Castori Marco, Morlino Silvia, Ghibellini Giulia, Celletti Claudia, Camerota Filippo, Grammatico Paola
Am J Med Genet C Semin Med Genet. 2015 Mar;169C(1):84-96. doi: 10.1002/ajmg.c.31426. Epub 2015 Feb 5.
Ehlers-Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility. In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache. In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs. Gathered data are fragmented and generally have a low level of evidence. Headache is reported in no less than 1/3 of the patients. Migraine results the most common type in the hypermobility type of EDS. Other possibly related headache disorders include tension-type headache, new daily persistent headache, headache attributed to spontaneous cerebrospinal fluid leakage, headache secondary to Chiari malformation, cervicogenic headache and neck-tongue syndrome, whose association still lacks of reliable prevalence studies. The underlying pathogenesis seems complex and variably associated with cardiovascular dysautonomia, cervical spine and temporomandibular joint instability/dysfunction, meningeal fragility, poor sleep quality, pain-killer drugs overuse and central sensitization. Particular attention is posed on a presumed subclinical cervical spine dysfunction. Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients' needs and nurturing future research.
埃勒斯-当洛综合征（EDS）是一组日益增多的遗传性结缔组织疾病的统称，主要表现为全身关节活动过度、皮肤过度伸展以及血管和内脏脆弱。与其他已知的伴有严重心血管受累的遗传性结缔组织疾病（如马凡综合征）不同，大多数EDS患者的寿命几乎正常，但却受到疼痛、疲劳和头痛等致残症状的严重限制。在这项工作中，我们回顾了相关文献，重点关注EDS中头痛的患病率、特征和可能的致病机制。收集到的数据零散，且总体证据水平较低。至少1/3的患者报告有头痛症状。偏头痛是活动过度型EDS中最常见的类型。其他可能相关的头痛疾病包括紧张型头痛、新发性每日持续性头痛、自发性脑脊液漏所致头痛、小脑扁桃体下疝畸形继发头痛、颈源性头痛和颈舌综合征，其关联仍缺乏可靠的患病率研究。潜在的发病机制似乎很复杂，与心血管自主神经功能障碍、颈椎和颞下颌关节不稳定/功能障碍、脑膜脆弱、睡眠质量差、止痛药过度使用和中枢敏化等因素存在不同程度的关联。特别关注了一种假定的亚临床颈椎功能障碍。标准治疗通常只是对症治疗，且往往效果不佳。文中讨论了评估和管理程序，以便为满足实际患者的需求和推动未来研究奠定一些基础。
