From the Erasmus School of Health Policy & Management (ESHPM) (V.H.-W., S.G., T.K., W.B., I.C.R., M.V., J.E.), Institute for Medical Technology Assessment (iMTA) (V.H.-W., S.G., T.K., I.C.R., M.V.), and Erasmus Centre for Health Economics Rotterdam (EsCHER) (V.H.-W., S.G., T.K., W.B., I.C.R., M.V., J.E.), Erasmus University Rotterdam; Academic Center for Epileptology Kempenhaeghe (L.W.), Heeze; Stichting Epilepsie Instellingen Nederland (SEIN) (J.A.), Heemstede; Leiden University Medical Center (S.C.); Huygens & Versteegh (M.V.), Zwijndrecht, the Netherlands.
Neurology. 2024 Mar 26;102(6):e209178. doi: 10.1212/WNL.0000000000209178. Epub 2024 Feb 28.
The aim of this study was to evaluate whether people living with severe medically refractory epilepsy (PSRE) benefit from a seizure dog.
An individual-level stepped-wedge randomized controlled trial was conducted. The study was conducted in the Netherlands among adults with daily to weekly seizures. All participants were included simultaneously (on June 1, 2019) while receiving usual care. Then, during the 36-month follow-up, they received a seizure dog in a randomized sequence. Participants kept a seizure diary and completed 3-monthly surveys. Seizure frequency was the primary outcome. Secondary outcomes included seizure-free days, seizure severity, health-related quality of life (HRQoL), and well-being. Data were analyzed using generalized linear mixed modeling (GLMM). The models assumed a delayed intervention effect, starting when the seizure dog reached an advanced stage of training. Effects were calculated as changes per 28-day period with the intervention.
Data were collected from 25 participants, of whom 20 crossed over to the intervention condition. The median follow-up was 19 months with usual care and 12 months with the intervention. On average, participants experienced 115 (SD 164) seizures per 28-day period in the usual care condition and 73 (SD 131) seizures in the intervention condition. Seven participants achieved a reduction of 50% or more at the end of follow-up. GLMM indicated a 3.1% decrease in seizure frequency for each consecutive 28-day period with the intervention (0.969, 95% CI 0.960-0.977). Furthermore, an increase in the number of seizure-free days was observed (1.012, 95% CI 1.009, 1.015), but no effect on seizure severity measured with the NHS3. Generic HRQoL scores improved, as reflected in the decrease in EQ-5D-5L utility decrement (0.975, 95% CI 0.954-0.997). Smaller improvements were observed on overall self-rated HRQoL, epilepsy-specific HRQoL, and well-being, measured with the EQ VAS, QOLIE-31-P, and ICECAP-A, respectively.
Seizure dogs reduce seizure frequency, increase the number of seizure-free days, and improve the quality of life of PSRE. The magnitude of the effect on generic HRQoL indicates that seizure dogs benefit PSRE beyond the impact on seizure frequency alone. Early discontinuation of seizure dog partnerships suggests that this intervention is not suitable for all PSRE and requires further study.
This study was registered in the Dutch Trial Register (NL6682) on November 28, 2017. Participants were enrolled on June 1, 2019.
This study provides Class III evidence that seizure dogs are associated with a decrease in seizure frequency in adult patients with medically refractory epilepsy.
本研究旨在评估患有严重药物难治性癫痫（PSRE）的患者是否受益于癫痫犬。
进行了一项个体水平的逐步楔形随机对照试验。该研究在荷兰进行，参与者为每天至每周发作一次的成年人。所有参与者同时被纳入（2019 年 6 月 1 日），同时接受常规护理。然后，在 36 个月的随访期间，他们按照随机顺序接受了癫痫犬。参与者记录癫痫发作日记并完成每 3 个月一次的调查。癫痫发作频率是主要结局。次要结局包括无癫痫发作天数、癫痫发作严重程度、健康相关生活质量（HRQoL）和幸福感。使用广义线性混合模型（GLMM）进行数据分析。该模型假设干预的延迟效应，从癫痫犬达到高级训练阶段开始。通过每 28 天干预期的变化来计算效果。
从 25 名参与者中收集了数据，其中 20 名参与者交叉到干预组。常规护理的中位随访时间为 19 个月，干预组为 12 个月。在常规护理条件下，参与者平均每 28 天经历 115（SD 164）次癫痫发作，在干预条件下经历 73（SD 131）次癫痫发作。在随访结束时，有 7 名参与者的癫痫发作频率降低了 50%或更多。GLMM 表明，每连续 28 天接受干预，癫痫发作频率降低 3.1%（0.969，95%CI 0.960-0.977）。此外，观察到无癫痫发作天数增加（1.012，95%CI 1.009，1.015），但 NHS3 测量的癫痫发作严重程度没有影响。通用 HRQoL 评分有所改善，反映在 EQ-5D-5L 效用递减减少（0.975，95%CI 0.954-0.997）。在整体自我报告的 HRQoL、癫痫特异性 HRQoL 和幸福感方面，观察到较小的改善，分别用 EQ VAS、QOLIE-31-P 和 ICECAP-A 进行测量。
癫痫犬可降低癫痫发作频率、增加无癫痫发作天数并改善 PSRE 的生活质量。对通用 HRQoL 的影响程度表明，癫痫犬对 PSRE 的益处不仅限于对癫痫发作频率的影响。癫痫犬合作关系的早期终止表明，这种干预措施并不适合所有 PSRE，需要进一步研究。
本研究于 2017 年 11 月 28 日在荷兰试验注册处（NL6682）注册。参与者于 2019 年 6 月 1 日入组。
本研究提供了 III 级证据，表明癫痫犬与药物难治性癫痫成年患者的癫痫发作频率降低有关。
