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Comparison of a simple method for quantitation of intraepidermal nerve fibres with a standard image analysis method using hypothenar skin

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Abstract

Objectives

To compare a simpler method for counting intraepidermal nerve fibres with a standard computer based image analysis method in normal subjects with skin taken from the hypothenar region.

Methods

In 40 healthy controls (mean age 41.1 years, range 21–71, 24 Chinese, 11 Indian, 5 Malay, 30 females) intraepidermal nerve fibres per length of epidermis were determined using immunoperoxidase staining with the panaxonal antibody PGP 9.5. Under brightfield microscopy, two methods of determining the length of the epidermis were compared. A simpler method employing a microscope intraocular lens ruler was compared with the more complex gold standard using image software analysis .

Results

Intraepidermal nerve fibres per length of epidermis using the intraocular ruler method were 3.07 nerve fibres/mm (2SD 1.56). The image software analysis obtained values of 3.05 nerve fibres/mm (2SD 1.54). Correlation between the two tests was excellent (r=0.999 p=<0.00001). Epidermal nerve fibre counts from hypothenar skin are lower than in more proximal sites.

Conclusion

A simple method for counting intraepidermal nerve fibres produces results similar to those using standard software image analysis. This should help the implementation of this technique for wider use.

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Abbreviations

CI::

Confidence Interval

DAB::

Diaminobenzidine

IENFD::

Intraepidermal nerve fibre density

MRC::

Medical Research Council

PGP 9.5::

Protein Gene Product 9.5

SD::

Standard Deviation

References

  1. Alhady SMA, Sivanantharajah K, (1969) Keloids in various races Plastic & Reconstructive Surgery 44:564–566

    Article  CAS  Google Scholar 

  2. Barohn RJ, (1998) Intraepidermal nerve fiber assessment: a new window on peripheral neuropathy Arch Neurol. 55:1505–1506

    Article  PubMed  CAS  Google Scholar 

  3. Chang YC, Lin WM, Hsieh ST, (2004) Effects of aging on human skin innervation Neuroreport 15:149–153

    Article  PubMed  Google Scholar 

  4. Chien HF, Tseng TJ, Lin WM, Yang CC, Chang YC, Chen RC, Hsieh ST, (2001) Quantitative pathology of cutaneous nerve terminal degeneration in the human skin Acta Neuropathol (Berl) 102:455–461

    CAS  Google Scholar 

  5. Faerman I, Faccio E, Calb I, Razumny J, Franco N, Dominguez A, Podesta HA, (1982) Autonomic neuropathy in the skin: a histological study of the sympathetic nerve fibres in diabetic anhidrosis Diabetologia 22:96–99

    Article  PubMed  CAS  Google Scholar 

  6. Goransson LG, Mellgren SI, Lindal S, Omdal R, (2004) The effect of age and gender on epidermal nerve fiber density Neurology 62:774–777

    PubMed  CAS  Google Scholar 

  7. Herrmann DN, Griffin JW, Hauer P, Cornblath DR, McArthur JC, (1999) Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies Neurology 53:1634–1640

    PubMed  CAS  Google Scholar 

  8. Hilliges M, Johansson O, (1999) Comparative analysis of numerical estimation methods of epithelial nerve fibers using tissue sections J Peripher Nerv Syst. 4:53–57

    PubMed  CAS  Google Scholar 

  9. Hirai A, Yasuda H, Joko M, Maeda T, Kikkawa R, (2000) Evaluation of diabetic neuropathy through the quantitation of cutaneous nerves J Neurol Sci. 172:55–62

    Article  PubMed  CAS  Google Scholar 

  10. Holland NR, Stocks A, Hauer P, Cornblath DR, Griffin JW, McArthur JC, (1997) Intraepidermal nerve fiber density in patients with painful sensory neuropathy Neurology 48:708–711

    PubMed  CAS  Google Scholar 

  11. Johansson O, Wang L, Hilliges M, Liang Y, (1999) Intraepidermal nerves in human skin: PGP 9.5 immunohistochemistry with special reference to the nerve density in skin from different body regions J Peripher Nerv Syst. 4:43–52

    PubMed  CAS  Google Scholar 

  12. Kennedy WR, Wendelschafer-Crabb G, (1996) Utility of skin biopsy in diabetic neuropathy Semin Neurol. 16:163–171

    Article  PubMed  CAS  Google Scholar 

  13. Kennedy WR, Wendelschafer-Crabb G, (1999) Utility of the skin biopsy method in studies of diabetic neuropathy Electroencephalogr Clin Neurophysiol Suppl. 50:553–559

    PubMed  CAS  Google Scholar 

  14. Kennedy WR, Wendelschafer-Crabb G, Johnson T, (1996) Quantitation of epidermal nerves in diabetic neuropathy Neurology 47:1042–1048

    PubMed  CAS  Google Scholar 

  15. Koskinen M, Hietaharju A, Kylaniemi M, Peltola J, Rantala I, Udd B, Haapasalo H, (2005) A quantitative method for the assessment of intraepidermal nerve fibers in small-fiber neuropathy J Neurol. 252:789–794

    Article  PubMed  Google Scholar 

  16. Lauria G, Holland N, Hauer P, Cornblath DR, Griffin JW, McArthur JC, (1999) Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy J Neurol Sci. 164:172–178

    Article  PubMed  CAS  Google Scholar 

  17. Lauria G, Sghirlanzoni A, Lombardi R, Pareyson D, (2001) Epidermal nerve fiber density in sensory ganglionopathies: clinical and neurophysiologic correlations Muscle Nerve 24:1034–1039

    Article  PubMed  CAS  Google Scholar 

  18. Levy DM, Terenghi G, Gu XH, Abraham RR, Springall DR, Polak JM, (1992) Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function Diabetologia 35:889–897

    Article  PubMed  CAS  Google Scholar 

  19. McArthur JC, Stocks EA, Hauer P, Cornblath DR, Griffin JW, (1998) Epidermal nerve fiber density: normative reference range and diagnostic efficiency Arch Neurol. 55:1513–1520

    Article  PubMed  CAS  Google Scholar 

  20. McCarthy BG, Hsieh ST, Stocks A, Hauer P, Macko C, Cornblath DR, Griffin JW, McArthur JC, (1995) Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy Neurology 45:1848–1855

    PubMed  CAS  Google Scholar 

  21. Pan CL, Tseng TJ, Lin YH, Chiang MC, Lin WM, Hsieh ST, (2003) Cutaneous innervation in Guillain-Barre syndrome: pathology and clinical correlations Brain 126:386–397

    Article  PubMed  Google Scholar 

  22. Periquet MI, Novak V, Collins MP, Nagaraja HN, Erdem S, Nash SM, Freimer ML, Sahenk Z, Kissel JT, Mendell JR, (1999) Painful sensory neuropathy: prospective evaluation using skin biopsy Neurology 53:1641–1647

    PubMed  CAS  Google Scholar 

  23. Polydefkis M, Allen RP, Hauer P, Earley CJ, Griffin JW, McArthur JC, (2000) Subclinical sensory neuropathy in late-onset restless legs syndrome Neurology 55:1115–1121

    PubMed  CAS  Google Scholar 

  24. Scott LJ, Griffin JW, Luciano C, Barton NW, Banerjee T, Crawford T, McArthur JC, Tournay A, Schiffmann R, (1999) Quantitative analysis of epidermal innervation in Fabry disease Neurology 52:1249–1254

    PubMed  CAS  Google Scholar 

  25. Taylor SC, (2003) Epidemiology of skin diseases in people of color Cutis 71:271–275

    PubMed  Google Scholar 

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Acknowledgements

This research was in part financed by the National Medical Research Council of Singapore (grant no. 0466/2000).

Part of this material has been presented at the American Association of Electrodiagnostic Medicine, September 16–20, 2003 San Francisco, CA, USA.

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Authors and Affiliations

  1. Department of Medicine Division of Neurology, Yong Loo Lin School of Medicine, 5 Lower Kent Ridge Road, 119074, Singapore, Singapore

    Einar P.V. Wilder-Smith & Adeline Chow

Authors
  1. Einar P.V. Wilder-Smith
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  2. Adeline Chow
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Corresponding author

Correspondence to Einar P.V. Wilder-Smith.

Additional information

Received in revised form: 22 December 2005

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Wilder-Smith, E.P., Chow, A. Comparison of a simple method for quantitation of intraepidermal nerve fibres with a standard image analysis method using hypothenar skin. J Neurol 253, 1011–1015 (2006). https://doi.org/10.1007/s00415-006-0147-6

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  • DOI: https://doi.org/10.1007/s00415-006-0147-6

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