Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a parkinsonian patient treated with fetal allografts

Abstract

Background: Since 1985, treatment of idiopathic Parkinson's disease (PD) by surgical transfer of adult or fetal chromaffin tissue or of fetal central neural tissue to the brains of afflicted patients has been attempted, with variable clinical results. Neuropathologic studies of the status of these transplants are few and show wide variation in degree of graft survival.

Methods: We report the case of a 52-year-old man, who, 23 months earlier, received both intrastriatal implantation and intraventricular infusion of tissues derived from fetuses of 15 to 16 weeks and 5 to 6 weeks gestational age. Clinical improvement, as measured by increased amounts of "on" time with reduced levodopa requirements, seemed to occur over the subsequent months. He died suddenly at home after a several-hours interval of progressive lethargy and breathing difficulties.

Results: At autopsy, the diagnosis of PD was confirmed. Intrastriatal graft sites were identified, but contained no viable neurons; astrogliosis, focal microgliosis, and mixed inflammatory response, suggesting allograft rejection, were present. Surprisingly, the intraventricular tissues survived and showed ectodermal and mesenchymal, but no neural, differentiation, as well as cellular response; the left lateral and fourth ventricles were filled completely by this proliferated tissue.

Conclusions: By intraventricular infusion, tissues from early-gestation sources can engraft successfully, grow, and survive for at least 23 months in the brain of a PD patient. However, contamination by, or differentiation into, nonneural tissues can occur, can lead to proliferation of tissues within ventricular spaces, and may result in ventricular obstruction. Grafts, whether intraventricular or intraparenchymal, are capable of inciting host responses, which in turn may limit their long-term survival. Finally, post-transplant clinical improvement in symptoms of PD may be unrelated to survival of engrafted neurons.