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Thomas Krøigård, Martin Wirenfeldt, Toke K Svendsen, Søren H Sindrup
Background: Cold-induced peripheral neuropathy has been described in individuals exposed to severe cold resulting in pain, hypersensitivity to cold, hyperhidrosis, numbness, and skin changes. Nerve conduction studies and thermal detection thresholds are abnormal in symptomatic patients, and intraepidermal nerve fiber density (IENFD) in skin biopsies is reduced. Case presentation: A 41-year-old male was included as a healthy subject in a study of the spontaneous variability of quantitative sensory testing (QST), nerve conduction studies (NCS), and IENFD...
March 2018: Brain and Behavior
Vincenzo Provitera, Christopher H Gibbons, Gwen Wendelschafer-Crabb, Vincenzo Donadio, Dino F Vitale, Adam Loavenbruck, Annamaria Stancanelli, Giuseppe Caporaso, Rocco Liguori, Ningshan Wang, Lucio Santoro, William R Kennedy, Maria Nolano
BACKGROUND: We aimed to test the clinical utility of leg to thigh intraepidermal nerve fiber (IENF) density ratio as a parameter to discriminate between length-dependent small fiber neuropathy (SFN) and small fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small fiber pathology. METHODS: We retrospectively evaluated thigh and leg IENF density in 314 subjects with small fiber pathology (173 with distal symmetrical length-dependent SFN and 141 with non length-dependent SFSG)...
March 1, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
M P Pereira, H Lüling, A Dieckhöfer, S Steinke, C Zeidler, K Agelopoulos, S Ständer
BACKGROUND: Topical capsaicin shows efficacy in the treatment of brachioradial pruritus, however its mechanisms of action remain unclear. OBJECTIVE: The effect of capsaicin on the epidermis (i.e. peripheral expression of non-neuronal sensory receptors on keratinocytes, morphological changes in innervation) is still unknown. We aimed to investigate the effect of topical capsaicin on keratinocyte expression of TRP channels and on the intraepidermal nerve fibre density (IENFD) in patients with brachioradial pruritus...
February 10, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Mathilde Duchesne, Aurore Danigo, Laurence Richard, Jean-Michel Vallat, Shahram Attarian, Pierre-Marie Gonnaud, Arnaud Lacour, Yann Péréon, Tania Stojkovic, Klaus-Armin Nave, Viviane Bertrand, Serguei Nabirotchkin, Daniel Cohen, Claire Demiot, Laurent Magy
Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of Charcot-Marie-Tooth diseases, is a demyelinating neuropathy caused by a deletion encompassing the gene coding for PMP22, a myelin protein of the peripheral nervous system. Although myelinated fibers are mostly involved in CMT1A, some patients experience neuropathic pain. We thus investigated whether unmyelinated fibers are lost in CMT1A. Skin biopsies were taken from the distal portion of the leg of 80 patients with CMT1A as part of the PXT30003-01 study and processed for quantification of intraepidermal nerve fiber density (IENFD)...
February 2, 2018: Journal of Neuropathology and Experimental Neurology
Steven E Harte, Daniel J Clauw, John M Hayes, Eva L Feldman, Irene C St Charles, Christopher J Watson
Introduction: Neuroimaging reveals increased glutamate within the insula of patients with fibromyalgia (FM), suggesting a link between FM symptoms and increased central excitatory neurotransmission. Many patients with FM also present with decreased intraepidermal nerve fiber density (IENFD), consistent with small fiber pathology. It remains unknown, however, whether either of these mechanistic findings represent a cause or a consequence of the other. This study tests the hypothesis that an excitatory imbalance within the insula leads to small fiber pathology...
May 2017: Pain Reports (Baltimore, Md.)
Krish Chandrasekaran, Anjaneyulu Muragundla, Tyler G Demarest, Joungil Choi, Avinash R Sagi, Neda Najimi, Pranith Kumar, Anmol Singh, Cheng-Ying Ho, Gary Fiskum, Lauren G Koch, Steven L Britton, James W Russell
Objectives: There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function. Methods: Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268...
December 2017: Annals of Clinical and Translational Neurology
Liang-Yan Wu, Mei Li, Min-Li Qu, Xin Li, Lin-Hua Pi, Zi Chen, Shan-Lei Zhou, Xiao-Qing Yi, Xia-Jie Shi, Jing Wu, Shan Wang
Small fiber neuropathy (SFN) is a common complication in diabetes, and is characterized by decreased intraepidermal nerve fiber density (IENFD). Semaphorin 3A (Sema3A), which is produced by keratinocytes, has a chemorepulsive effect on intraepidermal nerve fibers. mTOR signaling can mediate local protein synthesis that is critical for growth of axons and dendrites. Therefore, this study aimed to investigate whether Sema3A is up-regulated in diabetic keratinocytes via the mTOR-mediated p70 S6K and 4E-BP1 signaling pathways, and furthermore whether it is involved in the pathogenesis of diabetic SFN...
December 5, 2017: Molecular and Cellular Endocrinology
Binbin Sun, Shuangyi Fan, Kai Yao, Yifan Li, Xusheng Huang
Mercury and its compounds possess strong neurotoxicity and patients with mercury poisoning often report pain and numbness in the distal extremities that conform to the "stocking-glove" pattern. However, no study has investigated whether damage to small nerve fibers is associated with mercury poisoning. The aims of the present study were to evaluate the effects of different doses of mercury chloride (HgCl2 ) on intraepidermal nerve fibers density (IENFD) and Langerhans cells (LCs) in the plantar skin of rats and to assess the possible relationship between changes in IENFD and sensory testing...
November 23, 2017: Journal of the Peripheral Nervous System: JPNS
Bo Sun, Yifan Li, Lizhi Liu, Zhaohui Chen, Li Ling, Fei Yang, Jiexiao Liu, Hong Liu, Xusheng Huang
INTRODUCTION: To date, there are no validated screening scales for small fiber neuropathy (SFN). This study investigated the Small-Fiber Neuropathy and Symptom Inventory Questionnaire (SFN-SIQ) as well as the Small Fiber Neuropathy Screening List (SFNSL) for SFN diagnosis. METHODS: Fifty-five patients were divided into SFN and mixed fiber damage groups. Relevant scales, nerve conduction studies (NCS) and skin biopsies were performed. Relationships between the intraepidermal nerve fiber density (IENFD) and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined...
October 27, 2017: International Journal of Neuroscience
Hafize Nalan Güneş, Can Ebru Bekircan-Kurt, Ersin Tan, Sevim Erdem-Özdamar
Small fiber neuropathy (SFN), due to loss of A-delta and unmyelinated C fibers, is a cause of neuropathic pain. Although the patients with vitamin B12 deficiency are included in SFN studies in the literature, there is no histopathological study investigating the small fiber loss solely in patients with vitamin B12 deficiency. In this pilot study, we aim to demonstrate the intraepidermal nerve fiber density (IENFD) in skin punch biopsy of patients with vitamin B12 deficiency. Ten patients with vitamin B12 deficiency suffering from neuropathic pain and as control group ten patients with vitamin B12 deficiency without neuropathic pain were included...
October 19, 2017: Acta Neurologica Belgica
Gidon J Bönhof, Alexander Strom, Sonja Püttgen, Bernd Ringel, Jutta Brüggemann, Kálmán Bódis, Karsten Müssig, Julia Szendroedi, Michael Roden, Dan Ziegler
AIMS/HYPOTHESIS: The determinants and mechanisms of the development of diabetic sensorimotor polyneuropathy as a painful (DSPN+p) or painless (DSPN-p) entity remain unclear. We examined the degree of cutaneous nerve fibre loss and regeneration in individuals with type 2 diabetes with DSPN+p or DSPN-p compared with individuals with recent-onset type 2 diabetes and corresponding healthy volunteers. METHODS: In this cross-sectional study, skin biopsies taken from the distal lateral calf were obtained from individuals with recent-onset type 2 diabetes (n = 32) from the German Diabetes Study, with DSPN+p (n = 34) and DSPN-p (n = 32) from the PROPANE study, and volunteers with normal glucose tolerance (n = 50)...
December 2017: Diabetologia
Linda Cj Oudejans, Marieke Niesters, Michael Brines, Albert Dahan, Monique van Velzen
Small fiber pathology with concomitant chronic neuropathic pain is a common complication of sarcoidosis. The gold standard of diagnosis of small fiber neuropathy (SFN) is the quantification of small nerve fibers in skin biopsies in combination with patient history and psychophysical tests; a new technique is the quantification of small nerve fibers in the cornea using cornea confocal microscopy (CCM). Here, we studied small fiber morphology in sarcoidosis patients with neuropathic pain using skin biopsies, CCM, and quantitative sensory testing (QST)...
2017: Journal of Pain Research
Eun Hee Sohn, Kyu Sang Song, Ju Yeon Lee, Ae Young Lee
BACKGROUND AND PURPOSE: The objective of this study was to find a sensitive method for the early detection of diabetic polyneuropathy (DPN) and determine the relationship between the functions of somatic and autonomic small nerve fibers in DPN. METHODS: Patients with type 2 diabetes mellitus and DPN based on clinical symptoms, signs, intraepidermal nerve fiber density (IENFD), and findings in the quantitative sudomotor axon reflex test (QSART) were enrolled retrospectively...
October 2017: Journal of Clinical Neurology
K Milian-Ciesielska, L Chmura, G Dyduch, C Jagers, E Radwanska, D Adamek
Lichen sclerosus (LS) is a chronic and inflammatory disease causing sensory symptoms such as itch and pain and affecting most frequently genital skin of women. Intraepidermal nerve fiber density (IENFD) was examined immunohistologically in 20 vulvar skin biopsies of patients affected by LS and in 20 control vulvar skin biopsies, in order to determine if these sensory sensations originate in changes in the epidermal innervation. Obtained results show fewer protein gene product 9.5 (PGP 9.5) positive intraepidermal nerve fibers (IENF) in LS tissues compared to controls (P = 0...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Malik Bechakra, Barthold N Schüttenhelm, Tiziana Pederzani, Pieter A van Doorn, Chris I de Zeeuw, Joost L M Jongen
Skin biopsies from patients with neuropathic pain often show changes in epidermal innervation, although it remains to be elucidated to what extent such changes can be linked to a particular subgroup of nerve fibers and how these changes are correlated with pain intensity. Here, we investigated to what extent behavioral signs of hyperalgesia are correlated with immunohistochemical changes of peptidergic and non-peptidergic epidermal nerve fibers in a rat model of nerve injury-induced pain. Rats subjected to unilateral partial ligation of the sciatic nerve developed significant mechanical and thermal hyperalgesia as tested by the withdrawal responses of the ipsilateral footpad to von Frey hairs and hotplate stimulation...
August 17, 2017: Journal of Comparative Neurology
Roser Velasco, Xavier Navarro, Miguel Gil-Gil, Mireia Herrando-Grabulosa, Aina Calls, Jordi Bruna
CONTEXT: Neuropathic pain can be present in patients developing chemotherapy-induced peripheral neuropathy (CIPN). Nerve growth factor (NGF) is trophic to small sensory fibers and regulates nociception. OBJECTIVES: We investigated the changes in serum NGF and intraepidermal nerve fiber density in skin biopsies of cancer patients receiving neurotoxic chemotherapy in a single-center prospective observational study. METHODS: Patients were evaluated before and after chemotherapy administration...
December 2017: Journal of Pain and Symptom Management
Uazman Alam, Maria Jeziorska, Ioannis N Petropoulos, Omar Asghar, Hassan Fadavi, Georgios Ponirakis, Andrew Marshall, Mitra Tavakoli, Andrew J M Boulton, Nathan Efron, Rayaz A Malik
OBJECTIVES: Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against a range of established measures of nerve damage in patients with diabetic neuropathy. METHODS: In this cross sectional study, thirty subjects with Type 1 diabetes without neuropathy (T1DM), thirty one T1DM subjects with neuropathy (DSPN) and twenty seven non-diabetic healthy control subjects underwent detailed assessment of neuropathic symptoms and neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy and corneal confocal microscopy (CCM)...
2017: PloS One
Bo Sun, Li-Zhi Liu, Yi-Fan Li, Zhao-Hui Chen, Li Ling, Fei Yang, Fang Cui, Xu-Sheng Huang
BACKGROUND: In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN...
July 20, 2017: Chinese Medical Journal
Gigi J Ebenezer, Ying Liu, Daniel P Judge, Kelly Cunningham, Shaun Truelove, Noel D Carter, Blessan Sebastian, Kelly Byrnes, Michael Polydefkis
OBJECTIVE: To determine the utility of skin biopsies as a biomarker of disease severity in subjects with amyloid neuropathy. METHODS: Five groups of patients were studied: (1) transthyretin (TTR) familial amyloidotic polyneuropathy (FAP; n = 20), (2) TTR mutation carriers without peripheral neuropathy (TTR-noPN; n = 10), (3) healthy controls (n = 20), (4) diabetic neuropathy disease controls (n = 20), and (5) patients with light-chain (AL) amyloid (n = 2)...
July 2017: Annals of Neurology
Teruaki Masuda, Mitsuharu Ueda, Genki Suenaga, Yohei Misumi, Masayoshi Tasaki, Ayane Izaki, Yukako Yanagisawa, Yasuteru Inoue, Hiroaki Motokawa, Sayaka Matsumoto, Mayumi Mizukami, Aiko Arimura, Takahisa Deguchi, Yoshihiko Nishio, Taro Yamashita, Yukihiro Inomata, Konen Obayashi, Yukio Ando
OBJECTIVE: To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis. METHODS: We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers. RESULTS: IENFD values were reduced in patients with the V30M mutation (1.9 ± 2...
June 6, 2017: Neurology
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