Future and current surgical therapies in Parkinson's disease.
OBJECTIVE
The mainstay of treatment for Parkinson's disease remains medical therapy. With improved surgical precision and decreased morbidity, stereotactic lesioning and deep brain stimulation have become more popular. New therapies currently in clinical trials include gene therapy and direct drug delivery to the brain. The present review discusses surgical therapies for the treatment of Parkinson's disease and the status of experimental strategies currently in preclinical and clinical testing.


RESULTS
Both stereotactic ablation and deep brain stimulation of the thalamus, globus pallidus interna, and subthalamic nucleus are discussed and compared in the current literature. New therapies such as drug infusions into the brain, gene therapy, and neural transplantation are in clinical trials and have been tested extensively in animals. Safety and efficacy of such therapies are discussed in recent literature.


CONCLUSIONS
Although medication remains the first and main line of treatment and the mainstay for Parkinson's disease, advances in techniques and safety of operations have made surgical interventions more popular. Thalamic surgery remains helpful only in a limited subset of patients with predominent tremor that is unresponsive to medication. Bilateral subthalamic nucleus DBS holds the most promising results for patients with tremor, severe motor fluctuations and dyskinesias from L-dopa, with the best improvements seen in daily activities and quality of life. Newer therapies currently in clinical trial include gene therapy to replace lost gamma-aminobutyric acid inputs to the subthalamic nucleus and globus pallidus interna/substantia nigra pars reticulata, and infusion of recombinant glial derived neurotrophic factor to support at-risk nigrostriatal neurons. Further developments in these areas, along with evolution in stem cell science that hopefully will permit replacement of lost neurons, may alter the nature of surgical practice in Parkinson's disease patients in the not too distant future.
Betchen
Simone A
SA
Weill Medical College of Cornell University, New York, NY 10021, USA. mik2002@med.cornell.edu
Kaplitt
Michael
M
D003342:Corpus Striatum / Q000473:pathology / Q000601:surgery; D004599:Electric Stimulation Therapy / Q000379:methods*; D016332:Fetal Tissue Transplantation / Q000379:methods / Q000639:trends; D005544:Forecasting; D015316:Genetic Therapy / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005917:Globus Pallidus / Q000473:pathology / Q000601:surgery; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics; D009474:Neurons / Q000473:pathology; D019635:Neurosurgical Procedures / Q000379:methods* / Q000639:trends*; D010300:Parkinson Disease / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends*; D013378:Substantia Nigra / Q000473:pathology / Q000601:surgery; D020531:Subthalamic Nucleus / Q000473:pathology / Q000601:surgery; D005680:gamma-Aminobutyric Acid / Q000235:genetics
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase