Challenges in multiple sclerosis; how to define occurence of progression

The challenges in MS are related to number of controversies in various aspects of disease but the relationship between relapses and disability progression, or aspects of MS as an inflammatory and/or neurodegenerative disease are extremely important because of its implications on prognosis and therapy of MS. MS was classically regarded as white matter inflammatory disease, while disability progression, brain and spinal cord atrophy were regarded as a consequence of global inflammation of NAWM and secondary involvement of grey matter. More recent histopathology studies, but also new, modern MRI techniques changed this view in MS as a prominent grey and white matter disease. Inflammatory demyelination of grey matter occurs early in MS sometimes even before occurrence of white matter lesions. Inspite of early therapy of MS with immunomodulatory drugs disability progression and neurodegeneration are still important and common part of MS pathogenesis. This indicate that treatment is not adequate to the predicted severity of MS, or perhaps to the basic pathogenetic mechanisms in MS. Beside acute clinical symptoms, conclusions about the severity of the disease are reflection of MRI sensitivity to detect focal WM lesions and insensitivity to detect grey matter lesions which correlate better with clinical symptoms. All presented studies and evaluations point to the necessity of changing the established diagnostic evaluation and treatment in MS. At the earliest stage of MS as well as in follow up of disease it would be necessary to apply a new MRI techniques more available for clinical practice such as DIR brain MR imaging at 3 T because of their sensitivity to detect grey matter lesions. In patient with present cortical lesions even in earliest stages of MS depending on severity of grey matter involvement more efficacious therapy like second or even third line therapy should start.