Simultaneous Quantification of Unmyelinated Nerve Fibers in Sural Nerve and in Skin

Peripheral polyneuropathies are common and their diagnosis may be challenging. We compared the results from sural-nerve and skin biopsies in 33 patients with a polyneuropathy and neuropathic pain examined in our hospital over a 6-year period. The biopsies were all from the same lower limb of each patient. Intraepidermal nerve fiber (IENF) densities in the skin were determined by fluorescence microscopy; unmyelinated fiber densities in sural-nerve biopsies (UFNB) were determined by electron microscopy. There was no correlation with age or gender in either biopsy type; there was a weak trend to correlation between UFNB density and IENF density, possibly because of the small sample size. The sensitivity of detection of quantitative abnormalities of unmyelinated fibers was better in the skin than in the nerves. Proximal and distal IENF densities were strongly correlated; and counts of UFNB were highly reproducible. Thus, quantification of unmyelinated fibers in sural-nerve and skin biopsies seem to be complementary. Sural-nerve biopsy may be required to confirm a specific diagnosis, to identify lesion mechanisms, and to devise therapeutic strategies, whereas skin biopsy seems to be more efficient in the follow-up of length-dependent polyneuropathies and in the diagnosis of neuropathic pain.

[1]  G. Lauria,et al.  Side and time variability of intraepidermal nerve fiber density , 2015, Neurology.

[2]  M. Nolano,et al.  European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society , 2010, Journal of the peripheral nervous system : JPNS.

[3]  C. Sommer,et al.  Processing of nerve biopsies: A practical guide for neuropathologists , 2011, Clinical neuropathology.

[4]  Jacques Fermanian,et al.  Development and validation of the Neuropathic Pain Symptom Inventory , 2004, Pain.

[5]  J. Pearson,et al.  Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia , 1978, Journal of the Neurological Sciences.

[6]  C. Sommer,et al.  Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition , 2010, The Lancet Neurology.

[7]  G. Wendelschafer‐Crabb,et al.  Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy , 2007, Journal of the Neurological Sciences.

[8]  T. Kanda Usefulness of sural nerve biopsy in the genomic era , 2009, Neuropathology : official journal of the Japanese Society of Neuropathology.

[9]  D. Herrmann,et al.  Non-length dependent small fibre neuropathy/ganglionopathy , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[10]  L. Richard,et al.  Value of Nerve Biopsy in Patients With Latent Malignant Hemopathy and Peripheral Neuropathy , 2015, Medicine.

[11]  J. McArthur,et al.  The utility of skin biopsy for prediction of progression in suspected small fiber neuropathy , 2006, Neurology.

[12]  G. Lauria,et al.  Skin biopsy: a new tool for diagnosing peripheral neuropathy , 2007, BMJ : British Medical Journal.

[13]  L. Santoro,et al.  Small nerve fiber involvement in CMT1A , 2015, Neurology.

[14]  J. Pollard,et al.  European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society — First Revision , 2010, European journal of neurology.

[15]  A. Aguayo,et al.  Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy. , 1971, Archives of neurology.

[16]  G. Lauria,et al.  MICROVASCULAR COMPLICATIONS — NEUROPATHY ( D ZIEGLER , SECTION EDITOR ) Small Fiber Neuropathy : Is Skin Biopsy the Holy Grail ? , 2012 .

[17]  R. VetrugnoMD,et al.  Sympathetic skin response , 2003 .

[18]  P. Bergh,et al.  European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society — First Revision , 2010, European journal of neurology.

[19]  J. McArthur,et al.  Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies , 1999, Neurology.

[20]  M. Chiang,et al.  Cutaneous innervation in chronic inflammatory demyelinating polyneuropathy , 2002, Neurology.

[21]  J. Ochoa Recognition of unmyelinated fiber disease: Morphologic criteria , 1978, Muscle & nerve.

[22]  J. McArthur,et al.  Sensory and Motor Denervation Influence Epidermal Thickness in Rat Foot Glabrous Skin , 1997, Experimental Neurology.

[23]  J. Valls-Solé,et al.  European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Fe‐deration of Neurological Societies and the Peripheral Nerve Society , 2010, European journal of neurology.

[24]  J. Vallat,et al.  Nerve biopsy: requirements for diagnosis and clinical value , 2011, Acta Neuropathologica.

[25]  T. Crawford,et al.  Small‐fiber sensory neuropathies: Clinical course and neuropathology of idiopathic cases , 1998, Annals of neurology.

[26]  E. Stålberg,et al.  Intraepidermal nerve fibre density, quantitative sensory testing and nerve conduction studies in a patient material with symptoms and signs of sensory polyneuropathy , 2006, European journal of neurology.

[27]  Giuseppe Lauria,et al.  Skin biopsy as a diagnostic tool in peripheral neuropathy , 2007, Nature Clinical Practice Neurology.

[28]  Y. Kuroiwa,et al.  Hereditary sensory radicular neuropathy , 1964, Neurology.

[29]  Pietro Cortelli,et al.  Sympathetic skin response: basic mechanisms and clinical applications. , 2003, Clinical autonomic research : official journal of the Clinical Autonomic Research Society.