Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies

PLoS One. 2016 Oct 17;11(10):e0164617. doi: 10.1371/journal.pone.0164617. eCollection 2016.

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.

Conclusion: 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.

MeSH terms

  • Adult
  • Arthrogryposis / metabolism
  • Arthrogryposis / pathology*
  • Brain / diagnostic imaging
  • Brain / physiology
  • Case-Control Studies
  • Cross-Sectional Studies
  • Evoked Potentials, Visual / physiology
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / physiology
  • Hereditary Sensory and Motor Neuropathy / metabolism
  • Hereditary Sensory and Motor Neuropathy / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myelin Proteins / genetics*
  • Myelin Proteins / metabolism
  • Retina / diagnostic imaging
  • Sequence Deletion
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Visual Cortex / diagnostic imaging
  • Visual Cortex / physiology
  • Visual Pathways / physiopathology*
  • White Matter / diagnostic imaging
  • White Matter / physiology

Substances

  • Myelin Proteins
  • PMP22 protein, human

Supplementary concepts

  • Tomaculous neuropathy

Grants and funding

This work was supported by the German Research Foundation (DFG Exc 257 to FP). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.