title: Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.
abstract: Autonomic and somatic denervation is well established in Parkinson's disease (PD).
  
  
  OBJECTIVE
  (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD.
  
  
  METHODS
  Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose.
  
  
  RESULTS
  PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction.
  
  
  CONCLUSIONS
  CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.
authors.affiliation: Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, UK; Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK. Electronic address: lewis.kass-iliyya@postgrad.manchester.ac.uk.
authors.forename: Lewis
authors.initials: L
authors.lastname: Kass-Iliyya
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK. Electronic address: saad.javed@student.manchester.ac.uk.
authors.forename: Saad
authors.initials: S
authors.lastname: Javed
authors.affiliation: Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, UK. Electronic address: david.gosal@srft.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Gosal
authors.affiliation: Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, UK; Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK. Electronic address: christopher.kobylecki@manchester.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kobylecki
authors.affiliation: Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, UK. Electronic address: andrew.marshall@manchester.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK; Weill Cornell Medical College, Doha, Qatar. Electronic address: inp2002@qatar-med.cornell.edu.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Petropoulos
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK; Weill Cornell Medical College, Doha, Qatar. Electronic address: g.ponirakis@gmail.com.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ponirakis
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK. Electronic address: mitra.tavakoli@manchester.ac.uk.
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK. Electronic address: maryam.ferdousi@manchester.ac.uk.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ferdousi
authors.affiliation: Department of Clinical Neuroscience, King's College, London, UK. Electronic address: chaudhuriray@hotmail.com.
authors.forename: Kallol Ray
authors.initials: KR
authors.lastname: Chaudhuri
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK. Electronic address: maria.jeziorska@manchester.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK; Weill Cornell Medical College, Doha, Qatar. Electronic address: ram2045@qatar-med.cornell.edu.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.affiliation: Department of Neurology, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, UK; Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK. Electronic address: monty.silverdale@srft.nhs.uk.
authors.forename: Monty A
authors.initials: MA
authors.lastname: Silverdale
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003315:Cornea / Q000294:innervation*; D004817:Epidermis / Q000294:innervation; D005260:Female; D005528:Foot / Q000294:innervation; D006339:Heart Rate; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D009431:Neural Conduction; D009882:Ophthalmic Nerve / Q000503:physiopathology*; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D010525:Peripheral Nerves / Q000503:physiopathology; D012684:Sensory Thresholds; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Confocal microscopy; Cornea; Intraepidermal nerve fiber density; Parkinson's disease; Small fiber neuropathy