Abstract

BackgroundPrediction of disability progression in patients with MS (pwMS) is challenging. So far, scarce evidence exists suggesting knowledge about how cognitive performance may potentially improve prediction of physical impairment and disability progression in MS. Therefore, we wanted to assess the prognostic value of cognitive performance regarding physical impairment and disability progression in pwMS. Methods85 patients (64% female; 60% relapse-remitting MS; mean age=36.78 ± 9.63 years) underwent clinical, neuropsychological (Brief Repeatable Battery for Neuropsychological Test (BRB-N)) and brain MRI (T1-weighted and T2-weighted FLAIR images) assessment at baseline and after an average of 7 years (SD=3.75) at follow-up. We assessed physical impairment and annualized disability progression (disability progression divided by follow-up duration) using the Expanded Disability Status Scale (EDSS). To compare patients with no or mild physical impairment (EDSS≤2.5) and patients with moderate to severe physical impairment (EDSS≥3.0), we used an EDSS score ≥3.0 as cut-off. Silent progression was defined by an EDSS worsening of at least 0.5 in the absence of relapses and inflammation in relapsing-remitting MS. ResultsIn hierarchical regression models (method “STEPWISE”, forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R²=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R²=0.257, β=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p<0.001) and silent progression (m=-2.19, SD=1.01, p=0.038). ConclusionPerformance in information processing speed might help to identify patients at risk for physical impairment. Therefore, neuropsychological assessment should be integrated in clinical standard care to support disease management in pwMS.

Highlights

  • The prediction of disability in patients with multiple sclerosis remains challenging due to the multifactorial causes of the disease

  • Significant predictors of the hierarchical binary-logistic or linear regression model to predict physical impairment, annualized EDSS progression or silent progression. b: b coefficient; β: β coefficient; base­ line (BL): baseline; EDSS: Expanded Disability Status Scale; FU: follow-up; OR: odds ratio; p: p-value; R2: coefficient of determination; showed impairment in IPS (SDMT): Symbol Digit Modalities Test; 95% CI: 95% confidence interval, *indicates p ≤0.05

  • Median annualized EDSS progression was 0.00 (IQR=0.14). 7 (15%) of 46 patients with relapsing-remitting MS (RRMS) met the criteria of silent progression within the FU duration

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Summary

Introduction

The prediction of disability in patients with multiple sclerosis (pwMS) remains challenging due to the multifactorial causes of the disease. Demographics (e.g. age), clinical (e.g. disease duration, clinical phenotype) and magnetic resonance imaging (MRI) parameters (e.g. lesion load, cortical thickness, brain volumes) improve prediction of physical impairment and disability progression (Briggs et al, 2019; Dekker et al, 2019). Results: In hierarchical regression models (method “STEPWISE”, forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R2=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R2=0.257, β=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p

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