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Sudomotor innervation in transthyretin amyloid neuropathy: Pathology and functional correlates
Author(s) -
Chao ChiChao,
Huang ChoMin,
Chiang HaoHua,
Luo KaiRen,
Kan HungWei,
Yang Naomi ChuChiao,
Chiang Hao,
Lin WheiMin,
Lai ShuMei,
Lee MingJen,
Shun ChiaTung,
Hsieh SungTsang
Publication year - 2015
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24438
Subject(s) - sudomotor , medicine , transthyretin , skin biopsy , denervation , polyneuropathy , endocrinology , pure autonomic failure , biopsy , pathology , gastroenterology , orthostatic vital signs , blood pressure
Objective 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. Methods 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). Results 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). Interpretation 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. Ann Neurol 2015;78:272℃283