Abstract
Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment in patients with severe dystonia. However, factors predicting outcome are largely unknown and motor improvement in DYT6 patients after DBS has been reported to be poorer as compared to, e.g., DYT1 patients. Here, we report the course of clinical improvement for up to 11 years of pallidal DBS in three male patients belonging to the same family with early-onset generalized or segmental dystonia due to a heterozygous THAP1 gene mutation (DYT6). All patients showed an initial effective response to pallidal DBS with a mean of 56.9 ± 11.7 % improvement in the Burke–Fahn–Marsden Dystonia motor and 45.5 ± 22.4 % in the disability score at 1-year follow-up. The long-term outcome of pallidal DBS was favorable in two patients (39, 67 % motor improvement, respectively). Our findings demonstrate that motor improvement is variable and may depend on disease severity, disease duration, and clinical presentation. Overall, our observation supports pallidal DBS as an important treatment option in patients with DYT6 dystonia.
Similar content being viewed by others
References
Albanese A, Bhatia K, Bressman SB et al (2013) Phenomenology and classification of dystonia: a consensus update. Mov Disord 28:863–873
Ozelius LJ, Hewett JW, Page CE et al (1997) The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet 17:40–48
Fuchs T, Gavarini S, Saunders-Pullman R et al (2009) Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia. Nat Genet 41:286–288
Bonetti M, Barzaghi C, Brancati F et al (2009) Mutation screening of the DYT6/THAP1 gene in Italy. Mov Disord Off J Mov Disord Soc 24:2424–2427
Bressman SBRD, Fuchs T, Heiman G, Ozelius LJ, Saunders-Pullman R (2009) Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol 8:441–446
Djarmati A, Schneider SA, Lohmann K et al (2009) Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. Lancet Neurol 8:447–452
Kupsch A, Benecke R, Muller J et al (2006) Pallidal deep-brain stimulation in primary generalized or segmental dystonia. New Engl J Med 355:1978–1990
Mueller J, Skogseid IM, Benecke R et al (2008) Pallidal deep brain stimulation improves quality of life in segmental and generalized dystonia: results from a prospective, randomized sham-controlled trial. Mov Disord Off J Mov Dis Soc 23:131–134
Vidailhet M, Vercueil L, Houeto J-L et al (2007) Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up study. Lancet Neurol 6:223–229
Volkmann J, Wolters A, Kupsch A et al (2012) Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial. Lancet Neurol 11:1029–1038
Coubes P, Cif L, El Fertit H et al (2004) Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results. J Neurosurg 101:189–194
Isaias IU, Alterman RL, Tagliati M (2008) Outcome predictors of pallidal stimulation in patients with primary dystonia: the role of disease duration. Brain J Neurol 131:1895–1902
Markun LC, Starr PA, Air EL, Marks WJ Jr, Volz MM, Ostrem JL (2012) Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia. Neurosurgery 71:325–330
Andrews C, Aviles-Olmos I, Hariz M, Foltynie T (2010) Which patients with dystonia benefit from deep brain stimulation? A metaregression of individual patient outcomes. J Neurol Neurosurg Psychiatry 81:1383–1389
Borggraefe I, Mehrkens JH, Telegravciska M, Berweck S, Botzel K, Heinen F (2010) 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 32:223–228
Tagliati M, Shils J, Sun C, Alterman R (2004) Deep brain stimulation for dystonia. Expert Rev Med Devices 1:33–41
Groen JL, Ritz K, Contarino MF et al (2010) DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation. Mov Disord 25:2420–2427
Panov F, Tagliati M, Ozelius LJ et al (2012) Pallidal deep brain stimulation for DYT6 dystonia. J Neurol Neurosurg Psychiatry 83:182–187
Zittel S, Moll CK, Bruggemann N et al (2010) Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families. Mov Off J Mov Disord Soc 25:2405–2412
Jech RBM, Křepelová A, Urgošík D, Havránková P, Růžička E (2011) DYT 6—a novel THAP1 mutation with excellent effect on pallidal DBS. Mov Off J Mov Disord Soc 26:924–925
França S, Linhares P, Rosas MJ, Volkmann J (2014) Pallidal deep brain stimulation in DYT6: significant long-term improvement of dystonia and disability. Mov Disord Clin Pract 1(2):118–120
Bruggemann N, Kuhn A, Schneider SA et al (2015) Short- and long-term outcome of chronic pallidal neurostimulation in monogenic isolated dystonia. Neurology 84:895–903
Lohmann K, Uflacker N, Erogullari A et al (2012) Identification and functional analysis of novel THAP1 mutations. Eur J Hum Genet 20:171–175
Silberstein P, Kuhn AA, Kupsch A et al (2003) Patterning of globus pallidus local field potentials differs between Parkinson’s disease and dystonia. Brain J Neurol 126:2597–2608
Cif L, Vasques X, Gonzalez V et al (2010) Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an open-label study. Mov Off J Mov Disord Soc 25:289–299
Vidailhet M, Vercueil L, Houeto JL et al (2005) Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. New Engl J Med 352:459–467
Grips E, Blahak C, Capelle HH et al (2007) Patterns of reoccurrence of segmental dystonia after discontinuation of deep brain stimulation. J Neurol Neurosurg Psychiatry 78:318–320
Vidailhet M, Jutras MF, Grabli D, Roze E (2013) Deep brain stimulation for dystonia. J Neurol Neurosurg Psychiatry 84:1029–1042
Barow E, Neumann WJ, Brucke C et al (2014) Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements. Brain J Neurol 137:3012–3024
Ruge D, Cif L, Limousin P et al (2011) Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms. Brain J Neurol 134:2106–2115
Acknowledgments
AAK, PK and GHS are supported by a grant from the German Research foundation (DFG), KFO247. KL is supported by a grant from the German Research Foundation (DFG, LO 1555/3-2).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
No conflict of interest.
Funding
The study was supported by the German Research Foundation (DFG) KFO 247 and LO 1553/3-2.
Financial disclosures
A.A. Kühn is funded by the DFG (KFO247) and received speakers honoraria or consultancies from Medtronic, Boston Scientific and St. Jude Medical, and travel grants from Ipsen Pharma and Merz.; P. Krause is funded by the DFG (KFO247); N. Brüggemann was funded by the German Research Foundation (BR 4328/1-1) and received speaker’s honoraria from the Schleswig–Holstein Chamber of pharmacists and the German Neurological Society. He received travel grants from Ipsen, Merz and St. Jude Medical; S. Völzmann: None; A. Horn is funded by the DFG (KFO247) and received grants from the junior clinical scientist programme and the Max-Rubner-Price of the Charité; A. Kupsch received grants from the German Research Council and the German Ministry of Education and Research, belongs to the Advisory Board ´Medtronic USA and received Honoraria from Allergan, Boehringer Ingelheim, Ipsen Pharma, Lundbeck, Medtronic, Merck, Merz Pharmaceuticals, Orion, St. Jude UCB; G.H. Schneider is supported by a grant from the DFG (KFO247); K. Lohmann received grants from the DFG, Dystonia Coalition.
Ethics
Not applicable. We present retrospective analysis of the regularly performed follow-up care. Anamnesis, performance of motor and disability scores (BFMDRS) and video recording is part of all of our follow-up examinations. Every patient in our clinic gives his individual consent for video documentation, as attached to this submission. Two of the patients presented here (patient A and C) have been implanted and investigated as part of a randomized, double-blind, multicentric national study investigating the effects of pallidal deep brain stimulation on generalized dystonia after informed consent (Study: A 121/02; Ethics: 1911 Si 286).
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Krause, P., Brüggemann, N., Völzmann, S. et al. Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation. J Neurol 262, 2739–2744 (2015). https://doi.org/10.1007/s00415-015-7908-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-015-7908-z