EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy

Abstract

Dear Sir, The article by Lauria et al. [1] comprehensively reviewed literatures of skin biopsy on diagnosis of peripheral neuropathy, and recommended technical aspects of applications. This is a very important article for both neurologists and pathologists. I would like to update some information raised in the article. Skin biopsy has become a new approach to diagnose peripheral neuropathy globally, not only in Europe and the US as mentioned in the review, but also in Asia. Our skin laboratory at National Taiwan University, Taipei, Taiwan was established in 1995, with works cited in the review [2–5]. It is an independent and a major laboratory in Asia, which has also received skin specimens for examinations from other regions. This suggests that skin biopsy with quantitation of intra-epidermal nerve fiber (IENF) density has entered the stage of clinical use. Age and gender have profound effects on skin innervation, and IENF densities are different among various parts of the body, including the upper limb [6]. These results suggest that in addition to neurophysiological parameters, age and gender need to be considered when interpreting IENF density, an important issue as pointed by this review and others [7]. In addition to quantitative difference between controls and neuropathic patients, axonal swelling and increased branching are indicators of ‘degenerating’ IENF in human studies [8], although their significance has been difficult to evaluate longitudinally in human studies. A parallel study in an animal model of small-fiber neuropathy clearly demonstrated the pathologic scenario [9]. In the initial stage of acrylamide intoxication, there were significant axonal swelling and increased branching with normal IENF density. IENF density was only reduced in the late stage of acrylamide intoxication. These longitudinal observations support the notion that axonal swelling and increased branching could be signs of pre-degeneration. These findings are reminiscent of degeneration of motor nerve terminals [10], suggesting that common mechanisms operate at the level of nerve terminals, e.g. calcium influx [11]. Certainly, more longitudinal studies in human neuropathies are required to test his hypothesis. In summary, Lauria et al. clearly set up the guideline of skin biopsy and related procedures to investigate small-fiber neuropathy. This is a milestone in standardizing and advocating the feasibility and applications of skin biopsy.