Skip to main content

Advertisement

Log in

An overview of the patient with ataxia

  • ENS TEACHING REVIEW
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Ataxia, a neurological sign characterized by the incoordination of voluntary movements, is the most prominent manifestation of cerebellar disease. The cardinal features of cerebellar dysfunction involve disturbances of stance, gait, eye movements, muscle tone, skilled movements, and speech. Classification and differential diagnosis of ataxic syndromes have intrinsic complexity owing to the variability in phenotypic presentations and in etiologies, which include trauma, toxic and metabolic causes, neoplasms, immune mechanisms, and genetic diseases. Pure cerebellar symptoms are rarely observed, while the clinical picture of both genetic and sporadic ataxia syndromes is sometimes complicated by the presence of extracerebellar neurological or multisystem extraneural pathology. Clinical presentation and assessment of the patients together with classification, genetic aspects, and principles in differential diagnosis of ataxias are briefly reviewed.

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

Access this article

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. Bertini E, des Portes V, Zanni G, et al. (2000) X-linked congenital ataxia: a clinical and genetic study. Am J Med Genet 92:53–56

    CAS  PubMed  Google Scholar 

  2. Bomar JM, Benke PJ, Slattery E, et al. (2003) Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Nature Genet 35:264–269

    CAS  PubMed  Google Scholar 

  3. Brazis PW, Masdeu JC, Biller J (2001) Cerebellum. In: Localization in clinical neurology. Lippincott Williams and Wilkins. Philadelphia, USA, pp 371–386

  4. Brice A (1998) Unstable mutations and neurodegenerative disorders. J Neurol 245:505–510

    CAS  PubMed  Google Scholar 

  5. Browne DL, Gancher ST, Nutt JG, et al. (1994) Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nature Genet 8:136–140

    CAS  PubMed  Google Scholar 

  6. Brunberg JA, Jacquemont S, Hagerman RJ, et al. (2002) Fragile X permutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunctions. AM J Neuroradiol 23:1760–1771

    Google Scholar 

  7. Brusco A, Gellera C, Cagnoli C, et al. (2004) Molecular genetics of hereditary ataxia. Arch Neurol 61:727–733

    PubMed  Google Scholar 

  8. Brussino A, Gellera C, Saluto A, et al. (2005) FMR1 gene premutation is a frequent cause of late onset sporadic cerebellar ataxia. Neurology 64:145–147

    CAS  PubMed  Google Scholar 

  9. Bryer A, Krause A, Bill P, et al. (2003) The hereditary adult-onset ataxias in South Africa. J Neurol Sci 216:47–54

    PubMed  Google Scholar 

  10. Bürk K, Fetter M, Abele M, et al. (1999) Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. J Neurol 246:789–797

    PubMed  Google Scholar 

  11. Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M (2001) Gluten sensitivity in sporadic and hereditary cerebellar ataxia. Ann Neurol 49:540–543

    CAS  PubMed  Google Scholar 

  12. Buttner N, Geschwind D, Jen J, et al. (1998) Oculomotor phenotypes in autosomal dominant ataxias. Arch Neurol 55:1353–1357

    CAS  PubMed  Google Scholar 

  13. Campuzano V, Montermini L, Moltò MD, et al. (1996) Friedreich’s Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion. Science 271:1423–1427

    CAS  PubMed  Google Scholar 

  14. Cavalier L, Ouahchi K, Kayden HJ, et al. (1998) Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet 62:301–310

    CAS  PubMed  Google Scholar 

  15. Coesmans M, Sillevis Smitt PA, Linden DJ, et al. (2002) Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol 53:325–336

    Google Scholar 

  16. Cogan D (1953) A type of congenital ocular motor apraxia presenting jerky head movements. Am J Ophthalmol 36:433–441

    CAS  PubMed  Google Scholar 

  17. De Michele G, Coppola G, Cocozza S, Filla A (2004) A pathogenetic classification of hereditary ataxias: Is the time ripe? J Neurol 251:913–922

    PubMed  Google Scholar 

  18. Di Donato S, Gellera C, Mariotti C (2001) The complex clinical and genetic classification of inherited ataxias. II Autosomal recessive ataxias. Neurol Sci 22:219–228

    CAS  PubMed  Google Scholar 

  19. Engert JC, Berubè P, Mercier J, et al. (2000) ARSACS, a spastic ataxia common in northeastern Canada, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet 24:120–125

    Article  CAS  PubMed  Google Scholar 

  20. Everett CM, Wood NW (2004) Trinucleotide repeats and neurodegenerative disease. Brain 127:2385–2405

    CAS  PubMed  Google Scholar 

  21. Ferland RJ, Eyaid W, Collura RV, et al. (2004) Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nature Genet 36:1008–1013

    CAS  PubMed  Google Scholar 

  22. Furman JM, Perlman S, Baloh RW (1983) Eye movements in Friedreich’s ataxia. Arch Neurol 40:343–346

    CAS  PubMed  Google Scholar 

  23. Gellera C, Pareyson D, Castellotti B, et al. (1997) Very late onset Friedreich’s ataxia without cardiomyopathy is associated with limited GAA expansion in the X25 gene. Neurology 49:1153–1155

    CAS  PubMed  Google Scholar 

  24. Hagerman RJ, Leehey M, Heinrichs W, et al. (2001) Intention tremor, parkinsonism and generalized brain atrophy in male carriers of fragile X Neurology 57:127–130

    CAS  PubMed  Google Scholar 

  25. Harding AE (1983) Classification of hereditary ataxias and paraplegias. Lancet 1:1151–1155

    CAS  PubMed  Google Scholar 

  26. Harding AE (1993) Clinical features and classification of inherited ataxias. Adv Neurol 61:1–14

    CAS  PubMed  Google Scholar 

  27. Jen JC, Baloh RW (2002) Genetics of episodic ataxia. In: Fahn et al. (eds) Advances in Neurology, Myoclonus and paroxysmal dyskinesias.Vol 89. Lippincott Williams and Wilkins. Philadelphia, pp 459–561

  28. Jodice C, Mantuano E, Veneziano L, et al. (1997) Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. Hum Mol Genet 6:1973–1978

    CAS  PubMed  Google Scholar 

  29. Klostermann W, Zühlke C, Heide W, et al. (1997) Slow saccades and other eye movement disorders in spinocerebellar atrophy type 1. J Neurol 244:105–111

    CAS  PubMed  Google Scholar 

  30. Lamarche JB, Lemieux B, Lieu HB (1984) The neuropathology of typical Friedreich’s ataxia in Quebec. Can J Neurol Sci 11:592–600

    CAS  PubMed  Google Scholar 

  31. Lang B, Dale RC, Vincent A (2003) New autoantibody mediated disorder of the central nervous system. Curr Opin Neurol 16:351–357

    CAS  PubMed  Google Scholar 

  32. Le Ber I, Bouslam N, Rivaud-Péchoux S, et al. (2004) Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain 127:759–767

    PubMed  Google Scholar 

  33. Le Ber I, Moreira MC, Rivaud-Péchoux S, et al. (2003) Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain 126:2761–2772

    PubMed  Google Scholar 

  34. Lewis RF, Ledrman HM, Crawford TO (1999) Ocular motor abnormalities in Ataxia telangiectasia. Ann Neurol 46:287–295

    CAS  PubMed  Google Scholar 

  35. Montermini L, Richter A, Morgan K, et al. (1997) Phenotypic variability in Friedreich Ataxia: role of the associated GAA Triplet Repeat Expansion. Ann Neurol 41:675–682

    CAS  PubMed  Google Scholar 

  36. Moreira MC, Barbot C, Tachi N, et al. (2001) Homozygosity mapping of Portuguese and Japanese form of ataxia oculomotor apraxia to 9p13, and evidence for genetic heterogeneity. Am J Hum Genet 68:501–508

    CAS  PubMed  Google Scholar 

  37. Nystuen A, Benke PJ, Merren J, Stone EM, Sheffield Van C (1996) A cerebellar ataxia locus identified by DNA pooling to search for linkage disequilibrium in an isolated population from the Cayman islands. Hum Mol Genet 5:525–531

    CAS  PubMed  Google Scholar 

  38. Oh AK, Jacobson KM, Jen JC, Baloh RW (2001) Slowing of voluntary and involuntary saccades: an early sign in spinocerebellar ataxia type 7. Ann Neurol 49:801–804

    CAS  PubMed  Google Scholar 

  39. Ophoff RA, Terwindt GM, Vergouwe MN, et al. (1996) Familial hemiplegic migraine and episodic ataxia type 2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–552

    CAS  PubMed  Google Scholar 

  40. Rivaud-Pechoux S, Durr A, Gaymard B, et al. (1998) Eye movement abnormalities correlate with genotype in autosomal dominant cerebellar ataxia type I. Ann Neurol 43:297–302

    CAS  PubMed  Google Scholar 

  41. Schöls L, Bauer P, Schmidt T, Schulte T, Riess O (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3:291–304

    PubMed  Google Scholar 

  42. Shams’ili S, Grefkens J, de Leeuw B, et al. (2004) Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 126:1409–1418

    Google Scholar 

  43. Shimazaki H, Takiyama Y, Sakoe K, et al. (2002) Early-onset ataxia with ocular motor apraxia and hypoalbuminemia. Neurology 59:590–595

    CAS  PubMed  Google Scholar 

  44. Silveira I, Miranda C, Guimaraes L, et al. (2002) Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol 59:623–629

    CAS  PubMed  Google Scholar 

  45. Storey E, Tuck K, Hester R, et al. (2004) Inter-rater reliability of the International Cooperative Ataxia rating scale (ICARS). Mov Disord 19:190–212

    PubMed  Google Scholar 

  46. Taroni F, Di Donato S (2004) Pathways to motor incoordination: the inherited ataxias. Nat Rev Neurosci 5:641–655

    CAS  PubMed  Google Scholar 

  47. Trouillas P, Takayanagi T, Hallet M, et al. (1997) International cooperative ataxia rating scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 145:205–211

    CAS  PubMed  Google Scholar 

  48. Walshe JM (1999) Penicillamine: the treatment of first choice for patients with Wilson’s disease. Mov Disord 14:545–550

    CAS  PubMed  Google Scholar 

  49. Wenning GK, Colosimo C, Geser F, Poewe W (2004) Multiple system atrophy. Lancet Neurol 3:93–103

    Article  PubMed  Google Scholar 

  50. Wenning GK, Tison F, Seppi K, et al. (2004) Development and validation of the Unified Multiple System Atrophy rating scale (UMSARS). Mov Disord 19:1391–1402

    PubMed  Google Scholar 

  51. Wollmann T, Nieto-Barco A, Monton-Alvarex F, Barroso-Ribal J (2004) Friedreich’s ataxia: analysis of magnetic resonance imaging parameters and their correlates with cognitive and motor slowing. Rev Neurol (Paris) 38:217–222

    CAS  PubMed  Google Scholar 

  52. Yee RD, Cogan DG, Zee DS (1976) Ophthalmoplegia and dissociated nystagmus in abetalipoproteinemia. Arch Ophthalmol 94:571–575

    CAS  PubMed  Google Scholar 

  53. Zeviani M, Di Donato S (2004) Mitochondrial disorders. Brain 127:2153–2172

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefano Di Donato MD.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mariotti, C., Fancellu, R. & Di Donato, S. An overview of the patient with ataxia. J Neurol 252, 511–518 (2005). https://doi.org/10.1007/s00415-005-0814-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-0814-z

Key words

Navigation