Dopamine cell implantation in Parkinson's disease: long-term clinical and (18)F-FDOPA PET outcomes.
Dopamine cell implantation in Parkinson's disease: long-term clinical and (18)F-FDOPA PET outcomes.
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DOI：
10.2967/jnumed.109.066811
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Eidelberg D
中科院分区：
文献类型：
--
作者：
Ma Y;Tang C;Chaly T;Greene P;Breeze R;Fahn S;Freed C;Dhawan V;Eidelberg D
我们之前报道过一项1年双盲、安慰剂对照的胚胎多巴胺细胞植入治疗帕金森病的研究结果。在盲法期结束时，我们发现18f -氟多巴（18F-FDOPA） PET的壳核摄取显著增加，反映了移植物的活力。尽管如此，临床改善仅在年轻（年龄≤60岁）的移植受者中是显著的，正如统一帕金森病评定量表（UPDRS）运动评分的降低所表明的那样。我们现在报告了移植后随访2年的33名原始试验参与者的长期临床和PET结果，其中15名受试者又随访了2年。采用重复测量方差分析评估UPDRS运动评分、尾状核和壳核18F-FDOPA摄取的纵向变化。这些变化之间随时间的关系通过分析受试者内部相关性来评估。我们发现UPDRS运动评分随移植后时间的推移而下降（P < 0.001）。对于年轻的移植受者和男性，1岁时的临床改善相对更好，但这些年龄和性别差异在长期随访中并不明显。在移植后的所有时间点，壳核18F-FDOPA摄取明显增加（P < 0.001），且不受年龄或性别的影响。在整个研究过程中，移植后壳核PET信号的变化与临床结果显著相关（P < 0.02）。体素水平的图像分析显示，在1 y时，后壳核植入部位的双侧18F-FDOPA摄取显著增加（P < 0.001）。在植入后2和4 y，该区域的PET信号进一步增强。同时，该分析揭示了未移植尾状核和腹侧壳核的放射性示踪剂摄取逐渐下降。移植后的临床改善与术前基线时该区域PET信号的保留有关。这些结果表明，移植后临床获益和移植物活力可持续4年。此外，临床（而非影像学）结果对受试者1岁时的年龄和性别的依赖性可能不会长期存在。最后，在整个移植后时间过程中，影像学变化与临床结果可靠相关。
We have previously reported the results of a 1-y double-blind, placebo-controlled study of embryonic dopamine cell implantation for Parkinson’s disease. At the end of the blinded phase, we found a significant increase in putamen uptake on 18F-fluorodopa (18F-FDOPA) PET reflecting the viability of the grafts. Nonetheless, clinical improvement was significant only in younger (age ≤ 60 y) transplant recipients, as indicated by a reduction in Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores. We now report long-term clinical and PET outcomes from 33 of the original trial participants who were followed for 2 y after transplantation and 15 of these subjects who were followed for 2 additional years. Longitudinal changes in UPDRS motor ratings and caudate and putamen 18F-FDOPA uptake were assessed with repeated-measures ANOVA. Relationships between these changes over time were evaluated by the analysis of within-subject correlations. We found that UPDRS motor ratings declined over time after transplantation (P < 0.001). Clinical improvement at 1 y was relatively better for the younger transplant recipients and for men, but these age and sex differences were not evident at longer-term follow-up. Significant increases in putamen 18F-FDOPA uptake were evident at all posttransplantation time points (P < 0.001) and were not influenced by either age or sex. Posttransplantation changes in putamen PET signal and clinical outcome were significantly intercorrelated (P < 0.02) over the course of the study. Image analysis at the voxel level revealed significant bilateral increases in 18F-FDOPA uptake at 1 y (P < 0.001) in the posterior putamen engraftment sites. PET signal in this region increased further at 2 and 4 y after engraftment. Concurrently, this analysis disclosed progressive declines in radiotracer uptake in the nonengrafted caudate and ventrorostral putamen. Clinical improvement after transplantation correlated with the retention of PET signal in this region at the preoperative baseline. These results suggest that clinical benefit and graft viability are sustained up to 4 y after transplantation. Moreover, the dependence of clinical (but not imaging) outcomes on subject age and sex at 1 y may not persist over the long term. Last, the imaging changes reliably correlate with clinical outcome over the entire posttransplantation time course.
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影响因子：
14.5
作者：
Mendez, I;Sanchez-Pernaute, R;Isacson, O
通讯作者：
Isacson, O
影响因子：
11.2
作者：
Ma, YL;Feigin, A;Eidelberg, D
通讯作者：
Eidelberg, D
影响因子：
11.2
作者：
Olanow, CW;Goetz, CG;Freeman, TB
通讯作者：
Freeman, TB
影响因子：
--
作者：
BLAND, JM;ALTMAN, DG
通讯作者：
ALTMAN, DG
影响因子：
11.2
作者：
Wenning, GK;Odin, P;Lindvall, O
通讯作者：
Lindvall, O