title: Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS).
  
  
  METHODS
  We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models.
  
  
  RESULTS
  VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (β = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (β = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (β = -2.551, 95% CI = -3.910 to -1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6μm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON.
  
  
  CONCLUSIONS
  Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS.
authors.affiliation: Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Gabilondo
authors.forename: Elena H
authors.initials: EH
authors.lastname: Martínez-Lapiscina
authors.forename: Eloy
authors.initials: E
authors.lastname: Martínez-Heras
authors.forename: Elena
authors.initials: E
authors.lastname: Fraga-Pumar
authors.forename: Sara
authors.initials: S
authors.lastname: Llufriu
authors.forename: Santiago
authors.initials: S
authors.lastname: Ortiz
authors.forename: Santiago
authors.initials: S
authors.lastname: Bullich
authors.forename: Maria
authors.initials: M
authors.lastname: Sepulveda
authors.forename: Carles
authors.initials: C
authors.lastname: Falcon
authors.forename: Joan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.forename: Bernardo
authors.initials: B
authors.lastname: Sanchez-Dalmau
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
mesh_terms: D000293:Adolescent; D000328:Adult; D001369:Axons / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis*; D009410:Nerve Degeneration / Q000473:pathology*; D012160:Retina / Q000473:pathology; D013569:Synapses / Q000473:pathology*; D014793:Visual Cortex / Q000473:pathology*; D014795:Visual Pathways / Q000473:pathology*; D055815:Young Adult