We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

中文翻译：

---

纯粹自主神经衰竭的表型转化：一项多中心前瞻性纵向队列研究

我们的目的是描述表型转变之前患有纯自主神经衰竭 (PAF) 的患者的临床特征，这些特征可用作进展 α-突触核蛋白相关的大脑神经变性的预测标记。诊断为 PAF 的患者在 8 个中心（7 个美国中心和 1 个欧洲中心）进行评估，并参加纵向观察队列研究 (NCT01799915)。受试者接受了运动、睡眠、嗅觉、认知和自主功能的详细评估，并进行前瞻性随访，以确定他们是否患有帕金森病或痴呆症长达 10 年。我们确定了帕金森病 (PD)、路易体痴呆 (DLB) 或多系统萎缩 (MSA) 的发病病例，并计算了表型转化的风险比作为临床特征的函数。共有 209 名中位病程为 6 年（IQR：3-10）的 PAF 参与者入组。其中 149 人在办公室或远程医疗访问中提供了后续信息。平均随访 3 年后，48 名 (33%) 参与者发生表型转变（42% 转变为 PD，35% 转变为 DLB，23% 转变为 MSA）。从研究入组到任何诊断的更快的表型转换与泌尿和性功能障碍相关[HR 5.9，95% CI：1.6-22，HR：3.6，95% CI：1.1-12]，其次是微妙的运动体征[HR：2.7，入组时出现95%CI：1.2-6]、吞咽困难[HR 2.5，95%CI：1.4-4.5]和言语变化[HR：2.4，95%CI：1.1-4.8]。报告笔迹恶化的受试者更有可能表型转变为 PD（HR：2.6，95% CI：1.1-5.9，），而那些报告处理器具有困难的受试者更有可能表型转变为 DLB（HR：6.8，95% CI：1.2- 38）。PAF 发病年龄较小的患者 [HR: 11, 95%CI: 2.6-46]、嗅觉保留 [HR: 8.7, 95%CI: 1.7-45]、无汗 [HR: 1.8, 95%CI: 1- 3.1，p=0.042] 和严重泌尿系统问题 [HR 1.6，95%CI：1-2.5，p=0.033] 更有可能表型转化为 MSA。PD 的最佳自主神经预测因子是倾斜台测试期间心率增加缓慢（HR：6.1，95％CI：1.4-26）。PAF 患者在进入研究后表型转化为明显的 CNS 突触核蛋白病的每年风险估计为 12% (95% CI: 9%-15%)。