Chao Chi-Chao, Huang Cho-Min, Chiang Hao-Hua, Luo Kai-Ren, Kan Hung-Wei, Yang Naomi Chu-Chiao, Chiang Hao, Lin Whei-Min, Lai Shu-Mei, Lee Ming-Jen, Shun Chia-Tung, Hsieh Sung-Tsang
Department of Neurology, National Taiwan University Hospital.
Department of Anatomy and Cell Biology, National Taiwan University College of Medicine.
Ann Neurol. 2015 Aug;78(2):272-83. doi: 10.1002/ana.24438. Epub 2015 Jul 1.
Autonomic neuropathy is a major component of familial amyloid polyneuropathy (FAP) due to mutated transthyretin, with sudomotor failure as a common manifestation. This study aimed to investigate the pathology and clinical significance of sudomotor denervation.
Skin biopsies were performed on the distal leg of FAP patients with a follow-up duration of 3.8 ± 1.6 years. Sudomotor innervation was stained with 2 markers: protein gene product 9.5 (PGP 9.5), a general neuronal marker, and vasoactive intestinal peptide (VIP), a sudomotor nerve functional marker, followed by quantitation according to sweat gland innervation index (SGII) for PGP 9.5 (SGIIPGP 9.5) and VIP (SGIIVIP).
There were 28 patients (25 men) with Ala97Ser transthyretin and late onset (59.9 ± 6.0 years) disabling neuropathy. Autonomic symptoms were present in 22 patients (78.6%) at the time of skin biopsy. The SGIIPGP 9.5 and SGIIVIP of FAP patients were significantly lower than those of age- and gender-matched controls. The reduction of SGIIVIP was more severe than that of SGIIPGP 9.5 (p = 0.002). Patients with orthostatic hypotension or absent sympathetic skin response at palms were associated with lower SGIIPGP 9.5 (p = 0.019 and 0.002, respectively). SGIIPGP 9.5 was negatively correlated with the disability grade at the time of skin biopsy (p = 0.004), and was positively correlated with the interval from the time of skin biopsy to the time of wheelchair usage (p = 0.029).
This study documented the pathological evidence of sudomotor denervation in FAP. SGIIPGP 9.5 was functionally correlated with autonomic symptoms, autonomic tests, ambulation status, and progression of disability.
自主神经病变是由突变型转甲状腺素蛋白引起的家族性淀粉样多神经病（FAP）的主要组成部分，汗腺功能衰竭是其常见表现。本研究旨在探讨汗腺去神经支配的病理学及临床意义。
对随访时间为3.8±1.6年的FAP患者小腿远端进行皮肤活检。用两种标记物对汗腺神经支配进行染色：一种是蛋白基因产物9.5（PGP 9.5），一种通用的神经元标记物；另一种是血管活性肠肽（VIP），一种汗腺神经功能标记物，然后根据汗腺神经支配指数（SGII）对PGP 9.5（SGIIPGP 9.5）和VIP（SGIIVIP）进行定量分析。
有28例（25例男性）携带Ala97Ser转甲状腺素蛋白且发病较晚（59.9±6.0岁）的致残性神经病患者。在进行皮肤活检时，22例患者（78.6%）存在自主神经症状。FAP患者的SGIIPGP 9.5和SGIIVIP显著低于年龄和性别匹配的对照组。SGIIVIP的降低比SGIIPGP 9.5更严重（p = 0.002）。伴有体位性低血压或手掌无交感神经皮肤反应的患者，其SGIIPGP 9.5较低（分别为p = 0.019和0.002）。SGIIPGP 9.5与皮肤活检时的残疾分级呈负相关（p = 0.004），与从皮肤活检到使用轮椅的时间间隔呈正相关（p = 0.029）。
本研究记录了FAP中汗腺去神经支配的病理学证据。SGIIPGP 9.5在功能上与自主神经症状、自主神经测试、行走状态及残疾进展相关。
