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Studies of large longitudinal cohorts of patients with multiple sclerosis (MS) have emphasized the prognostic value of conventional MRI markers, at least during early stages. Advanced imaging metrics derived from quantitative MRI and PET provide relevant information about microstructural damage within and outside visible lesions that may be more sensitive to predict long-term disability. Here, we summarize the most recent findings regarding the prognostic value of imaging markers throughout MS stages.In clinically isolated syndrome, the presence of at least one brain or spinal cord T2 lesion strongly increases the risk of conversion to clinically definite MS (hazard ratio ranging from 5 to 11). Similarly, the occurrence of new white matter lesions is strongly predictive of subsequent relapse rate and response to current disease modifying therapies. Beyond white matter lesions, volumetric changes in the grey matter and normal-appearing tissue damage are more sensitive prognostic markers for physical and cognitive disability, especially in progressive MS.Although white matter lesion number and volume still remains the imaging metric used in daily clinical practice, further development of advanced imaging predictors of long-term disability should allow a better stratification of patients in future clinical trials aimed at promoting repair or neuroprotection.