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Small-fiber neuropathy, also known as small-fiber sensory/peripheral neuropathy, is a peripheral nerve disease that selectively affects small diameter nerve fibers. These fibers innervate the skin, and aid in temperature perception, nociception (pain), and autonomic regulation. Common symptoms with peripheral neuropathy include:
Symptoms of small fiber neuropathy (SFN) correlate with a decrease in the number, density and length of small nerve fibers in the epidermis of skin biopsy specimens1. Standard electrophysiological tests for nerve injury such as nerve conduction tests and electromyograms (NCS and EMG, respectively) are gross measures of large nerves and cannot give information about the health of small sensory nerve fibers2. Current consensus is that small fiber neuropathy is extremely under-recognized3. An early diagnosis is important since detection of reduced small nerve fiber density can predict the progression to a larger-spread neuropathy.2 Small fiber neuropathy can result from many underlying disorders, including:
Performing a skin biopsy to analyze and quantify nerve fibers in the epidermis is a relatively simple and convenient way to identify and monitor small fiber neuropathies. Studies support the high sensitivity and specificity of skin biopsy in detecting small nerve fiber loss and it has been used not only in diagnosis, but also to evaluate disease progression and treatment success4,5. ENFD studies have been found to have 88.4% sensitivity in detection, compared with 54.6% for clinical exam alone2. Moreover, the test can detect early nerve fiber damage even in asymptomatic patients6.
Back to topDifferent areas of the body have different densities of intra-epidermal nerve fibers (IENF); generally, the average IENF density decreases the further one moves from the dorsal root ganglia. For example, IENF density is higher at the trunk than at the thigh and a lower density is found at the calf as compared to the thigh. IENF loss is more marked at distal anatomic locations (length-dependent), which is why the calf (10cm above the lateral malleolus) is the most common biopsy site for testing for small fiber neuropathy4. There are two to three standard biopsy sites for length-dependent sensory neuropathy. The sites are located on the lateral leg and have well-established, given normative values. The advantage to performing two or three biopsies on the same leg (for example, one distal leg and one proximal thigh) is the results can paint a clear picture of the progression of small fiber neuropathy.
Back to topThe ENFD test is a simple 3mm punch biopsy of skin from the leg, performed under local anesthetic. Once the sample is received at the lab, small sensory nerve fibers are stained and easily visualized under a microscope. A video on how the procedure is performed and post-biopsy care instructions can be found at www.advanced-lab.com. Biopsy kits include everything needed for the procedure except gloves, 1% or 2% lidocaine with epinephrine and a syringe. The requisition form, fixative, sterile punch biopsy tool kit, instructions and pre-paid express shipping materials are all provided.
Back to topResults include assessment of IENF density through a pathological review by neurological experts. Reports are mailed to the ordering physician, but can also be viewed more rapidly via Advanced Laboratory Services web portal.
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This test was developed and its performance characteristics determined by Advanced Laboratory Services. It has not been cleared or approved by the U.S. Food and Drug Administration.