Treatment of Generalized Dystonia

  • Naomi Lubarr
  • Susan Bressman
Movement Disorders

Opinion statement

The armamentarium for clinicians treating patients with generalized dystonia, previously restricted to only a few oral medications that often caused intolerable side effects, has been radically expanded in the past decade with the widespread application of deep brain stimulation (DBS). With DBS, patients who in the past would have been restricted to a life of severe motor disability from a young age can now lead lives with only minimal symptoms. Although DBS should therefore be considered as a treatment option for any patient with severe, medically refractory dystonia, important questions remain about patient selection, including what factors predict which patients will benefit from DBS, and when in the course of disease DBS should be performed. Reports show that patients with primary dystonia respond better than those with secondary dystonia, and limb and axial muscles may improve more than cranial dystonia. Some studies also suggest that shorter duration of disease may be associated with better outcomes. However, it is important to note that even among those thought to respond best to DBS, i.e. patients with primary generalized dystonia, there is a subset that will have significant and sustained clinical benefit with oral medications. It is therefore important that adequate trials of oral medications be attempted prior to referral for surgery. On the other hand, once it is clear that medical therapies are not providing significant benefit or are not well tolerated, children with disabling generalized primary dystonia should be referred quickly for DBS. The dramatic clinical improvement that can be seen with DBS can restore normal or near-normal functioning and avoid the physical and emotional costs of an extended period of decreased physical and social functioning. In general, a levodopa trial should always be considered as the first treatment at the time of presentation of any patient with childhood-onset limb dystonia, in order to exclude dopa-responsive dystonia. Once a diagnosis of primary generalized dystonia is established, we typically initiate treatment with trihexyphenidyl, titrating slowly up to a high dose. We then frequently add baclofen as a second agent. If clinical improvement at that point is inadequate and the dystonia is causing significant functional impairment, we then consider referral for DBS.


Dystonia Deep Brain Stimulation Essential Tremor Cervical Dystonia Botulinum Toxin Injection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No potential conflicts of interest relevant to this article were reported.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Fahn S. Concept and classification of dystonia. Adv Neurol. 1988;50:1–8.PubMedGoogle Scholar
  2. 2.•
    Clot F, Grabli D, Cazeneuve C, Roze E, Castelnau P, Chabrol B, et al. Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia. Brain. 2009;132(Pt 7):1753–63.PubMedCrossRefGoogle Scholar
  3. 3.
    Nygaard TG, Takahashi H, Heiman GA, Snow BJ, Fahn S, Calne DB. Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia. Ann Neurol. 1992;32(5):603–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Harwood G, Hierons R, Fletcher NA, Marsden CD. Lessons from a remarkable family with dopa-responsive dystonia. J Neurol Neurosurg Psychiatry. 1994;57(4):460–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Greene P, Shale H, Fahn S. Experience with high dosages of anticholinergic and other drugs in the treatment of torsion dystonia. Adv Neurol. 1988;50:547–56.PubMedGoogle Scholar
  6. 6.
    Bressman SB, Greene PE. Treatment of hyperkinetic movement disorders. Neurol Clin. 1990;8(1):51–75.PubMedGoogle Scholar
  7. 7.
    Bernard G, Vanasse M, Chouinard S. A case of secondary dystonia responding to levodopa. J Child Neurol. 2010;25(6):780–1.PubMedCrossRefGoogle Scholar
  8. 8.
    Neubauer D, Frelih J, Zupancic N, Kopac S, Cindro-Heberle L. Pyruvate dehydrogenase deficiency presenting as dystonia and responding to levodopa. Dev Med Child Neurol. 2005;47(7):504.PubMedCrossRefGoogle Scholar
  9. 9.
    Head RA, de Goede CG, Newton RW, Walter JH, McShane MA, Brown RM, et al. Pyruvate dehydrogenase deficiency presenting as dystonia in childhood. Dev Med Child Neurol. 2004;46(10):710–2.PubMedCrossRefGoogle Scholar
  10. 10.
    Shimoizumi H, Okabe I, Kodama H, Yanagisawa M. Methylmalonic acidemia with bilateral MRI high intensities of the globus pallidus. No To Hattatsu. 1993;25(6):554–7.PubMedGoogle Scholar
  11. 11.
    Burke RE, Fahn S, Marsden CD. Torsion dystonia: a double-blind, prospective trial of high-dosage trihexyphenidyl. Neurology. 1986;36(2):160–4.PubMedGoogle Scholar
  12. 12.
    Rice J, Waugh MC. Pilot study on trihexyphenidyl in the treatment of dystonia in children with cerebral palsy. J Child Neurol. 2009;24(2):176–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Sanger TD, Bastian A, Brunstrom J, Damiano D, Delgado M, Dure L, et al. Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. J Child Neurol. 2007;22(5):530–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Ford B, Greene PE, Louis ED, Bressman SB, Goodman RR, Brin MF, et al. Intrathecal baclofen in the treatment of dystonia. Adv Neurol. 1998;78:199–210.PubMedGoogle Scholar
  15. 15.
    Albright AL, Barry MJ, Shafton DH, Ferson SS. Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol. 2001;43(10):652–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Motta F, Stignani C, Antonello CE. Effect of intrathecal baclofen on dystonia in children with cerebral palsy and the use of functional scales. J Pediatr Orthop. 2008;28(2):213–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Albright AL, Ferson SS. Intraventricular baclofen for dystonia: techniques and outcomes. Clinical article. J Neurosurg Pediatr. 2009;3(1):11–4.PubMedCrossRefGoogle Scholar
  18. 18.•
    Guay DR. Tetrabenazine, a monoamine-depleting drug used in the treatment of hyperkinetic movement disorders. Am J Geriatr Pharmacother. 2010;8(4):331–73.PubMedCrossRefGoogle Scholar
  19. 19.
    Papapetropoulos S, Singer C. Improvement of cervico-trunco-brachial segmental dystonia with topiramate. J Neurol. 2006;253(4):535–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Sullivan KL, Hauser RA, Louis ED, Chari G, Zesiewicz TA. Levetiracetam for the treatment of generalized dystonia. Parkinsonism Relat Disord. 2005;11(7):469–71.PubMedCrossRefGoogle Scholar
  21. 21.
    Zesiewicz TA, Louis ED, Sullivan KL, Menkin M, Dunne PB, Hauser RA. Substantial improvement in a Meige’s syndrome patient with levetiracetam treatment. Mov Disord. 2004;19(12):1518–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Hering S, Wenning GK, Seppi K, Poewe W, Mueller J. An open trial of levetiracetam for segmental and generalized dystonia. Mov Disord. 2007;22(11):1649–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Tarsy D, Ryan RK, Ro SI. An open-label trial of levetiracetam for treatment of cervical dystonia. Mov Disord. 2006;21(5):734–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Paliwal VK, Gupta PK, Pradhan S. Gabapentin as a rescue drug in D-penicillamine-induced status dystonicus in patients with Wilson disease. Neurol India. 2010;58(5):761–3.PubMedCrossRefGoogle Scholar
  25. 25.••
    Dressler D. Botulinum toxin for treatment of dystonia. Eur J Neurol. 2010;17 Suppl 1:88–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Dressler D, Benecke R. Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol. 2003;49(1):34–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Naumann M, Carruthers A, Carruthers J, Aurora SK, Zafonte R, Abu-Shakra S, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX(R)) across multiple indications. Mov Disord. 2010;25(13):2211–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Kupsch A, Benecke R, Muller J, Trottenberg T, Schneider GH, Poewe W, et al. Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med. 2006;355(19):1978–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P, Benabid AL, Cornu P, et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005;352(5):459–67.PubMedCrossRefGoogle Scholar
  30. 30.•
    Andrews C, Aviles-Olmos I, Hariz M, Foltynie T. Which patients with dystonia benefit from deep brain stimulation? A metaregression of individual patient outcomes. J Neurol Neurosurg Psychiatry. 2010;81(12):1383–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Speelman JD, Contarino MF, Schuurman PR, Tijssen MA, de Bie RM. Deep brain stimulation for dystonia: patient selection and outcomes. Eur J Neurol. 2010;17 Suppl 1:102–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Isaias IU, Alterman RL, Tagliati M. Outcome predictors of pallidal stimulation in patients with primary dystonia: the role of disease duration. Brain. 2008;131(Pt 7):1895–902.PubMedCrossRefGoogle Scholar
  33. 33.
    Vasques X, Cif L, Gonzalez V, Nicholson C, Coubes P. Factors predicting improvement in primary generalized dystonia treated by pallidal deep brain stimulation. Mov Disord. 2009;24(6):846–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Borggraefe I, Mehrkens JH, Telegravciska M, Berweck S, Botzel K, Heinen F. Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia–report of six patients and literature-based analysis of predictive outcomes variables. Brain Dev. 2010;32(3):223–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Isaias IU, Alterman RL, Tagliati M. Deep brain stimulation for primary generalized dystonia: long-term outcomes. Arch Neurol. 2009;66(4):465–70.PubMedCrossRefGoogle Scholar
  36. 36.
    Cif L, Vasques X, Gonzalez V, Ravel P, Biolsi B, Collod-Beroud G, et al. Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an open-label study. Mov Disord. 2010;25(3):289–99.PubMedGoogle Scholar
  37. 37.•
    Haridas A, Tagliati M, Osborn I, Isaias I, Gologorsky Y, Bressman SB, et al. Pallidal deep brain stimulation for primary dystonia in children. Neurosurgery. 2011;68(3):738–43.PubMedCrossRefGoogle Scholar
  38. 38.
    Lipsman N, Ellis M, Lozano AM. Current and future indications for deep brain stimulation in pediatric populations. Neurosurg Focus. 2010;29(2):E2.PubMedCrossRefGoogle Scholar
  39. 39.
    Mehrkens JH, Borggraefe I, Feddersen B, Heinen F, Botzel K. Early globus pallidus internus stimulation in pediatric patients with generalized primary dystonia: long-term efficacy and safety. J Child Neurol. 2010;25(11):1355–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Groen JL, Ritz K, Contarino MF, van de Warrenburg BP, Aramideh M, Foncke EM, et al. DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation. Mov Disord. 2010;25(14):2420–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Zittel S, Moll CK, Bruggemann N, Tadic V, Hamel W, Kasten M, et al. Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families. Mov Disord. 2010;25(14):2405–12.PubMedCrossRefGoogle Scholar
  42. 42.•
    Vidailhet M, Yelnik J, Lagrange C, Fraix V, Grabli D, Thobois S, et al. Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study. Lancet Neurol. 2009;8(8):709–17.PubMedCrossRefGoogle Scholar
  43. 43.
    Mikati MA, Yehya A, Darwish H, Karam P, Comair Y. Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. Eur J Paediatr Neurol. 2009;13(1):61–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Krause M, Fogel W, Tronnier V, Pohle S, Hortnagel K, Thyen U, et al. Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration. Mov Disord. 2006;21(12):2255–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Castelnau P, Cif L, Valente EM, Vayssiere N, Hemm S, Gannau A, et al. Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. Ann Neurol. 2005;57(5):738–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Wadia PM, Lim SY, Lozano AM, Adams JR, Poon YY, Diaz CT, et al. Bilateral pallidal stimulation for x-linked dystonia parkinsonism. Arch Neurol. 2010;67(8):1012–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Oyama G, Fernandez HH, Foote KD, Zeilman P, Hwynn N, Jacobson 4th CE, et al. Differential response of dystonia and Parkinsonism following globus pallidus internus deep brain stimulation in X-linked dystonia-parkinsonism (Lubag). Stereotact Funct Neurosurg. 2010;88(5):329–33.PubMedCrossRefGoogle Scholar
  48. 48.
    Gruber D, Trottenberg T, Kivi A, Schoenecker T, Kopp UA, Hoffmann KT, et al. Long-term effects of pallidal deep brain stimulation in tardive dystonia. Neurology. 2009;73(1):53–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Chang EF, Schrock LE, Starr PA, Ostrem JL. Long-term benefit sustained after bilateral pallidal deep brain stimulation in patients with refractory tardive dystonia. Stereotact Funct Neurosurg. 2010;88(5):304–10.PubMedCrossRefGoogle Scholar
  50. 50.
    Capelle HH, Blahak C, Schrader C, Baezner H, Kinfe TM, Herzog J, et al. Chronic deep brain stimulation in patients with tardive dystonia without a history of major psychosis. Mov Disord. 2010;25(10):1477–81.PubMedCrossRefGoogle Scholar
  51. 51.
    Gruber D, Kuhn AA, Schoenecker T, Kivi A, Trottenberg T, Hoffmann KT, et al. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord. 2010;25(11):1733–43.PubMedCrossRefGoogle Scholar
  52. 52.
    Kurtis MM, San Luciano M, Yu Q, Goodman RR, Ford B, Raymond D, et al. Clinical and neurophysiological improvement of SGCE myoclonus-dystonia with GPi deep brain stimulation. Clin Neurol Neurosurg. 2010;112(2):149–52.PubMedCrossRefGoogle Scholar
  53. 53.
    Kuncel AM, Turner DA, Ozelius LJ, Greene PE, Grill WM, Stacy MA. Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus-dystonia syndrome. Clin Neurol Neurosurg. 2009;111(3):303–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Alterman RL, Snyder BJ. Deep brain stimulation for torsion dystonia. Acta Neurochir Suppl. 2007;97(Pt 2):191–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Alterman RL, Miravite J, Weisz D, Shils JL, Bressman SB, Tagliati M. Sixty hertz pallidal deep brain stimulation for primary torsion dystonia. Neurology. 2007;69(7):681–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Halbig TD, Gruber D, Kopp UA, Schneider GH, Trottenberg T, Kupsch A. Pallidal stimulation in dystonia: effects on cognition, mood, and quality of life. J Neurol Neurosurg Psychiatry. 2005;76(12):1713–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Pillon B, Ardouin C, Dujardin K, Vittini P, Pelissolo A, Cottencin O, et al. Preservation of cognitive function in dystonia treated by pallidal stimulation. Neurology. 2006;66(10):1556–8.PubMedCrossRefGoogle Scholar
  58. 58.•
    Napolitano F, Pasqualetti M, Usiello A, Santini E, Pacini G, Sciamanna G, et al. Dopamine D2 receptor dysfunction is rescued by adenosine A2A receptor antagonism in a model of DYT1 dystonia. Neurobiol Dis. 2010;38(3):434–45.PubMedCrossRefGoogle Scholar
  59. 59.•
    Cao S, Hewett JW, Yokoi F, Lu J, Buckley AC, Burdette AJ, et al. Chemical enhancement of torsinA function in cell and animal models of torsion dystonia. Dis Model Mech. 2010;3(5–6):386–96.PubMedCrossRefGoogle Scholar
  60. 60.
    Mariotti P, Fasano A, Contarino MF, Della Marca G, Piastra M, Genovese O, et al. Management of status dystonicus: our experience and review of the literature. Mov Disord. 2007;22(7):963–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Jech R, Bares M, Urgosik D, Cerna O, Klement P, Adamovicova M, et al. Deep brain stimulation in acute management of status dystonicus. Mov Disord. 2009;24(15):2291–2.PubMedCrossRefGoogle Scholar
  62. 62.
    Elkay M, Silver K, Penn RD, Dalvi A. Dystonic storm due to Batten’s disease treated with pallidotomy and deep brain stimulation. Mov Disord. 2009;24(7):1048–53.PubMedCrossRefGoogle Scholar
  63. 63.
    Teive HA, Munhoz RP, Souza MM, Antoniuk SA, Santos ML, Teixeira MJ, et al. Status dystonicus: study of five cases. Arq Neuropsiquiatr. 2005;63(1):26–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Beth Israel Medical CenterPhillips Ambulatory Care CenterNew YorkUSA

Personalised recommendations