In patients with advanced disease that is poorly responsive to pharmacotherapy, worthwhile benefit may follow thalamotomy (for conspicuous tremor) or posteroventral pallidotomy. Ablative surgical procedures, however, have generally been replaced by functional, reversible lesions induced by high-frequency deep brain stimulation, which has a lower morbidity.
Stimulation of the subthalamic nucleus or globus pallidus by an implanted electrode and stimulator has yielded good results for the management of the clinical fluctuations occurring in advanced parkinsonism. The anatomic substrate for such therapy is indi-cated in Figure 28–1. Such procedures are contraindicated in patients with secondary or atypical parkinsonism, dementia, or failure to respond to dopaminergic medication.
In a controlled trial of the transplantation of dopaminergic tis-sue (fetal substantia nigra tissue), symptomatic benefit occurred in younger (less than 60 years old) but not older parkinsonian patients. In another trial, benefits were inconsequential. Furthermore, uncontrollable dyskinesias occurred in some patients in both studies, perhaps from a relative excess of dopamine from continued fiber outgrowth from the transplant. Additional basic studies are required before further trials of cellular therapies—inparticular, stem cell therapies—are undertaken, and such approaches therefore remain investigational.