Can Nerve Fiber Density Testing Facilitate Earlier Treatment Of Diabetic Neuropathy?
In their study, Umapathi, et al., demonstrated a mean ankle intraepidermal nerve fiber density of 9.1 mm in non-symptomatic diabetic patients in comparison to 13.0 mm in non-diabetic control patients. 13 The reduction in epidermal nerve fiber density in patients with diabetes was not associated with age, hemoglobin A1c, height, weight or duration of diabetes.
Researchers have similarly demonstrated the association of diminished epidermal nerve fiber density with increasing loss of pinprick sensitivity.15 Studies have also shown that diminished intraepidermal nerve fiber density is associated with diminished heat-pain perception. 16
Shun, et al., demonstrated intraepidermal nerve fiber density to be lower in patients with diabetes than in age-sex matched, non-diabetic control patients. They further demonstrated a negative correlation between the duration of diabetes and epidermal nerve fiber density, and a strong correlation between reduced epidermal nerve fiber density and heat perception. 17
The intraepidermal nerve fiber density diminishes in a length-dependent manner at the ankle joint with aging. 18 Chang, et al., demonstrated an epidermal nerve fiber density of 7.80 fibers/mm in individuals greater than 60 years of age and an epidermal nerve fiber density of 13.55 fibers/mm in young adults aged 13 to 39. 19 In addition to the effects of aging, males demonstrate increased nerve fiber density reduction at the ankle in comparison to females. 20
Pertinent Insights On Therapeutic Implications
A major advantage of this technique is the earlier opportunity to provide remittive therapy. Combining this remittive therapy with adequate control of diabetes may thwart the development of sensory, motor or autonomic peripheral neuropathic disease.
Head has suggested that a variety of alternatives may provide relief of neuropathic symptoms. Such alternative medicines include alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, vitamin B, glutathione, folate, pyridoxine, biotin, myo-inositol, omega 3 and omega 6 fatty acids, L-arginine, L-glutamate, taurine, N-acetylcysteine, zinc, magnesium, chromium and St. John’s Wort. 21
I personally employ a proprietary combination of L-methyl folate, piradoxine and methylcobalamin (Metanx, PamLab) for the management of peripheral neuropathy for these patients. By utilizing the intraepidermal nerve fiber density study to identify the presence of neuropathy prior to the onset of symptomatology, one can combine control of diabetes with the use of the aforementioned agents to reverse or interdict evolving sensory, motor and autonomic neuropathy.
Physicians are increasingly utilizing surgical decompression of the peripheral nerves for the treatment of symptomatic diabetic neuropathy in order to restore sensory function or reduce the paresthesias or dysthesias secondary to diabetic neuropathy. 22,23 The intraepidermal nerve fiber density study may demonstrate the presence of medial plantar nerve neuropathy prior to the demonstration of abnormal routine nerve conduction studies. 24
One can easily perform the intraepidermal nerve fiber density study in the office setting. The test facilitates the identification of patients with peripheral neuropathy prior to the onset of symptoms or positive clinical or electrophysiologic testing. One should consider this study when assessing all patients presenting to the office for an initial diabetic foot evaluation.
Physicians can use this test to establish the presence of previously undiagnosed and non-symptomatic peripheral neuropathy. This, in turn, facilitates the early institution of remittive therapy. Hopefully, use of the test will help physicians thwart the progression of peripheral neuropathy.
One can also utilize a repeat epidermal nerve fiber density study to establish the presence of peripheral entrapment neuropathy in the absence of electrodiagnostic studies, which become positive only after large fiber disease is present.