EDITORIAL REVIEW Small fiber involvement in peripheral neuropathies

Introduction Small fiber involvement in different patterns of peripheral neuropathy has stirred much interest during the past few years due to the role played by these fibers in pain perception and the availability of new techniques of skin biopsy that permit the study of nerve endings [1]. The use of protein gene product 9.5 (PGP 9.5) as a panaxonal marker in skin biopsies has led to identification of small fiber lesions in a variety of conditions that were not previously considered as potential causes of small fiber neuropathy. Small nerve fibers include the unmyelinated and the myelinated fibers smaller than 7 mm diameter. They are much more numerous than larger myelinated fibers. They are currently being explored by clinical examination, including quantitative sensory testing, but also by histometric study of nerve biopsy specimens, and more recently skin biopsies and by several techniques exploring the autonomic response [2]. There is a marked variation in unmyelinated fiber density ranging between 19 000 and 65 000 per mm endoneurial area [3]. A small proportion of these consists of post-ganglionic autonomic fibers. Small nerve fibers are often predominantly affected in human neuropathies and yet there is virtually no peripheral neuropathy in which the large myelinated fibers are totally spared morphologically. As stated in a recent review [2], there is no agreement in the literature regarding the amount of large-fiber dysfunction that can coexist and still allow the diagnosis of small-fiber neuropathy.