Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial - 23/01/12

Doi : 10.1016/S1474-4422(11)70308-8

Michael S Okun, DrMD ^a,^⁎ , Bruno V Gallo, MD ^c, George Mandybur, MD ^e, Jonathan Jagid, MD ^d, Kelly D Foote, MD ^b, Fredy J Revilla, MD ^f, Ron Alterman, MD ^g, Joseph Jankovic, MD ⁱ, Richard Simpson, MD ^j, Fred Junn, MD ^k, Leo Verhagen, MD ^l, Jeff E Arle, MD ^m, Blair Ford, MD ⁿ, Robert R Goodman, MD ^o, R Malcolm Stewart, MD ^p, Stacy Horn, DO ^q, Gordon H Baltuch, MD ^r, Brian H Kopell, MD ^s, Frederick Marshall, MD ^t, DeLea Peichel, BS ^u, Rajesh Pahwa, MD ^v, Kelly E Lyons, PhD ^v, Alexander I Tröster, PhD ^w, Jerrold L Vitek, MD ^x, Michele Tagliati, MD ^h

for the SJM DBS Study Group^{^‡}
For study group members see end of Article

^a Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida College of Medicine, Gainesville, FL, USA

^b Department of Neurological Surgery, University of Florida College of Medicine, Gainesville, FL, USA

^c Department of Neurology, School of Medicine, University of Miami, Miami, FL, USA

^d Department of Neurosurgery, School of Medicine, University of Miami, Miami, FL, USA

^e Department of Neurosurgery, The Neuroscience Institute/Mayfield Clinic, University of Cincinnati College of Medicine, Cincinnati, OH, USA

^f Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA

^g Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY, USA

^h Department of Neurology, Cedars-Sinai, Los Angeles, CA, USA

ⁱ Department of Neurology, Baylor College of Medicine, Houston, TX, USA

^j Department of Neurosurgery, The Methodist Hospital Physician Organization, Houston, TX, USA

^k Department of Neurosurgery, Oakwood Hospital and Health System, Dearborn, MI, USA

^l Rush University Medical Center Neurological Sciences, Chicago, IL, USA

^m Department of Neurosurgery, Lahey Clinic, Burlington, MA, USA

ⁿ Movement Disorder Group, Columbia University Medical Center, New York, NY, USA

^o The Neurological Institute of New York, Columbia University Medical Center, New York, NY, USA

^p Texas Health Presbyterian Dallas Movement Disorder Center, Dallas, TX, USA

^q Department of Neurology, Parkinson’s Disease and Movement Disorders Center, UPHS: Pennsylvania Hospital, Philadelphia, PA, USA

^r Department of Neurosurgery, Parkinson’s Disease and Movement Disorders Center, UPHS: Pennsylvania Hospital, Philadelphia, PA, USA

^s Department of Neurosurgery, Medical College Wisconsin, Milwaukee, WI, USA

^t Neurology Department, University of Rochester, Rochester, NY, USA

^u Clinical Research Department, St Jude Medical Neuromodulation Division, Plano, TX, USA

^v Parkinson’s Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, KS, USA

^w Department of Neurology, University of North Carolina - Chapel Hill, Chapel Hill, NC, USA

^x Department of Neurology, University of Minnesota School of Medicine, Minneapolis, MN, USA

^* Correspondence to: Dr Michael S Okun, University of Florida College of Medicine, Center for Movement Disorders and Neurorestoration, 3450 Hull Road, 4th Floor, Gainesville, FL 32607, USA

Summary

Background

The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson’s disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus.

Methods

This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18–80 years, had Parkinson’s disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients’ diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474.

Findings

Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87–4·16]; p=0·003). Unified Parkinson’s disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups.

Interpretation

Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation.

Funding

St Jude Medical Neuromodulation Division.

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Plan

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Methods

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Randomisation and masking

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Statistical analysis

Role of the funding source

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Vol 11 - N° 2

P. 140-149 - février 2012 Retour au numéro

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Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial - 23/01/12

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