Frontiers in the surgical treatment of Parkinson’s disease

Abstract

Despite the continued refinement of medical and surgical therapies, the treatment of Parkinson's disease (PD) remains challenging. Current treatment strategies are largely focused on managing the motor symptoms of the disease, either by dopamine-based medications or, in advanced stages, by the application of deep brain stimulation to more stably alter the function of the basal ganglia. Important advances have been made in the last decade, but unfortunately a number of the motor symptoms of late-stage PD remain poorly treated, and while currently available therapies address the symptoms of the disease, they fail to alter the course of the disease itself. This has spurred basic and clinical exploration on a number of fronts. Several centers have examined novel stimulation targets to treat refractory symptoms of gait difficulty and axial imbalance. Basic and clinical researchers are examining whether the use of deep brain stimulation might slow the progress of the disease and thus be a useful neuroprotective therapy if initiated earlier in the progression of the disease. An expanded understanding of the genetic and cellular events that underlie PD has led some researchers to explore the use of neurotrophic factors or genetic restoration to preserve threatened neuronal populations. Finally, there has been much research on the use of fetal mesencephalic or stem cell populations to restore dopaminergic function. In this report, we will examine each of these potential new surgical therapies and the promise they may hold for the future treatment of PD.

Deep Brain Stimulation: Technology at the Cutting Edge

“…In addition, these pharmacological therapies are also associated with serious and debilitating motor complications, such as dyskinesias 19. However, significant advances in stereotactic and functional neurosurgical techniques over the last 15 years in response to these shortcomings have led to new strategies in the treatment of advanced PD using electrical stimulation 20-22…”

Neuromodulation: selected approaches and challenges

“…; Remple et al . ; Poewe ). These technological improvements, combined with increased understanding of neuropsychiatric pathophysiology, have generated marked increase in the application of restorative neurosurgical techniques, such as electrical stimulation of specific brain nuclei, known as DBS.…”

Gene Therapy in Parkinsonʼs Disease

“…Although the exact mechanism of action for DBS is not clear, it is proposed that the generated impulses suppress neural activity, which in the case of subthalamic nucleus DBS (STN-DBS), dampens the PD-increased STN abnormal activity resulting in an overall improvement of tremors, rigidity and akinesias. (54, 57, 60, 62, 65, 69–71, 75–79) Often DBS-treated patients are able to reduce their L-dopa dose by ~50–60% resulting in a decrease in dyskinesias and report an improved quality of life. (71, 76, 77, 79) Unfortunately, much like L-dopa therapy, the efficacy of DBS declines as PD progresses.…”