Noninvasive and minimally invasive detection and monitoring of peripheral neuropathies

Abstract

Peripheral neuropathies are diverse and require a multidimensional approach for detection and monitoring in a clinical and research setting. This review describes non- and minimally-invasive measures of distal predominantly sensory polyneuropathy (DSP), the most common form of neuropathy. A combination of clinical and electrophysiologic assessment with nerve-conduction studies (NCSs) suffices for the detection and characterization of most DSPs. NCS are insensitive to variants of DSP that predominantly affect small diameter sensory nerve fibers (SFNs) and cutaneous nerve terminals that subserve pain and thermal sensation. Skin biopsy with assessment of epidermal nerve fiber density permits objective detection and monitoring of SFNs. Conventional clinical and NCS measures have limitations as outcomes in experimental therapeutics in DSP. For clinical trials, biopsy evaluation of epidermal innervation and emerging noninvasive imaging approaches (in vivo confocal microscopy of corneal innervation and of Meissner corpuscles in the skin) hold promise as surrogate markers that are complementary to traditional DSP measures.

Keywords::

• clinical trial
• corneal confocal microscopy
• diagnosis
• epidermal nerve fiber density
• evoked potential
• in vivo reflectance confocal microscopy
• Meissner corpuscle
• nerve-conduction study
• noninvasive
• outcome measure
• peripheral neuropathy
• quantitative sensory testing
• skin biopsy

Financial & competing interests disclosure

The author currently receives grant support from the NIH for a study of in vivo RCM of MCs in HIV infection (NS058259–01A1), and is a site principal investigator for a Sanofi-Aventis multicenter, randomized, double-blind, placebo controlled study of the effect of SSR180575 on the rate of regeneration of ENFs in patients with mild DPN. The author’s clinical and research effort involves use of some of the procedures described in this special report including NCS, skin biopsy, QST and in vivo RCM of MCs. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.