CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are Patterns of Retinal and MRI Changes Heterogeneous and Thus Not Predictable?

PLoS One. 2015 Nov 13;10(11):e0142272. doi: 10.1371/journal.pone.0142272. eCollection 2015.

Abstract

Background: To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration.

Methods: 28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study.

Results: There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability.

Conclusions: Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Atrophy / pathology*
  • Brain / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Retina / pathology*
  • Tomography, Optical Coherence
  • Visual Pathways / pathology*
  • Young Adult

Grants and funding

This study was funded by the Multiple Sklerose Forschungsgesellschaft Wien (www.msges.or.at) and by the Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Vienna, Austria (http://www.karllandsteiner.at/institute/neuroimmunologische_neurodegenerative_erkrankungen.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.