丘脑中央中核脑深部电刺激术治疗 Lennox-Gastaut 综合征（ESTEL 试验）。

DBS of Thalamic Centromedian Nucleus for Lennox-Gastaut Syndrome (ESTEL Trial).

机构信息

Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC, Australia.

Department of Neurology, Austin Health, Heidelberg, VIC, Australia.

出版信息

Ann Neurol. 2022 Feb;91(2):253-267. doi: 10.1002/ana.26280. Epub 2021 Dec 28.

DOI:10.1002/ana.26280

PMID:34877694

Abstract

OBJECTIVE

Prior uncontrolled studies have reported seizure reductions following deep brain stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS), but evidence from randomized controlled studies is lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for the treatment of LGS.

METHODS

We conducted a prospective, double-blind, randomized study of continuous, cycling stimulation of CM-DBS, in patients with LGS. Following pre- and post-implantation periods, half received 3 months of stimulation (blinded phase), then all received 3 months of stimulation (unblinded phase). The primary outcome was the proportion of participants with ≥50% reduction in diary-recorded seizures in stimulated versus control participants, measured at the end of the blinded phase. A secondary outcome was the proportion of participants with a ≥50% reduction in electrographic seizures on 24-hour ambulatory electroencephalography (EEG) at the end of the blinded phase.

RESULTS

Between November 2017 and December 2019, 20 young adults with LGS (17-37 years;13 women) underwent bilateral CM-DBS at a single center in Australia, with 19 randomized (treatment, n = 10 and control, n = 9). Fifty percent of the stimulation group achieved ≥50% seizure reduction, compared with 22% of controls (odds ratio [OR] = 3.1, 95% confidence interval [CI] = 0.44-21.45, p = 0.25). For electrographic seizures, 59% of the stimulation group had ≥50% reduction at the end of the blinded phase, compared with none of the controls (OR= 23.25, 95% CI = 1.0-538.4, p = 0.05). Across all patients, median seizure reduction (baseline vs study exit) was 46.7% (interquartile range [IQR] = 28-67%) for diary-recorded seizures and 53.8% (IQR = 27-73%) for electrographic seizures.

INTERPRETATION

CM-DBS in patients with LGS reduced electrographic rather than diary-recorded seizures, after 3 months of stimulation. Fifty percent of all participants had diary-recorded seizures reduced by half at the study exit, providing supporting evidence of the treatment effect. ANN NEUROL 2022;91:253-267.

摘要

目的

先前未经控制的研究报告，深部脑刺激（DBS）可减少 Lennox-Gastaut 综合征（LGS）患者的癫痫发作，但缺乏随机对照研究的证据。我们旨在正式评估 DBS 对中脑中央核（CM）治疗 LGS 的疗效和安全性。

方法

我们对 LGS 患者进行了 CM-DBS 的前瞻性、双盲、随机研究。在植入前后期间，一半接受 3 个月的刺激（盲法期），然后所有接受 3 个月的刺激（非盲法期）。主要结局是在盲法期结束时，与对照参与者相比，记录在案的癫痫发作减少≥50%的参与者比例，通过日记记录。次要结局是在盲法期结束时，24 小时动态脑电图（EEG）上记录的癫痫发作减少≥50%的参与者比例。

结果

2017 年 11 月至 2019 年 12 月，澳大利亚一家中心对 20 名患有 LGS 的年轻成年人（17-37 岁；13 名女性）进行了双侧 CM-DBS 手术，其中 19 名随机分组（治疗组，n=10；对照组，n=9）。与对照组（比值比[OR]=3.1，95%置信区间[CI]为 0.44-21.45，p=0.25）相比，刺激组有 50%的患者癫痫发作减少≥50%，而对照组有 22%的患者癫痫发作减少≥50%。在盲法期结束时，刺激组有 59%的患者电记录癫痫发作减少≥50%，而对照组无一例患者（OR=23.25，95%CI 为 1.0-538.4，p=0.05）。在所有患者中，与基线相比，日记记录的癫痫发作减少中位数（四分位距[IQR]：28-67%）为 46.7%，电记录癫痫发作减少中位数（IQR：27-73%）为 53.8%。