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Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation

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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.

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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).

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Authors and Affiliations

  1. Department of Neurology, Charité, University Medicine Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    P. Krause, S. Völzmann, A. Horn & A. Kühn

  2. Institute of Neurogenetics and Department of Neurology, University of Lubeck, Lubeck, Germany

    N. Brüggemann & K. Lohmann

  3. Department of Neurosurgery, Charité, University Medicine Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    G.-H. Schneider

  4. Department of Neurology and Stereotactic Neurosurgery, Otto-von-Guericke-University, Magdeburg, Germany

    A. Kupsch

Authors
  1. P. Krause
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  2. N. Brüggemann
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  3. S. Völzmann
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  4. A. Horn
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  5. A. Kupsch
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  6. G.-H. Schneider
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  7. K. Lohmann
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  8. A. Kühn
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Corresponding author

Correspondence to A. Kühn.

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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).

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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

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  • DOI: https://doi.org/10.1007/s00415-015-7908-z

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