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Research paper
A dam for retrograde axonal degeneration in multiple sclerosis?
  1. L J Balk1,
  2. J W R Twisk2,
  3. M D Steenwijk3,
  4. M Daams3,4,
  5. P Tewarie1,
  6. J Killestein1,
  7. B M J Uitdehaag1,
  8. C H Polman1,
  9. A Petzold1
  1. 1Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands
  2. 2Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands
  3. 3Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands
  4. 4Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VU University Medical Center, Amsterdam, The Netherlands
  1. Correspondence to L J Balk, Department of Neurology, VU University Medical Centre, De Boelelaan 1118, MS Centrum VUmc, PK 0-Z-126, Amsterdam 1081 HZ, The Netherlands; L.balk{at}


Objective Trans-synaptic axonal degeneration is a mechanism by which neurodegeneration can spread from a sick to a healthy neuron in the central nervous system. This study investigated to what extent trans-synaptic axonal degeneration takes place within the visual pathway in multiple sclerosis (MS).

Methods A single-centre study, including patients with long-standing MS and healthy controls. Structural imaging of the brain (MRI) and retina (spectral-domain optical coherence tomography) were used to quantify the extent of atrophy of individual retinal layers and the primary and secondary visual cortex. Generalised estimation equations and multivariable regression analyses were used for comparisons.

Results Following rigorous quality control (OSCAR-IB), data from 549 eyes of 293 subjects (230 MS, 63 healthy controls) were included. Compared with control data, there was a significant amount of atrophy of the inner retinal layers in MS following optic neuritis (ON) and also in absence of ON. For both scenarios, atrophy stopped at the level of the inner nuclear layer. In contrast, there was significant localised atrophy of the primary visual cortex and secondary visual cortex in MS following ON, but not in MS in absence of ON.

Interpretation These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.

  • Multiple Sclerosis
  • Neuroophthalmology

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