Moving in the Right Direction: Deep Brain Stimulation for PD
Moving in the Right Direction: Deep Brain Stimulation for PD
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports no financial relationship relevant to this field of study.
Synopsis: Deep brain stimulation of the subthalamic nucleus improved "off" motor symptoms and quality of life in advanced Parkinson's disease, but was associated with an increased rate of serious adverse events.
Source: Deuschl G, et al. A Randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006;355:896-908. Erratum in: N Engl J Med. 2006;355:1289.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an FDA-approved treatment for advanced Parkinson's disease (PD), but there is a need for additional large, randomized, controlled trials to clarify the safety and efficacy of this procedure. In this study, an unblinded, randomized-pairs design was used to compare STN DBS with medical management alone. Subjects (n = 156) were recruited from 10 academic medical centers in Germany and Austria, and then enrolled in pairs (78 pairs), with one subject randomly assigned to bilateral STN DBS (plus medications) and the other to best medical therapy. Study subjects were < 75 years old, diagnosed with idiopathic PD for at least 5 years, experiencing disabling motor symptoms or dyskinesias, and did not have dementia, major psychiatric illness, or contraindications to surgery. Surgical techniques were based on the protocol of the enrolling institution. Primary end points were the changes in quality of life on the Parkinson's Disease Questionnaire (PDQ-39), and the severity of motor symptoms in the "off" state (after 12 hour medication withdrawal) on the Unified Parkinson's Disease Rating Scale part III (UPDRS III). Secondary end points included changes in self-reported activities of daily living scores (UPDRS part II and Schwab and England Disability Scale).
Six months after enrollment, an intention-to-treat analysis showed that subjects who received DBS had 1) a greater improvement in PDQ-39 quality of life scores in 50/78 pairs (P = 0.02) and 2) a greater improvement in motor scores on the UPDRS-III during medication withdrawal in 55/78 pairs (P < 0.001). The DBS group, as a whole, had a mean improvement of 25% in the PDQ-39, with benefits in mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort; they did not show improvement in social support, cognition, or communication. The DBS group also had a 41% improvement in the mean UPDRS-III motor scores 12 hours after medication withdrawal. In contrast, the mean PDQ-39 and UPDRS-III scores were unchanged in the medical management group. Activities of daily living scores on the UPDRS-II during medication withdrawal showed a 39% improvement in the DBS group, compared with a 5% worsening in the non-DBS group. Serious adverse events were significantly more common in the DBS group (13% vs 4%, P < 0.04), and included a fatal intracerebral hemorrhage during surgery and a suicide 5 months after randomization.
Commentary
DBS is a highly effective intervention for advanced PD that can improve cardinal motor symptoms (tremor, rigidity, and bradykinesia) and reduce disabling motor complications, such as dyskinesias and end-of-dose "wearing off." Selection of appropriate surgical candidates is critical, since the procedure does not help midline symptoms such as postural instability, and can worsen non-motor symptoms such as cognitive impairment. Adverse events include not only expected problems such as stroke and infection, but also neuropsychiatric disorders and suicidality.
The results of this study add to a growing body of literature supporting the role for STN DBS in carefully selected patients with advanced PD. They show that DBS can improve quality of life and "off" motor disability in relatively young, non-demented patients whose symptoms are poorly controlled with medications alone. Study limitations include the relatively brief follow up time and the lack of blinded raters; several of the authors also had financial ties to Medtronic, Inc., which makes the DBS hardware. Future studies are needed to clarify the ideal patient characteristics, surgical techniques, and timing of surgical intervention, so that physicians will be able to provide patients with individualized, evidence-based treatment recommendations.
Deep brain stimulation of the subthalamic nucleus improved "off" motor symptoms and quality of life in advanced Parkinson's disease, but was associated with an increased rate of serious adverse events.Subscribe Now for Access
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