Skip to main content
SpringerLink
Log in

Cognitive and Psychiatric Evaluation in SYNE1 Ataxia

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

SYNE1 gene mutations were identified as a cause of late-onset pure cerebellar syndrome. Non-cerebellar symptoms, including cognitive impairment, were already described in this condition. The aim of this study was to perform a detailed cognitive and psychiatric description of patients with SYNE1 gene mutations. We performed neuropsychological and psychiatric evaluations of six patients with SYNE1 ataxia and compared their performance with 18 normal controls paired for age and education level. SYNE1 ataxia patients present cognitive dysfunction, characterized by impairment in attention and processing speed domains. Otherwise, the psychiatric assessment reported low levels of overall behavioral symptoms with only some minor anxiety-related complaints. Although this is a small sample of patients, these results suggest that SYNE1 ataxia patients may represent a model to investigate effects of cerebellar degeneration in higher hierarchical cognitive functions. For further studies, abstract thinking impairment in schizophrenia may be related to dysfunction in cerebellum pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abrahão A, Pedroso J, Braga-Neto P, Bor-Seng-Shu E, Aguiar P, Barsottini O. Milestones in Friedreich ataxia: more than a century and still learning. Neurogenetics. 2015;16(3):151–60.

    Article  PubMed  Google Scholar 

  2. Teive H, Ashizawa T. Primary and secondary ataxias. Curr Opin Neurol. 2015;28(4):413–22.

    Article  PubMed  PubMed Central  Google Scholar 

  3. van de Warrenburg B, Schouten M, de Bot S, Vermeer S, Meijer R, Pennings M, et al. Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene-disease associations and unanticipated rare disorders. Eur J Hum Genet. 2016;24(10):1460–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gros-Louis F, Dupre N, Dion P, Fox M, Laurent S, Verreault S, et al. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat Genet. 2007;39(1):80–5.

    Article  CAS  PubMed  Google Scholar 

  5. Noreau A, Bourassa C, Szuto A, Levert A, Dobrzeniecka S, Gauthier J, et al. SYNE1 mutations in autosomal recessive cerebellar ataxia. JAMA Neurol. 2013;70(10):1296–31.

    PubMed  Google Scholar 

  6. Gama MT, Houle G, Noreau A, Dionne-Laporte A, Dion P, Rouleau G, et al. SYNE1 mutations cause autosomal-recessive ataxia with retained reflexes in Brazilian patients. Mov Disord. 2016;31(11):1754–6.

    Article  CAS  PubMed  Google Scholar 

  7. Schmahmann J, Sherman J. The cerebellar cognitive affective syndrome. Brain. 1998;121(Pt 4):561–79.

    Article  PubMed  Google Scholar 

  8. Schmahmann J. The cerebellum and cognition. Neurosci Lett. 2018;30467(18):1.

    Google Scholar 

  9. Braga-Neto P, Pedroso J, Alessi H, Dutra L, Felicio A, Minett T, et al. Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features. Cerebellum. 2012;11(2):549–56.

    Article  PubMed  Google Scholar 

  10. Braga-Neto P, Dutra L, Pedroso J, Barsottini O. Cognitive dysfunction in spinocerebellar ataxia type 3: variable topographies and patterns. Mov Disord. 2014;29(1):156–7.

    Article  PubMed  Google Scholar 

  11. Kawai Y, Suenaga M, Watanabe H, Sobue G. Cognitive impairment in spinocerebellar degeneration. Eur Neurol. 2009;61(5):257–68.

    Article  CAS  PubMed  Google Scholar 

  12. Laforce R, Jr B, Bouchard J, Rouleau G, Bouchard R, Dupre N. Cognitive impairment in ARCA-1, a newly discovered pure cerebellar ataxia syndrome. Cerebellum. 2010;9(3):433–53.

    Article  Google Scholar 

  13. Frank B, Maschke M, Groetschel H, Berner M, Schoch B, Hein-Kropp C, et al. Aphasia and neglect are uncommon in cerebellar disease: negative findings in a prospective study in acute cerebellar stroke. Cerebellum. 2010;9(4):556–66.

    Article  PubMed  Google Scholar 

  14. Richter S, Gerwig M, Aslan B, Wilhelm H, Schoch B, Dimitrova A, et al. Cognitive functions in patients with MR-defined chronic focal cerebellar lesions. J Neurol. 2007;254(9):1193–203.

    Article  PubMed  Google Scholar 

  15. Malloy-Diniz L, Lasmar V, Gazinelli L, Fuentes D, Salgado J. O teste de aprendizagem auditivo-verbal de rey: normas para uma população brasileira. Rev Bras Neurol. 2000;36:79–83.

    Google Scholar 

  16. Oliveira MS, Rigoni MS. Figuras Complexas de Rey: Teste de cópia e de reprodução de memória de figuras geométricas complexas [Rey's Complex Figures: Test copy and reproduction memory complex geometries]. São Paulo, SP: Casa do Psicólogo; 2010.

  17. D’Elia L, Satz P, Uchiyama C, White T. In: Rabelo I, Pacanaro S, Rossetti M, Leme I, editors. Teste de trilhas coloridas: manual profissional. 1st ed. Casa do Psicólogo: São Paulo; 2010.

    Google Scholar 

  18. Nascimento E. Escala de inteligência para adultos: adaptação e padronização de uma amostra brasileira - WAIS III. 1a ed. São Paulo: Casa do Psicólogo; 2004.

  19. Brucki S, Malheiros S, Okamoto I, Bertolucci P. Normative data on the verbal fluency test in the animal category in our milieu. Arq Neuropsiquiatr. 1997;55(1):56–61.

    Article  CAS  PubMed  Google Scholar 

  20. Brucki S, Rocha M. Category fluency test: effects of age, gender and education on total scores, clustering and switching in Brazilian Portuguese-speaking subjects. Braz J Med Biol Res. 2004;37(12):1771–7.

    Article  CAS  PubMed  Google Scholar 

  21. Campanholo K, Romão M, Machado M, Serrao V, Coutinho D, Benute G, et al. Performance of an adult Brazilian sample on the trail making test and stroop test. Dement Neuropsychol. 2014;8(1):26–31.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Miotto E, Sato J, Lucia M, Camargo C, Scaff M. Development of an adapted version of the Boston Naming Test for Portuguese speakers. Rev Bras Psiquiatr. 2010;32(3):279–82.

    Article  PubMed  Google Scholar 

  23. First MB, Spitzer RL, Gibbon M, Williams J. Structured Clinical interview for DSM-IV axis I disorders—patient edition (SCID-I/P, version 2.0). New York: Biometrics Research Department; 1996.

  24. Higuchi C, Ortiz B, Berberian A, Noto A, Cordeiro Q, Belangero S, et al. Factor structure of the Positive and Negative Syndrome Scale (PANSS) in Brazil—convergent validation of the Brazilian version. Rev Bras Psiquiatr. 2014;36:336–9.

    Article  PubMed  Google Scholar 

  25. Kay S, Flszbein A, Opfer L. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76.

    Article  CAS  PubMed  Google Scholar 

  26. Stefanis N, Hanssen M, Smirnis N, Avramopoulos D, Evdokimidis I, Stefanis C, et al. Evidence that three dimensions of psychosis have a distribution in the general population. Psychol Med. 2002;32:347–358.1.

    Article  CAS  PubMed  Google Scholar 

  27. Williams J. Standardizing the Hamilton Depression Rating Scale: past, present, and future. Eur Arch Psychiatry Clin Neurosci. 2001;251(suppl 2):II6–II12.

    Article  PubMed  Google Scholar 

  28. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–5.

    Article  CAS  PubMed  Google Scholar 

  29. Young R, Biggs J, Ziegler V, Meyer D. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133(5):429–35.

    Article  CAS  PubMed  Google Scholar 

  30. Guy W. Clinical global impression scale. The ECDEU assessment manual for psychopharmacology-revised Volume DHEW Publ No ADM. 1996;76(338):218–22.

    Google Scholar 

  31. Endicott J, Spitzer R, Fleiss J, Cohen J. The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry. 1976;33(6):766–71.

    Article  CAS  Google Scholar 

  32. Stoodley C, Valera E, Schmahmann J. Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage. 2012;59(2):1560–70.30.

    Article  PubMed  Google Scholar 

  33. Schmahmann J, Weilburg J, Sherman J. The neuropsychiatry of the cerebellum—insights from the clinic. Cerebellum. 2007;6(3):254–67162524.

    Article  PubMed  Google Scholar 

  34. Schmahmann J. The cerebrocerebellar system: anatomic substrates of the cerebellar contribution to cognition and emotion. Int Rev Psychiatry. 2001;13:247–60.

    Article  Google Scholar 

  35. Heath R, Franklin D, Shraberg D. Gross pathology of the cerebellum in patients diagnosed and treated as functional psychiatric disorders. J Nerv Ment Dis. 1979;167:585–92.

    Article  CAS  PubMed  Google Scholar 

  36. Heath R, Harper J. Ascending projections of the cerebellar fastigial nucleus to the hippocampus, amygdala, and other temporal lobe sites: evoked potential and histological studies in monkeys and cats. Exp Neurol. 1974;45:268–87.

    Article  CAS  PubMed  Google Scholar 

  37. Nashold D, Slaughter J. Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg. 1969;31:172–86.

    Article  PubMed  Google Scholar 

  38. Van Overwalle F, Baetens K, Marien P, Vandekerckhove M. Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies. Neuroimage. 2014;86:554–72.

    Article  PubMed  Google Scholar 

  39. Wiethoff S, Hersheson J, Bettencourt C, Wood N, Houlden H. Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations. J Neurol. 2016;263(8):1503–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mademan I, Harmuth F, Giordano I, Timmann D, Magri S, Deconinck T, et al. Multisystemic SYNE1 ataxia: confirming the high frequency and extending the mutational and phenotypic spectrum. Brain. 2016;139(8):32–46.

    Article  Google Scholar 

  41. Stoodley C, Schmahmann J. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46(7):831–44.33.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Braga-Neto P, Dutra L, Pedroso J, Felicio A, Alessi H, Santos-Galduroz R, et al. Cognitive deficits in Machado-Joseph disease correlate with hypoperfusion of visual system areas. Cerebellum. 2012;11(4):1037–44.

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Maria Thereza Drumond Gama and Pedro Braga-Neto contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Ataxia Unit, Universidade Federal de São Paulo, Sao Paulo, Brazil

    Maria Thereza Drumond Gama, Livia Almeida Dutra, Helena Alessi, Lilia Alves Maria, Orlando G. P. Barsottini & José Luiz Pedroso

  2. Division of Neurology, Department of Clinical Medicine, Universidade Federal do Ceará, Fortaleza, Brazil

    Pedro Braga-Neto

  3. Center of Health Sciences, Universidade Estadual do Ceará, Fortaleza, Brazil

    Pedro Braga-Neto

  4. Department of Psychiatry, Universidade Federal de São Paulo, Sao Paulo, Brazil

    Ary Araripe Gadelha & Bruno Bertolucci Ortiz

  5. Division of Endocrinology and Metabolism, Laboratory of Molecular & Translational Endocrinology (LEMT), Universidade Federal de São Paulo, Sao Paulo, Brazil

    Ilda Kunii, Silvia Regina Correia-Silva & Magnus R. Dias da Silva

  6. Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Canada

    Patrick A. Dion & Guy A. Rouleau

  7. Department of Neurology, State University of Campinas, Campinas, Sao Paulo, Brazil

    Marcondes Cavalcante França Jr

Authors
  1. Maria Thereza Drumond Gama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro Braga-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Livia Almeida Dutra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helena Alessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lilia Alves Maria
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ary Araripe Gadelha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bruno Bertolucci Ortiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ilda Kunii
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Silvia Regina Correia-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Magnus R. Dias da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Patrick A. Dion
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Guy A. Rouleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marcondes Cavalcante França Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Orlando G. P. Barsottini
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. José Luiz Pedroso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Orlando G. P. Barsottini.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Statement

Patients signed an informed consent and allowed publication of this data.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gama, M.T.D., Braga-Neto, P., Dutra, L.A. et al. Cognitive and Psychiatric Evaluation in SYNE1 Ataxia. Cerebellum 18, 731–737 (2019). https://doi.org/10.1007/s12311-019-01033-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-019-01033-5

Keywords

Search

Navigation