Enhancing our understanding of white matter changes in early multiple sclerosis.

Abstract

This scientific commentary refers to ‘Permeability of the blood–brain barrier predicts conversion from optic neuritis to multiple sclerosis’, by Cramer et al. (doi:10.1093/brain/awv203). The cause of multiple sclerosis remains one of the great mysteries of neurology. Despite its clinico-neuropathological characterization almost 150 years ago by Charcot, we continue to gain fundamental knowledge about multiple sclerosis pathology. A major roadblock to the better understanding of multiple sclerosis, and many chronic CNS diseases, is the lack of adequate longitudinal histological analyses of the CNS. These are needed to show the early development of individual lesions as well as the changes in neuropathology over the years. How do multiple sclerosis lesions begin? Neuroimaging has provided clues by revealing that lesions commence with blood–brain barrier (BBB) breakdown as indicated by gadolinium enhancement. In the BECOME study in which monthly gadolinium-enhanced brain MRIs were performed in 75 subjects with multiple sclerosis for 2 years, more than 95% of new lesions seen on T2-weighted/FLAIR magnetic resonance began with gadolinium enhancement (Cadavid et al. , 2009). However, we do not know what precedes BBB breakdown. It is likely that subtle focal or global changes occur prior to gadolinium enhancement within the normal-appearing CNS. To understand early events in lesion development, investigators often focus on patients who are at the early stages of a single demyelinating event, so-called ‘clinically isolated syndrome’ (CIS). In this issue of Brain , Cramer and co-workers examine patients with CIS limited to the optic nerves to determine whether subtle changes in BBB permeability are also present …