Uneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson's Disease

TLDR

Autografting of dopamine‑producing tissue into the striatum is being explored as a treatment for Parkinson’s disease. The study aimed to identify the optimal striatal subregion for autograft implantation by examining dopamine loss patterns in post‑mortem tissue from eight idiopathic Parkinson’s patients. The authors measured dopamine concentrations across putamen and caudate subdivisions in these autopsy samples. They found near‑complete depletion of dopamine in the putamen—especially its caudal portions—while the caudate retained substantial dopamine except for the dorsal rostral part, indicating that motor deficits stem mainly from putamen loss and that the caudal putamen is the preferred site for dopamine autografts.

Abstract

Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.