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[Preprint]. 2024 Aug 26:2024.08.26.24312580.

doi: 10.1101/2024.08.26.24312580.

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study

M Guidetti¹, T Bocci^{1

2}, M De Pedro Del Álamo³, G Deuschl⁴, A Fasano^{5

6

7

8}, R Martinez Fernandez^{3

9}, C Gasca-Salas^{3

9}, C Hamani^{10

11

12}, J K Krauss¹³, A A Kühn^{14

15

16

17

18}, P Limousin¹⁹, S Little²⁰, A M Lozano^{5

6

21}, N V Maiorana¹, S Marceglia²², M S Okun^{23

24}, S Oliveri^{1

2}, J L Ostrem²⁰, E Scelzo², A Schnitzler^{25

26}, P A Starr^{27

28

29}, Y Temel³⁰, L Timmermann³¹, G Tinkhauser³², V Visser-Vandewalle³³, J Volkmann³⁴, A Priori^{1

2}

Affiliations

¹ "Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
² Clinical Neurology Unit, "Azienda Socio-Sanitaria Territoriale Santi Paolo e Carlo", Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
³ HM CINAC, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.
⁴ Department of Neurology University Hospital Schleswig-Holstein, Campus Kiel and Christian Albrechts-University of Kiel Kiel Germany.
⁵ Krembil Research Institute, University Health Network, Toronto, ON, Canada.
⁶ CRANIA Center for Advancing Neurotechnological Innovation to Application, University of Toronto, ON, Canada.
⁷ KITE, University Health Network, Toronto, ON, Canada.
⁸ Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Division of Neurology, University of Toronto, Toronto, ON, Canada.
⁹ Instituto Carlos III, CIBERNED, Madrid, Spain.
¹⁰ Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, M4N 3M5, ON, Canada.
¹¹ Harquail Centre for Neuromodulation, 2075 Bayview Avenue, Toronto, M4N 3M5, ON, Canada.
¹² Department of Surgery, University of Toronto, 149 College Street, Toronto, M5T 1P5, ON, Canada.
¹³ Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
¹⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁵ Bernstein Center for Computational Neuroscience, Humboldt-Universität, Berlin, Germany.
¹⁶ NeuroCure, Exzellenzcluster, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany.
¹⁸ Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁹ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom.
²⁰ Movement Disorders and Neuromodulation Centre, University of California San Francisco, San Francisco, California, USA.
²¹ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
²² Department of Engineering and Architecture, University of Trieste, Trieste, Italy.
²³ Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, United States.
²⁴ Department of Neurosurgery, Norman Fixel Institute for Neurological Diseases, University of Florida, United States.
²⁵ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
²⁶ Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
²⁷ UCSF Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
²⁸ UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁹ UCSF Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
³⁰ Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands.
³¹ Department of Neurology, University Hospital of Marburg, Marburg, Germany.
³² Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
³³ Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
³⁴ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.

PMID: 39252901
PMCID: PMC11383503
DOI: 10.1101/2024.08.26.24312580

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study

M Guidetti et al. medRxiv. 2024.

[Preprint]. 2024 Aug 26:2024.08.26.24312580.

doi: 10.1101/2024.08.26.24312580.

Authors

Affiliations

¹ "Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
² Clinical Neurology Unit, "Azienda Socio-Sanitaria Territoriale Santi Paolo e Carlo", Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
³ HM CINAC, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.
⁴ Department of Neurology University Hospital Schleswig-Holstein, Campus Kiel and Christian Albrechts-University of Kiel Kiel Germany.
⁵ Krembil Research Institute, University Health Network, Toronto, ON, Canada.
⁶ CRANIA Center for Advancing Neurotechnological Innovation to Application, University of Toronto, ON, Canada.
⁷ KITE, University Health Network, Toronto, ON, Canada.
⁸ Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Division of Neurology, University of Toronto, Toronto, ON, Canada.
⁹ Instituto Carlos III, CIBERNED, Madrid, Spain.
¹⁰ Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, M4N 3M5, ON, Canada.
¹¹ Harquail Centre for Neuromodulation, 2075 Bayview Avenue, Toronto, M4N 3M5, ON, Canada.
¹² Department of Surgery, University of Toronto, 149 College Street, Toronto, M5T 1P5, ON, Canada.
¹³ Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
¹⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁵ Bernstein Center for Computational Neuroscience, Humboldt-Universität, Berlin, Germany.
¹⁶ NeuroCure, Exzellenzcluster, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany.
¹⁸ Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁹ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, United Kingdom.
²⁰ Movement Disorders and Neuromodulation Centre, University of California San Francisco, San Francisco, California, USA.
²¹ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
²² Department of Engineering and Architecture, University of Trieste, Trieste, Italy.
²³ Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, United States.
²⁴ Department of Neurosurgery, Norman Fixel Institute for Neurological Diseases, University of Florida, United States.
²⁵ Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
²⁶ Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
²⁷ UCSF Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
²⁸ UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁹ UCSF Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
³⁰ Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands.
³¹ Department of Neurology, University Hospital of Marburg, Marburg, Germany.
³² Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
³³ Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
³⁴ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.

PMID: 39252901
PMCID: PMC11383503
DOI: 10.1101/2024.08.26.24312580

Update in

Will adaptive deep brain stimulation for Parkinson's disease become a real option soon? A Delphi consensus study.
Guidetti M, Bocci T, De Pedro Del Álamo M, Deuschl G, Fasano A, Martinez-Fernandez R, Gasca-Salas C, Hamani C, Krauss JK, Kühn AA, Limousin P, Little S, Lozano AM, Maiorana NV, Marceglia S, Okun MS, Oliveri S, Ostrem JL, Scelzo E, Schnitzler A, Starr PA, Temel Y, Timmermann L, Tinkhauser G, Visser-Vandewalle V, Volkmann J, Priori A. Guidetti M, et al. NPJ Parkinsons Dis. 2025 May 5;11(1):110. doi: 10.1038/s41531-025-00974-5. NPJ Parkinsons Dis. 2025. PMID: 40325017 Free PMC article.

Abstract

Importance: If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS.

Observations: We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias.

Conclusions and relevance: Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

Keywords: DBS; Deep Brain Stimulation; Delphi consensus; Parkinson’s disease; adaptive DBS; closed-loop DBS; movement disorders; neuromodulation.

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Conflict of interest statement

Declaration of interest M.G., N.V.M., S.O., T.B., E.S., Y.T., C.H., P.L. declare no conflict of interest. M.A.P is a consultant for Boston Scientific, Insightec, Medtronic and Abbott. She has received reimbursement of travel expenses to attend scientific meetings by Palex, Boston Scientific and Medtronic. She has received speaker honoraria from Palex. G. Deuschl G.D. has served as a consultant for Boston Scientific and Cavion and as DSMB member for Functional Neuromodulation. He has received royalties from Thieme Publishers and funding from the German Research Council (SFB 1261, T1). A.F. has received payments as consultant and/or speaker from Abbott, Boston Scientific, Ceregate, Inbrain Neuroelectronics, Medtronic, Iota and has received research support from Boston Scientific, Medtronic. R.M.F. has received speaker honoraria from the Spanish Neurological Society research foundation, Insightec, Palex, Bial and Zambon; has a consulting agreement with Treefrog Therapeutics; has received Reimbursement of travel expenses to attend scientific meetings by Palex, Zambon, the International Parkinson and Movement Disorder Society, the IAPDRD and the World Parkinson Congress; and has received research funding from Instituto de Salud Carlos III, Madrid, Spain for health research projects (PI21 Proyectos de investigacion en salud, AES 2021). C.G.S. has received lecture honoraria from Exeltis, Zambon, Palex, Insightec, Fundacion ACE, Societa Italiana Parkinson e Disordini del Movimento and Asociacion Madrilena de Neurologia, and reimbursement of travel expenses to attend scientific conferences from Boston Scientific and Esteve. J.K.K. is a consultant to Medtronic, Boston Scientific, aleva and Inomed A.A.K. is a consultant to Medtronic, Boston Scientific and Teva. S.L. is a consultant for Iota Biosciences and has previously received honorarium from Medtronic. S. L. research is support by NINDS NIH grants R01NS131405, K23NS120037 and Wellcome discovery award 226645/Z/22/Z A.M.L. is a consultant to Abbott, Boston Scientific, Insightec, Medtronic and Functional Neuromodulation (Scientific Director). M.S.O. serves as Medical Advisor in the Parkinson Foundation, and has received research grants from NIH, Parkinson Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. M.S.O. ‘s research is supported by: R01 NS131342 NIH R01 NR014852, R01NS096008, UH3NS119844, U01NS119562. M.S.O. is PI of the NIH R25NS108939 Training Grant. M.S.O. has received royalties for publications with Hachette Book Group, Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). M.S.O. is an associate editor for New England Journal of Medicine Journal Watch Neurology and JAMA Neurology. M.S.O. has participated in CME and educational activities (past 12–24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not M.S.O. receives grants from industry. M.S.O. 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. J.L.O. received consulting payments from Abbott, Acorda, Jazz, Adamas, AcureX and Aspen as well as research or training grants from Biogen, Boston scientific, Medtronic, Neuroderm, Runelabs, Abbvie, Merz, Amneal and Acadia. A.S. received consulting fees from Abbott, Zambon, and Abbvie, and speaker honoraria from bsh medical communication, Abbott, Kyowa Kirin, Novartis, Abbvie, and Alexion, GE Healtcare. The institution of AS, not AS personally, received funding by the Deutsche Forschungsgemeinschaft, the Brunhilde Moll Foundation, and Abbott. P.A.S. is compensated for time spent on the data safety and monitoring board for Neuralink, Inc. L.T. received occasional payments as a consultant for Boston Scientific, L.T. received honoraria as a speaker on symposia sponsored by Boston Scientific, AbbVIE, Novartis, Neuraxpharm, Teva, the Movement Disorders Society und DIAPLAN. The institution of L.T., not L.T. personally received funding by Boston Scientific, the German Research Foundation, the German Ministry of Education and Research, the Otto-Loewi-Foundation and the Deutsche Parkinson Vereinigung. Neither L.T. nor any member of his family holds stocks, stock options, patents or financial interests in any of the above-mentioned companies or their competitors. Lars Timmermann serves as the president of the German Neurological Society without any payment or any income. G.T. received financial support from Boston Scientific and Medtronic; Research agreement with RuneLabs and Medtronic not related to the present work V.V.V. received occasional payments as a consultant or speaker on symposia from Boston Scientific and Medtronic. J. Volkmann JV reports grants and personal fees from Medtronic, grants and personal fees from Boston Scientific, personal fees from Abbott outside the submitted work. JV was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295) - JV received consulting and lecture fees from Boston Scientific, Medtronic and Newronika. Research grants from the German Research Foundation, the German Ministry of Research and Education, Boston Scientific and Medtronic. Lecture Honoraria from UCB, Zambon, Abbott. A.P. and S.M. are founders and shareholders of Newronika Spa, Italy.

Figures

**Fig.1.. Percentage of agreement for the 21 statements on the technical aspects of adaptive DBS (Statement 1–21) among the Delphi Panel members, as result of the third round.**
A consensus was reached for Statement 1 (80% of the responses fell in the response label “Agree”), Statement 3 (85% of the responses fell in the response label “Strongly Disagree”), Statement 8 (80% of the responses fell in the response label “Strongly Agree”), Statement 14 (90% of the responses fell in the response label “Undecided”), Statement 15 (90% of the responses fell in the response label “Undecided”), Statement 18 (85% of the responses fell in the response label “Undecided”), and Statement 20 (90% of the responses fell in the response label “Agree”). DBS = Deep Brain Stimulation; S = statement.

**Fig.2.. Percentage of agreement for the 21 statements on the clinical aspects of adaptive DBS (Statement 22–42) among the Delphi Panel members, as result of the third round.**
A consensus was reached for Statement 22 (85% of the responses fell in the response label “Agree”), Statement 25 (85% of the responses fell in the response label “Agree”), Statement 30 (90% of the responses fell in the response label “Agree”), Statement 31 (95% of the responses fell in the response label “Agree”), Statement 32 (90% of the responses fell in the response label “Agree”), Statement 35 (80% of the responses fell in the response label “Agree”), Statement 37 (80% of the responses fell in the response label “Agree”), and Statement 38 (80% of the responses fell in the response label “Undecided”). DBS = Deep Brain Stimulation; S = statement.

See this image and copyright information in PMC

References

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This is a preprint.

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study

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Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study

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Conflict of interest statement

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