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Asymptomatic small fiber neuropathy in diabetes mellitus: investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials

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Ragé, Michaël [UCL] Van Acker, Nathalie Knaapen, Michiel W M Timmers, Maarten Streffer, Johannes Hermans, Michel [UCL] Sindic, Christian [UCL] Plaghki, Léon [UCL]

This study aimed at evaluating the performance of a battery of morphological and functional tests for the assessment of small nerve fiber loss in asymptomatic diabetic neuropathy (DNP). Patients diagnosed for ≥10 years with type 1 (n = 10) or type 2 (n = 13) diabetes mellitus (DM) without conventional symptoms or signs of DNP were recruited and compared with healthy controls (n = 18) and patients with overt DNP (n = 5). Intraepidermal nerve fiber density (IENFd) was measured with PGP9.5 immunostaining on punch skin biopsies performed at the distal leg. Functional tests consisted of quantitative sensory testing (QST) for light-touch, cool, warm and heat pain detection thresholds and brain-evoked potentials with electrical (SEPs) and CO(2) laser stimulation [laser-evoked potentials (LEPs)] of hand dorsum and distal leg using small (0.8 mm(2)) and large (20 mm(2)) beam sizes. Results confirmed a state of asymptomatic DNP in DM, but only at the distal leg. Defining a critical small fiber loss as a reduction of IENFd ≤-2 z scores of healthy controls, this state prevailed in type 2 (30%) over type 1 DM (10%) patients despite similar disease duration and current glycemic control. LEPs with the small laser beam performed best in terms of sensitivity (91%), specificity (83%) and area-under-the ROC curve (0.924). Although this performance was not statically different from that of warm and cold detection threshold, LEPs offer an advantage over QST given that they bypass the subjective report and are therefore unbiased by perceptual factors.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Journal of Neurology : official journal of the European Neurological Society" - Vol. 258, no.10, p. 1852-1864 (2011)
Peer reviewed yes
Publisher Dr. DietrichSteinkopff Verlag ((Germany) Heidelberg)
issn 0340-5354
e-issn 1432-1459
Publication status Publié
Affiliations UCL - SSS/IONS - Institute of NeuroScience
UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire
UCL - (SLuc) Service d'endocrinologie et de nutrition
UCL - (SLuc) Service de neurologie
UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
MESH Subject Adult ; Immunohistochemistry ; Lasers ; Male ; Middle Aged ; Nerve Fibers ; Sensitivity and Specificity ; Sensory Thresholds ; Skin ; Biopsy ; Diabetes Mellitus ; Diabetic Neuropathies ; Early Diagnosis ; Electric Stimulation ; Evoked Potentials, Somatosensory ; Female ; Humans
Links
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Bibliographic reference Ragé, Michaël ; Van Acker, Nathalie ; Knaapen, Michiel W M ; Timmers, Maarten ; Streffer, Johannes ; et. al. Asymptomatic small fiber neuropathy in diabetes mellitus: investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials. In: Journal of Neurology : official journal of the European Neurological Society, Vol. 258, no.10, p. 1852-1864 (2011)
Permanent URL http://hdl.handle.net/2078.1/132381