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Neuromyelitis optica (NMO) and multiple sclerosis (MS) both result in acute injury (i.e. attacks or relapses) to the central nervous system with focal demyelination and axonal loss that varies in severity along a spectrum. A variety of non-invasive structural imaging and functional tools can be used to investigate mechanisms of white matter injury and secondary axonal injury in MS and NMO. These include advanced magnetic resonance imaging (MRI) measures of myelin water fraction; optical coherence tomography (OCT) for retinal nerve fibre layer thickness and total macular volume; and transcranial magnetic stimulation (TMS) to determine cortical excitability and integrity of cortical spinal pathways.First, the relationship between a functional measure using TMS and a structural measure of myelin in the cortico-spinal tract was examined. Structural changes were found in the descending motor output pathway white matter in NMO along with abnormal TMS measures, suggesting that there is greater spinal cord involvement and more extensive axonal loss found in NMO compared to MS.Next, OCT was used as a measure of the anterior visual pathway and myelin water imaging of the posterior visual pathway; the effects of damage to one part of the visual system on the other was studied. Retrograde degeneration to the retina and anterograde degeneration to the optic radiations from the optic nerve was observed in both MS and NMO subjects with optic neuritis history. A correlation between the measures indicating that damage to one part may cause damage to another part of the visual pathway. Finally, damage was observed in optic pathway in MS patients without optic neuritis history suggesting that there is damage in the absence of lesions in the optic nerve.Finally, myelin water imaging was used to investigate if the disease burden of lesions regulate the level of damage to the normal appearing white matter (NAWM) tracts. The lack of correlation between disease burden of lesions and NAWM myelin water imaging in MS suggested that damage to the NAWM was mediated by processes independent of lesions.These techniques can be used to study and better understand demyelinating diseases such as MS and NMO.

Magnetic Resonance Imaging (MRI) measures of T₁ relaxation provide a sensitive and reproducible measure of water content in vivo. In the present study T₁ histograms were used to monitor changes in the brain water content of multiple sclerosis (MS) patients initiating Disease Modifying Therapies (DMT). The initiation of DMT, which target inflammation, is associated with a decrease in brain volume (BV) greater than would be expected by natural history alone. Reductions in BV may reflect worsening disease in untreated patients; however for patients treated with DMT, reductions in BV early in the treatment course may represent a clinical improvement due to initial anti-inflammatory effects of therapy and the resulting decrease in edema. The initial change in BV upon starting DMT is termed pseudoatrophy, a reversible decrease in BV due to a loss of water from the brain parenchyma. Patients with clinically definite MS planning on initiating DMT were recruited and scanned at two time points prior to initiating therapy and two time points after initiating therapy to determine the change in water content of the brain.