Department of Brain, Repair and Rehabilitation, University College London Queen Square Institute of Neurology, London, UK.
Autonomic Unit, The National Hospital for Neurology and Neurosurgery, London, UK.
Ann Neurol. 2021 Apr;89(4):753-768. doi: 10.1002/ana.26018. Epub 2021 Feb 1.
The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response.
We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head-up tilt. Eleven patients received immunotherapy.
At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8-61.3] to 5.2 [1.4-8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0-3.3] to 4.5 [3.0-6.3], p = 0.02), pupillary constriction to light (12.0 [5.5-18.0] to 19.0 [10.6-23.8]%, p = 0.02), saliva production (0.01 [0.01-0.05] to 0.08 [0.02-0.20] g/min, p = 0.03), and COMPASS-31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy.
Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753-768.
本研究旨在通过多模态测试方案评估神经节乙酰胆碱受体抗体（gAChR-Ab）阳性自身免疫性自主神经节病患者，以明确其完整的临床表型，并探索量化免疫治疗反应的生物标志物。
我们对 2005 年至 2019 年间确诊的 13 名自主神经衰竭且 gAChR-Ab＞100pM 的自身免疫性自主神经节病患者（7 名女性，年龄 21-69 岁）进行了队列研究。自 2018 年起，所有患者均接受心血管、瞳孔、泌尿、汗腺、泪腺和唾液测试，并使用综合自主症状评分（COMPASS-31）自主症状问卷进行纵向评估。直立倾斜试验时，通过计算收缩压随时间的变化来计算直立不耐受比值。11 名患者接受了免疫治疗。
在首次评估时，所有 13 名患者均存在心血管和瞳孔功能障碍，8 名患者中有 7 名存在节后汗腺功能障碍，11 名患者中有 9 名存在尿潴留和干眼症，8 名患者中有 6 名存在口干症。免疫治疗后，直立不耐受比值（33.3[17.8-61.3]至 5.2[1.4-8.2]，p=0.007）、深吸气时心率反应（1.5[0.0-3.3]至 4.5[3.0-6.3]，p=0.02）、瞳孔对光的收缩（12.0[5.5-18.0]至 19.0[10.6-23.8]%，p=0.02）、唾液分泌（0.01[0.01-0.05]至 0.08[0.02-0.20]g/min，p=0.03）和 COMPASS-31 评分（52 至 17，p=0.03）均显著改善。直立不耐受比值与基线时（r=0.841，p=0.01）和免疫治疗后（r=0.889，p=0.02）的自主症状相关。一名发病 32 年后的患者皮肤样本的免疫荧光分析显示，供应皮肤自主附属器和表皮的神经纤维丧失，免疫治疗后明显改善。
自身免疫性自主神经节病患者表现出广泛的交感和副交感自主神经衰竭的客观证据，免疫治疗后有显著改善。定量自主神经生物标志物应用于明确初始缺陷，指导治疗决策，并记录治疗反应。
