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Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis

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Abstract

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao’s brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

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Authors and Affiliations

  1. Multiple Sclerosis Centre of the Veneto Region, Padua, Italy

    Andrea Lazzarotto, Monica Margoni, Silvia Franciotta, Sofia Zywicki, Alice Riccardi & Paolo Gallo

  2. Department of Neuroscience, University Hospital of Padua, Giustiniani 5, 35100, Padua, Italy

    Andrea Lazzarotto, Monica Margoni, Silvia Franciotta, Sofia Zywicki, Alice Riccardi & Paolo Gallo

  3. Padova Neuroscience Center–PNC, Padua, Italy

    Andrea Lazzarotto, Monica Margoni & Paolo Gallo

  4. Department of Mathematics, University of Padua, Padua, Italy

    Davide Poggiali

  5. Neuroradiology Unit, University Hospital of Padua, Padua, Italy

    Mariagiulia Anglani

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  1. Andrea Lazzarotto
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  2. Monica Margoni
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  3. Silvia Franciotta
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Contributions

Study concept and design: LA, MM, FS, FA, and GP. MRI analysis and interpretation: LA and AM. Critical revision of the manuscript: LA, MM, FA, and GP. Statistical analysis of the data: LA. Neuropsychological assessment administration and interpretation: RA. Study supervision: GP.

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Correspondence to Andrea Lazzarotto.

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Conflict of Interest

LA has received travel grant from Roche, Sanofi-Genzyme, Merk serono, and Teva. MM has received travel grant from Sanofi-Genzyme, Merk serono, Teva, Biogen, and Mylan, and has received a personal fee from Novartis. FS has nothing to declare. ZF has received travel grant from Roche, Sanofi-Genzyme, Merk serono, Teva, Biogen, and Novartis. MA has received travel grant from Sanofi-Genzyme. AR reports grants and personal fees from Novartis, grants and personal fees from Biogen Idec, grants from Teva, and grants from Merck Serono during the conduct of the study. PD has nothing to declare. MA has nothing to declare. FA has received honoraria from Novartis, Teva, and Almirall. GP reports grants and personal fees from Merck Serono, grants and personal fees from Biogen Idec, grants and personal fees from Genzyme Sanofi, grants and personal fees from Bayer Schering Pharma, grants and personal fees from Novartis, grants and personal fees from Teva, grants from University of Padua, Department of Neurosciences DNS, grants from Veneto Region of Italy, grants from Italian Association for Multiple Sclerosis (AISM), and grants from the Italian Ministry of Public Health during the conduct of the study.

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Lazzarotto, A., Margoni, M., Franciotta, S. et al. Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis. Cerebellum 19, 192–200 (2020). https://doi.org/10.1007/s12311-019-01096-4

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