Quantification of sweat gland innervation: a clinical-pathologic correlation.
OBJECTIVE
To evaluate a novel method to quantify the density of nerve fibers innervating sweat glands in healthy control and diabetic subjects, to compare the results to an unbiased stereologic technique, and to identify the relationship to standardized physical examination and patient-reported symptom scores.


METHODS
Thirty diabetic and 64 healthy subjects had skin biopsies performed at the distal leg and distal and proximal thigh. Nerve fibers innervating sweat glands, stained with PGP 9.5, were imaged by light microscopy. Sweat gland nerve fiber density (SGNFD) was quantified by manual morphometry. As a gold standard, three additional subjects had biopsies analyzed by confocal microscopy using unbiased stereologic quantification. Severity of neuropathy was measured by standardized instruments including the Neuropathy Impairment Score in the Lower Limb (NIS-LL) while symptoms were measured by the Michigan Neuropathy Screening Instrument.


RESULTS
Manual morphometry increased with unbiased stereology (r = 0.93, p < 0.01). Diabetic subjects had reduced SGNFD compared to controls at the distal leg (p < 0.001), distal thigh (p < 0.01), and proximal thigh (p < 0.05). The SGNFD at the distal leg of diabetic subjects decreased as the NIS-LL worsened (r = -0.89, p < 0.001) and was concordant with symptoms of reduced sweat production (p < 0.01).


CONCLUSIONS
We describe a novel method to quantify the density of nerve fibers innervating sweat glands. The technique differentiates groups of patients with mild diabetic neuropathy from healthy control subjects and correlates with both physical examination scores and symptoms relevant to sudomotor dysfunction. This method provides a reliable structural measure of sweat gland innervation that complements the investigation of small fiber neuropathies.
Gibbons
Christopher H
CH
Autonomic and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA 02215, USA.
Illigens
Ben M W
BM
Wang
Ningshan
N
Freeman
Roy
R
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D002452:Cell Count / Q000379:methods; D003929:Diabetic Neuropathies / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010336:Pathology / Q000379:methods*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000294:innervation / Q000473:pathology*; D013545:Sweat Glands / Q000294:innervation / Q000473:pathology*; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000378:metabolism; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
D015415:Biomarkers; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase