The contribution of brain reorganisation to recovery in patients with optic neuritis.

Abstract

In this thesis, the mechanisms of damage and repair in clinically isolated optic neuritis (ON) were investigated in vivo, by combining magnetic resonance imaging (MRI), electrophysiology and optical coherence tomography (OCT). ON is a demyelinating, inflammatory condition of the optic nerve, which may be the first presentation of multiple sclerosis. The visual prognosis is generally good, despite optic nerve demyelination and axonal loss, but some patients fail to recover. The aim of this thesis was to determine the reasons underlying recovery. The hypothesis was that neuroplastic grey matter reorganisation might contribute to visual outcome. Structural MRI, electrophysiology and OCT were used to quantify optic nerve oedema, inflammation, myelination and neuroaxonal loss, and optic radiation and visual cortical pathology, in a cohort of patients with acute ON, followed up over the following year. Visual functional MRI (fMRI) was employed to investigate neuroplasticity. Acutely, measures of optic nerve inflammation and conduction block were associated with the severity of acute visual loss, and were used to inform an fMRI analysis, in order to dissect complex structure-function interactions. Evidence was found for neuroplasticity in dorsal higher visual areas, which may act to modulate acute visual dysfunction. Subsequent longitudinal analyses identified associations between early fMRI activation in the lateral occipital complexes, a ventral stream higher visual area, and longer term visual outcome, which were evident on stimulation of either eye, and independent of measures of myelination and neuroaxonal loss in the visual pathways. A quadrant-specific fMRI stimulation paradigm was used to investigate recovery from visual field defects, finding no evidence for field defect-specific neuroplastic responses. It was concluded that cortical neuroplasticity appears more important to recovery from ON than was previously thought, and its contribution is independent of measures of tissue damage. This may provide a target for future therapeutic approaches in demyelinating disease.