Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease.
Two patients with advanced Parkinson's disease were followed for 6 months before, and 18 months after, receiving stereotaxic grafts of fetal mesencephalic tissue from aborted human fetuses. Parameters studied included a series of standardized tests of movement, response to levodopa, electrophysiological recording of the motor readiness potential, and positron emission tomography (PET) with ligands based upon levodopa and upon the dopamine reuptake inhibitor nomifensine. The patients each received stereotaxic implantation of ventral mesencephalic tissue containing midbrain dopamine neurons from aborted human fetuses of 8 to 10 weeks gestational age into the caudate and putamen of one hemisphere. Throughout their 18-month course, the patients were treated with cyclosporine, azathioprine, and glucocorticoids to minimize the risk of graft rejection. There were no significant complications from the procedure, but there was also no major change in their assessment of impairment on the Hoehn and Yahr scale. However, significant changes were observed in clinical, electrophysiological, and PET measures. Changes in these parameters, apparent at 6 months postoperatively, were described in detail in a previous report. The purpose of this present report is to provide follow-up data from the subsequent year with an emphasis on longitudinal evaluation methodology. Standardized clinical testing showed a small but long-term improvement in the first of the two patients. Following the operation, she was able to walk in "off" periods, which she had not been able to do preoperatively. This improvement was accompanied by increased walking speed and reduction in the time necessary to perform a series of pronation and supination movements using both hands. Although these improvements have continued throughout the postoperative period, they have not alleviated her basic neurological impairment. The second patient showed similar improvement during the first 6 months; she then reverted to her preoperative status at the end of the 18-month follow-up period. The electrophysiological recordings were consistent with the clinical findings. Both patients had significant changes in the motor readiness (bereitschafts) potential amplitude, which was greatest 5 to 7 months postoperation. The amplitude of the potential declined subsequently for both patients, but remained significantly elevated over the preoperative baseline for patient 1. The analysis of the PET scans was somewhat compromised by technical problems in the preoperative scans. However, they are also consistent with the clinical data. In comparisons of the operated and the unoperated sides, fluoro-dopa showed increased uptake in the caudate nucleus of patient 1 at 6 months and at 13 months.(ABSTRACT TRUNCATED AT 400 WORDS)
Hoffer
B J
BJ
Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262.
Leenders
K L
KL
Young
D
D
Gerhardt
G
G
Zerbe
G O
GO
Bygdeman
M
M
Seiger
A
A
Olson
L
L
Strömberg
I
I
Freedman
R
R
D016380:Brain Tissue Transplantation; D003265:Contingent Negative Variation; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology; D009043:Motor Activity / Q000502:physiology; D009420:Nervous System / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D009627:Nomifensine / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D009627:Nomifensine; D007980:Levodopa; D004298:Dopamine