Quantitation of sudomotor innervation in skin biopsies of patients with diabetic neuropathy

Kai Ren Luo, Chi Chao Chao, Yi Tsun Chen, Cho Min Huang, Naomi Chu Chiao Yang, Hung Wei Kan, Siang Heng Wang, Wei Shiung Yang, Sung Tsang Hsieh

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)930-938
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number10
Publication statusPublished - Oct 2011
Externally publishedYes


  • Autonomic neuropathy
  • Diabetic neuropathy
  • Neurodegeneration
  • Sudomotor neuropathy
  • Sweat gland innervation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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