they were seizure free at three months on HFS and LFS, respectively. After a median follow up time of 6.6 mo (IQR 6.2-8.1), patients had a median 77% seizure frequency reduction (IQR 15 – 83, W=51, p=0.046). Median SFR for HFS was 58% (IQR 0 – 82) while median SFR for LFS was 75% (IQR 0-79); these were not statistically different (W=-23, p=0.2). Five patients showed fewer seizures with LFS, while three showed fewer seizures with HFS (Figure 1).
Conclusions:
Preliminary evidence from this ongoing prospective comparative trial suggests LFS is an effective alternative to HFS ANT-DBS.
References:
1 Fisher R, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy Epilepsia. 2010 May;51:899-908.
2 Koubeissi MZ, et al. Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy Epilepsy & behavior : E&B. 2022 Mar 25;130:108667.
3 Alcala-Zermeno JL, et al. Responsive neurostimulation with low-frequency stimulation Epilepsia. 2023 Feb;64:e16-e22.
4 Lundstrom BN, et al. Chronic subthreshold cortical stimulation and stimulation-related EEG biomarkers for focal epilepsy Brain communications. 2019;1:fcz010.
Funding: Research was supported by NIH NINDS K23NS112339 (BNL) and R01NS129622 (BNL).