title: Quantitation of sudomotor innervation in skin biopsies of patients with diabetic neuropathy.
abstract: Previous assessments of the sudomotor system have depended on functional tests, and only a few studies document the pathologic findings of postganglionic nerve degeneration quantitatively and at the ultrastructural level. We developed a quantitative system of sudomotor innervation in skin biopsies of the distal leg by immunostaining of nerve fibers with anti-protein gene product 9.5 (PGP9.5) and by counterstaining with Congo red. A computerized area-based morphometric analysis was used to quantify the sweat gland innervation index (SGII), defined as the area of nerve fibers normalized to the area of sweat glands. This approach reduced the variations in measurements of sweat gland areas compared to the commonly used method by ∼5.6-fold (2.47% ± 2.54% vs 13.97% ± 14.24%, p < 0.001); hence, variations in SGII were also reduced. We examined 35 Type 2 diabetic patients (24 men and 11 women; mean age, 56.5 ± 12.8 years), with symmetrical length-dependent neuropathy and reduced intraepidermal nerve fiber density (0.76 ± 0.95 fibers/mm). By light and electron microscopy, PGP9.5-positive nerve terminals surrounded Congo red-positive sweat gland secretory coils in controls; these periglandular nerve terminals were either absent or markedly reduced in diabetic patients. Diabetic patients had lower SGII values than age- and sex-matched controls (2.60% ± 1.96% vs 4.84% ± 1.51%, p < 0.0001). The SGII values were lower in patients with anhidrosis of the feet versus those with normal sweating of the feet (0.89% ± 0.71% vs 3.10% ± 1.94%, p < 0.01). Thus, skin biopsy offers combined assessment of sudomotor innervation.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kai-Ren
authors.initials: KR
authors.lastname: Luo
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
authors.forename: Yi-Tsun
authors.initials: YT
authors.lastname: Chen
authors.forename: Cho-Min
authors.initials: CM
authors.lastname: Huang
authors.forename: Naomi Chu-Chiao
authors.initials: NC
authors.lastname: Yang
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Kan
authors.forename: Siang-Heng
authors.initials: SH
authors.lastname: Wang
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods; D003929:Diabetic Neuropathies / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology; D015203:Reproducibility of Results; D012867:Skin / Q000294:innervation* / Q000473:pathology*; D018709:Statistics, Nonparametric; D013545:Sweat Glands / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase