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Brain Volume and Diffusion Markers as Predictors of Disability and Short-Term Disease Evolution in Multiple Sclerosis - AJNR News Digest
August 2014
Brain

Brain Volume and Diffusion Markers as Predictors of Disability and Short-Term Disease Evolution in Multiple Sclerosis

Philipp Sämann

Philipp Sämann

For patients with multiple sclerosis (MS), MRI has gained an essential role in treatment management. In particular, quantitative markers of neuroaxonal damage have emerged as long-term predictors of MS-related disability and as surrogate markers of immuno­modulatory efficacy.1 Exceeding a certain threshold of neuroaxonal pathology might accelerate a patient’s transition to secondary-progressive MS or “sustained progression.”2 We compared the sensitivity of longitudinal MRI markers and investigated which markers predict clinical pro­gression over a rather short period of 1 year.3 Analysis pipelines for apparent diffusion coefficient (ADC) histogram analysis, white matter lesion load quantification, and calculation of the brain parenchymal fraction (BPF) were applied to 54 patients with MS at baseline and after a median 12 months. Clinical monitoring of patients (87% under immuno­modulatory therapy) included the sensitive MS Functional Composite (MSFC) score.

We replicated that ADC histogram analysis provides robust pre­dictors of the MSFC score (maximal R2=0.576, P<.001), incorporated cognition and fine motor skill subscores, and Expanded Disability Status Scale score. Longitudinal changes beyond age-related changes were noted for ADC histogram markers and BPF. As a novel finding, we emphasized that stronger diffusivity alterations and stronger brain volume loss at baseline predicted MSFC decline over a median 12 months (A. multiple linear re­gression, mean ADC as emerging marker, R2=0.203, P=.003; B. group comparison [progressive vs stable MSFC development]: lower baseline BPF in the progressive MS patient group, P=.001).

Clinically, this indicates that surrogate markers of neuroaxonal pathology hold information on the risk for disease progression in the following year—in

the absence of intermittent relapses and in patients still mostly (86%) classified as having relapsing-remitting MS. These results extend pre¬vious observations that related lower baseline brain volumes to MSFC progression over 6.6 years.4 Results are further encouraging in that robust MRI diffusion and volumetric markers can help identify MS subgroups for which neuro­protection (and effective immunomodulation) is particularly relevant. We now direct combined mo­le­cu­lar/MRI studies towards the question of which molecular, including genetic, patterns define MS subgroups that are particularly prone to develop brain atrophy.

References

  1. Miller DH, Barkhof F, Frank JA, et al. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 2002;125:1676–95, 10.1093/brain/awf177
  2. Trapp BD, Ransohoff R, Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 1999;12:295–302
  3. Sämann PG, Knop M, Golgor E, et al. Brain volume and diffusion markers as predictors of disability and short-term disease evolution in multiple sclerosis. AJNR Am J Neuroradiol 2012;33:1356–62
  4. Rudick RA, Lee J-C, Nakamura K, et al. Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci 2009;282:106–11, 10.1016/j.jns.2008.11.018

 

Read this article at AJNR.org . . .