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Impact of Inflammation on Brain Volume in Multiple Sclerosis

Jojy Cheriyan, MD; Soyeon Kim, PhD; Leo J. Wolansky, MD; Stuart D. Cook, MD; Diego Cadavid, MD
Arch Neurol. 2012;69(1):82-88. doi:10.1001/archneurol.2011.674.
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Objective To study changes in brain volume measured monthly in patients treated for relapsing multiple sclerosis due to loss of tissue and the appearance of inflammation.

Design and Patients The results from T2/fluid-attenuated inversion recovery axial images from 13 consecutive monthly 3-T brain magnetic resonance imaging tests conducted on 74 patients diagnosed with relapsing multiple sclerosis in the BECOME study were used to calculate whole brain volumes using automated software analysis tools. The patients had been randomized to receive treatment with interferon beta-1b or glatiramer acetate. Ongoing inflammation was studied by counting the number of combined active lesions and measuring the volume of gadolinium enhancement. A mixed-effects model was used to analyze brain volumes over time.

Results There was a significant decrease in brain volume over time but there was no difference in its rate of change by age, sex, frequency of ongoing inflammation, multiple sclerosis type, or randomized treatment assignment. The mean rate of brain volume change per month from multivariable models was −1.1 cm3 (95% CI, −1.5 to −0.6) and during times of magnetic resonance imaging activity, it increased transiently by an average of 1.2 cm3/lesion (95% CI, 0.7 to 1.7) and 7.1 cm3/1 cm3 of gadolinium volume. In a model with both measures, combined active lesions were independent predictors of brain volume but gadolinium volume was not.

Conclusion Two major changes in brain volume occur in patients with relapsing multiple sclerosis, a steady decrease likely due to tissue loss with overlapping transient increases due to the appearance of inflammation.

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Figure. Actual and fitted brain volumes at baseline and months 1 to 12 in 4 randomly selected patients with relapsing-remitting multiple sclerosis or clinically isolated demyelinating syndrome at risk of multiple sclerosis assigned to treatment with interferon beta-1b or glatiramer acetate. The cohort was stratified by quartiles of estimated change in brain volume, and a single participant was selected at random from each quartile. A-D, Participants from first through fourth quartiles, from fastest to slowest decline. The number of combined active lesions (CALs) and gadolinium volume are shown on the horizontal axis. A multivariable model was fit to the data, which included a random intercept and slope and fixed effects for CALs, visit month, age at baseline, and sex. The model showed CALs were positively associated with brain volume, with each lesion corresponding to a 1.2-cm3 (95% CI, 0.7 to 1.7) higher brain volume. Actual brain volume was calculated from the axial fluid-attenuated inversion recovery sequences. The expected brain volume trajectory was based on the multivariable model setting CALs to zero. The expected brain volume was based on the model with actual observed number of CALs.




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