Spinal cord atrophy and disability in multiple sclerosis over four years

• multiple sclerosis
• spinal cord atrophy
• disability

It is natural to focus on spinal cord damage as a major factor in disability. Indeed, interest in the use of MRI to study the spinal cord in multiple sclerosis, and its relation to locomotor disability, has been on the increase for over 10 years. The paper by Lin et al (pp 1090–1094)¹ is the first medium term follow up (four years) of spinal cord atrophy in both untreated patients and patients treated with interferon β-1a.

Initial studies of the cord concentrated on the visible lesions seen with conventional MRI, and results were perhaps disappointing, with little direct influence of acute and chronic damage as seen on conventional T2 weighted scans. More recently, with methods capable of detecting more subtle abnormalities such as magnetisation transfer imaging or T1 mapping, stronger correlations (albeit still weak) with expanded disability status scale (EDSS) scores are emerging.² It is thought that, in addition to macroscopic lesions located in the cord, repeated acute insults in the central nervous system cause Wallerian degeneration and axonal loss; this can extend to the cord—whether the primary site is in the cord or the cerebrum—and while the damage is not seen as a focal lesion, rarefaction of the axons nevertheless occurs throughout the cord, leading to diffuse pathological changes and cord atrophy.³ Atrophy of the cord may therefore be another important indicator of disease progression, and of the impact of the disease on a major contributor to disability and quality of life. Indeed, cord atrophy appears to be greater in the progressive forms of multiple sclerosis, although it can be observed even in patients at the earliest clinical stage of the disease.⁴ Measurements of cord atrophy rates might make an important contribution to the long term evaluation of therapeutic efficacy of new treatments for multiple sclerosis, especially in primary progressive disease.

Unfortunately, treatment with interferon β and other compounds has thus far been shown to have little effect on cerebral atrophy. As atrophy is likely to be the end result of acute events that may have happened some time ago, the problem may be that short term follow up (a few years) is insufficient to show any long term benefit of treatment. Alternatively, it could be that some underlying damaging process is still ongoing, even when acutely disabling events are suppressed by treatment. The paper by Lin et al extends finding in the cerebrum to the spinal cord, and adds to this disappointment. Despite using what is clearly a very reproducible measure of cord area, capable of detecting low atrophy rates, the rate seems to have been unmodified by interferon β-1a treatment. There have been several recent studies (including Lin’s) showing a correlation between cerebral and cord atrophy rates and EDSS score at follow up,⁵ so the importance of slowing atrophy is not in doubt. The remaining question is whether any of the existing treatments, or putative new ones, will have an impact on the disabling aspects of multiple sclerosis in the long term.