title: Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies.
abstract: BACKGROUND
  The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients.
  
  
  METHODS
  Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study. Participants underwent neurological examination including visual acuity, visual evoked potential (VEP) examination, optical coherence tomography (OCT), and magnetic resonance imaging with calculation of brain atrophy, regarding grey and white matter, and voxel based morphometry (VBM), in addition answered the National Eye Institute's 39-item Visual Functioning Questionnaire (NEI-VFQ). Thirteen patients and 6 HC were additionally examined with magnetic resonance spectroscopy (MRS).
  
  
  RESULTS
  All patients had normal visual acuity, but reported reduced peripheral vision in comparison to HC in the NEI-VFQ (p = 0.036). VEP latency was prolonged in patients (P100 = 103.7±5.7 ms) in comparison to healthy subjects (P100 = 99.7±4.2 ms, p = 0.007). In OCT, peripapillary retinal nerve fiber layer thickness RNFL was decreased in the nasal sector (90.0±15.5 vs. 101.8±16.5, p = 0.013), and lower nasal sector RNFL correlated with prolonged VEP latency (Rho = -0.405, p = 0.012). MRS revealed reduced tNAA (731.4±45.4 vs. 814.9±62.1, p = 0.017) and tCr (373.8±22.2 vs. 418.7±31.1, p = 0.002) in the visual cortex in patients vs. HC. Whole brain volume, grey and white matter volume, VBM and metabolites in a MRS sensory cortex control voxel did not differ significantly between patients and HC.
  
  
  CONCLUSIONS
  PMP22 deletion leads to functional, metabolic and macro-structural alterations in the afferent visual system of HNPP patients. Our data suggest a functional relevance of these changes for peripheral vision, which warrants further investigation and confirmation.
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander U
authors.identifier: http://orcid.org/0000-0002-9768-014X
authors.initials: AU
authors.lastname: Brandt
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Meinert-Bohn
authors.affiliation: Institute of Neuropathology, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jan Leo
authors.initials: JL
authors.lastname: Rinnenthal
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Mikolajczak
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Oberwahrenbrock
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Papazoglou
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Caspar F
authors.initials: CF
authors.lastname: Pfüller
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Schinzel
authors.affiliation: Department of Neurology, University of Giessen-Marburg, Marburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité -Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hahn
authors.affiliation: NeuroCure Clinical Research Center, Charité -Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Bellmann-Strobl
mesh_terms: D000328:Adult; D001176:Arthrogryposis / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000502:physiology; D015417:Hereditary Sensory and Motor Neuropathy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000000981:diagnostic imaging; D017384:Sequence Deletion; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014793:Visual Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D014795:Visual Pathways / Q000503:physiopathology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000502:physiology
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human