Background/objective: Occipital nerve stimulation (ONS) has become an established therapy for medically intractable chronic cluster headache (MICCH), but unfortunately, one third of the patients do not respond satisfactorily. Reliable predictors of treatment success would help physicians improve indication for ONS in MICCH. Although a recent report suggested several factors that were associated with treatment failure (early onset of cluster headache [CH], chronic cluster headache [CCH], and smoking) this study was small, did not use a formal model, efficacy was poorly defined, and the follow-up was only of short duration. Here, we retrospectively sought: (i) reproduction of these associations and (ii) identification of possible other associations in our previously published double-blind randomized controlled "Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache" (ICON) trial, and long-term follow-up, of the efficacy of ONS in MICCH.

Methods: Data from the double-blind randomized controlled ICON trial, and its prospective open-label extension, were analyzed in this prospective cohort study in the Netherlands (October 12, 2010, to December 20, 2020) for: (i) relative differences in attack frequency and (ii) subjective satisfaction with effect between baseline and at 4 and 24 weeks, and 2 and 5 years, after ONS implantation. Formal statistical models were used to: (i) verify the previously detected associations and (ii) identify possible other associations.

Results: Early onset of CH and smoking did not predict efficacy of ONS. Relative reduction in attack frequency at 24 weeks (B = 0.44, 95% confidence interval [CI] 0.13-0.76; p = 0.007) and the time since onset of CCH (B = 4.04, 95% CI 1.16-6.92; p = 0.007) appeared to be the only factors that were associated with objective efficacy at 2 years, and relative attack reduction after 2 years was the only factor associated with objective efficacy at 5 years (B = 0.501, 95% CI 0.186-0.815; p = 0.003). The odds of experiencing subjective satisfaction with ONS after 2 years increased with a later debut of CCH (adjusted odds ratio [aOR] 1.06, 95% CI 1.01-1.12; p = 0.033) and greater relative reduction in attack frequency at 24 weeks (aOR 1.02, 95% CI 1.00-1.04; p = 0.017).

Conclusion: In a controlled setting, early onset of CH, CCH, and smoking were not associated with treatment success of ONS for MICCH, as previously suggested by others in an uncontrolled setting. Early response at 24 weeks after initiation of ONS was the only factor that was associated with long-term efficacy, which was identified. Since a large proportion of patients with MICCH improve with ONS, we recommend offering ONS to all patients with MICCH.

Keywords: chronic cluster headache; medically intractable chronic cluster headache; neuromodulation; occipital nerve stimulation.

© 2025 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.

背景/目的：

枕神经刺激（ONS）已成为治疗医学上难以控制的慢性丛集性头痛（MICCH）的一种公认疗法，但遗憾的是，三分之一的患者对这种治疗方法反应不佳。可靠的预后指标可以帮助医生提高ONS在MICCH中的适应症选择。虽然最近的一项研究报告了与治疗失败相关的几个因素（早期出现的丛集性头痛[CH]、慢性丛集性头痛[CCH]和吸烟），但该研究规模较小，没有使用正式模型，疗效定义不明确，并且随访时间较短。因此，在我们之前发表的双盲随机对照“枕神经刺激在医学上难以控制的慢性丛集性头痛”（ICON）试验以及长期随访中，本研究回顾性地寻找：

• 验证这些相关性的重现性；
• 识别可能存在的其他相关因素。

方法：

在这项在荷兰进行的前瞻性队列研究（2010年10月12日至2020年12月20日）中，我们分析了双盲随机对照ICON试验及其前瞻性开放标签扩展的数据。具体来说，我们在ONS植入后基线、4周和24周以及2年和5年后的时间点上比较了：

• 发作频率的相对差异；
• 对ONS效果的主观满意度。

我们使用正式统计模型来验证先前检测到的相关性并识别可能存在的其他相关因素。

结果：

CH早期出现和吸烟不能预测ONS的效果。24周时攻击频率相对减少（B = 0.44，95%可信区间[CI] 0.13-0.76；P = 0.007）和CCH的发病时间（B = 4.04, 95% CI 1.16-6.92; P = 0.007）似乎是唯一与两年后客观疗效相关的因素，而在两年后的攻击频率相对减少是五年后唯一的疗效相关因素（B = 0.501，95%可信区间[CI] 0.186-0.815；P = 0.003）。CCH的后期发作 (校正优势比[aOR] 1.06, 95% CI 1.01-1.12; P = 0.033) 和24周时攻击频率相对减少 (aOR 1.02，95% 可信区间[CI] 1.00-1.04；P = 0.017) 增加了患者在两年后对ONS感到主观满意的几率。

结论：

在一个受控环境中，早期出现的CH、CCH和吸烟不是如先前其他研究者在非受控设置下所建议的那样与ONS治疗MICCH的成功有关。24周时对ONS的早期反应是唯一与长期疗效相关的因素。

关键词：

慢性丛集性头痛；医学上难以控制的慢性丛集性头痛；神经调节；枕神经刺激。

© 2025 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.