The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Intraepidermal Nerve Fibers Are Indicators of Small-Fiber Neuropathy in Both Diabetic and Nondiabetic Patients
Abstract
OBJECTIVE—Small-fiber neuropathies may be symptomatic yet escape detection by standard tests. We hypothesized that morphologic changes in intraepidermal nerves would correlate with clinical measures of small-fiber neuropathy. RESEARCH DESIGN AND METHODS—We studied 25 diabetic and 23 nondiabetic patients with neuropathy defined by signs, symptoms, and quantitative testing and 20 control subjects. Skin biopsies were obtained from forearm, thigh, proximal leg, and distal leg, and nerves identified using immunofluorescence with antibody to protein gene product (PGP) 9.5. RESULTS—Mean dendritic length (MDL) (P < 0.01) and intraepidermal nerve fiber density (IENF) (P < 0.001) progressively decreased from proximal to distal sites only in patients with neuropathy. There was a significant reduction in IENF when comparing control subjects and patient groups in the distal leg (P < 0.001). MDL was significantly decreased in the thigh (P < 0.005) and in the proximal (P < 0.01) and distal (P < 0.002) leg in patients compared with control subjects. IENF was not significantly altered in diabetic patients of <5 years’ duration, but significantly decreased in patients with >5 years’ duration. MDL showed a linear decrease with increasing duration of diabetes. Distal leg IENF showed significant negative correlations with warm (P < 0.02) and cold (P < 0.05) thermal threshold, heat pain (P < 0.05), pressure sense (P < 0.05), and neurological disability score total sensory (P < 0.03) and total neuropathy (P < 0.03) values. CONCLUSIONS—IENF was not significantly altered in these patients at <5 years’ duration of diabetes, but fell significantly after 5 years of diabetes. MDL exhibited a linear loss with time, suggesting a different mechanism of change. MDL and IENF together may prove a useful end point in therapeutic trials for neuropathy.
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Cites
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Sumner, C. J., Sheth, S., Griffin, J. W., Cornblath, D. R., & Polydefkis, M. (2003) · Neurology · doi:10.1212/wnl.60.1.108 · Cited by 708 · cited 1×
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ResultDetection, characterization, and staging of polyneuropathy: Assessed in diabetics
Dyck, P. J. (1988) · Muscle & Nerve · doi:10.1002/mus.880110106 · Cited by 555
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Painful sensory neuropathy: Prospective evaluation using skin biopsy
Periquet, M. I., Novak, V., Collins, M. P., Nagaraja, H. N., Erdem, S., Nash, S. M., Freimer, M. L., Sahenk, Z., Kissel, J. T., & Mendell, J. R. (1999) · Neurology · doi:10.1212/wnl.53.8.1641 · Cited by 377
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Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy
Polydefkis, M., Yiannoutsos, C. T., Cohen, B. A., Hollander, H., Schifitto, G., Clifford, D. B., Simpson, D. M., Katzenstein, D., Shriver, S., Hauer, P., et al. (2002) · Neurology · doi:10.1212/wnl.58.1.115 · Cited by 297
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Cited by
Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890
Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study
Lauria, G., Bakkers, M., Schmitz, C., Lombardi, R., Penza, P., Devigili, G., Smith, A. G., Hsieh, S., Mellgren, S. I., Umapathi, T., et al. (2010) · Journal of the Peripheral Nervous System · doi:10.1111/j.1529-8027.2010.00271.x · Cited by 518
Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy
Iqbal, Z., Azmi, S., Yadav, R., Ferdousi, M., Kumar, M., Cuthbertson, D. J., Lim, J., Malik, R. A., & Alam, U. (2018) · Clinical Therapeutics · doi:10.1016/j.clinthera.2018.04.001 · Cited by 487
Vinik, A. I., Nevoret, M.-L., Casellini, C., & Parson, H. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.06.001 · Cited by 366
Self-citationDiabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments
Obrosova, I. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.07.004 · Cited by 272
Metadata
- Authors
- Pittenger, G. L., Ray, M., Burcus, N. I., McNulty, P., Basta, B., & Vinik, A. I.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2004-08-01
- Volume
- 27
- Issue
- 8
- Pages
- 1974-1979
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2085384724
- Cited by
- 263
- References
- 26
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- closed
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