Abstract：
BACKGROUND: Preventive treatment for refractory chronic cluster headache (rCCH) is challenging and many therapies have been tried.
OBJECTIVE: To study what could be considered the therapy of choice in rCCH through a systematic review and meta-analysis.
METHODS: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in PROSPERO (ID CRD42021290983). A systematic search was performed in MEDLINE, Embase, Cochrane, clinicaltrials.gov, and the WHO\'s-International-Clinical-Trials-Registry-Platform. Studies on the preventive treatment for rCCH as defined by the European Headache Federation consensus statement were included. A meta-analysis of the pooled response rate was conducted for the different therapies.
RESULTS: Of 336 results, 45 were eligible for inclusion. Most articles studied the effect of neuromodulation as a preventive treatment for rCCH. The most studied neuromodulation technique was occipital nerve stimulation (ONS), with a pooled response rate in the meta-analysis of 57.3% (95% CI 0.481-0.665). Deep brain stimulation (DBS) was the second most studied treatment with a pooled response rate of 77.0% (95% CI 0.594-0.957). DBS results were more heterogeneous than ONS, which could be related to the different stimulation targets in DBS studies, and reported more serious adverse events than in ONS studies. The remaining therapies (anti-CGRP pathway drugs, warfarin, ketamine-magnesium infusions, serial occipital nerve blocks, clomiphene, onabotulinum toxin A, ketogenic diet, sphenopalatine ganglion radiofrequency or stimulation, vagus nerve stimulation, percutaneous bioelectric current stimulation, upper cervical cord stimulation, and vidian neurectomy) present weaker results or have less quality of evidence.
CONCLUSIONS: The results of this systematic review and meta-analysis suggest that ONS could be the first therapeutic strategy for patients with rCCH based on the current evidence.
OBJECTIVE: To study what could be considered the therapy of choice in rCCH through a systematic review and meta-analysis.
METHODS: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in PROSPERO (ID CRD42021290983). A systematic search was performed in MEDLINE, Embase, Cochrane, clinicaltrials.gov, and the WHO\'s-International-Clinical-Trials-Registry-Platform. Studies on the preventive treatment for rCCH as defined by the European Headache Federation consensus statement were included. A meta-analysis of the pooled response rate was conducted for the different therapies.
RESULTS: Of 336 results, 45 were eligible for inclusion. Most articles studied the effect of neuromodulation as a preventive treatment for rCCH. The most studied neuromodulation technique was occipital nerve stimulation (ONS), with a pooled response rate in the meta-analysis of 57.3% (95% CI 0.481-0.665). Deep brain stimulation (DBS) was the second most studied treatment with a pooled response rate of 77.0% (95% CI 0.594-0.957). DBS results were more heterogeneous than ONS, which could be related to the different stimulation targets in DBS studies, and reported more serious adverse events than in ONS studies. The remaining therapies (anti-CGRP pathway drugs, warfarin, ketamine-magnesium infusions, serial occipital nerve blocks, clomiphene, onabotulinum toxin A, ketogenic diet, sphenopalatine ganglion radiofrequency or stimulation, vagus nerve stimulation, percutaneous bioelectric current stimulation, upper cervical cord stimulation, and vidian neurectomy) present weaker results or have less quality of evidence.
CONCLUSIONS: The results of this systematic review and meta-analysis suggest that ONS could be the first therapeutic strategy for patients with rCCH based on the current evidence.
摘要：
背景：难治性慢性丛集性头痛（rCCH）的预防性治疗具有挑战性，并且已经尝试了许多疗法。
目的：通过系统评价和荟萃分析，研究在rCCH中可以考虑的治疗选择。
方法：本综述遵循系统评价和荟萃分析指南的首选报告项目进行。该协议在PROSPERO（IDCRD42021290983）中注册。在MEDLINE中进行了系统搜索，Embase,科克伦,clinicaltrials.gov,和世界卫生组织的国际临床试验注册平台。包括欧洲头痛联合会共识声明所定义的rCCH预防性治疗的研究。对不同疗法的合并反应率进行荟萃分析。
结果：在336个结果中，45人符合入选条件。大多数文章研究了神经调节作为rCCH预防性治疗的效果。研究最多的神经调节技术是枕神经刺激（ONS），荟萃分析中的合并缓解率为57.3%（95%CI0.481-0.665）。深部脑刺激（DBS）是第二大研究的治疗方法，合并反应率为77.0％（95％CI0.594-0.957）。DBS结果比ONS更异构，这可能与DBS研究中不同的刺激目标有关，并报告了比ONS研究更严重的不良事件。其余的治疗方法（抗CGRP途径药物，华法林,氯胺酮镁输液,连续枕骨神经阻滞,克罗米芬,onabotulinum毒素A,生酮饮食，蝶腭神经节射频或刺激，迷走神经刺激,经皮生物电流刺激，上颈髓刺激，和vidian神经切除术）的结果较弱或证据质量较低。
结论：本系统综述和荟萃分析的结果表明，根据目前的证据，ONS可能是rCCH患者的第一个治疗策略。
目的：通过系统评价和荟萃分析，研究在rCCH中可以考虑的治疗选择。
方法：本综述遵循系统评价和荟萃分析指南的首选报告项目进行。该协议在PROSPERO（IDCRD42021290983）中注册。在MEDLINE中进行了系统搜索，Embase,科克伦,clinicaltrials.gov,和世界卫生组织的国际临床试验注册平台。包括欧洲头痛联合会共识声明所定义的rCCH预防性治疗的研究。对不同疗法的合并反应率进行荟萃分析。
结果：在336个结果中，45人符合入选条件。大多数文章研究了神经调节作为rCCH预防性治疗的效果。研究最多的神经调节技术是枕神经刺激（ONS），荟萃分析中的合并缓解率为57.3%（95%CI0.481-0.665）。深部脑刺激（DBS）是第二大研究的治疗方法，合并反应率为77.0％（95％CI0.594-0.957）。DBS结果比ONS更异构，这可能与DBS研究中不同的刺激目标有关，并报告了比ONS研究更严重的不良事件。其余的治疗方法（抗CGRP途径药物，华法林,氯胺酮镁输液,连续枕骨神经阻滞,克罗米芬,onabotulinum毒素A,生酮饮食，蝶腭神经节射频或刺激，迷走神经刺激,经皮生物电流刺激，上颈髓刺激，和vidian神经切除术）的结果较弱或证据质量较低。
结论：本系统综述和荟萃分析的结果表明，根据目前的证据，ONS可能是rCCH患者的第一个治疗策略。
