Deep-Brain Stimulation Better Than Best Medical Therapy in Advanced Parkinson Disease

In the latest issue of JAMA, a large, multicenter, randomized, rater-blinded VA study reveals that DBS, when compared with best medical therapy, significantly improved several motor and functional outcome measures* at 6 months, in 255 patients with advanced PD. These efficacy data essentially mirror those of a smaller, randomized study of DBS vs medical therapy in a younger set of PD patients.

However, in the latest study, DBS was more frequently associated with falls, gait disturbance, imbalance, depression, and dystonia than medical therapy, and surgical-site infection and pain were respectively experienced by 10% and 9% of patients who received DBS. These patients were also more likely to experience serious adverse events, most of which related to surgery, the stimulation device, or stimulation therapy. One patient who received DBS died as a result of cerebral hemorrhage. Nevertheless, an important finding of the study is that younger and older (≥70 years of age) patients tolerated DBS equally well.

The procedure, which has become increasingly popular for PD during the last decade, involves the stereotactic placement of stimulation electrodes in the bilateral subthalamic nucleus or globus pallidus internus under local anesthesia. The exact site of electrode implantation is ultimately determined by its intraoperative clinical effect on PD symptoms at the lowest possible level of stimulation. Each electrode is connected to a pulse generator (eg, Medtronic's Kinetra), which is implanted just below the clavicle under general anesthesia. According to Deuschl et al, the standard pulse setting for DBS stimulation in PD is 60 μsec at 130 Hz (C below "middle C"?); voltage settings are individualized per patient.

DBS is intended to modulate activity of the basal-ganglia loop, a complex neuronal circuit that is involved in the genesis of higher cortical behavior—including motor and cognitive tasks. The substantia nigra, which degenerates in PD, activates this circuit. In the case of PD, loss of substantia-nigra input into the basal-ganglia loop results in the overactivity of some cell groups, like those in the subthalamic nucleus or globus pallidus internus. DBS is intended to attenuate this overactivity. (The second phase of the JAMA study will specifically compare the separate effects of DBS on these 2 different subcortical areas.) 

What isn't known is the optimal timing of DBS and its long-term effects, including neuropsychiatric effects. According to Deuschl (in an accompanying JAMA editorial), most patients undergo the procedure more than 10 years after disease onset, when PD is advanced. He anticipates that the use of DBS for PD will increase, as the population ages. Data from 55 medical centers are currently available for more than 5300 PD patients who have undergone DBS.

For more info about DBS and PD, see the web sites for the NINDS and the National Parkinson Foundation.

VA = Veterans Affairs.

* Mean "on" time without troubling dyskinesias (the primary endpoint), motor function, and quality-of-life measures.

Depiction of DBS from the FDA.