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

Singhan T M Krishnan, Cristian Quattrini, Maria Jeziorska, Rayaz A Malik, Gerry Rayman, Singhan T M Krishnan, Cristian Quattrini, Maria Jeziorska, Rayaz A Malik, Gerry Rayman

Abstract

Objective: 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 intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD).

Research design and methods: Fifteen healthy control subjects, 10 subjects with type 2 diabetes and painful neuropathy (PFN), and 12 subjects with type 2 diabetes and painless neuropathy (PLN) were studied. LDIflare and QST were performed on the dorsum of the foot, and dermal NFD was determined.

Results: Results of both large- and small-fiber quantitative sensory tests were abnormal in patients with PLN but not those with PFN compared with control subjects. Dermal NFD was also significantly reduced in the PLN group compared with control subjects (205.8 +/- 165.3 vs. 424.9 +/- 176.3 [mean +/- SD]; P = 0.003) but not in the PFN group (307.6 +/- 164.5). In contrast, the LDIflare (square centimeters) was reduced in both PFN (1.59 +/- 0.41) and PLN (1.51 +/- 0.56) groups compared with control subjects (4.38 +/- 1.4) (P < 0.001 for both). NFD correlated significantly with the LDIflare (r = 0.57, P < 0.0001).

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

Figures

Figure 1
Figure 1
Correlation of LDIflare and NFD. The LDIflare results correlated significantly with dermal NFD (r = 0.57; P < 0.0001) in all subjects combined and within control subjects (•) (r = 0.53; P < 0.05) and in the PFN group (▴) (r = 0.71; P < 0.05) but not in the PLN group (▪) (r = 0.38; P = 0.22).

References

    1. Levitt NS, Stansberry KB, Wynchank S, Vinik AI: The natural progression of autonomic neuropathy and autonomic function tests in a cohort of people with IDDM. Diabetes Care 19:751–754, 1996
    1. Celiker R, Basgoze O, Bayraktar M: Early detection of neurological involvement in diabetes mellitus. Electromyogr Clin Neurophysiol 36:29–35, 1996
    1. Vinik AI, Erbas T, Stansberry KB, Pittenger GL: Small fiber neuropathy and neurovascular disturbances in diabetes mellitus. Exp Clin Endocrinol Diabetes 109:451–473, 2001
    1. Galer BS, Gianas A, Jensen MP: Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 47:123–128, 2000
    1. Dyck PJ, O'Brien PC, Kosanke JL, Gillen DA, Karnes JL: A 4, 2, and 1 stepping algorithm for quick and accurate estimation of cutaneous sensation threshold. Neurology 43:1508–1512, 1993
    1. Gruener G, Dyck PJ: Quantitative sensory testing: methodology, applications, and future directions. J Clin Neurophysiol 11:568–583, 1994
    1. Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giuliani MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH: Quantitative sensory testing: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 60:898–904, 2003
    1. Gelber DA, Pfeifer MA, Broadstone VL, Munster EW, Peterson M, Arezzo JC, Shamoon H, Zeidler A, Clements R, Greene DA: Components of variance for vibratory and thermal threshold testing in normal and diabetic subjects. J Diabetes Complications 9:170–176, 1995
    1. Rayman G, Malik RA, Sharma AK, Day JL: Microvascular response to tissue injury and capillary ultrastructure in the foot skin of type I diabetic patients. Clin Sci (Lond) 89:467–474, 1995
    1. Krishnan ST, Rayman G: The LDIflare: a novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes. Diabetes Care 27:2930–2935, 2004
    1. Polydefkis M, Hauer P, Griffin JW, McArthur JC: Skin biopsy as a tool to assess distal small fiber innervation in diabetic neuropathy. Diabetes Technol Ther 3:23–28, 2001
    1. Smith AG, Howard JR, Kroll R, Ramachandran P, Hauer P, Singleton JR, McArthur J: The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci 228:65–69, 2005
    1. Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, Hann AW, Hussein A, Jackson N, Johnson KE, Ryder CH, Torkington R, Van Ross ER, Whalley AM, Widdows P, Williamson S, Boulton AJ: The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med 19:377–384, 2002
    1. Paisley AN, Abbott C, van Schie C, Boulton AJM: A comparison of the Neuropen against standard quantitative sensory-threshold measures for assessing peripheral nerve function. Diabet Med 19:400–405, 2002
    1. Tesfaye S, Kempler P: Painful diabetic neuropathy. 48:805–807, 2005
    1. Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC: The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 127:1606–1615, 2004
    1. Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, Marshall A, Boulton AJ, Efron N, Malik RA: Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes 56:2148–2154, 2007
    1. Quattrini C, Jeziorska M, Boulton AJ, Malik RA: Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. Diabetes Care 31:140–145, 2008
    1. Lauria G, Morbin M, Lombardi R, Borgna M, Mazzoleni G, Sghirlanzoni A, Pareyson D: Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies. Neurology 61:631–636, 2003
    1. Sorensen L, Molyneaux L, Yue DK: The relationship among pain, sensory loss, and small nerve fibers in diabetes. Diabetes Care 29:883–887, 2006
    1. Loseth S, Stalberg E, Jorde R, Mellgren SI: Early diabetic neuropathy: thermal thresholds and intraepidermal nerve fibre density in patients with normal nerve conduction studies. J Neurol 255:1197–1202, 2008
    1. Quattrini C, Harris ND, Malik RA, Tesfaye S: Impaired skin microvascular reactivity in painful diabetic neuropathy. Diabetes Care 30:655–659, 2007
    1. Dabby R, Vaknine H, Gilad R, Djaldetti R, Sadeh M: Evaluation of cutaneous autonomic innervation in idiopathic sensory small-fiber neuropathy. J Peripher Nerv Syst 12:98–101, 2007
    1. Vlckova-Moravcova E, Bednarik J, Dusek L, Toyka KV, Sommer C: Diagnostic validity of epidermal nerve fiber densities in painful sensory neuropathies. Muscle Nerve 37:50–60, 2008
    1. Lauria G, Devigili G: Skin biopsy as a diagnostic tool in peripheral neuropathy. Nat Clin Pract Neurol 3:546–557, 2007

Source: PubMed

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