--that can be useful to diagnose small-fiber syndromes, such as quantitative (thermal) sensory testing and various autonomic tests (many autonomic functions are controlled by the small fibers, and people with small-fiber conditions often have disruptions in sweating, blood pressure with postural changes, and the like), but the skin biopsy is the current gold standard. It was the only test for me that was unequivocally abnormal--I had 2% of normal intraepidermal small fiber density with my first one (I've had others later to track my case--I was up to 11% on my last one--but I am unusual in that I had an acute onset body-wide burning neuropathy that seems to have been monophasic and is slowly resolving over years, though it's doubtful I'll get full recovery).

A small-fiber neuropathy cannot be ruled out if the skin biopsy is normal--but normal is usually defined as falling between the fifht and ninety-fifth percentile of intraepidermal small fiber density (as designated by the original norming process researched at Johns Hopkins). One can fall into that rnage and still show abnormal branching, swelling, or other morphological changes that are suggestive of small-fiber neuropathy.

The problem is that the pathologists trained in deciphering this are few and far between--it's why skin biopsy is only done at a small number of centers, though Hopkins has a program whereby a physician can send in skin samples to be analyzed there. Moreover, rarely will even an abnormal skin biopsy point to a cause of the neuropathy. But if the biopsy is abnormal that's pretty much a slam-dunk that you've got small-fiber involvement.