Abnormal LDIflare but normal quantitative sensory testing and dermal nerve fiber density in patients with painful diabetic neuropathy

Abstract

Objectives: Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small fiber damage include quantitative sensory testing (QST) and determining intra-epidermal nerve fibre density (IENFD). We recently described a reproducible physiological technique, the LDIflare, which assesses small fiber function and as such may reflect early dysfunction prior to structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal NFD.

Methods: Fifteen healthy controls (HC), 10 subjects with type 2 diabetes and painful (PFN) and 12 with painless (PLN) neuropathy were studied. LDIflare, QST and dermal NFD were determined on the dorsum of the foot.

Results: Both large and small fiber quantitative sensory tests were abnormal in patients with painless but not painful neuropathy compared to controls. Dermal NFD was also significantly reduced in the painless neuropathy group compared with controls (205.8+/−165.3 v 424.9+/−176.3; Mean+/−SD; p=0.003) but not in the painful group (307.6+/−164.5). In contrast, the LDIflare (cm2) was reduced in both painful (1.59+/−0.41) and painless (1.51+/−0.56) groups compared to controls (4.38+/−1.4), p<0.001 for both. NFD correlated significantly with the LDIflare (r=0.57, p<0.0001).

Conclusion: The LDIflare demonstrated impaired small fiber function in patients with painful neuropathy when other assessments revealed no abnormality. We believe that this method has potential diagnostic value, particularly as it is non-invasive, has excellent reproducibility and correlates with NFD. Furthermore, it may have an important role in assessing preventative therapies in early neuropathy.