EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy

Lauria, Giuseppe; Cornblath, David R.; Johansson, Ӧlle; McArthur, Justin C.; Mellgren, Svein Ivar; Nolano, Maria; Rosenberg, N R; Sommer, Claudia

doi:10.1111/j.1468-1331.2005.01260.x

Cited by 502 publications

(497 citation statements)

References 69 publications

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“…Images were captured digitally using a Zeiss microscope and software with the help of a Nikon digital camera. The average intraepidermal nerve fibers density (IENFD) and length were measured using standardized measurement protocols and compared to controls (Lauria et al, 2005).…”

Section: Skin Biopsymentioning

confidence: 99%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-β isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/ group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-β1 and TGF-β2 mRNA, but not TGF-β3, was increased at 4 and 12 weeks. In sciatic nerve TGF-β3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-β formed homoand heterodimers, of which β 2 /β 3 , β 1 /β 1 , and β 1 /β 3 were significantly increased, while that of the TGF-β 2 /β 2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-β neutralizing antibody prevents the increase in total TGF-β protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-β2 > β1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-β neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-β isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-β neutralizing antibody. These findings implicate upregulation of TGF-β in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy.

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Section: Skin Biopsymentioning

confidence: 99%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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“…Intersections of immunoreactive fibers with hemispheres were marked while focusing through the zaxis of each sample site. Only those fibers within the epidermis and clearly crossing dermal-epidermal border were considered for quantification (Lauria et al, 2005). The stereological parameters were as follows: sampling grid, 225 Â 155 lm; radius of the hemisphere, 13 lm; and guard zones, 10% of section thickness.…”

Section: Quantification Of Fiber Lengthmentioning

confidence: 99%

Long‐Term Effects of Neonatal Capsaicin Treatment on Intraepidermal Nerve Fibers and Keratinocyte Proliferation in Rat Glabrous Skin

Martínez‐Martínez

Toscano-Márquez

Gutiérrez‐Ospina

2010

The Anatomical Record

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Innervation is required to preserve several aspects of skin homeostasis. Previous studies in rodents have shown that sciatic nerve transection leads to epidermal thinning and reduced keratinocyte proliferation. As the sciatic nerve is composed of sensory and motor axons, it is not clear whether skin alterations reflect motor or sensory disturbances. In this study, we used neonatal capsaicin treatment to evaluate whether sensory chemical denervation affects keratinocyte proliferation at 1, 3, and 6 months of age. Using design-based stereological methods, we estimated the total length of intraepidermal nerve fibers (IENF) that were of peptidergic type and the number of bromodeoxyuridine-labeled (BrdU þ ) nuclei in the hind paw glabrous epidermis of control and capsaicin-treated rats. We found that the treatment decreased the total fiber length of IENF immunoreactive for both protein gene product 9.5 (PGP þ ) and of IENF immunoreactive for calcitonin gene-related peptide (CGRP þ ). The length of PGP þ fibers decreased by 83%, 81%, and 77% and that of CGRP þ fibers decreased by 48%, 58%, and 58% at 1, 3, and 6 months, respectively. Double-immunofluorescence staining for neural beta III tubulin and CGRP revealed that the majority of the remaining fibers in the epidermis after capsaicin treatment were of peptidergic type. The number of BrdU þ nuclei was similar in both groups. Our findings suggest that IENF present after capsaicin treatment are sufficient to maintain epidermal replacement. Anat Rec, 294:173-184, 2011. V V C 2010 Wiley-Liss, Inc.

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“…Mehrere Studien in den letzten Jahren haben gezeigt, dass die Hautbiopsie eine sensitive und effiziente Methode zur Diagnostik der Small-Fiber-Neuropathie darstellt [9][10][11][12] [12], die Sensitivität wird je nach Studie mit 45-89% angegeben [11]. Bei einigen Patienten liess sich eine verminderte Nervenfaserdichte bei normalem Neurographiebefund und für einen isolierten Befall der kleinen Fasern untypischen Symptomen feststellen.…”

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Die Bestimmung der intraepidermalen Nervenfaserdichte in der Hautbiopsie - eine valide Methode zur Diagnostik von isolierten Small Fiber Neuropathien Erste Erfahrungen an der neurologischen Universitätsklinik Basel

2011

Swiss Arch Neurol Psychiatr

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SummaryEvaluation of intra-epidermal nerve fibre density in skin biopsy Background: Small fibre neuropathy is a sensory neuropathy affecting small, thinly myelinated Ad-fibres and unmyelinated C-fibres. It clinically presents with burning pain and sensory symptoms. As nerve conduction studies mainly detect large fibre function, they often show normal values. Skin biopsy is a new, minimally invasive and painless tool for the diagnosis of small fibre neuropathy.Objective: Evaluation of the newly established method of skin biopsies for the diagnosis of small fibre neuropathy at the University Hospital Basel.Material/Methods: Between 2007 and 2009, a total of 50 patients presenting with neuropathic symptoms were examined clinically, electrophysiologically and by skin biopsies at the University Hospital Basel. Biopsies were taken under local anaesthesia, using a 3-mm punch. Three sections of each specimen were stained immunohistochemically with anti-protein-geneproduct 9.5 antibody. The intra-epidermal nerve fibres were counted and assessed according to published normative values.Results: Out of the 50 patients presenting with neuropathic symptoms, 35 had normal nerve conduction studies. In 28 of these patients, a reduced intra-epidermal nerve fibre density was found, suggesting a pure small fibre neuropathy. Atotal of 7patients had neuropathic symptoms without reduction of intra-epidermal nerve fibres. In addition, skin biopsies of 15 patients with clinically and electrophysiologically diagnosed polyneuropathy were analysed. In all of these patients an involvement of small fibres was detected. Aetiological work-up for each patient resulted in findings consistent with previously published data: pure small fibre neuropathy was associated with impaired glucose tolerance in 7.1% (2 patients), diabetes in 7.1% (2 patients), MGUS in 7.1% (2 patients) and with polyarthritis, alcoholtoxicity, hepatitis B, hepatitis C, Sjögren's syndrome and sarcoidosis in 3.5% (1 patient). In 57.1% (16 patients), the neuropathy was classified as idiopathic small fibre neuropathy.Conclusions: Skin biopsy proves to be an effective and sensitive method for the diagnosis of small fibre neuropathy. It is especially helpful in patients with an isolated lesion of small fibres where nerve conduction studies show normal values. Our results are consistent with the published data and applicable in a tertiary referral centre.

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EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy

Cited by 502 publications

References 69 publications

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Long‐Term Effects of Neonatal Capsaicin Treatment on Intraepidermal Nerve Fibers and Keratinocyte Proliferation in Rat Glabrous Skin

Die Bestimmung der intraepidermalen Nervenfaserdichte in der Hautbiopsie - eine valide Methode zur Diagnostik von isolierten Small Fiber Neuropathien Erste Erfahrungen an der neurologischen Universitätsklinik Basel

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