--that I've written about a number of times here (you can look up posts under my name if you'd like), but the essence is that the determination of what is a small-fiber neuropathy through skin biopsy is based on a very strict statistical determination--the McArthur protocols, so named after the lead researcher at Johns Hopkins who was involved in the age-based "norming" of both experimental and control subjects at Hopkins when this procedure was first being developed.

The strictness of the statistical window--you are considered to have small-fiber neuropathy if you are below the fifth percentile or above ninety-fifth percentile in intraepidermal nerve fiber density for age-matched "normals"--probably leaves a lot to be desired, especially among doctors not familiar with how the protocol was developed (and by that I mean most of them). One big problem is that since almost no one gets a skin biopsy to measure nerve fibers unless one has symptoms, there's no "pre-morbid" comparison for a symptomatic person. For instance, you may be considered normal if you are in the twentieth percentile, but who knows where you were before symptoms started? To me, if, for example, you've gone from the fiftieth to the twentieth percentile, you've got a neuropathic process ongoing--but almost no one knows their pre-symptomatic numbers. So, the chances for false negatives are considerable.

This is why there is also supposed to be an analysis of the condition of the small fibers--are there deposits, swellings, excessive branchings, other signs of deterioration--included in the biopsy reports. Depending on who does the reports, though, these may or may not be there.

One good thing about skin biopsy is that it is sufficiently non-invasive that it may be repeated at the same areas over time. If one has biopsies a year apart and a big movement in numbers is seen, that may be more enlightening than the absolute numbers. I've discussed this with neurologists at Hopkins and Cornell, though, and many do think the numerical criteria for definite small-fiber neuropathy are set too strictly.