We used immunohistochemistry and confocal microscopy applied to fingertip punch biopsy to study glabrous skin innervation in 14 healthy subjects. In addition to epidermal nerve fibers, we quantified mechanoreceptors and their myelinated afferents. Using digital images and dedicated software, we calculated caliber, internodal and nodal length, and G-ratio of the last four internodes of the myelinated endings. In our skin samples, we found a mean density of 59.0 +/- 29.3 myelinated endings per square millimeter with a mean diameter of 3.3 +/- 0.5 microm and an internodal length of 79.1 +/- 13.8 microm. These findings indicate that Abeta fibers undergo drastic changes in their course from the nerve trunk to the target organ, with repeated branching and consequent tapering and shortening of internodal length. Our work demonstrates that skin biopsy can give information on the status of large myelinated endings as well as unmyelinated sensory and autonomic nerves. Since distal endings are primarily involved in distal axonopathy, skin biopsy can be more suitable than sural nerve biopsy to detect early abnormalities. In addition to diagnostic applications, this technique allows clarification of the mode of termination of Abeta fibers and their relationship with mechanoreceptors, leading to relevant electrophysiological speculations.

No abstract

Although the involvement of large myelinated sensory fibers in Friedreich's ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been described. We demonstrate an involvement of cutaneous unmyelinated sensory and autonomic nerve fibers in FA patients. We performed a morphological and functional study of cutaneous nerve fibers in 14 FA patients and in a population of control subjects. We used immunohistochemical techniques and confocal microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip, and compared the density of epidermal nerve fibers (ENFs) with the results of mechanical pain sensation and thermal and tactile thresholds performed on hand dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a statistically significant loss of ENFs, a reduced innervation of sweat glands, arrector pilorum muscles and arterioles, and an impairment of thermal and tactile thresholds and mechanical pain detection.

Patients with RA may have electrophysiologic and histologic findings of peripheral nerve damage, even in the absence of clinical evidence of peripheral nerve involvement.

Objective-To verify if GAA expansion size in Friedreich's ataxia could account for the severity of sensory neuropathy. Methods-Retrospective study of 56 patients with Friedreich's ataxia selected according to homozygosity for GAA expansion and availability of electrophysiological findings. Orthodromic sensory conduction velocity in the median nerve was available in all patients and that of the tibial nerve in 46 of them. Data of sural nerve biopsy and of a morphometric analysis were available in 12 of the selected patients. The sensory action potential amplitude at the wrist (wSAP) and at the medial malleolus (m mal SAP) and the percentage of myelinated fibres with diameter larger than 7, 9, and 11 µm in the sural nerve were correlated with disease duration and GAA expansion size on the shorter (GAA1) and larger (GAA2) expanded allele in each pair. Pearson's correlation test and stepwise multiple regression were used for statistical analysis. Results-A significant inverse correlation between GAA1 size and wSAP, m mal SAP, and percentage of myelinated fibres was found. Stepwise multiple regression showed that GAA1 size significantly affects electrophysiological and morphometric data, whereas duration of disease has no eVect. Conclusion-The data suggest that the severity of the sensory neuropathy is probably genetically determined and that it is not progressive (J Neurol Neurosurg Psychiatry 1999;66:93-96)