--to enumerate intraepidermal nerve fiber density and to examine the condition of the small, unmyelinated nerve fibers are the side to back of the calf, a few inches above the ankle, and the side of the thigh, close to the middle of the thigh but usually a bit closer to pelvic bone than to knee.

You can see how the Therapath video instructions and protocols correspond to these areas--Therapath may get a little more exacting than I do, but the areas mentioned are generally the same.

The reasons for this have to do with the original research done on skin fiber density at Johns Hopkins some decades back to establish the norms. these are known as the McArthur protocols and can be googled (or you can look them up here on Neurotalk--I've posted a lot about them in the past). It was found at the time that the easiest places to enumerate from were those areas (and a number of different areas were tried at first, but there was less consistency person to person, or even with the same person over time, for a lot of them). And yes, the reason for the -slightly-above-the-ankle and mid-thigh placements are to see if the neuropathy has a length dependent gradient, as many neuropathies (though not all) from the most common causes do. Some neuros at major research universities may also take a sample from the back of the upper arm right above the elbow, which is an area that has also been 'normed' by research to a considerable extent.

The EXACT spot on the calf or thigh that the sample is taken from may matter less than the densities or the condition of the nerves discovered. Since skin biopsy is simple and non-invasive (it's the electron microscope analysis needed that keeps it from being done in more places by more physicians), it can be repeated from the same areas over time and the results tracked to see if there is stability/deterioration/improvement. (I've had four series done over almost ten years now, and my neurologist lets me remind him of exactly where the samples are to be taken from--and we look for the small scar to confirm.)

As I've written a lot about, when the McArthur protocols were established, the researchers rather arbitrarily defined the fifth percentile and the ninety-fifth percentile of the densities they measured from hundreds of "normal' research subjects as the cut-off points for definite evidence of small-fiber neuropathy. The problem with this, I feel, is that few people have their densities measured when they are not symptomatic, so it is very hard to know at what percentile level they started at. That means, for example, that someone who measures at say, the fifteenth percentile is not in most cases given a diagnosis of small-fiber neuropathy. There's no way to tell, though, if that person started at a much higher percentile and IS experiencing de-enervation. This is why the analysis is also supposed to include a thorough examination of the condition of the nerves--is there swelling, excessive branching, does it look as if the nerves are undergoing axonal deterioration, etc. The true value of the numbers may be if they change significantly over time when taken from the same area.