Maria Petracca1,2, Gary Cutter3, Sirio Cocozza1,4, Leorah Freeman5, John Kangarlu1, Monica Margoni1,6, Matteo Moro1,7, Stephen Krieger1, Mohamed Mounir El Mendili1,8, Amgad Droby1,9,10,11, Jerry S Wolinsky12, Fred Lublin1, Matilde Inglese1,13,14. 1. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 2. Department of Human Neurosciences, Sapienza University, Rome, Italy. 3. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA. 4. Department of Advanced Biomedical Sciences, University "Federico II", Naples, Italy. 5. Department of Neurology, Dell Medical School, The University of Texas at Austin, Houston, Texas, USA. 6. Padova Neuroscience Centre, University of Padua, Padua, Italy. 7. Department of Informatics, Bioengineering, Robotics and Systems Engineering (DIBRIS), University of Genova, Genova, Italy. 8. Aix Marseille Univ, CNRS, CRMBM, Marseille, France. 9. Laboratory for Early Markers of Neurodegeneration (LEMON), Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 10. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 11. Sagol School for Neuroscience, Tel Aviv University, Tel Aviv, Israel. 12. University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA. 13. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy. 14. Ospedale Policlinico San Martino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Genoa, Italy.
Abstract
BACKGROUND AND PURPOSE: Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. AIM: We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. METHODS: Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25-foot walk test [T25FWT] score worsening, nine-hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. RESULTS: Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). CONCLUSION: Among the explored outcomes, single time-point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest.
BACKGROUND AND PURPOSE: Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. AIM: We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. METHODS: Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25-foot walk test [T25FWT] score worsening, nine-hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. RESULTS: Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). CONCLUSION: Among the explored outcomes, single time-point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest.