The Cerebellum

, Volume 17, Issue 2, pp 204–212 | Cite as

Personality and Neuropsychological Profiles in Friedreich Ataxia

  • Sabrina Sayah
  • Jean-Yves Rotgé
  • Hélène Francisque
  • Marcela Gargiulo
  • Virginie Czernecki
  • Damian Justo
  • Khadija Lahlou-Laforet
  • Valérie Hahn
  • Massimo Pandolfo
  • Antoine Pelissolo
  • Philippe Fossati
  • Alexandra Durr
Original Paper


Friedreich ataxia, an autosomal recessive mitochondrial disease, is the most frequent inherited ataxia. Many studies have attempted to identify cognitive and affective changes associated with the disease, but conflicting results have been obtained, depending on the tests used and because many of the samples studied were very small. We investigated personality and neuropsychological characteristics in a cohort of 47 patients with genetically confirmed disease. The neuropsychological battery assessed multiple cognition domains: processing speed, attention, working memory, executive functions, verbal memory, vocabulary, visual reasoning, emotional recognition, and social cognition. Personality was assessed with the Temperament and Character Inventory, and depressive symptoms were assessed with the Beck Depression Inventory. We found deficits of sustained attention, processing speed, semantic capacities, and verbal fluency only partly attributable to motor deficit or depressed mood. Visual reasoning, memory, and learning were preserved. Emotional processes and social cognition were unimpaired. We also detected a change in automatic processes, such as reading. Personality traits were characterized by high persistence and low self-transcendence. The mild cognitive impairment observed may be a developmental rather than degenerative problem, due to early cerebellum dysfunction, with the impairment of cognitive and emotional processing. Disease manifestations at crucial times for personality development may also have an important impact on personality traits.


Friedreich ataxia Cerebellum Neuropsychology Personality Emotional recognition Social cognition 



This study is an ancillary substudy of EFACTS (European Friedreich Ataxia Consortium for Translational Studies, NCT02069509) coordinated by M. Pandolfo. We thank the participants for their patience, and Aurelie Guignebert, Martine Frischmann, and Mathieu Anheim for fruitful initial discussions.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: classical and atypical phenotypes. J Neurochem. 2013;126(s1):103–17.CrossRefPubMedGoogle Scholar
  2. 2.
    Pousset F, Legrand L, Monin M-L, Ewenczyk C, Charles P, Komajda M, et al. A 22-year follow-up study of long-term cardiac outcome and predictors of survival in Friedreich ataxia. JAMA Neurol. 2015;72(11):1334–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Campuzano V, Montermini L, Moltò MD, Pianese L, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271(5254):1423.CrossRefPubMedGoogle Scholar
  4. 4.
    Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S, et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet. 1997;6(11):1771–80.CrossRefPubMedGoogle Scholar
  5. 5.
    Cossée M, Dürr A, Schmitt M, Dahl N, Trouillas P, Allinson P, et al. Friedreich’s ataxia: point mutations and clinical presentation of compound heterozygotes. Ann Neurol. 1999;45(2):200–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Anheim M, Mariani L-L, Calvas P, Cheuret E, Zagnoli F, Odent S, et al. Exonic deletions of FXN and early-onset Friedreich ataxia. Arch Neurol. 2012;69(7):912–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med. 1996;335(16):1169–75.CrossRefPubMedGoogle Scholar
  8. 8.
    Lecocq C, Charles P, Azulay J-P, Meissner W, Rai M, N’Guyen K, et al. Delayed-onset Friedreich’s ataxia revisited. Mov Disord. 2016;31(1):62–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Koeppen AH, Mazurkiewicz JE. Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol. 2013;72(2):78–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain J Neurol. 1998;121(Pt 4):561–79.CrossRefGoogle Scholar
  11. 11.
    Manto M, Mariën P. Schmahmann’s syndrome—identification of the third cornerstone of clinical ataxiology. Cerebellum Ataxias. 2015;2:2.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum—insights from the clinic. Cerebellum. 2007;6(3):254–67.CrossRefPubMedGoogle Scholar
  13. 13.
    Fiske ST, Taylor SE. Social cognition: from brains to culture. 2nd edition. Los Angeles: Sage; 2013.Google Scholar
  14. 14.
    Hoche F, Guell X, Sherman JC, Vangel MG, Schmahmann JD. Cerebellar contribution to social cognition. Cerebellum. 2015; 1–12.Google Scholar
  15. 15.
    Van Overwalle F, Baetens K, Mariën P, Vandekerckhove M. Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies. NeuroImage. 2014;86:554–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Van Overwalle F, D’aes T, Mariën P. Social cognition and the cerebellum: a meta-analytic connectivity analysis. Hum Brain Mapp. 2015;36(12):5137–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Mantovan MC, Martinuzzi A, Squarzanti F, Bolla A, Silvestri I, Liessi G, et al. Exploring mental status in Friedreich’s ataxia: a combined neuropsychological, behavioral and neuroimaging study. Eur J Neurol Off J Eur Fed Neurol Soc. 2006;13(8):827–35.Google Scholar
  18. 18.
    Nieto A, Correia R, de Nóbrega E, Montón F, Hess S, Barroso J. Cognition in Friedreich ataxia. Cerebellum. 2012;11(4):834–44.CrossRefPubMedGoogle Scholar
  19. 19.
    Nieto A, Correia R, de Nóbrega E, Montón F, Barroso J. Cognition in late-onset Friedreich ataxia. Cerebellum. 2013;12(4):504–12.CrossRefPubMedGoogle Scholar
  20. 20.
    Wollmann T, Barroso J, Monton F, Nieto A. Neuropsychological test performance of patients with Friedreich’s ataxia. J Clin Exp Neuropsychol. 2002;24(5):677–86.CrossRefPubMedGoogle Scholar
  21. 21.
    de Nóbrega E, Nieto A, Barroso J, Montón F. Differential impairment in semantic, phonemic, and action fluency performance in Friedreich’s ataxia: possible evidence of prefrontal dysfunction. J Int Neuropsychol Soc. 2007;13(6):944–52.CrossRefPubMedGoogle Scholar
  22. 22.
    Dogan I, Tinnemann E, Romanzetti S, Mirzazade S, Costa AS, Werner CJ, et al. Cognition in Friedreich’s ataxia: a behavioral and multimodal imaging study. Ann Clin Transl Neurol. 2016;3(8):572–87.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cloninger CR, Przybeck TR, Svrakic DM. The Temperament and Character Inventory (TCI): a guide to its development and use. Center for Psychobiology of Personality, Washington University St. Louis; 1994.Google Scholar
  24. 24.
    Pélissolo A, Lépine J-P. Normative data and factor structure of the Temperament and Character Inventory (TCI) in the French version. Psychiatry Res. 2000;94(1):67–76.CrossRefPubMedGoogle Scholar
  25. 25.
    Raven JC, Court JH. Raven’s progressive matrices and vocabulary scales. Oxford: Oxford Psychologists Press; 1998.Google Scholar
  26. 26.
    Deltour JJ. Echelle de vocabulaire de Mill Hill de JC Raven. Adapt Fr Normes Eur Mill Hill Stand Progress Matrices Raven PM38 Braine--Château Ed L’application Tech Mod. 1993.Google Scholar
  27. 27.
    Rieu D, Bachoud-Lévi A-C, Laurent A, Jurion E, Dalla BG. Adaptation française du «Hopkins verbal learning test». Rev Neurol (Paris). 2006;162(6):721–8.CrossRefGoogle Scholar
  28. 28.
    Gronwall D, Sampson H. The psychological effects of concussion. New York: Oxford University Press; 1974.Google Scholar
  29. 29.
    Naegele B, Mazza S. Test d’attention auditive soutenue PASAT modifié. De Boeck Supérieur: Louvain-La-Neuve; 2013.Google Scholar
  30. 30.
    Golden CJ. Stroop color and word test. Chicago: Stoelting Co.; 1978.Google Scholar
  31. 31.
    Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol. 1935;18(6):643.CrossRefGoogle Scholar
  32. 32.
    Gregory C, Lough S, Stone V, Erzinclioglu S, Martin L, Baron-Cohen S, et al. Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer’s disease: theoretical and practical implications. Brain. 2002;125(4):752–64.CrossRefPubMedGoogle Scholar
  33. 33.
    Stone VE, Baron-Cohen S, Knight RT. Frontal lobe contributions to theory of mind. J Cogn Neurosci. 1998;10(5):640–56.CrossRefPubMedGoogle Scholar
  34. 34.
    Funkiewiez A, Bertoux M, de Souza LC, Lévy R, Dubois B. The SEA (Social cognition and Emotional Assessment): a clinical neuropsychological tool for early diagnosis of frontal variant of frontotemporal lobar degeneration. Neuropsychology. 2012;26(1):81.CrossRefPubMedGoogle Scholar
  35. 35.
    Ekman P, Friesen WV. Pictures of facial affect. Palo Alto: Consulting Psychologists Press; 1975.Google Scholar
  36. 36.
    Beck AT, Steer RA, Brown GK. Inventaire de dépression de Beck. 2ème édition ed. Paris: les Éditions du centre de psychologie appliquée; 1998.Google Scholar
  37. 37.
    Klopper F, Delatycki MB, Corben LA, Bradshaw JL, Rance G, Georgiou-Karistianis N. The test of everyday attention reveals significant sustained volitional attention and working memory deficits in Friedreich ataxia. J Int Neuropsychol Soc. 2011;17(01):196–200.CrossRefPubMedGoogle Scholar
  38. 38.
    Vlachos F, Papathanasiou I, Andreou G. Cerebellum and reading. Folia Phoniatr Logop. 2007;59(4):177–83.CrossRefPubMedGoogle Scholar
  39. 39.
    Travis KE, Leitner Y, Feldman HM, Ben-Shachar M. Cerebellar white matter pathways are associated with reading skills in children and adolescents. Hum Brain Mapp. 2015;36(4):1536–53.CrossRefPubMedGoogle Scholar
  40. 40.
    De NÓbrega É, Nieto A, Barroso J, MontÓn F. Differential impairment in semantic, phonemic, and action fluency performance in Friedreich’s ataxia: possible evidence of prefrontal dysfunction. J Int Neuropsychol Soc. 2007;13(06):944–52.CrossRefPubMedGoogle Scholar
  41. 41.
    Nachbauer W, Bodner T, Boesch S, Karner E, Eigentler A, Neier L, et al. Friedreich ataxia: executive control is related to disease onset and GAA repeat length. Cerebellum. 2014;13(1):9–16.CrossRefPubMedGoogle Scholar
  42. 42.
    White M, Lalonde R, Botez-Marquard T. Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich’s ataxia. Acta Neurol Scand. 2000;102(4):222–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Cloninger CR, Zohar AH. Personality and the perception of health and happiness. J Affect Disord. 2011;128(1):24–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry. 1993;50(12):975–90.CrossRefPubMedGoogle Scholar
  45. 45.
    Kaasinen V, Maguire RP, Kurki T, Brück A, Rinne JO. Mapping brain structure and personality in late adulthood. NeuroImage. 2005;24(2):315–22.CrossRefPubMedGoogle Scholar
  46. 46.
    Jokela M, Hakulinen C, Singh-Manoux A, Kivimäki M. Personality change associated with chronic diseases: pooled analysis of four prospective cohort studies. Psychol Med. 2014;44(12):2629–40.CrossRefPubMedGoogle Scholar
  47. 47.
    Boz C, Gazioglu S, Altunayoglu V, Hocaoglu C. Effect of serotonergic antidepressant therapy on temperament and character scales in patients with chronic tension-type headache. Psychiatry Clin Neurosci. 2007;61(5):534–42.CrossRefPubMedGoogle Scholar
  48. 48.
    Conrad R, Schilling G, Bausch C, Nadstawek J, Wartenberg HC, Wegener I, et al. Temperament and character personality profiles and personality disorders in chronic pain patients. Pain. 2007;133(1–3):197–209.CrossRefPubMedGoogle Scholar
  49. 49.
    Kahraman H, Orhan FO, Sucakli MH, Ozer A, Koksal N, Sen B. Temperament and character profiles of male COPD patients. J Thorac Dis. 2013;5(4):406–13.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Dolan RJ. A cognitive affective role for the cerebellum. Brain. 1998;121(4):545–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Picerni E, Petrosini L, Piras F, Laricchiuta D, Cutuli D, Chiapponi C, et al. New evidence for the cerebellar involvement in personality traits. Front Behav Neurosci. 2013;7:133.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Laricchiuta D, Petrosini L, Piras F, Macci E, Cutuli D, Chiapponi C, et al. Linking novelty seeking and harm avoidance personality traits to cerebellar volumes. Hum Brain Mapp. 2014;35(1):285–96.CrossRefPubMedGoogle Scholar
  53. 53.
    Petrosini L, Cutuli D, Picerni E, Laricchiuta D. Cerebellum and personality traits. Cerebellum. 2015;14(1):43–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Reetz K, Dogan I, Hilgers R-D, Giunti P, Mariotti C, Durr A, et al. Progression characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS): a 2 year cohort study. Lancet Neurol. 2016;15(13):1346–54.CrossRefPubMedGoogle Scholar
  55. 55.
    Rezende TJR, Martinez ARM, Faber I, Girotto K, Pedroso JL, Barsottini OG, et al. Structural signature of classical versus late-onset friedreich’s ataxia by multimodality brain MRI. Hum Brain Mapp. 2017;38(8):4157–68.CrossRefPubMedGoogle Scholar
  56. 56.
    Braga-Neto P, Pedroso JL, Alessi H, Dutra LA, Felício AC, Minett T, et al. Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features. Cerebellum. 2012;11(2):549–56.CrossRefPubMedGoogle Scholar
  57. 57.
    Stefanescu MR, Dohnalek M, Maderwald S, Thürling M, Minnerop M, Beck A, et al. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich’s ataxia. Brain. 2015;138(5):1182–97.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sabrina Sayah
    • 1
    • 2
  • Jean-Yves Rotgé
    • 2
    • 3
  • Hélène Francisque
    • 4
  • Marcela Gargiulo
    • 1
    • 5
    • 6
  • Virginie Czernecki
    • 7
  • Damian Justo
    • 8
  • Khadija Lahlou-Laforet
    • 9
  • Valérie Hahn
    • 8
  • Massimo Pandolfo
    • 10
  • Antoine Pelissolo
    • 11
  • Philippe Fossati
    • 2
    • 3
  • Alexandra Durr
    • 1
    • 2
    • 12
  1. 1.AP-HP, Genetic DepartmentPitié-Salpêtrière University HospitalParisFrance
  2. 2.ICM, Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR7225Sorbonne Universités – UPMC Université Paris VI UMR_S1127ParisFrance
  3. 3.AP-HP, Service de PsychiatriePitié-Salpêtrière University HospitalParisFrance
  4. 4.APHP, Hôpitaux Universitaires Saint Louis Lariboisière Fernand-WidalParisFrance
  5. 5.Institut de MyologiePitié-Salpêtrière University HospitalParisFrance
  6. 6.Laboratoire de Psychologie Clinique et Psychopathologie, EA 4056Université Paris Descartes, Sorbonne Paris Cité, Institut de PsychologieParisFrance
  7. 7.AP-HP, Département des Maladies du Système NerveuxPitié-Salpêtrière University HospitalParisFrance
  8. 8.Unité de neurologie de la Mémoire et du LangageCentre Hospitalier Sainte-AnneParisFrance
  9. 9.Unité de Psychologie et Psychiatrie de Liaison et d’UrgencesHôpital Européen Georges Pompidou, Service de Psychiatrie Adulte et du Sujet Agé, Hôpitaux Universitaires Paris-OuestParisFrance
  10. 10.Service de Neurologie, Hôpital ErasmeUniversité Libre de BruxellesBrusselsBelgium
  11. 11.AP-HP, Service de PsychiatrieHôpitaux Universitaires Henri-MondorCréteilFrance
  12. 12.ICM, Institut du Cerveau et de la Moelle épinière, Groupe Hospitalier Pitié-SalpêtrièreParis Cedex 13France

Personalised recommendations