The efficacy and limits of magnetic resonance–guided focused ultrasound pallidotomy for Parkinson’s disease: a Phase I clinical trial

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OBJECTIVE

Recently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson’s disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia.

METHODS

A prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.

RESULTS

Unilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the “medication-off” UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects.

CONCLUSIONS

In the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.

Clinical trial registration no.: NCT02003248 (clinicaltrials.gov)

ABBREVIATIONS DBS = deep brain stimulation; ET = essential tremor; GPi = globus pallidus interna; MRgFUS = MR-guided focused ultrasound; PD = Parkinson’s disease; RF = radiofrequency; UDysRS = Unified Dyskinesia Rating Scale; UPDRS = Unified Parkinson’s Disease Rating Scale.
Article Information

Contributor Notes

Correspondence Jin Woo Chang: Yonsei University College of Medicine, Seoul, Korea. jchang@yuhs.ac.INCLUDE WHEN CITING Published online August 10, 2018; DOI: 10.3171/2018.2.JNS172514.Disclosures Dr. Chang: grants from the Michael J. Fox Foundation, Focused Ultrasound Surgery Foundation, and other funding from InSightec.

© AANS, except where prohibited by US copyright law.

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References
  • 1

    Aarsland DCreese BPolitis MChaudhuri KRffytche DHWeintraub D: Cognitive decline in Parkinson disease. Nat Rev Neurol 13:2172312017

  • 2

    Alkhani ALozano AM: Pallidotomy for Parkinson disease: a review of contemporary literature. J Neurosurg 94:43492001

  • 3

    American Institute of Ultrasound in Medicine Bioeffects Committee: Bioeffects considerations for the safety of diagnostic ultrasound. J Ultrasound Med 7 (9 Suppl):S1S381988

    • Search Google Scholar
    • Export Citation
  • 4

    Blomstedt PHariz MI: Are complications less common in deep brain stimulation than in ablative procedures for movement disorders? Stereotact Funct Neurosurg 84:72812006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Bond AEDallapiazza RHuss DWarren ALSperling SGwinn R: A randomized, sham-controlled trial of transcranial magnetic resonance-guided focused ultrasound thalamotomy trial for the treatment of tremor-dominant, idiopathic Parkinson disease. Neurosurgery 63 (Suppl 1):1542016

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Bulluss KJPereira EAJoint CAziz TZ: Pallidotomy after chronic deep brain stimulation. Neurosurg Focus 35(5):E52013

  • 7

    Chang WSJung HHKweon EJZadicario ERachmilevitch IChang JW: Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry 86:2572642015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Chang WSJung HHZadicario ERachmilevitch ITlusty TVitek S: Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull. J Neurosurg 124:4114162016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Chung SJHong SHKim SRLee MCJeon SR: Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson’s disease. Eur Neurol 56:1131182006

  • 10

    de Bie RMde Haan RJNijssen PCRutgers AWBeute GNBosch DA: Unilateral pallidotomy in Parkinson’s disease: a randomised, single-blind, multicentre trial. Lancet 354:166516691999

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Dewhirst MWViglianti BLLora-Michiels MHanson MHoopes PJ: Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. Int J Hyperthermia 19:2672942003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Dobrakowski PPMachowska-Majchrzak AKLabuz-Roszak BMajchrzak KGKluczewska EPierzchała KB: MR-guided focused ultrasound: a new generation treatment of Parkinson’s disease, essential tremor and neuropathic pain. Interv Neuroradiol 20:2752822014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Elias WJLipsman NOndo WGGhanouni PKim YGLee W: A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 375:7307392016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Fine JDuff JChen RChir BHutchison WLozano AM: Long-term follow-up of unilateral pallidotomy in advanced Parkinson’s disease. N Engl J Med 342:170817142000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Fox SHKatzenschlager RLim SYRavina BSeppi KCoelho M: The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov Disord 26 (Suppl 3):S2S412011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Hua ZGuodong GQinchuan LYaqun ZQinfen WXuelian W: Analysis of complications of radiofrequency pallidotomy. Neurosurgery 52:891012003

  • 17

    Jeanmonod DWerner BMorel AMichels LZadicario ESchiff G: Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus 32(1):E12012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Jenne JW: Non-invasive transcranial brain ablation with high-intensity focused ultrasound. Front Neurol Neurosci 36:941052015

  • 19

    Jung HHKim SJRoh DChang JGChang WSKweon EJ: Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry 20:120512112015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Krack PMartinez-Fernandez RDel Alamo MObeso JA: Current applications and limitations of surgical treatments for movement disorders. Mov Disord 32:36522017

  • 21

    Laitinen LVBergenheim ATHariz MI: Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76:53611992

  • 22

    Lang AELozano AMMontgomery EDuff JTasker RHutchinson W: Posteroventral medial pallidotomy in advanced Parkinson’s disease. N Engl J Med 337:103610421997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Lipsman NSchwartz MLHuang YLee LSankar TChapman M: MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 12:4624682013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Lozano AMLang AEGalvez-Jimenez NMiyasaki JDuff JHutchinson WD: Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 346:138313871995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Magara ABühler RMoser DKowalski MPourtehrani PJeanmonod D: First experience with MR-guided focused ultrasound in the treatment of Parkinson’s disease. J Ther Ultrasound 2:112014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Martin EJeanmonod DMorel AZadicario EWerner B: High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol 66:8588612009

  • 27

    Merello MNouzeilles MIKuzis GCammarota ASabe LBetti O: Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: a prospective randomized comparison. Mov Disord 14:50561999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Moser DZadicario ESchiff GJeanmonod D: MR-guided focused ultrasound technique in functional neurosurgery: targeting accuracy. J Ther Ultrasound 1:32013

  • 29

    Munhoz RPCerasa AOkun MS: Surgical treatment of dyskinesia in Parkinson’s disease. Front Neurol 5:652014

  • 30

    Na YCChang WSJung HHKweon EJChang JW: Unilateral magnetic resonance-guided focused ultrasound pallidotomy for Parkinson disease. Neurology 85:5495512015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Nakamura KChristine CWStarr PAMarks WJ Jr: Effects of unilateral subthalamic and pallidal deep brain stimulation on fine motor functions in Parkinson’s disease. Mov Disord 22:6196262007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    O’Brien WD Jr: Ultrasound-biophysics mechanisms. Prog Biophys Mol Biol 93:2122552007

  • 33

    Sapareto SADewey WC: Thermal dose determination in cancer therapy. Int J Radiat Oncol Biol Phys 10:7878001984

  • 34

    Spindola BLeite MAOrsini MFonoff ELandeiro JAPessoa BL: Ablative surgery for Parkinson’s disease: Is there still a role for pallidotomy in the deep brain stimulation era? Clin Neurol Neurosurg 158:33392017

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Vitek JLBakay RAFreeman AEvatt MGreen JMcDonald W: Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol 53:5585692003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Vykhodtseva NSorrentino VJolesz FABronson RTHynynen K: MRI detection of the thermal effects of focused ultrasound on the brain. Ultrasound Med Biol 26:8718802000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Wu ZKumon RELaughner JIEfimov IRDeng CX: Electrophysiological changes correlated with temperature increases induced by high-intensity focused ultrasound ablation. Ultrasound Med Biol 41:4324482015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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