Changes of unmyelinated nerve fibers in sural nerve in amyotrophic lateral sclerosis, Parkinson’s disease and multiple system atrophy

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Abstract
Quantitative changes in unmyelinated nerve fibers (UMNFs) of sural nerves in patients of amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and multiple system atrophy (MSA) were evaluated using autopsy materials whose pathological diagnosis had been confirmed by careful postmortem examinations. Ordinary ALS cases demonstrated no involvement in cutaneous UMNFs; however, the patients with long survival due to the application of ventilatory support showed bimodality in UMNF diameter histograms, and a patient with involvement of systems other than motor pathways showed an abnormal value in two indices: a low percentage of subunits containing axon(s) and a high mean number of Schwann cell profiles per axon. A significant reduction of the mean value of UMNF density (21%) was found in PD patients. Because the density of myelinated nerve fibers did not show any significant decrease as compared with age-matched controls, the change of nerve fibers in peripheral nervous system was considered to be confined to UMNFs in PD. Elderly PD cases showed enhanced changes in the ageing process, as expressed by the two indices described above. In MSA, the mean value of UMNF density was significantly decreased (23%), and this decrease almost paralleled that of myelinated nerve fiber density. Abnormal values for the two indices described above were found and two out of four cases demonstrated bimodality in the diameter histogram of UMNFs. Unlike MSA, ALS and PD have not been included in the disorders with cutaneous UMNF involvement. Our results supply the first evidence of morphological changes in cutaneous UMNFs in PD cases. In ordinary ALS cases, the emergence of such morphological changes is suggested in cases with long survival.