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Original research
Unilateral focused ultrasound subthalamotomy in early Parkinson’s disease: a pilot study
  1. Raúl Martínez Fernández1,2,
  2. Elena Natera Villalba1,3,
  3. Rafael Rodriguez-Rojas1,2,
  4. Marta del Álamo1,
  5. Jose A Pineda-Pardo1,2,
  6. Ignacio Obeso1,
  7. David Mata-Marín1,4,
  8. Pasqualina Guida1,4,
  9. Tamara Jimenez-Castellanos1,5,
  10. Diana Pérez-Bueno6,
  11. Alicia Duque7,
  12. Jorge U Máñez Miró1,4,
  13. Carmen Gasca-Salas1,2,
  14. Michele Matarazzo1,2,
  15. Jose A Obeso1,2
  1. 1 HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  2. 2 Instituto Carlos III, CIBERNED, Madrid, Spain
  3. 3 PhD Medicine Program, Universidad Autonoma de Madrid, Madrid, Spain
  4. 4 PhD Neuroscience Program, Universidad Autonoma de Madrid, Madrid, Spain
  5. 5 PhD Epidemiology and Public Health Program, Universidad Autonoma de Madrid, Madrid, Spain
  6. 6 Anesthesia Department, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  7. 7 Neuroradiology Department, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  1. Correspondence to Professor Jose A Obeso, HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, 28938, Spain; jobeso.hmcinac{at}hmhospitales.com

Abstract

Background Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson’s disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD).

Methods Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients’ impression of change.

Results Twelve patients with PD (median age 52.0 (IQR 49.8–55.3) years, median time from diagnosis 3.0 (2.1–3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment.

Conclusion Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted.

Trial registration number NCT04692116

  • PARKINSON'S DISEASE
  • ULTRASOUND

Data availability statement

Data are available upon reasonable request. Deidentified participant data from RMF (rmartinez.hmcinac@hmhospitales.com) upon reasonable request.

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Data availability statement

Data are available upon reasonable request. Deidentified participant data from RMF (rmartinez.hmcinac@hmhospitales.com) upon reasonable request.

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Footnotes

  • RMF and ENV are joint first authors.

  • Twitter @ElenaNatera, @matarazzomd

  • RMF and ENV contributed equally.

  • Contributors RMF, ENV and JAO conceptualised the research, developed and wrote the protocol, participated in FUS treatments, assessed patients during clinical visits, participated in the acquisition, analysis and interpretation of data, wrote the first draft of the manuscript, and reviewed subsequent versions for content. RRR participated in FUS treatments, analysed MRI data, provided imaging figures and revised the manuscript for content. MdA, JAPP, TJC, DPB, CGS and MM participated in FUS treatments and revised the manuscript for content. IO, DMM and PG performed neuropsychological assessments and revised the manuscript for content. AD analysed MRI data and revised the manuscript for content. JUMM revised the manuscript for content. RMF and JAO are guarantors of the work.

  • Funding This study was supported by Fundación de Investigación HM Hospitales and Fundación MAPFRE. ENV was supported in 2021 for this specific project by a fellowship from the Movement Disorders Group of the Spanish Neurology Society (Sociedad Española de Neurología, SEN) granted by Zambon.

  • Competing interests RMF has received speaker honoraria from Insightec, Bial, Zambon and Boston Scientific, and reimbursement of travel expenses to attend scientific conferences from Insightec and Bial. ENV was supported in 2021 by a fellowship from the Movement Disorders Group of the Spanish Neurology Society (Sociedad Española de Neurología) granted by Zambon and has received honoraria for lectures from Zambon and Palex. RRR has received speaker honoraria from Insightec and Zambon. MdA has received speaker honoraria from Insightec and Boston Scientific and reimbursement of travel expenses to attend scientific conferences from Boston Scientific and Medtronic. JAPP declares no conflicts of interest nor additional disclosures to report. DMM declares no conflicts of interest nor additional disclosures to report. PG declares no conflicts of interest nor additional disclosures to report. TJC has received speaker honoraria from Insightec and Zambon. DPB declares no conflicts of interest nor additional disclosures to report. AD declares no conflicts of interest nor additional disclosures to report. JUMM has received speaker honoraria from Insightec, Bial, Zambon, UCB Pharma, Lundbeck and Italfarmaco, and reimbursement of travel expenses to attend scientific conferences from Insightec and Bial. CGS has received speaker honoraria from Exeltis, Esteve and Fundación ACE, and a grant from Asociacion Madrileña de Neurologia, funded by Bial. MM has received speaker honoraria from Teva Pharmaceutical Industries and Novartis and reimbursement of travel expenses to attend scientific conferences from Lundbeck and Cerevel Therapeutics. JAO has received honoraria for lecturing and reimbursement of travel expenses to attend scientific meetings by Insightec.

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

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