Introduction

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease of the central nervous system, characterized by non-uniform clinical manifestations and a variable disease progression [1]. In MS, the combined role of brain and spinal cord MRI damage in predicting medium-term disease evolution still needs to be fully elucidated. Against this background, aim of this study was to evaluate the independent role of brain and cervical cord damage in predicting 5-year clinical disability worsening in a multicentre cohort of MS patients, recruited from 9 European sites.

Methods

Baseline 3.0 T brain and cervical cord T2- and 3D T1-weighted MRI sequences were acquired in 367 MS patients (326 relapse-onset, 41 progressive-onset) and 179 healthy controls [2]. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (interquartile range=4.5-5.5). Clinical worsening was defined as an EDSS score increase ≥1.5 when baseline EDSS was=0.0; an EDSS score increase ≥1.0 when baseline EDSS≤5.5; and an EDSS score increase ≥0.5 when baseline EDSS was ≥6.0 [3]. Generalized linear mixed models with L1-penalized variable selection identified the 5-year predictors of EDSS worsening, secondary progressive (SP) MS conversion in relapsing-remitting (RR) MS, and reaching EDSS=3.0, 4.0 and 6.0 milestones.

Results

At follow-up, 120/367 (33%) MS patients worsened clinically and 36/256 (14%) RRMS patients evolved to SPMS. MS patients reaching EDSS=3.0 at 5 year were 20 (out of 152, 13%), while MS patients reaching EDSS=4.0 at 5 years were 30 (out of 209, 14%), and patients reaching EDSS=6.0 at 5 years were 37 (out of 288, 13%). Significant predictors of clinical worsening at univariate analysis are shown in Figure 1. At multivariate analysis, predictors of clinical worsening were progressive- vs relapse-onset MS (standardized beta [b]=0.97), baseline EDSS score (b=0.41), higher cord lesion number (b=0.41), lower normalized cortical volume (b=-0.15) and cord cross-sectional area (CSA) (b=-0.28) (C-index=0.81). Significant predictors of SPMS conversion at univariate analysis are shown in Figure 2. At multivariate analysis, older age (b=0.86), higher EDSS score (b=1.40) and cord lesion number (b=0.87) independently predicted SPMS conversion (C-index=0.91). Significant univariate predictors of reaching clinically-relevant EDSS milestones are shown in Figure 3. At multivariate analysis, predictors of reaching EDSS=3.0 (C-index=0.88) were higher baseline EDSS score (b=1.49) and cord lesion number (b=1.02), and lower normalized cortical volume (b=-0.56). Baseline age (b=0.30), higher EDSS score (b=2.03), higher cord lesion number (b=0.66), and lower cord CSA (b=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS score (b=1.87) and higher cord lesion number (b=0.54) predicted EDSS=6.0 (C-index=0.91).

Discussion

Cortical atrophy and spinal cord damage independently predicted 5-year disability worsening in MS. Focal spinal cord lesions had a role in predicting both evolution to a progressive phenotype and disability milestones. In addition, cord atrophy was one of the determinants of locomotor disability.

Conclusions

In MS patients, cortical atrophy and spinal cord lesions and cord atrophy independently predicted 5-year disability worsening, reaching of EDSS milestones and SPMS conversion. The combined assessment of brain and spinal cord damage may better identify MS patients who will have disease progression after 5 years.

Acknowledgements

No acknowledgement found.

References

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