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Original research
Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis
  1. Carlo Alberto Artusi1,
  2. Alok Dwivedi2,
  3. Alberto Romagnolo1,
  4. Sara Bortolani1,
  5. Luca Marsili3,
  6. Gabriele Imbalzano1,
  7. Andrea Sturchio3,
  8. Elizabeth G Keeling3,
  9. Maurizio Zibetti1,
  10. Maria Fiorella Contarino4,5,
  11. Alfonso Fasano6,7,
  12. Michele Tagliati8,
  13. M S Okun9,
  14. Alberto J Espay3,
  15. Leonardo Lopiano1,
  16. Aristide Merola10
  1. 1 Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy
  2. 2 Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
  3. 3 Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA
  4. 4 Department of Neurology, Haga Teaching Hospital, The Hague, The Netherlands
  5. 5 Leids Universitair Medisch Centrum, Leiden, The Netherlands
  6. 6 Morton and Gloria Shulman Movement Disorders Clinic. Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada
  7. 7 Krembil Research Institute, Toronto, Ontario, Canada
  8. 8 Department of Neurology, Cedars Sinai Medical Center, Los Angeles, California, USA
  9. 9 Department of Neurology, University of Florida, Gainesville, Florida, USA
  10. 10 Department of Neurology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  1. Correspondence to Dr Carlo Alberto Artusi, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin 10126, Italy; caartusi{at}gmail.com

Abstract

Objective Genetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common monogenic dystonias.

Methods This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. We searched PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-surgical and post-surgical assessments using the Burke–Fahn–Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke–Fahn–Marsden Disability Score (BFMDS). We performed (i) meta-analysis for each gene mutation; (ii) weighted ordinary linear regression analyses to compare BFMMS and BFMDS outcomes between DYT-TOR1A and other monogenic dystonias, adjusting for age and disease duration and (iii) weighted linear regression analysis to estimate the effect of age, sex and disease duration on GPi DBS outcomes. Results were summarised with mean change and 95% CI.

Results DYT-TOR1A (68%, 38.4 points; p<0.001), DYT-THAP1 (37% 14.5 points; p<0.001) and NBIA/DYT-PANK2 (27%, 21.4 points; p<0.001) improved in BFMMS; only DYT-TOR1A improved in BFMDS (69%, 9.7 points; p<0.001). Improvement in DYT-TOR1A was significantly greater than in DYT-THAP1 (BFMMS −31%), NBIA/DYT-PANK2 (BFMMS −35%; BFMDS −53%) and CHOR/DYT-ADCY5 (BFMMS −36%; BFMDS −42%). Worse motor outcomes were associated with longer dystonia duration and older age at dystonia onset in DYT-TOR1A, longer dystonia duration in DYT/PARK-TAF1 and younger age at dystonia onset in DYT-SGCE.

Conclusions GPi DBS outcomes vary across monogenic dystonias. These data serve to inform patient selection and prognostic counselling.

  • dystonia
  • deep brain stimulation
  • globus pallidus
  • genetics
  • monogenic
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Footnotes

  • Contributors CAA: Design and conceptualised study; acquisition of data; drafted the manuscript for intellectual content. AKD: Analysed the data; interpreted the data; revised the manuscript for intellectual content. AR: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. SB: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. LM: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. GI: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. AS: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. EK: Acquisition of data; interpreted the data; revised the manuscript for intellectual content. MZ: Revised the manuscript for intellectual content; interpreted the data. MFC: Revised the manuscript for intellectual content; interpreted the data. AF: Revised the manuscript for intellectual content; interpreted the data. MT: Revised the manuscript for intellectual content; interpreted the data. MO: Revised the manuscript for intellectual content; interpreted the data. AJE: Revised the manuscript for intellectual content; interpreted the data. LL: Revised the manuscript for intellectual content; interpreted the data. AM: Design and conceptualised study; interpreted the data; drafted the manuscript for intellectual content.

  • Funding CAA received travel grants from Zambon and Abbvie, and educational grants from Ralpharma. AD is supported as a co-investigator by the NIH (1R01HL125016-01), (1 R21 HL143030-01) and (1R21 AI133207) grants and as a collaborator in NIH R21 AI118228 grant. He has been also serving as a statistician in CPRIT grants (PP180003, PP170068, PP170004, PP140164, 140211, PP110156, PP150031 and PP130083), CCTST K12 (consultant) award, Coldwell (co-investigator) and TMF (co-investigator). AD is a director of Biostatistics & Epidemiology Consulting Lab at the TTUHSC EP. AR received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Medtronic, Lusofarmaco and UCB Pharma. MZ received speaker's honoraria from Medtronic, Lundbeck, UCB Pharma and AbbVie. LL has received honoraria for lecturing and travel grants from, UCB Pharma, AbbVie, DOC, Zambon and Bial. MFC received travel support from Boston Scientific. Advisory board: Medtronic, Boston Scientific. Independent consultant for Medtronic for research and educational issues. Received a grant from the Stichting Parkinson Fonds. The DBS center of the Haga Teaching Hospital/LUMC received compensation for DBS training activities from Medtronic and an unrestricted educational grant from Medtronic. AF reports grants, personal fees and non-financial support from Abbvie, grants, personal fees and non-financial support from Boston Scientific, grants, personal fees and non-financial support from Medtronic, personal fees from Chiesi, personal fees and non-financial support from Ipsen, personal fees from UCB, grants and personal fees from Sunovion, outside the submitted work. MT received grant support from the Cure Parkinson Trust and Drown Foundation; personal compensation as a consultant/scientific advisory board member for Abbott, Boston Scientific, Medtronic and Revance; honoraria from Boston Scientific, Medtronic, the American Academy of Neurology. MSO serves as a consultant for the Parkinson’s Foundation, and has received research grants from NIH, Parkinson’s Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association and the UF Foundation. MSO DBS research is supported by: R01 NR014852 and R01NS096008. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MSO is an associate editor for New England Journal of Medicine Journal Watch Neurology. MSO has participated in CME and educational activities on movement disorders sponsored by the Academy for Healthcare Learning, PeerView, Prime, QuantiaMD, WebMD/Medscape, Medicus, MedNet, Einstein, MedNet, Henry Stewart, American Academy of Neurology, Movement Disorders Society and by Vanderbilt University. The institution and not MSO receives grants from Medtronic, Abbvie, Abbott and Allergan and the PI has no financial interest in these grants. MSO has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. AJE received grant support from the NIH, Great Lakes Neurotechnologies and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, TEVA, Impax, Acadia, Acorda, InTrance, Cynapsus/Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from Abbvie, UCB, USWorldMeds, Lundbeck, Acadia, the American Academy of Neurology, and the Movement Disorders Society. LL received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie. AM is supported by NIH (KL2 TR001426) and received speaker honoraria from CSL Behring, Cynapsus Therapeutics, Theravance, Abbott, and AbbVie. He received grant support from Lundbeck.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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