Contents lists available at ScienceDirect Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard The Bayesian risk estimate at onset (BREMSO) correlates with cognitive and physical disability in patients with early multiple sclerosis Marianne Said a,1 , Nabil K. El Ayoubi a,1 , Salem Hannoun a,b , Ribal Haddad a , Leslie Saba c , Youmna Jalkh a , Bassem I Yamout a , Samia J Khoury a,b, ⁎ a Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, PO Box: 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon b Abu-Haidar Neuroscience Institute, American University of Beirut Medical Center, PO Box: 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon c UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland ARTICLE INFO Keywords: Multiple sclerosis Bayesian Risk Estimate for MS at Onset (BREMSO) Predictive score Multiple sclerosis severity score (MSSS) Symbol digit modalities test (SDMT) Magnetic resonance imaging (MRI) ABSTRACT Background: Prevention of long-term disability is the goal of therapeutic intervention in Relapsing Remitting MS (RRMS). The Bayesian Risk Estimate for MS at Onset (BREMSO) gives an individual risk score predicting disease evolution into Secondary Progressive MS (SPMS). We investigated whether BREMSO correlates with physical disability, cognitive dysfunction, and regional brain atrophy early in MS. Methods: One hundred RRMS patients with at least two years of follow-up were enrolled. BREMSO score as well as Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Severity Score (MSSS), Timed 25-Foot Walk Test (T25-FW) and 9-Hole Peg Test (9-HPT), were assessed. Intracranial volume (ICV), subcortical gray matter structures and corpus callosum (CC) were automatically segmented on MRI images and their volumes measured. Results: BREMSO score correlated negatively with SDMT at visit1 (β = -0.33, p = 0.019), visit2 (β = -0.34, p = 0.017) and visit3 (β = -0.34, p = 0.014), and positively with MSSS at visit1 (r = 0.38, p = 0.006), visit2 (r=0.47, p < 0.0001) and visit3 (r = 0.42, p = 0.002), but not with T25-FW and 9-HPT. BREMSO negatively correlated with CC volume at baseline (p < 0.03). No correlations were found with ICV and subcortical gray matter. Conclusions: BREMSO score at onset correlated with physical disability (MSSS), cognitive function (SDMT) and CC volume measurements in patients with early MS. 1. Introduction Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS that affects more than two million people worldwide. It is the most common cause of permanent disability in young adults and the peak incidence is between age 20 and 40 (Weiner and Stankiewicz, 2012). MS is characterized by regression of both motor and cognitive abilities that evolve independently (Chiaravalloti and DeLuca, 2008). Cognitive impairment (CI) symptoms affect primarily processing speed, attention and executive functions (Hankomäki et al., 2014) and are usually under-recognized and not commonly clinically quantified due to time and cost limitations (Patti, 2009). Nonetheless, CI has a major impact on the patient's quality of life; it affects work performance, management of family tasks and daily routine. Cogni- tively-impaired MS patients are often more limited in independence (Fischer, 2001). Moreover, CI occurs in up to 70% of patients and can be seen in radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS) and all phases of MS (including pediatric onset) (Jongen et al., 2012). In addition, cognitive impairment could be more subtle in one third of patients with early MS (Amato et al., 2010) and predicts disease progression to SPMS (Moccia et al., 2016). The Symbol Digit Modalities Test (SDMT) is a standardized test used clinically to https://doi.org/10.1016/j.msard.2018.09.003 Received 6 March 2018; Received in revised form 3 September 2018; Accepted 6 September 2018 Abbreviations: BREMSO, Bayesian risk estimate for MS at onset; CC, Corpus callosum; CI, Cognitive impairment; CIS, Clinically isolated syndrome; DMTs, Disease modifying treatments; EDSS, Expanded disability status scale; FLAIR, Fluid-attenuated inversion recovery; GM, Grey matter; ICV, Intracranial volume; MRI, Magnetic resonance imaging; MSFC, MS functional composite; MSSS, Multiple sclerosis severity score; 9-HPT, 9-Hole peg test; PASAT, Paced auditory serial addition test; RIS, Radiologically isolated syndrome; RRMS, Relapsing remitting multiple sclerosis; SD, Standard deviation; SDMT, Symbol digit modalities test; SPMS, Secondary progressive multiple sclerosis; T25-FW, Timed 25-foot walk test ⁎ Corresponding author at: Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, PO Box: 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon 1 Authors contributed equally to this work E-mail address: sk88@aub.edu.lb (S.J. Khoury). Multiple Sclerosis and Related Disorders 26 (2018) 96–102 2211-0348/ © 2018 Elsevier B.V. All rights reserved. T