LAS VEGAS—In addition to reducing the symptoms of early-stage Parkinson’s disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) may alter the course of the disease, according to research presented at the 17th Annual Meeting of the North American Neuromodulation Society. Animal studies suggest that DBS of the STN protects against the progressive loss of nigral cells associated with Parkinson’s disease. Researchers have evaluated the technique’s safety in humans and plan a phase II study to investigate whether DBS offers neuroprotection.
Clinical experience with DBS has provided anecdotal evidence for such an effect in humans. Fifteen years after implantation, patients with advanced Parkinson’s disease continue to return to the clinic for generator replacements, said Peter Konrad, MD, PhD, Associate Professor of Neurosurgery and Biomedical Engineering at Vanderbilt University Medical Center in Nashville. If these patients had received medical therapy alone, they likely would have more disease burden than they actually have, or possibly be bedridden, he added.
DBS Is Associated With Neuroprotection in Animals
A study published in Brain in 2007 examined four groups of monkeys. One group received medical treatment and an STN lesion, one group received medical treatment and DBS of the STN, one group received medical treatment alone, and one group received no treatment. The number of dopaminergic cells in the substantia nigra pars compacta was significantly higher among animals that received medical treatment and DBS or lesion than among animals that had not received medical treatment or alteration of the STN. Both the lesion and the DBS appeared to reduce the amount of additional nigral cell loss. Administering the lesion or DBS outside the STN did not have any effect on cell loss.
In a more recent study, researchers found that DBS of the STN protected nigral cell count in rats with early-stage Parkinson’s disease. Implants that were placed outside the STN did not seem to affect nigral cell death, noted Dr. Konrad. Glutamate can be neurotoxic at high levels, and investigators speculate that DBS may reduce further cell death in the nigra by controlling glutamate output from the STN, he added.
Early DBS May Be Safe in Humans
Dr. Konrad and colleagues conducted a prospective, randomized pilot trial of DBS in 30 patients with early Parkinson’s disease (ie, Hoehn–Yahr stage 2). Fifteen participants received DBS implantation and optimal drug therapy, and 15 patients received optimal drug therapy alone. At the end of the trial, patients discontinued their medicines for one week and were rated on the Unified Parkinson’s Disease Rating Scale (UPDRS). “There does not appear to be any clinical difference in risk for patients undergoing early versus later implantation of DBS,” said Dr. Konrad.
The group plans to follow up the 30 participants for five additional years, discontinue their medications once more, and examine their UPDRS scores. The study is powered to evaluate the safety of DBS of the STN, but not to determine whether the treatment is neuroprotective. The group does plan to address the latter question in a phase II, randomized, multicenter study, however. The patient population will be large enough to provide “meaningful” evidence about the effect of early STN stimulation, concluded Dr. Konrad.