--that increased intraepidermal nerve fiber density as measured through staining may represent an early phase of small-fiber damage, as the body attempts to fight the process through increased branchings. Of course, it may be hard to distinguish this in a skin-biopsy "snapshot" from nerve regeneration.

A good electron microscope analysis can often distinguish these increased branchings from regeneration by looking for evidence of fiber deterioration, notably in the form of fiber swellings. But one needs to have such things looked for, and by an experienced micro-pathologist.

Take a look at this, which sort of summarizes this obervational difficulty:


http://www.medscape.org/viewarticle/563262_5



Fortunately, skin biopsy, while it generally cannot reveal a cause for neuropathy, is reproducable over time, so density and condition of nerve fibers in the same body areas can be repeatedly sampled and often that is a better indicator if neuropathy is progressing, healing, or merely stable.