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  • Review Article
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Diagnosis of dystonic syndromes—a new eight-question approach

Nature Reviews Neurology volume 8, pages 275–283 (2012)Cite this article

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Abstract

Dystonia is a syndrome of abnormal involuntary movements that are repetitive, twisting or patterned, and can result in abnormal postures. Dystonia may be generalized or focal, and can occur as a primary syndrome or secondary to another disease—over 50 clinical conditions are reported to cause dystonia. Classification of dystonia is based on genetic background, anatomical distribution, age at onset, and neurodegenerative processes. In many cases, manifestations of dystonia are identical regardless of the aetiology, which makes accurate diagnosis challenging, if not impossible, without additional investigations. Exhaustive lists of the causes of dystonia are not practical to aid clinicians when attempting to determine if a hyperkinetic movement can be diagnosed as dystonic. The existing diagnostic algorithms for dystonic syndromes rely on the clinician's experience, without a streamlined diagnostic pathway. Non-specialist clinicians and neurologists may, therefore, find diagnosis of dystonic syndromes difficult. In this Review, an eight-question approach is proposed, with a summary of the evidence for investigations that enable successful diagnosis of dystonic syndromes. The aim of this approach is to inform both specialists and general neurologists on the appropriate diagnostic test for each patient who presents with a possible dystonic syndrome.

Key Points

  • Dystonia is a hyperkinetic movement disorder that manifests as repetitive twisting movements and abnormal postures

  • A wide variety of genetic, neurodegenerative and metabolic disorders are associated with clinical signs of dystonia

  • Diagnoses of dopa-responsive dystonia and Wilson disease should always be considered in cases of young-onset dystonia

  • Hemidystonia is almost always caused by a structural brain lesion and requires imaging for accurate diagnosis

  • Consideration of the eight key diagnostic questions in each patient should lead to appropriate investigations and ensure that the likely cause of the movement disorder is established

  • If new symptoms occur, or if dystonia spreads from the anatomical distribution at onset, the key questions should be reconsidered to ensure that rare causes of dystonia are not missed

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Figure 1: Abnormal twisting movements in patients with dystonia.
Figure 2: MRI abnormalities as a sign of specific dystonic syndromes.
Figure 3: Acanthocytes in a patient with neuroacanthocytosis.

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References

  1. Fahn, S. The varied clinical expressions of dystonia. Neurol. Clin. 2, 541–554 (1984).

    Article  CAS  PubMed  Google Scholar 

  2. Albanese, A. & Lalli, S. Is this dystonia? Mov. Disord. 24, 1725–1731 (2009).

    Article  PubMed  Google Scholar 

  3. Schneider, S. A. & Bhatia, K. P. Secondary dystonia--clinical clues and syndromic associations. Eur. J. Neurol. 17, 52–57 (2010).

    Article  PubMed  Google Scholar 

  4. Kanovsky, P. Dystonia: a disorder of motor programming or motor execution? Mov. Disord. 17, 1143–1147 (2002).

    Article  PubMed  Google Scholar 

  5. Grunewald, R. A., Yoneda, Y., Shipman, J. M. & Sagar, H. J. Idiopathic focal dystonia: a disorder of muscle spindle afferent processing? Brain 120, 2179–2185 (1997).

    Article  PubMed  Google Scholar 

  6. Frasson, E. et al. Somatosensory disinhibition in dystonia. Mov. Disord. 16, 674–682 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Rona, S., Berardelli, A., Vacca, L., Inghilleri, M. & Manfredi, M. Alterations of motor cortical inhibition in patients with dystonia. Mov. Disord. 13, 118–124 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Kaji, R. & Murase, N. Sensory function of basal ganglia. Mov. Disord. 16, 593–594 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Hallett, M. Is dystonia a sensory disorder? Ann. Neurol. 38, 139–140 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Tinazzi, M., Squintani, G. & Berardelli, A. Does neurophysiological testing provide the information we need to improve the clinical management of primary dystonia? Clin. Neurophysiol. 120, 1424–1432 (2009).

    Article  PubMed  Google Scholar 

  11. Nemeth, A. H. The genetics of primary dystonias and related disorders. Brain 125, 695–721 (2002).

    Article  PubMed  Google Scholar 

  12. Albanese, A. et al. A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force. Eur. J. Neurol. 13, 433–444 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Defazio, G., Abbruzzese, G., Livrea, P. & Berardelli, A. Epidemiology of primary dystonia. Lancet Neurol. 3, 673–678 (2004).

    Article  PubMed  Google Scholar 

  14. Nutt, J. G., Muenter, M. D., Aronson, A., Kurland, L. T. & Melton, L. J. 3rd. Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov. Disord. 3, 188–194 (1988).

    Article  CAS  PubMed  Google Scholar 

  15. Asgeirsson, H., Jakobsson, F., Hjaltason, H., Jonsdottir, H. & Sveinbjornsdottir, S. Prevalence study of primary dystonia in Iceland. Mov. Disord. 21, 293–298 (2006).

    Article  PubMed  Google Scholar 

  16. A prevalence study of primary dystonia in eight European countries. J. Neurol. 247, 787–792 (2000).

  17. Ferraz, H. B. & Andrade, L. A. Symptomatic dystonia: clinical profile of 46 Brazilian patients. Can. J. Neurol. Sci. 19, 504–507 (1992).

    CAS  PubMed  Google Scholar 

  18. Wenning, G. K. et al. Prevalence of movement disorders in men and women aged 50–89 years (Bruneck Study cohort): a population-based study. Lancet Neurol. 4, 815–820 (2005).

    Article  PubMed  Google Scholar 

  19. Kiriakakis, V., Bhatia, K. P., Quinn, N. P. & Marsden, C. D. The natural history of tardive dystonia. A long-term follow-up study of 107 cases. Brain 121, 2053–2066 (1998).

    Article  PubMed  Google Scholar 

  20. Geyer, H. L. & Bressman, S. B. The diagnosis of dystonia. Lancet Neurol. 5, 780–790 (2006).

    Article  PubMed  Google Scholar 

  21. Jankovic, J., Tsui, J. & Bergeron, C. Prevalence of cervical dystonia and spasmodic torticollis in the United States general population. Parkinsonism Relat. Disord. 13, 411–416 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Bressman, S. B. Dystonia update. Clin. Neuropharmacol. 23, 239–251 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Elia, A. E., Lalli, S. & Albanese, A. Differential diagnosis of dystonia. Eur. J. Neurol. 17, 1–8 (2010).

    Article  PubMed  Google Scholar 

  24. Deuschl, G., Bain, P. & Brin, M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov. Disord. 13, 2–23 (1998).

    Article  PubMed  Google Scholar 

  25. Gupta, A. & Lang, A. E. Psychogenic movement disorders. Curr. Opin. Neurol. 22, 430–436 (2009).

    Article  PubMed  Google Scholar 

  26. Chan, J., Brin, M. F. & Fahn, S. Idiopathic cervical dystonia: clinical characteristics. Mov. Disord. 6, 119–126 (1991).

    Article  CAS  PubMed  Google Scholar 

  27. Martino, D. et al. The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia. Mov. Disord. 25, 407–412 (2010).

    Article  PubMed  Google Scholar 

  28. Greene, P. E. & Bressman, S. Exteroceptive and interoceptive stimuli in dystonia. Mov. Disord. 13, 549–551 (1998).

    Article  CAS  PubMed  Google Scholar 

  29. Lalli, S. & Albanese, A. The diagnostic challenge of primary dystonia: evidence from misdiagnosis. Mov. Disord. 25, 1619–1626 (2010).

    Article  PubMed  Google Scholar 

  30. Garcia-Cazorla, A. et al. Inborn errors of metabolism and motor disturbances in children. J. Inherit. Metab. Dis. 32, 618–629 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. van Rootselaar, A. F., van Westrum, S. S., Velis, D. N. & Tijssen, M. A. The paroxysmal dyskinesias. Pract. Neurol. 9, 102–109 (2009).

    Article  PubMed  Google Scholar 

  32. O'Riordan, S. et al. Age at onset as a factor in determining the phenotype of primary torsion dystonia. Neurology 63, 1423–1426 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Schwarz, C. S. & Bressman, S. B. Genetics and treatment of dystonia. Neurol. Clin. 27, 697–718, vi (2009).

    Article  PubMed  Google Scholar 

  34. Bressman, S. B. et al. Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann. Neurol. 26, 612–620 (1989).

    Article  CAS  PubMed  Google Scholar 

  35. Valente, E. M. et al. The role of DYT1 in primary torsion dystonia in Europe. Brain 121, 2335–2339 (1998).

    Article  PubMed  Google Scholar 

  36. Trender-Gerhard, I. et al. Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients. J. Neurol. Neurosurg. Psychiatry 80, 839–845 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Asmus, F. & Gasser, T. Dystonia-plus syndromes. Eur. J. Neurol. 17, 37–45 (2010).

    Article  PubMed  Google Scholar 

  38. Furukawa, Y. et al. Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia. Neurology 53, 1032–1041 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Schiller, A., Wevers, R. A., Steenbergen, G. C., Blau, N. & Jung, H. H. Long-term course of L-dopa-responsive dystonia caused by tyrosine hydroxylase deficiency. Neurology 63, 1524–1526 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Schneider, S. A. et al. Severe tongue protrusion dystonia: clinical syndromes and possible treatment. Neurology 67, 940–943 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Narbona, J., Obeso, J. A., Tunon, T., Martinez-Lage, J. M. & Marsden, C. D. Hemi-dystonia secondary to localised basal ganglia tumour. J. Neurol. Neurosurg. Psychiatry 47, 704–709 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Marsden, C. D., Obeso, J. A., Zarranz, J. J. & Lang, A. E. The anatomical basis of symptomatic hemidystonia. Brain 108, 463–483 (1985).

    Article  PubMed  Google Scholar 

  43. Perlmutter, J. S. & Raichle, M. E. Pure hemidystonia with basal ganglion abnormalities on positron emission tomography. Ann. Neurol. 15, 228–233 (1984).

    Article  CAS  PubMed  Google Scholar 

  44. Pettigrew, L. C. & Jankovic, J. Hemidystonia: a report of 22 patients and a review of the literature. J. Neurol. Neurosurg. Psychiatry 48, 650–657 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Heiman, G. A. et al. Increased risk for recurrent major depression in DYT1 dystonia mutation carriers. Neurology 63, 631–637 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Ghilardi, M. F. et al. Impaired sequence learning in carriers of the DYT1 dystonia mutation. Ann. Neurol. 54, 102–109 (2003).

    Article  PubMed  Google Scholar 

  47. Bressman, S. B. et al. Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol. 8, 441–446 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Houlden, H. et al. THAP1 mutations (DYT6) are an additional cause of early-onset dystonia. Neurology 74, 846–850 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Muller, U. The monogenic primary dystonias. Brain 132, 2005–2025 (2009).

    Article  PubMed  Google Scholar 

  50. Schneider, S. A., Bhatia, K. P. & Hardy, J. Complicated recessive dystonia parkinsonism syndromes. Mov. Disord. 24, 490–499 (2009).

    Article  PubMed  Google Scholar 

  51. Kinugawa, K. et al. Myoclonus-dystonia: an update. Mov. Disord. 24, 479–489 (2009).

    Article  PubMed  Google Scholar 

  52. Hedrich, K. et al. Myoclonus-dystonia: detection of novel, recurrent, and de novo SGCE mutations. Neurology 62, 1229–1231 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Muller, B. et al. Evidence that paternal expression of the ɛ-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia. Am. J. Hum. Genet. 71, 1303–1311 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Muthane, U. et al. Clinical features of adult GM1 gangliosidosis: report of three Indian patients and review of 40 cases. Mov. Disord. 19, 1334–1341 (2004).

    Article  PubMed  Google Scholar 

  55. Krystkowiak, P. et al. Dystonia after striatopallidal and thalamic stroke: clinicoradiological correlations and pathophysiological mechanisms. J. Neurol. Neurosurg. Psychiatry 65, 703–708 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kostic, V. S., Stojanovic-Svetel, M. & Kacar, A. Symptomatic dystonias associated with structural brain lesions: report of 16 cases. Can. J. Neurol. Sci. 23, 53–56 (1996).

    Article  CAS  PubMed  Google Scholar 

  57. Kim, J. S. et al. Focal hand dystonia secondary to Basal Ganglia germinoma. J. Clin. Neurol. 3, 150–153 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Lee, M. S. & Marsden, C. D. Movement disorders following lesions of the thalamus or subthalamic region. Mov. Disord. 9, 493–507 (1994).

    Article  CAS  PubMed  Google Scholar 

  59. Cho, C. & Samkoff, L. M. A lesion of the anterior thalamus producing dystonic tremor of the hand. Arch. Neurol. 57, 1353–1355 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Tuschl, K. et al. Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia—a new metabolic disorder. J. Inherit. Metab. Dis. 31, 151–163 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Chang, L. W. The neurotoxicology and pathology of organomercury, organolead, and organotin. J. Toxicol. Sci. 15 (Suppl. 1), 125–151 (1990).

    Article  CAS  PubMed  Google Scholar 

  62. Forstl, H., Krumm, B., Eden, S. & Kohlmeyer, K. Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation. J. Neurol. 239, 36–38 (1992).

    Article  CAS  PubMed  Google Scholar 

  63. Geschwind, D. H., Loginov, M. & Stern, J. M. Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am. J. Hum. Genet. 65, 764–772 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mancini, F. et al. Secondary cervical dystonia in iatrogenic hypoparathyroidism associated with extensive brain calcifications. Funct. Neurol. 21, 165–166 (2006).

    PubMed  Google Scholar 

  65. Hayflick, S. J. et al. Genetic, clinical, and radiographic delineation of Hallervorden–Spatz syndrome. N. Engl. J. Med. 348, 33–40 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Gregory, A., Polster, B. J. & Hayflick, S. J. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J. Med. Genet. 46, 73–80 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Hayflick, S. J., Hartman, M., Coryell, J., Gitschier, J. & Rowley, H. Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. AJNR Am. J. Neuroradiol. 27, 1230–1233 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. McNeill, A. et al. T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology 70, 1614–1619 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Chinnery, P. F. et al. Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. Brain 130, 110–119 (2007).

    Article  PubMed  Google Scholar 

  70. Morgan, N. V. et al. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat. Genet. 38, 752–754 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Takeuchi, Y. et al. A case of aceruloplasminaemia: abnormal serum ceruloplasmin protein without ferroxidase activity. J. Neurol. Neurosurg. Psychiatry 72, 543–545 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. McNeill, A., Pandolfo, M., Kuhn, J., Shang, H. & Miyajima, H. The neurological presentation of ceruloplasmin gene mutations. Eur. Neurol. 60, 200–205 (2008).

    Article  PubMed  Google Scholar 

  73. Demarquay, G. et al. Clinical report of three patients with hereditary hemochromatosis and movement disorders. Mov. Disord. 15, 1204–1209 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Prashanth, L. K., Taly, A. B., Sinha, S., Arunodaya, G. R. & Swamy, H. S. Wilson's disease: diagnostic errors and clinical implications. J. Neurol. Neurosurg. Psychiatry 75, 907–909 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Walshe, J. M. & Yealland, M. Wilson's disease: the problem of delayed diagnosis. J. Neurol. Neurosurg. Psychiatry 55, 692–696 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ala, A., Borjigin, J., Rochwarger, A. & Schilsky, M. Wilson disease in septuagenarian siblings: raising the bar for diagnosis. Hepatology 41, 668–670 (2005).

    Article  PubMed  Google Scholar 

  77. Liebeskind, D. S., Wong, S. & Hamilton, R. H. Faces of the giant panda and her cub: MRI correlates of Wilson's disease. J. Neurol. Neurosurg. Psychiatry 74, 682 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tan, E. K. & Chan, L. L. Movement disorders associated with hyperthyroidism: expanding the phenotype. Mov. Disord. 21, 1054–1055 (2006).

    Article  PubMed  Google Scholar 

  79. Kempster, P. A., Brenton, D. P., Gale, A. N. & Stern, G. M. Dystonia in homocystinuria. J. Neurol. Neurosurg. Psychiatry 51, 859–862 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Burlina, A. P., Zara, G., Hoffmann, G. F., Zschocke, J. & Burlina, A. B. Management of movement disorders in glutaryl-CoA dehydrogenase deficiency: anticholinergic drugs and botulinum toxin as additional therapeutic options. J. Inherit Metab. Dis. 27, 911–915 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Torres, R. J. & Puig, J. G. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch–Nyhan syndrome. Orphanet J. Rare Dis. 2, 48 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Kolker, S. et al. Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). J. Inherit. Metab. Dis. 30, 5–22 (2007).

    Article  CAS  PubMed  Google Scholar 

  83. Testai, F. D. & Gorelick, P. B. Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. Arch. Neurol. 67, 148–153.

  84. Walker, R. H. et al. Neurologic phenotypes associated with acanthocytosis. Neurology 68, 92–98 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Hardie, R. J. et al. Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. Brain 114, 13–49 (1991).

    PubMed  Google Scholar 

  86. Danek, A. & Walker, R. H. Neuroacanthocytosis. Curr. Opin. Neurol. 18, 386–392 (2005).

    Article  PubMed  Google Scholar 

  87. Lee, J. H., Lee, S. M. & Baik, S. K. Demonstration of striatopallidal iron deposition in chorea-acanthocytosis by susceptibility-weighted imaging. J. Neurol. 258, 321–322 (2010).

    Article  PubMed  Google Scholar 

  88. Stevenson, V. L. & Hardie, R. J. Acanthocytosis and neurological disorders. J. Neurol. 248, 87–94 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Danek, A. et al. Neuroacanthocytosis: new developments in a neglected group of dementing disorders. J. Neurol. Sci. 229–230, 171–186 (2005).

    Article  PubMed  Google Scholar 

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Acknowledgements

We wish to thank Dr Andrew Guirguis, Haematologist, for assistance with production of the image of the acanthocytes. We also wish to thank the patients who kindly gave permission for their image to be used in this manuscript.

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Authors and Affiliations

  1. Department of Neurology, Alfred Hospital, Commercial Road, Melbourne, 3004, VIC, Australia

    Kelly L. Bertram

  2. Van Cleef Roet Centre for Nervous Diseases, Monash University, Alfred Hospital, Commercial Road, Melbourne, 3004, VIC, Australia

    David R. Williams

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K. L. Bertram and D. R. Williams contributed equally to researching data for the article, discussion of content, writing, and review and/or editing of the manuscript before submission.

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Correspondence to David R. Williams.

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D. R. Williams has received honoraria for consulting and speaking, and has received grant support from Ipsen. K. L. Bertram has received speaker's honoraria and research support from Ipsen.

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Bertram, K., Williams, D. Diagnosis of dystonic syndromes—a new eight-question approach. Nat Rev Neurol 8, 275–283 (2012). https://doi.org/10.1038/nrneurol.2012.39

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