Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study

Lauria, Giuseppe; Bakkers, Mayienne; Schmitz, Christoph; Lombardi, Raffaella; Penza, Paola; Devigili, Grazia; Smith, A. Gordon; Hsieh, Sung Tsieh; Mellgren, Svein Ivar; Umapathi, Thirugnanam; Ziegler, Dan; Faber, Catharina G.; Merkies, Ingemar S.J.

doi:10.1111/j.1529-8027.2010.00271.x

Cited by 420 publications

(409 citation statements)

References 54 publications

(60 reference statements)

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“…1,35 Also, as found by others, 7,8,13,36 ENFs/ mm were significantly higher in thigh than in leg and decreased density was related to old age and male gender. For illustrative purposes, we show values and regression lines for males and females combined and we place abnormality at the 2.5th percentile value, rather than at the 5th percentile value, ignoring gender differences.…”

supporting

confidence: 65%

Epidermal nerve fibers

et al. 2012

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Objectives: Our first objective was to explore the value of estimating 95% confidence intervals (CIs) of epidermal nerve fibers (ENFs)/mm for number of sections to be evaluated and for confidently judging normality or abnormality. Our second objective was to introduce a new continuous measure combining nerve conduction and ENFs/mm. Methods:The 95% CI studies were performed on 1, 1-2, 1-3 ---1-10 serial skip sections of 3-mm punch biopsies of leg and thigh of 67 healthy subjects and 23 patients with diabetes mellitus.Results: Variability of differences of ENFs/mm counts (and 95% CIs) from evaluation of 1, 1-2, 1-3 ---1-9 compared with 1-10 serial skip sections decreased progressively without a break point with increasing numbers of sections evaluated. Estimating 95% CIs as sections are evaluated can be used to judge how many sections are needed for adequate evaluation, i.e., only a few when counts and 95% CIs are well within the range of normality or abnormality and more when values are borderline. Also provided is a methodology to combine results of nerve conduction and ENFs/mm as continuous measures of normality or abnormality.Conclusion: Estimating 95% CIs of ENFs/mm is useful to judge how many sections should be evaluated to confidently declare counts to be normal or abnormal. Also introduced is a continuous measure of both large-fiber (nerve conduction) and small-fiber (ENFs/mm) normal structures/functions spanning the range of normality and abnormality for use in therapeutic trials. Neurology Enumeration of nerve endings in skin has been used to study differences among species, 1,2 development, maturation and aging, 3,4 and disease. 5,6 Light microscopic analysis of immune-stained intraepidermal nerve fibers (ENFs) and reference values were introduced to serve as objective and spatial indications of painful and small-fiber sensory polyneuropathy, "possibly useful for therapeutic trials." [7][8][9] The technique of biopsy was found to be acceptable to patients, and the estimation of ENFs/mm had high intraobserver and interobserver reproducibility.8 A somewhat different approach using punch skin biopsy, a blister technique with immunofluorescence and confocal microscopy, was also described (reviewed in Kennedy and Wendelschafer-Crabb 10 and Kennedy et al. 11). A series of reports showed the value of ENFs/mm in the diagnosis of painful small-fiber sensory polyneuropathy, especially in patients with few or no neurologic signs or test abnormalities.

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confidence: 65%

Epidermal nerve fibers

et al. 2012

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“…Indeed, an inverse relationship between age and intraepidermal nerve fibre density has been previously described [18,19]; the influence of sex, height, weight and BMI is less certain [18,20,21].…”

Section: Discussionmentioning

confidence: 99%

Small fibre dysfunction, microvascular complications and glycaemic control in type 1 diabetes: a case–control study

2011

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Aims/hypothesis The aim of this study was to determine the influence of microvascular disease on C-fibre function in patients with type 1 diabetes of moderate duration. Methods The axon-reflex flare area induced on the dorsum of the foot by local skin heating to 47°C was measured with a laser Doppler imager (LDI) in sex-, age-and heightmatched groups with type 1 diabetes, with and without microvascular disease (MV+ and MV−, respectively) and in healthy controls (HC). Each group consisted of 24 individuals and all were free from clinical neuropathy (neuropathy disability score <3 and Toronto clinical neuropathy score <5

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“…Skin biopsies have shown 88.4% diagnostic efficacy (Devigili et al., 2008). A standard skin punch biopsy 3 mm in diameter can be taken 10 cm proximal to the lateral malleolus (Lauria et al., 2010). Morphometric examination of epidermal and dermal nerves is very helpful, especially for investigating small nerve fiber abnormalities, inaccessible to neurophysiological tests.…”

Section: Diagnostic Techniquesmentioning

confidence: 99%

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

2016

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IntroductionChemotherapy‐induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti‐cancer drugs are: platinum‐based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.MethodsHere, in this paper, based on our experience and current knowledge, we provide a short review of the most common, neuropathy‐inducing anti‐cancer drugs, describe the most prevalent neuropathy symptoms produced by each of them, and outline preventive measures and treatment guidelines for cancer patients suffering from neuropathy and for their health care providers.ResultsPatients should be encouraged to report any signs of neuropathic pain, alteration in sensory perception, tingling, numbness, burning, increased hot/cold sensitivity and motor dysfunctions as early as possible. If known neurotoxic chemotherapeutics are used, a neurological examination with electrophysiological evaluation should be implemented early in the course of treatment so, both patients and physicians would be better prepared to cope with possible neurotoxic effects.ConclusionsThe use of neurotoxic chemotherapeutics should be closely monitored and if clinically permitted, that is, if a patient shows signs of cancer regression, drug doses should be reduced or combined with other less neurotoxic anti‐cancer medication. If not counteractive, the use of over the counter antineuropathic supplements such as calcium or magnesium might be encouraged. If physically possible, patients should also be encouraged to exercise regularly and avoid factors that might increase nerve damage such as excessive drinking, smoking, or sitting in a cramped position.

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Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study

Cited by 420 publications

References 54 publications

Epidermal nerve fibers

Epidermal nerve fibers

Small fibre dysfunction, microvascular complications and glycaemic control in type 1 diabetes: a case–control study

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

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