Diagnosis, prognosis and therapeutic monitoring in MS

Professor David Miller and Professor Alan Thompson

The new MS Society programme grant is focused on the identification of early MR markers of prognosis and pathogenetic mechanisms. Progress in detecting such markers will elucidate new treatments strategies and enable their implementation for those most likely to benefit before disability develops.

Cohorts of patients with clinically isolated syndromes and early relapsing remitting and primary progressive MS are being followed; the neurological and cognitive status after 5 years is being related to earlier MR measures. The imaging techniques are studying lesions, normal appearing whiter matter, grey matter and atrophy in the brain and spinal cord. Abnormalities in the normal appearing white and grey matter have been identified from symptom onset. Serial studies in those with clinically isolated syndromes (mainly optic neuritis patients studied in collaboration with Dr Gordon Plant, Moorfields Eye Hospital) have identified modifications to the existing McDonald criteria for MS that improve their accuracy.

The MRI Trial Analysis Unit managed by Mr David MacManus provides central MRI analysis for multicentre clinical trials in MS. In the last two years it has been engaged in the analysis of phase II and III trials of several agents including natalizumab, rosiglitazone and dimethylfumaric acid. In addition to measuring therapeutic effects on lesions, there is focus on the measurement of atrophy and abnormalities in normal appearing tissues. Although the latter are more technically challenging in multicentre trials, they have potential to provide a better indication of disease progression. Cerebral atrophy will be the primary outcome measure of an upcoming phase II trial of lamotrigine in secondary progressive MS (Dr Raj Kapoor is the principal investigator in this trial funded by the MS Society). In collaboration with Professor Nick Fox (Dementia Research Group), a PhD fellow is investigating the relative utility of multiple methods that are currently used to evaluate atrophy in MS.

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