Hannah - I am by no means an expert in this area but i can tell u about what my neuro did - i just had the biopsy on the 19th and am also still waiting. My neuro took 2 samples one from my upper thigh and one from my ankle (i have also heard of a sample being taken from the calf). My neuro said that the reason for these placements is that these are the areas that are standard and have the most data to compare to for analysis. The fact that you did have only one taken is kind of odd BUT my neuro said that the reason to take 2 is to see if it is a length dependent neuropathy or not. The single sample can still be analyzed for small fiber nerve density however . Where was you biopsy taken from. Also were your samples sent to therapath labs in new york (this is where mine were sent). Also about the idea that if your normal was in 50th -- it is true that they can take a sample from a sight that is expected to have normal density for you however observation of the single site can still show mildly abnormal (less than 10th percentile) results or other problems with the nerves (i think something about swelling of the nerves) both which can yield suspision of SFN and may then yield another biopsy later for conformation.

Hope this helps some! I know what you are going through some what waiting for these results is driving me insane (my symptoms sound very similar to your too)
Hang in there!

"Where was you biopsy taken from. Also were your samples sent to therapath labs in new york (this is where mine were sent). "

Thank you very much for your helpful response. Yes, the samples were sent to Therapath. On their website I see they provide a video for physicians, and two or three minutes into the 5 minute video they show how the locations are mapped out. Watching that video (which I did this afternoon) confirmed my impression that the person who did mine did it incorrectly (I had other reasons for doubting already). Clearly this video is there so doctors can learn to do the biopsies properly (which is great for patients who don't live near a major medical center where it might be more standard practice already). The procedure is illustrated very clearly. In the video they actually use a measuring tape to get to the correct areas for the samples.

When you say you had one from the ankle, how close to the actual ankle? For Therapath it looked like on the foot itself was an option, otherwise it would be on the calf (which they referred to as "distal leg" -about 10 cm above the ankle). Did you actually get one done in front of or behind the ankle bone (and really close to the ankle)? That would be interesting to know if you did, and also to know how they classified it (distal leg? or foot?)

I really would like to know how precise these locations need to be for the results to be valid. Maybe if yours was really close to the ankle and yet was classified as "distal leg"-- but still ok by you and your neurologist -- then maybe my sample would be ok in terms of location. Mine was at least several inches from what would seem to be the target according to that Therapath physician instructional video.

Sorry for asking and thanks very much for having responded already and having shared your experience (including that it was therapath).

Take care and happy new year!

Hannah --

My sample was taken behine the ankle bone and maybe like and inch up (toward leg) I am not sure how this was classified but I am confident that my neuro picked usable sites for the biopsy (she is an SFN neurologist who does them for Ohio State on a monthly basis), Maybe this means that it is a more general area needed to look at the nerves? I am not sure ... where was yours taken?

Oh dont worry about the amount of questions! Glad to help

The best way to describe mine I think is if one imagines a clock face centered at the lateral malleolus. 12 o'clock is straight up my leg, 6 pm is pointing straight down to the floor (if I am standing). Given this orientation my biopsy would be on the 1:30 line from center, and at most 3 cm from the center, not 10 cm.

I don't think it is actually so different from yours, except mine is up and in front of the ankle bone, instead of up and behind.

I wonder why Therapath calls for the sample to be 10 cm away from the lateral malleolus.

Does anyone know if there is usually a large difference between the resulting nerve count numbers for the sample site on the foot as opposed to distal leg? I'm sure thigh to foot makes a difference especially if the neuropathy is in one place and not (or not yet) in the other.

I think the location of my biopsy is more or less in between those two sites with standard data (as specified by Therapath), that is between the "distal leg" location and the "foot" location.

Thank you again for being so helpful and writing back.

--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.

Thanks, Glenn, for a detailed explanation as per your usual. I wanted to reply as I was disturbed by Hannah's question, it didn't seem like she was given a serious skin biopsy. Mine was as you described, but then it was done at Hopkins, the third one was at the upper thigh near the hip, but my legs are very long so this may have affected the sites. Ankle and just above the knee were the others. All showed deterioration, but in a clearly length dependent and progressive pattern. Information from one site only would seem very incomplete.

Thanks Susanne C." Information from one site only would seem very incomplete" - it did seem that way to me too. Thank you for posting.

Thank you, glenntaj, for the extremely helpful and detailed information.