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      Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

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          Abstract

          Objective

          There is an unmet need for better diagnostic tools to further delineate clinical subsets of heterogeneous chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP) and multifocal motor neuropathy ( MMN) to facilitate treatment decisions. Corneal confocal microscopy ( CCM) is a noninvasive and reproducible nerve imaging technique. This study evaluates the potential of CCM as a diagnostic surrogate in CIDP and MMN.

          Methods

          In a cross‐sectional prospective approach, 182 patients and healthy controls were studied using CCM to quantify corneal nerve damage and immune cell infiltration.

          Results

          Patients with CIDP and MMN had a reduction in corneal nerve fiber ( CNF) measures and an increase in corneal immune cell infiltrates. In CIDP, CNF parameters decreased with increasing duration of disease. The number of dendritic cells in proximity to CNFs was increased in patients with early disease and correlated with the degree of motor affection. A further reduction in CNF parameters and an increase in nondendritic cells were observed in patients with painful neuropathy. In CIDP patients with antineuronal antibodies the number of nondendritic cells was increased.

          Interpretation

          Our findings suggest that CNF loss may reflect severity of neuropathy and quantification of distinct cells around the CNF plexus may help in stratifying CIDP subtypes, clinical course, and disease activity. However, further longitudinal studies are required before CCM can be considered as a valid surrogate endpoint for patients with CIDP and MMN.

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          Most cited references52

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          Surrogate markers of small fiber damage in human diabetic neuropathy.

          Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied. They underwent a punch skin biopsy to quantify IENFs and CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and branch length showed a progressive reduction with increasing severity of neuropathy, which was significant in patients with mild, moderate, and severe neuropathy. CCM also showed a progressive reduction in corneal nerve fiber density (CNFD) and branch density, but the latter was significantly reduced even in diabetic patients without neuropathy. Both IENFD and CNFD correlated significantly with cold detection and heat as pain thresholds. Intraepidermal and corneal nerve fiber lengths were reduced in patients with painful compared with painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify small nerve fiber damage in diabetic patients. However, CCM quantifies small fiber damage rapidly and noninvasively and detects earlier stages of nerve damage compared with IENF pathology. This may make it an ideal technique to accurately diagnose and assess progression of human diabetic neuropathy.
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            Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype

            Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.
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              Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging.

              Diabetic peripheral neuropathy (DPN) is one of the most common long term complications of diabetes. Corneal confocal microscopy (CCM) image analysis is a novel non-invasive technique which quantifies corneal nerve fibre damage and enables diagnosis of DPN. This paper presents an automatic analysis and classification system for detecting nerve fibres in CCM images based on a multi-scale adaptive dual-model detection algorithm. The algorithm exploits the curvilinear structure of the nerve fibres and adapts itself to the local image information. Detected nerve fibres are then quantified and used as feature vectors for classification using random forest (RF) and neural networks (NNT) classifiers. We show, in a comparative study with other well known curvilinear detectors, that the best performance is achieved by the multi-scale dual model in conjunction with the NNT classifier. An evaluation of clinical effectiveness shows that the performance of the automated system matches that of ground-truth defined by expert manual annotation.
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                Author and article information

                Journal
                Ann Clin Transl Neurol
                Ann Clin Transl Neurol
                10.1002/(ISSN)2328-9503
                ACN3
                Annals of Clinical and Translational Neurology
                John Wiley and Sons Inc. (Hoboken )
                2328-9503
                28 December 2015
                February 2016
                : 3
                : 2 ( doiID: 10.1111/acn3.2016.3.issue-2 )
                : 88-100
                Affiliations
                [ 1 ] Department of Neurology Medical Faculty Research Group for Clinical and Experimental NeuroimmunologyHeinrich‐Heine University DusseldorfGermany
                [ 2 ] Department of Ophthalmology Medical FacultyHeinrich‐Heine University DusseldorfGermany
                [ 3 ] Centre for Endocrinology and Diabetes Institute of Human Development Faculty of Medical and Human SciencesCMFT and University of Manchester United Kingdom
                [ 4 ]Weill Cornell Medicine‐Qatar Education City DohaQatar
                Author notes
                [*] [* ] Correspondence

                Mark Stettner, Department of Neurology, Heinrich‐Heine University, Moorenstraße 5, 40225 Dusseldorf, Germany. Tel: 0211 / 81‐17880; Fax: 0211 / 81‐1628; E‐mail: mark.stettner@ 123456med.uni-duesseldorf.de

                Article
                ACN3275
                10.1002/acn3.275
                4748316
                26900579
                d1324854-c026-4647-b933-cd74eaebe7e6
                © 2015 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 05 August 2015
                : 07 November 2015
                : 15 November 2015
                Page count
                Pages: 13
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                acn3275
                February 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:10.02.2016

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