Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease - Methodology and 6-month to 1-year follow-up in 3 patients
Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease - Methodology and 6-month to 1-year follow-up in 3 patients
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DOI：
10.1159/000099859
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发表时间：
1997-01-01
影响因子：
1.7
通讯作者：
Brotchi, J
中科院分区：
文献类型：
--
作者：
Levivier, M;Dethy, S;Brotchi, J
为了开展新的帕金森病（PD）移植项目，我们对3例晚期PD患者进行胎儿腹侧中脑移植的安全性和有效性评估，纳入标准和临床评估严格遵循脑内移植核心评估方案。移植程序是基于先前在Lund（瑞典）和Creteil（法国）的研究小组所描述的技术，所有患者的壳核对侧的主要症状部位进行单侧移植。采用基于多平面相关的磁共振立体定向定位技术，在合拢前、合拢后和合拢后壳核中确定3种着床轨迹。选取当日流产的6 ~ 8周龄人胚胎制备胎儿腹侧中脑。在全身麻醉下，使用定制的微型注射器和连接在立体定向框架上的针头，沿着每个植入轨迹放置8个3 μ l的胎儿组织，间隔1mm。病人在神经外科手术后恢复得很顺利。术后早期MR清晰显示所有患者的植入轨迹到达壳核。3例患者随访时间分别为12个月、9个月和6个月。临床变化出现在移植后3至6个月之间，包括“on”期的增加和运动时间测试的定量双侧改善。统一帕金森氏病评定量表得分有所改善，僵硬度也有所改善。震颤没有变化，运动障碍有轻微和短暂的增加。神经心理学随访显示2例患者有轻微额叶改变。正电子发射断层扫描显示移植部位的f -18-氟多巴摄取增加。不良事件包括1例患者继发于免疫抑制的可逆性库欣综合征，另1例患者出现一过性精神错乱。本研究的结果是更广泛的移植计划的先决条件，与之前其他报道的结果一致，并表明，使用标准化的神经外科技术和评估方法，移植是一种可重复且安全的治疗方法，为晚期PD患者提供临床益处。
In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD, Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Creteil (France), The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen, Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 mu l of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of F-18-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.