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MR imaging and cognitive correlates of relapsing–remitting multiple sclerosis patients with cerebellar symptoms

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Abstract

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system, frequently associated with cognitive impairments. Damages of the cerebellum are very common features of patients with MS, although the impact of this clinical factor is generally neglected. Recent evidence from our group demonstrated that MS patients with cerebellar damages are characterized by selective cognitive dysfunctions related to attention and language abilities. Here, we aimed at investigating the presence of neuroanatomical abnormalities in relapsing–remitting MS patients with (RR-MSc) and without (RR-MSnc) cerebellar signs. Twelve RR-MSc patients, 14 demographically, clinically, and radiologically, matched RR-MSnc patients and 20 controls were investigated. All patients underwent neuropsychological assessment. After refilling of FLAIR lesions on the 3D T1-weighted images, VBM was performed using SPM8 and DARTEL. A correlation analysis was performed between VBM results and neuropsychological variables characterizing RR-MSc patients. Despite a similar clinical status, RR-MSc patients were characterized by more severe cognitive damages in attention and language domains with respect to RR-MSnc and controls. With respect to controls, RR-MSnc patients were characterized by a specific atrophy of the bilateral thalami that became more widespread (including motor cortex) in the RR-MSc group (FWE < 0.05). However, consistent with their well-defined neuropsychological deficits, RR-MSc group showed atrophies in the prefrontal and temporal cortical areas when directly compared with RR-MSnc group. Our results demonstrated that RR-MS patients having cerebellar signs were characterized by a distinct neuroanatomical profile, mainly involving cortical regions underpinning executive functions and verbal fluency.

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References

  1. Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG (2011) The cerebellar cognitive profile. Brain 134:3669–3683

    Article  Google Scholar 

  2. Schmahmann JD, Pandya DN (1989) Anatomical investigation of projections to the basis pontis from posterior parietal association cortices in rhesus monkey. J Comp Neurol 289:53–73

    Article  PubMed  CAS  Google Scholar 

  3. Middleton FA, Strick PL (2000) Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 31:236–250

    Article  PubMed  CAS  Google Scholar 

  4. Krienen FM, Buckner RL (2009) Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex 19:2485–2497

    Article  PubMed  Google Scholar 

  5. Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, Greicius MD (2009) Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci 29:8586–8594

    Article  PubMed  CAS  Google Scholar 

  6. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive and affective syndrome. Brain 121:561–579

    Article  PubMed  Google Scholar 

  7. Stoodley CJ, Schmahmann JD (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46:831–844

    Article  PubMed  Google Scholar 

  8. Bobholz JA, Rao SM (2003) Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol 16:283–288

    Article  PubMed  Google Scholar 

  9. Amato MP, Zipoli V, Portaccio E (2006) Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci 245:41–46

    Article  PubMed  Google Scholar 

  10. Rot U, Ledinek AH, Jazbec SS (2008) Clinical, magnetic resonance imaging, cerebrospinal fluid and electrophysiological characteristics of the earliest multiple sclerosis. Clin Neurol Neurosurg 110:233–238

    Article  PubMed  Google Scholar 

  11. Valentino P, Cerasa A, Chiriaco C, Nisticò R, Pirritano D, Gioia M, Lanza P, Canino M, Del Giudice F, Gallo O, Condino F, Torchia G, Quattrone A (2009) Cognitive deficits in multiple sclerosis patients with cerebellar symptoms. Mult Scler 15:854–859

    Article  PubMed  CAS  Google Scholar 

  12. Nocentini U, Bozzali M, Spanò B, Cercignani M, Serra L, Basile B, Mannu R, Caltagirone C, De Luca J (2012) Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. Brain Imaging Behav [Epub ahead of print]. doi:10.1007/s11682-012-9170-7

  13. Cerasa A, Passamonti L, Valentino P, Nisticò R, Pirritano D, Gioia MC, Chiriaco C, Mangone G, Perrotta P, Quattrone A (2012) Cerebellar-parietal dysfunctions in multiple sclerosis patients with cerebellar signs. Exp Neurol 237:418–426

    Article  PubMed  CAS  Google Scholar 

  14. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” [review]. Ann Neurol 58:840–846

    Article  PubMed  Google Scholar 

  15. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    Article  PubMed  CAS  Google Scholar 

  16. Steinberg M (1994) Interviewers guide to the structured clinical interview for DSM-IV disorders (SCID). American Psychiatric Press, Washington

    Google Scholar 

  17. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46:1121–1123

    Article  PubMed  CAS  Google Scholar 

  18. Gioia MC, Cerasa A, Liguori M, Passamonti L, Condino F, Vercillo L, Valentino P, Clodomiro A, Quattrone A, Fera F (2007) Impact of individual cognitive profile on visuo-motor reorganization in relapsing–remitting multiple sclerosis. Brain Res 1167:71–79

    Article  PubMed  CAS  Google Scholar 

  19. Cerasa A, Fera F, Gioia MC, Liguori M, Passamonti L, Nicoletti G, Vercillo L, Paolillo A, Clodomiro A, Valentino P, Quattrone A (2006) Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing–remitting multiple sclerosis. Brain Res Bull 69:597–605

    Article  PubMed  Google Scholar 

  20. Cerasa A, Bilotta E, Augimeri A, Cherubini A, Pantano P, Zito G, Lanza P, Valentino P, Gioia MC, Quattrone A (2012) A cellular neural network methodology for the automated segmentation of multiple sclerosis lesions. J Neurosci Method 203:193–199

    Article  Google Scholar 

  21. Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38:95–113

    Article  PubMed  Google Scholar 

  22. Mesaros S, Rocca MA, Absinta M, Ghezzi A, Milani N, Moiola L, Veggiotti P, Comi G, Filippi M (2008) Evidence of thalamic gray matter loss in pediatric multiple sclerosis. Neurology 70:1107–1112

    Article  PubMed  CAS  Google Scholar 

  23. Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci USA 97:11050–11055

    Article  PubMed  CAS  Google Scholar 

  24. Cerasa A, Messina D, Nicoletti G, Novellino F, Lanza P, Condino F, Arabia G, Salsone M, Quattrone A (2009) Cerebellar atrophy in essential tremor using an automated segmentation method. Am J Neuroradiol 30:1240–1243

    Article  PubMed  CAS  Google Scholar 

  25. Ceccarelli A, Rocca MA, Pagani E, Colombo B, Martinelli V, Comi G, Filippi MA (2008) A voxel-based morphometry study of grey matter loss in MS patients with different clinical phenotypes. Neuroimage 42:315–322

    Article  PubMed  Google Scholar 

  26. Stoodley CJ (2012) The cerebellum and cognition: evidence from functional imaging studies. Cerebellum 11:352–365

    Article  PubMed  Google Scholar 

  27. Fabbro F, Tavano A, Corti S, Bresolin N, De Fabritiis P, Borgatti R (2004) Long-term neuropsychological deficits after cerebellar infarctions in two young adult twins. Neuropsychologia 42:536–545

    Article  PubMed  CAS  Google Scholar 

  28. Ackermann H, Mathiak K, Riecker A (2007) The contribution of the cerebellum to speech production and speech perception: clinical and functional imaging data. Cerebellum 6:202–213

    Article  PubMed  Google Scholar 

  29. Stoodley CJ, Schmahmann JD (2009) Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 44:489–501

    Article  PubMed  Google Scholar 

  30. Lazeron RH, Rombouts SA, de Sonneville L, Barkhof F, Scheltens P (2003) A paced visual serial addition test for fMRI. J Neurol Sci 213:29–34

    Article  PubMed  Google Scholar 

  31. Deloire MS, Salort E, Bonnet M, Arimone Y, Boudineau M, Amieva H, Barroso B, Ouallet JC, Pachai C, Galliaud E, Petry KG, Dousset V, Fabrigoule C, Brochet B (2005) Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76:519–526

    Article  PubMed  CAS  Google Scholar 

  32. Rossi F, Giorgio A, Battaglini M, Stromillo ML, Portaccio E, Goretti B, Federico A, Hakiki B, Amato MP, De Stefano N (2012) Relevance of brain lesion location to cognition in relapsing multiple sclerosis. PLoS ONE 7:e44826. doi:10.1371/journal.pone.0044826

    Article  PubMed  CAS  Google Scholar 

  33. Chen SH, Desmond JE (2005) Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks. Neuroimage 24:332–338

    Article  PubMed  Google Scholar 

  34. Desmond JE, Chen SH, De Rosa E, Pryor MR, Pfefferbaum A, Sullivan EV (2003) Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study. Neuroimage 19:1510–1520

    Article  PubMed  Google Scholar 

  35. Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM, Zijdenbos A, Evans AC, Giedd JN, Rapoport JL (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 288:1740–1748

    Article  PubMed  Google Scholar 

  36. Bonnet MC, Allard M, Dilharreguy B, Deloire M, Petry KG, Brochet B (2010) Cognitive compensation failure in multiple sclerosis. Neurology 75:1241–1248

    Article  PubMed  CAS  Google Scholar 

  37. Clausi S, Bozzali M, Leggio MG, Di Paola M, Hagberg GE, Caltagirone C, Molinari M (2009) Quantification of gray matter changes in the cerebral cortex after isolated cerebellar damage: a voxel-based morphometry study. Neuroscience 162:827–835

    Article  PubMed  CAS  Google Scholar 

  38. Kutzelnigg A, Faber-Rod JC, Bauer J, Lucchinetti CF, Sorensen PS, Laursen H, Stadelmann C, Brück W, Rauschka H, Schmidbauer M, Lassmann H (2007) Widespread demyelination in the cerebellar cortex in multiple sclerosis. Brain Pathol 17:38–44

    Article  PubMed  Google Scholar 

  39. Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor R, Barker GJ, Thompson AJ, Miller DH (2004) Progressive grey matter atrophy in clinically early relapsing–remitting multiple sclerosis. Mult Scler 10:387–391

    Article  PubMed  CAS  Google Scholar 

  40. Rudick RA, Lee JC, Nakamura K, Fisher E (2009) Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci 282:106–111

    Article  PubMed  Google Scholar 

  41. Cerasa A, Gioia MC, Valentino P, Nisticò R, Chiriaco C, Pirritano D, Tomaiuolo F, Mangone G, Trotta M, Talarico T, Bilotti G, Quattrone A (2012) Computer-assisted cognitive rehabilitation of attention deficits for multiple sclerosis: a randomized trial with fMRI correlates. Neurorehabil Neural Repair doi:10.1177/1545968312465194

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Acknowledgements

This study has been supported by FISM—Fondazione Italiana Sclerosi Multipla—Cod. 2010/R/11.

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The authors declare that they have no conflict of interest.

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Correspondence to Antonio Cerasa or Aldo Quattrone.

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Cerasa, A., Valentino, P., Chiriaco, C. et al. MR imaging and cognitive correlates of relapsing–remitting multiple sclerosis patients with cerebellar symptoms. J Neurol 260, 1358–1366 (2013). https://doi.org/10.1007/s00415-012-6805-y

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  • DOI: https://doi.org/10.1007/s00415-012-6805-y

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