Development of in vivo markers of axonal loss and demyelination in optic neuritis.
Doctoral thesis, UCL (University College London).
Axonal loss and remyelination are major pathological substrates implicated in the balance between recovery and fixed disability that occurs following optic neuritis and other forms of relapse in multiple sclerosis. Optic neuritis is an ideal model for studying the functional consequences of a single demyelinating lesion. Several quantitative measures of vision can assess function of the anterior visual pathway, and electrophysiological testing can provide measures of axonal integrity and myelination. These measures are highly reproducible and permit the functional relevance of any structural changes to be determined. The studies presented in this thesis applied three retinal imaging techniques and three optic nerve MRI techniques to investigate the extent and functional significance of axonal loss and remyelination following optic neuritis. Two of the retinal imaging measures, optical coherence tomography (OCT) and scanning laser polarimetry, demonstrated functionally relevant neuroaxonal loss in patient with incomplete recovery following optic neuritis. In acute optic neuritis patients, OCT detected retinal nerve fibre layer (RNFL) thinning after three months and qualified acute peripapillary RNFL swelling in bulbar cases. MRI-detected optic nerve atrophy correlated well with OCT RNFL thinning supporting the hypothesis that axonal loss is the major substrate of atrophy. Furthermore, there was evidence from the atrophy study of retrograde degeneration from the optic nerve to RNFL to macula. Optic nerve diffusion tensor imaging demonstrated increased mean diffusivity and reduced fractional anisotropy in nerves affected by optic neuritis compatible with the process of axonal disruption or loss. Optic nerve magnetisation transfer ratio in affected optic nerves correlated with both visual evoked potential latency and RNFL thickness suggesting that MTR may not be an exclusive marker of myelination alone and also reflects co-existent axonal loss. Anterior visual pathway imaging may be useful in monitoring therapies that aim to prevent axonal loss and enhance remyelination in optic neuritis.
|Title:||Development of in vivo markers of axonal loss and demyelination in optic neuritis|
|Additional information:||Pending digitisation|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > IoN - Neuroinflammation|
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