Can Nerve Fiber Density Testing Facilitate Earlier Treatment Of Diabetic Neuropathy?

By Allen Mark Jacobs, DPM, FACFAS, FAPWCA­­

   Intraepidermal nerve fiber density testing is gaining enthusiastic acceptance for the diagnosis as well as the staging of diabetic neuropathy. Studies have demonstrated reduced intraepidermal nerve fiber density in patients with diabetes type 1 and type 2.1 One major advantage of intraepidermal nerve fiber density testing is the ability to detect the presence of evolving peripheral neuropathy in the presence of normal neurophysiologic studies. 2

   Electrodiagnostic studies are reflective of large fiber disease, which is frequently preceded by the presence of small fiber neuropathy between 2 and 10 years. 3 In addition, small fiber neuropathy frequently presents with symptoms such as pain or numbness in the absence of any clinically definable signs. Using an epidermal nerve fiber density study enables the clinician to diagnose peripheral neuropathy in its earliest stages prior to otherwise demonstrable objective evidence of disease. This provides the opportunity to employ therapy aimed at the reduction or reversal of evolving peripheral neuropathic disease.

   In addition to the diagnostic value of this test, the epidermal nerve fiber density study allows physicians to assess the response to treatment of peripheral neuropathy. 4 One can also use the intraepidermal nerve fiber density study to assess the regeneration of epidermal nerves in the diabetic and non-diabetic patient with neuropathy. 5

   Nerve fiber studies have demonstrated the regeneration of small fiber nerve loss associated with entrapment neuropathy following surgical decompression. This suggests that the intraepidermal nerve fiber density study may be of benefit for the preoperative and postoperative evaluation of entrapment neuropathy, and to gauge the response to decompression surgery for the patient with symptomatic diabetic entrapment neuropathy. 6

   Intraepidermal nerve fiber studies have demonstrated the neuroprotective effects of progesterone and its derivatives as well as testosterone on peripheral nerves. 7,8 Similarly, the testing has demonstrated enhanced cutaneous nerve regeneration with the utilization of 4-methylcatechol in resiniferatoxin-induced neuropathy. 9

   The technique for epidermal nerve fiber density testing consists of obtaining two 3.0-mm punch biopsy specimens from the supramalleolar area. I generally employ marcaine 0.5% with epinephrine 1/200,000 for anesthesia. I administer local anesthesia between the Achilles tendon and the fibular, 4 cm above the tip of the lateral malleolus. I place the specimens in an appropriate preservative and submit the specimens for the epidermal nerve fiber density study.

What The Literature Reveals

   In the patient with diabetic neuropathy, one can demonstrate reduced peripheral nerve branch density and reduced peripheral nerve branch length by utilizing intraepidermal nerve fiber density testing. Increasing severity of peripheral neuropathy, progressing from mild to severe neuropathy, is associated with an increasingly demonstrable loss of peripheral nerve branch density and length. 10

   DeSousa, et al., demonstrated reduced epidermal nerve fiber in 71 percent of patients with sensory neuropathy. They also noted morphological nerve changes in the presence of a normal epithelial nerve fiber density study in 21 percent of patients. 11 Other demonstrable morphologic features in the presence of peripheral neuropathy are epidermal axon swelling, dermal axon swelling, thinning of the subepidermal nerve plexus, sprouting of nerve terminals, encapsulation of nerve endings and immunoreactive basal cells. 12

   Intraepidermal nerve fiber density testing reliably identifies patients with early stage diabetic polyneuropathy prior to any clinical or electrophysiologic evidence of neuropathy. 13 Researchers have demonstrated the sensitivity of the intraepidermal study for the detection of peripheral neuropathy over other available tests such as quantitative sensory testing or electrodiagnostic studies. 14

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