ACCURATE: Asleep MRI-guided Versus Awake Microelectrode Recording Guided Deep Brain Stimulation in Parkinson's Disease: A Comparative Effectiveness Trial
Study Details
Study Description
Brief Summary
Rationale: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-accepted treatment for Parkinson's disease (PD). Traditionally, the procedure is performed awake and under local anaesthesia to facilitate intraoperative monitoring via microelectrode recording and test stimulation for exact electrode positioning. Advances in MR imaging allow for clear visualization of the STN and therefore direct targeting. Retrospective series suggest that MRI-guided and image (CT or MRI)-verified STN-DBS under general anaesthesia yields a similar motor outcome and quality of life (QoL) as awake and microelectrode recording-guided surgery with intra-operative clinical testing. MRI-guided and image (CT or MRI)- verified approach potentially has advantages in terms of patient experience and cost-effectiveness. The study proposed here is the first in the world to directly compare both methods.
Objective: To compare bilateral MRI-guided and CT-verified STN-DBS under general anaesthesia to awake microelectrode-guided bilateral STN-DBS with intra-operative clinical testing in terms of motor improvement.
Study design: A multicentre comparative effectiveness trial with a non-inferiority design. Study population: 158 PD people eligible for bilateral STN-DBS (79 in each arm).
Intervention: This study compares two modalities of standard treatment. One arm receives awake microelectrode recording guided bilateral STN-DBS under local anaesthesia with intraoperative clinical testing. The other arm receives MRI-guided and CT-verified bilateral STN-DBS under general anaesthesia.
Main study parameters/endpoints: The primary outcome is the change from baseline to one year in Unified Parkinson's Disease Rating Scale part III (UPDRS III) scores (OFF Medication) versus the postoperative scores (OFF medication and ON stimulation). Secondary objectives include patient experience, quality of life, adverse effects and complications, neuropsychological examination, non-motor symptoms (including psychiatric evaluation), reduction in anti-parkinsonian medication, activities of daily living (ADL) functioning and cost- effectiveness.
Condition or Disease | Intervention/Treatment | Phase |
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Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Awake MER-guided surgical procedure under local anesthesia with intraoperative testing Awake micro-electrode recording-guided surgical procedure under local anesthesia with intraoperative testing |
Procedure: bilateral STN deep brain stimulation
bilateral deep brain stimulation of the subthalamic nucleus in people with Parkinson's disease
|
Asleep MRI-guided and CT-verified surgical procedure Asleep MRI-guided and CT-verified surgical procedure |
Procedure: bilateral STN deep brain stimulation
bilateral deep brain stimulation of the subthalamic nucleus in people with Parkinson's disease
|
Outcome Measures
Primary Outcome Measures
- Unified Parkinson's Disease Rating Scale part III [12 months]
change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part III (min 0, max. 132; higher score means worse outcome)
Secondary Outcome Measures
- reduction in anti-parkinsonian medication [12 months]
change from baseline to 1 year in levodopa equivalent daily dose (LEDD)
- health-related quality of life [12 months]
change from baseline to 1 year in the 39-item Parkinson's Disease Questionnaire (PDQ-39; min. 0, max. 156; higher score means worse outcome)
- Non-motor aspects of experiences of daily living [12 months]
change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part I (min. 0, max. 52; higher score means worse outcome)
- Motor aspects of experiences of daily living measured [12 months]
change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part II (min. 0, max. 52; higher score means worse outcome)
- Motor complications after DBS surgery [12 months]
change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part IV (min. 0, max. 24; higher score means worse outcome)
- Patient experience and satisfaction [during hospitalization and follow up visits at approximately 2 weeks after surgery, 6 and 12 months]
Deep Brain Stimulation Patient Experience Rating Scale (min. 0, max. 224, higher score means better outcome)
- Depressive symptoms [12 months]
change from baseline to 1 year in Beck Depression Inventory-Second Edition (BDI-II; min. 0, max. 63, higher score means worse outcome)
- Non-Motor Symptoms [12 months]
change from baseline to 1 year in Non-Motor Symptoms Assessment Scale (NMSS) for Parkinson's disease (min. 0, max. 360, higher score means worse outcome)
- Impulsivity [12 months]
change from baseline to 1 year in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP; min. 0, max. 112, higher score means worse outcome)
- Cognitive impairment [12 months]
change from baseline to 1 year in Montreal Cognitive Assignment (MoCA; min. 0, max. 30, higher score means better outcome)
- Anxiety [12 months]
change from baseline to 1 year in Parkinson Anxiety Scale (PAS, min. 0, max. 12, higher score means worse outcome)
- Autonomic symptoms [12 months]
change from baseline to 1 year in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT, min. 0, max. 69, higher score means worse outcome)
- Neuropsychiatric symptoms [12 months]
change from baseline to 1 year in he Neuropsychiatric Inventory Questionnaire (NPI-Q, min. 0, max. 36, higher score means worse outcome)
- Patient's sleepiness [12 months]
change from baseline to 1 year in the Epworth Sleepiness Scale (ESS; min. 0, max. 24; higher score means worse outcome)
- Complications and (serious) adverse effects [12 months]
measured with a standardized check list
- Cost effectiveness [during hospitalization (range 3-5 days, median 4 days)]
measured indirectly by duration of operation and duration of hospitalization
Eligibility Criteria
Criteria
Inclusion Criteria:
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30-75 years of age
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Idiopathic Parkinson's disease (according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease)
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Disease duration ≥ 4 years
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Hoehn & Yahr ≤ 3 (in best ON-medication condition)
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Despite optimal pharmacological treatment, at least one of the following symptoms:
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Disturbing response fluctuation
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Dyskinesia
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Painful dystonia
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Drug-resistant tremor
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≥30% improvement of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score in a levodopa challenge test, except for tremor dominant PD. This is conform daily clinical practice in all participating centres.
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Written informed consent
Exclusion Criteria:
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Dementia (Montreal Cognitive Assessment ≤ 25)
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Previous neurosurgical procedures for PD
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Structural lesions on brain MRI
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Contra-indications for DBS surgery
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Contra-indications for MRI
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Current depression or history recurrent severe depression
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History of psychosis
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Need for nursing care
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Life expectancy < 2 years
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Radboud University Medical Center
- Maastricht University Medical Center
- HagaZiekenhuis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, Lanctin D, Hariz MI. An international survey of deep brain stimulation procedural steps. Stereotact Funct Neurosurg. 2013;91(1):1-11. doi: 10.1159/000343207. Epub 2012 Nov 13.
- Ashkan K, Blomstedt P, Zrinzo L, Tisch S, Yousry T, Limousin-Dowsey P, Hariz MI. Variability of the subthalamic nucleus: the case for direct MRI guided targeting. Br J Neurosurg. 2007 Apr;21(2):197-200.
- Binder DK, Rau GM, Starr PA. Risk factors for hemorrhage during microelectrode-guided deep brain stimulator implantation for movement disorders. Neurosurgery. 2005 Apr;56(4):722-32; discussion 722-32.
- Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y, Hand A, Schapira AH. The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study. Mov Disord. 2007 Oct 15;22(13):1901-11.
- Chen T, Mirzadeh Z, Chapple KM, Lambert M, Shill HA, Moguel-Cobos G, Tröster AI, Dhall R, Ponce FA. Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease. J Neurosurg. 2018 Mar 16;130(1):109-120. doi: 10.3171/2017.8.JNS17883.
- Chircop C, Dingli N, Aquilina A, Zrinzo L, Aquilina J. MRI-verified "asleep" deep brain stimulation in Malta through cross border collaboration: clinical outcome of the first five years. Br J Neurosurg. 2018 Aug;32(4):365-371. doi: 10.1080/02688697.2018.1478061. Epub 2018 May 26.
- Counelis GJ, Simuni T, Forman MS, Jaggi JL, Trojanowski JQ, Baltuch GH. Bilateral subthalamic nucleus deep brain stimulation for advanced PD: correlation of intraoperative MER and postoperative MRI with neuropathological findings. Mov Disord. 2003 Sep;18(9):1062-5.
- Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. Review.
- Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, Daniels C, Deutschländer A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908. Erratum in: N Engl J Med. 2006 Sep 21;355(12):1289.
- Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-S8. doi: 10.3233/JPD-181474. Review.
- Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059.
- Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.
- Gorgulho A, De Salles AA, Frighetto L, Behnke E. Incidence of hemorrhage associated with electrophysiological studies performed using macroelectrodes and microelectrodes in functional neurosurgery. J Neurosurg. 2005 May;102(5):888-96.
- Hariz M, Blomstedt P, Limousin P. The myth of microelectrode recording in ensuring a precise location of the DBS electrode within the sensorimotor part of the subthalamic nucleus. Mov Disord. 2004 Jul;19(7):863-864. doi: 10.1002/mds.20135.
- Hariz MI, Krack P, Melvill R, Jorgensen JV, Hamel W, Hirabayashi H, Lenders M, Wesslen N, Tengvar M, Yousry TA. A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes. Stereotact Funct Neurosurg. 2003;80(1-4):96-101.
- Ho AL, Ali R, Connolly ID, Henderson JM, Dhall R, Stein SC, Halpern CH. Awake versus asleep deep brain stimulation for Parkinson's disease: a critical comparison and meta-analysis. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):687-691. doi: 10.1136/jnnp-2016-314500. Epub 2017 Mar 1.
- Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967 May;17(5):427-42.
- Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5.
- LaHue SC, Ostrem JL, Galifianakis NB, San Luciano M, Ziman N, Wang S, Racine CA, Starr PA, Larson PS, Katz M. Parkinson's disease patient preference and experience with various methods of DBS lead placement. Parkinsonism Relat Disord. 2017 Aug;41:25-30. doi: 10.1016/j.parkreldis.2017.04.010. Epub 2017 Apr 17.
- Leentjens AF, Dujardin K, Pontone GM, Starkstein SE, Weintraub D, Martinez-Martin P. The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety scale. Mov Disord. 2014 Jul;29(8):1035-43. doi: 10.1002/mds.25919. Epub 2014 May 23.
- Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, Perret JE, Benabid AL. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet. 1995 Jan 14;345(8942):91-5.
- Marinus J, Visser M, Jenkinson C, Stiggelbout AM. Evaluation of the Dutch version of the Parkinson's Disease Questionnaire 39. Parkinsonism Relat Disord. 2008;14(1):24-7. Epub 2007 Aug 16.
- McClelland S 3rd. A cost analysis of intraoperative microelectrode recording during subthalamic stimulation for Parkinson's disease. Mov Disord. 2011 Jul;26(8):1422-7. doi: 10.1002/mds.23787. Epub 2011 Jun 14.
- Nakajima T, Zrinzo L, Foltynie T, Olmos IA, Taylor C, Hariz MI, Limousin P. MRI-guided subthalamic nucleus deep brain stimulation without microelectrode recording: can we dispense with surgery under local anaesthesia? Stereotact Funct Neurosurg. 2011;89(5):318-25. doi: 10.1159/000330379. Epub 2011 Sep 15.
- Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. Erratum in: J Am Geriatr Soc. 2019 Sep;67(9):1991.
- Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424. Review.
- Thissen AJ, van Bergen F, de Jonghe JF, Kessels RP, Dautzenberg PL. [Applicability and validity of the Dutch version of the Montreal Cognitive Assessment (moCA-d) in diagnosing MCI]. Tijdschr Gerontol Geriatr. 2010 Dec;41(6):231-40. Dutch.
- Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010 Nov 15;25(15):2649-53. doi: 10.1002/mds.23429. Review.
- Vinke RS, Selvaraj AK, Geerlings M, Georgiev D, Sadikov A, Kubben PL, Doorduin J, Praamstra P, Bloem BR, Bartels RHMA, Esselink RAJ. The Role of Microelectrode Recording and Stereotactic Computed Tomography in Verifying Lead Placement During Awake MRI-Guided Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease. J Parkinsons Dis. 2022;12(4):1269-1278. doi: 10.3233/JPD-223149.
- Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ. Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT. Mov Disord. 2004 Nov;19(11):1306-12.
- Weintraub D, Mamikonyan E, Papay K, Shea JA, Xie SX, Siderowf A. Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Mov Disord. 2012 Feb;27(2):242-7. doi: 10.1002/mds.24023. Epub 2011 Dec 1.
- Wodarg F, Herzog J, Reese R, Falk D, Pinsker MO, Steigerwald F, Jansen O, Deuschl G, Mehdorn HM, Volkmann J. Stimulation site within the MRI-defined STN predicts postoperative motor outcome. Mov Disord. 2012 Jun;27(7):874-9. doi: 10.1002/mds.25006. Epub 2012 Apr 19.
- Xiaowu H, Xiufeng J, Xiaoping Z, Bin H, Laixing W, Yiqun C, Jinchuan L, Aiguo J, Jianmin L. Risks of intracranial hemorrhage in patients with Parkinson's disease receiving deep brain stimulation and ablation. Parkinsonism Relat Disord. 2010 Feb;16(2):96-100. doi: 10.1016/j.parkreldis.2009.07.013. Epub 2009 Aug 13.
- Zrinzo L, Foltynie T, Limousin P, Hariz MI. Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg. 2012 Jan;116(1):84-94. doi: 10.3171/2011.8.JNS101407. Epub 2011 Sep 9. Review.
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