Evidence of altered epidermal nerve fiber morphology in adults with self-injurious behavior and neurodevelopmental disorders

The purpose of this preliminary study was to examine the morphology and neuropeptide density of epidermal nerve fibers quantified through skin biopsy samples from three adults with neurodevelopmental disorders and chronic self-injurious behavior (SIB) secondary to mental retardation compared with non-SIB normal IQ controls. A cross-sectional design was used with 3 mm punch skin biopsies collected from each participant from non-self-injurious body sites and compared with site-matched existing normal control skin samples. The study was conducted at an outpatient clinic. The primary dependent measure for the morphology analyses was the coefficient of variation (CV) to quantify the mean gap length between epidermal nerve fibers for each subject. Visual microscopic examination and quantitative analysis of the microscopy images suggested there were morphological abnormalities (increased CV) in the epidermal nerve fibers among the chronic SIB cases. Substance P (SP) fiber density was increased with 2 to 3 times as many fibers in SIB subjects as control subjects. Additional empirical work is needed to clarify the relation between sensory innervation of the skin and self-injury to improve assessment and treatment outcomes

A Device to Quantify Sweat in Single Sweat Glands to Diagnose Neuropathy

We devised an objective "Sensitive Sweat Test" (SST) that detects and quantifies early changes in the function of sudomotor nerves that activate sweat glands (SGs). The SST is designed to diagnose peripheral neuropathy early, when the probability for reversal is greatest. Chemotherapy induced and diabetic neuropathy are very common causes of neuropathy in the USA. Both result in peripheral numbness, pain, decreased sweating, abnormal circulation, and eventual weakness. Early recognition can provide a better opportunity to treat and halt neuropathy than discovery after the onset of nerve degeneration. We contend that early diagnosis can be achieved by sensitive monitoring of sweating. Unfortunately, the changes that first signal impending sweat deficiency escape detection by conventional clinical examination and current tests We contracted with several MN small business concerns (SBCs) to construct the SST miniature camera device Methods Skin sites on the medial calf and foot dorsum, each measuring 2 cm 2 were stimulated to sweat maximally by iontophoresis of 1% pilocarpine (2 ma, 5 min; Transparent tape thinly coated with starch was attached over the lens of the SST miniature camera. The skin test sites were prepped with a 1% iodine solution. The skin was wiped dry and immediately the camera was pressed against the skin, activating a switch to begin image collection and storage. As sweat water exited from each sweat pore it contacted iodine and starch and formed a tiny dark spot. The tape prevented formation of a drop. Instead, sweat was forced to flow centrifugally to form a flat expanding dark spot. The SST device imaged spots from >200 SGs at 1 frame/sec (area of 2 cm 2 ) for 60 to 90 seconds, until adjacent spots coalesced. The process was performed twice. Image analysis was done in the Mathworks Software, MATLAB version R2012a. Each individual sweat spot was identified and followed from frame to fram

Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function

The ability of capsaicin to excite and subsequently to desensitize a select group of small sensory neurons has made it a useful tool to study their function. For this reason, application of capsaicin to the skin has been used for a variety of painful syndromes. We examined whether intradermal injection of capsaicin produced morphological changes in cutaneous nerve fibers that would account for its analgesic properties by comparing cutaneous innervation in capsaicin-treated skin with psychophysical measures of sensation. At various times after capsaicin injection, nerve fibers were visualized immunohistochemically in skin biopsies and were quantified. In normal skin the epidermis is heavily innervated by nerve fibers immunoreactive for protein gene product (PGP) 9.5, whereas fibers immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP) are typically associated with blood vessels

Second-order spatial analysis of epidermal nerve fibers

Breakthroughs in imaging of skin tissue reveal new details on the distribution of nerve fibers in the epidermis. Preliminary neurologic studies indicate qualitative differences in the spatial patterns of nerve fibers based on pathophysiologic conditions in the subjects. Of particular interest is the evolution of spatial patterns observed in the progression of diabetic neuropathy. It appears that the spatial distribution of nerve fibers becomes more \u27clustered\u27 as neuropathy advances, suggesting the possibility of diagnostic prediction based on patterns observed in skin biopsies. We consider two approaches to establish statistical inference relating to this observation. First, we view the set of locations where the nerves enter the epidermis from the dermis as a realization of a spatial point process. Secondly, we treat the set of fibers as a realization of a planar fiber process. In both cases, we use estimated second-order properties of the observed data patterns to describe the degree and scale of clustering observed in the microscope images of blister biopsies. We illustrate the methods using confocal microscopy blister images taken from the thigh of one normal (disease-free) individual and two images each taken from the thighs of subjects with mild, moderate, and severe diabetes and report measurable differences in the spatial patterns of nerve entry points/fibers associated with disease status

Confocal microscopy study of nerves and blood vessels in untreated and treated port wine stains: preliminary observations.

Background and objectiveVascular ectasia in port wine stain birthmarks (PWS) might result from reduced innervation with loss of autonomic stimulation. We investigated this theory and evaluated nerve and blood vessel density, and mean blood vessel size in untreated and treated PWS skin.MethodsSkin biopsy specimens were obtained from uninvolved skin, untreated PWS, PWS with a good response to laser treatment and PWS with a poor response to laser treatment. Confocal microscopy was performed to determine nerve and blood vessel density, and mean blood vessel size.ResultsNerve density was significantly decreased in all PWS sites compared to uninvolved skin. Mean blood vessel diameter was larger in untreated compared to treated PWS. PWS with a good response to treatment had decreased nerve density but blood vessel density and mean diameter was relatively normal. PWS with a poor response to treatment had decreased nerve density but increased blood vessel density and mean blood vessel diameter compared to normal skin.ConclusionNerve density was decreased in all evaluated PWS sites and this may be a factor in lesion pathogenesis. PWS blood vessel size correlated with pulsed dye laser response and may prove to be a useful prognostic indicator of therapeutic outcome

Confocal microscopy study of nerves and blood vessels in untreated and treated port wine stains: preliminary observations.

Background and objectiveVascular ectasia in port wine stain birthmarks (PWS) might result from reduced innervation with loss of autonomic stimulation. We investigated this theory and evaluated nerve and blood vessel density, and mean blood vessel size in untreated and treated PWS skin.MethodsSkin biopsy specimens were obtained from uninvolved skin, untreated PWS, PWS with a good response to laser treatment and PWS with a poor response to laser treatment. Confocal microscopy was performed to determine nerve and blood vessel density, and mean blood vessel size.ResultsNerve density was significantly decreased in all PWS sites compared to uninvolved skin. Mean blood vessel diameter was larger in untreated compared to treated PWS. PWS with a good response to treatment had decreased nerve density but blood vessel density and mean diameter was relatively normal. PWS with a poor response to treatment had decreased nerve density but increased blood vessel density and mean blood vessel diameter compared to normal skin.ConclusionNerve density was decreased in all evaluated PWS sites and this may be a factor in lesion pathogenesis. PWS blood vessel size correlated with pulsed dye laser response and may prove to be a useful prognostic indicator of therapeutic outcome