Transplantation of adrenal medulla into the caudate nucleus as treatment for
Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of
dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma
catecholamines and metabolites before and after
transplantation. Conjugated
dopamine (the predominant form of
dopamine found in the CSF) and
homovanillic acid (the major
dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free
epinephrine and
norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine
catecholamines and metabolites. CSF
cortisol concentrations were not increased after
transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of
transplantation. The relative concentrations of
dopamine to
epinephrine or
norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the
glucocorticoid influence on
catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain
transplantation reported by others. Continued
transplantation studies in animal models of
parkinsonism are necessary for better elucidation of these factors.