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Front. Neurosci. | doi: 10.3389/fnins.2019.00440

Cognitive syndromes and c9orf72 mutation are not related to cerebellar degeneration in Amyotrophic Lateral Sclerosis

 Monica Consonni1*,  Eleonora Dalla Bella1,  Nigri Anna1, Chiara Pinardi1*,  Greta Demichelis1, Luca Porcu2, Cinzia Gellera1,  Viviana Pensato1,  Stefano F. Cappa3, 4, Maria G. Bruzzone5, Giuseppe Lauria1, 6 and  Stefania Ferraro1
  • 1Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy
  • 2Istituto Di Ricerche Farmacologiche Mario Negri, Italy
  • 3Istituto Universitario di Studi Superiori di Pavia (IUSS), Italy
  • 4Centro San Giovanni di Dio Fatebenefratelli (IRCCS), Italy
  • 5Istituto Neurologico Carlo Besta (IRCCS), Italy
  • 6Department of Biomedical Sciences and Clinics Luigi Sacco, Faculty of Medicine and Surgery, University of Milan, Italy

Objective The notion that cerebellar pathology may contribute to cognitive impairment in ALS, especially in patients with C9orf72 repeated expansion, has been inconsistently reported. This study aimed exploring the relationship between cerebellar involvement, cognitive impairment and C9orf72repeated expansion of patients with ALS.
Methods Quantitative in-vivo assessment of cerebellar lobules has been investigated in 66 non-demented patients with ALS and 28 healthy controls. Pathologic C9orf72 repeated expansion was found in 13 patients. Mild cognitive and/or behavioral impairment was diagnosed in 22 C9orf72 negative ALS patients. Measures of cortical volume (CV) and cortical thickness (CT) of cerebellar lobules of all participants were used for Principal Component Analysis (PCA) to identify clusters of lobular measures highly correlated with each other. PCA outcomes were used for between group comparisons and correlation analyses with neuropsychological and clinical features.
Results Disease severity measured with ALS functional rating scale and index of disease progression rate significantly correlated with CV reduction of the second PCA cluster loading CV measures of anterior lobules. In all patients, cognitive impairment, measured with verbal fluency, was related to CV reduction of the third cluster comprising posterior lobules. No specific cortical thinning or volume reduction of cerebellar clustering patterns could be detected in ALS subgroups.
Conclusion Our data show that specific patterns of subregional cerebellar involvement are associated with physical disability or cognitive impairment in ALS, in line with the topographic organization of the cerebellum. However, there was no specific correlation between cerebellar degeneration and cognitive syndromes or C9orf72 mutations.

Keywords: Cerebellum, Amyotrophic Lateral Sclerosis (ALS), cortical thickness, Cortical volume, cognitive impairment

Received: 15 Feb 2019; Accepted: 17 Apr 2019.

Edited by:

FOTEINI CHRISTIDI, National and Kapodistrian University of Athens Medical School, Greece

Reviewed by:

Mattia Siciliano, Second University of Naples, Italy
Michael Hornberger, University of East Anglia, United Kingdom  

Copyright: © 2019 Consonni, Dalla Bella, Anna, Pinardi, Demichelis, Porcu, Gellera, Pensato, Cappa, Bruzzone, Lauria and Ferraro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Monica Consonni, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy,
Dr. Chiara Pinardi, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy,