Evaluation of surgery for Parkinson’s disease (1999)

the Task Force on Surgery for Parkinson's Disease* PD is a common disorder affecting on average 100 per 100,000 population.Despite the large number of medications available for the treatment of early and moderately advanced PD, options specifically designed for the patient with advanced disease are limited.Surgery for PD dates from 1939-1940, when Bucy and Case 1 and Klemme 2 excised parts of the cerebral cortex to treat tremor and dystonia, but this type of surgery produced hemiparesis.Surgical basal ganglia lesions were introduced a few years later by Meyers, 3,4 who found that pallidotomy produced significant relief of tremor, rigidity, and dyskinesias, but with considerable mortality.Stereotaxic techniques to coagulate the globus pallidus in PD were introduced in the 1950s by Spiegel and Wycis, 5,6 and Cooper was an early advocate of pallidal surgery. 7Based on the anatomic connections between the pallidum and the thalamus, Hassler introduced the concept of surgery on the ventrolateral nucleus of the thalamus. 8,9icroelectrode recording allowed Narabayashi 10,11 to find that lesioning the ventral intermediate (Vim) nucleus of the thalamus was the most specific target to control the tremor in PD.Neurosurgery reached its peak in the 1960s, but declined after the introduction of levodopa.The recent resurgence of surgery was initiated by adrenal medullary transplantation.The premise of adrenal medullary transplants was that these cells, when transplanted into patients with advanced PD, would survive and function as a new source of dopamine.The theoretical advantages of adrenal tissue include that the tissue comes from the patient, eliminating the issue of immunologic rejection; dopamine is a normal intermediate compound made by the chromaffin cells; and chromaffin cells may have neuritic morphology when grown in culture.The disadvantages include the non-neuronal source and the rather modest survival rates of cells in laboratory transplantation studies.Isolated case reports of effective treatment of advanced PD with unilateral transplantation of adrenal medullary cells into the striatum in the 1980s led to several clinical trials testing the safety and efficacy of this procedure.Fetal mesencephalon transplantation was introduced subsequently and is based on several considerations.First, PD is associated with relatively selective degeneration of dopaminergic cells located in the substantia nigra, a portion of the mesencephalon.Second, replacement of dopaminergic activity by means of precursor drugs, receptor agonists, or inhibitors of dopamine catabolism improves the signs and symptoms of PD.Third, laboratory evidence in experimental animals has demonstrated that grafts of dopamine-containing neurons improve behavioral models of PD.Fourth, in these animal models, grafts reinnervate the striatum and form synaptic connections with host neurons.As a result, a small number of research teams have developed programs for human fetal mesencephalic cell grafts in PD patients.Several published reports exist, although each has a small number of cases, and often multiple reports pertain to the same patients, followed for varying periods of time or studied with different ancillary research protocols.Fetal transplantation poses several challenges not encountered with adrenal medullary transplants, including questions of the proper age of the fetus, preservation and implantation techniques, immunosuppression, and finally the ethical issues related to use of fetal material.