Alcala-Zermeno Juan Luis, Gregg Nicholas M, Osman Gamaleldin, Mandrekar Jayawant N, Starnes Keith, Worrell Gregory, Lundstrom Brian N
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Comprehensive Epilepsy Center, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Epilepsia. 2025 May 27. doi: 10.1111/epi.18479.
The effects of brain stimulation for diseases like epilepsy are delayed, making stimulation optimization difficult. The parameters for anterior thalamic nuclei (ANT) deep brain stimulation (DBS) for focal drug-resistant epilepsy management are often restricted to those used in the SANTE landmark trial. There is little evidence regarding effective alternatives, and low-frequency stimulation is typically neglected. We prospectively compare a widely differing stimulation parameter set to typical settings.
This randomized, modified crossover, open trial compares the efficacy and safety of an alternative set of parameters using continuous low-frequency stimulation (cLFS) with a longer pulse width (7 Hz, 200 μs, continuous) compared to SANTE's intermittent high-frequency stimulation (iHFS) with a short pulse width (145 Hz, 90 μs, cycling 1 min on/5 min off). After 3 months on a randomly assigned first set, patients are switched to the other settings, unless seizure-free. Patients are re-evaluated after 3 more months, which marks the completion of the trial. After that, they can either remain on the same settings or switch back.
Sixteen patients with a median baseline seizure frequency of 13.8 seizures/month (interquartile range [IQR] = 2.7-22.8) were included in the analysis. At trial completion (median follow-up = 30 weeks, IQR = 26-35), ANT-DBS significantly reduced median seizure frequency (62%, IQR = 18-81, Wilcoxon test statistic [W] = 99, p = .008). Both iHFS (33%, IQR = 0-65, W = 81, p = .02) and cLFS (73%, IQR = 30-79, W = 105, p = .001) significantly reduced median seizure frequency. cLFS showed improved median seizure frequency reduction compared to iHFS (W = 63, p = .03) and was not associated with any moderate or severe adverse effects.
Results support cLFS for ANT-DBS as a safe and effective alternative to typical iHFS parameters. Stimulation with widely differing parameter sets may be as effective as or, in some situations, more effective than typical stimulation parameters.
脑刺激对癫痫等疾病的疗效具有延迟性，这使得刺激优化变得困难。用于局灶性耐药性癫痫治疗的丘脑前核（ANT）深部脑刺激（DBS）参数通常局限于在SANTE标志性试验中使用的参数。关于有效替代方案的证据很少，低频刺激通常被忽视。我们前瞻性地比较了一组差异很大的刺激参数与典型设置。
这项随机、改良交叉、开放试验比较了使用连续低频刺激（cLFS）且脉宽更长（7Hz，200μs，连续）的一组替代参数与SANTE的间歇性高频刺激（iHFS）且脉宽较短（145Hz，90μs，1分钟开/5分钟关循环）的疗效和安全性。在随机分配的第一组设置上治疗3个月后，除非无癫痫发作，患者切换到另一组设置。再过3个月后对患者进行重新评估，这标志着试验完成。之后，他们可以继续使用相同的设置或切换回原来的设置。
16例患者纳入分析，基线癫痫发作频率中位数为每月13.8次发作（四分位间距[IQR]=2.7-22.8）。在试验完成时（随访中位数=30周，IQR=26-35），ANT-DBS显著降低了癫痫发作频率中位数（62%，IQR=18-81，Wilcoxon检验统计量[W]=99，p=0.008）。iHFS（33%，IQR=0-65，W=81，p=0.02）和cLFS（73%，IQR=30-79，W=105，p=0.001）均显著降低了癫痫发作频率中位数。与iHFS相比，cLFS显示出更好的癫痫发作频率降低效果（W=63，p=0.03），且与任何中度或重度不良反应均无关联。
结果支持将ANT-DBS的cLFS作为典型iHFS参数的一种安全有效的替代方案。使用差异很大的参数集进行刺激可能与典型刺激参数一样有效，或在某些情况下更有效。
