司来吉兰对早期帕金森病患者多巴胺能神经元的影响

背景：司来吉兰可有效缓解早期帕金森病的运动障碍症状，但对于早期帕金森病预后的影响争议甚多。神经影像学的研究进展使得帕金森病多巴胺能神经元的变性程度客观标记成为可能。目的：利用影像学观察研究司来吉兰对早期帕金森病多巴胺能神经元的影响。设计：以患者为研究对象的随机对照实验。单位：一所军队医院的神经内科和一所军医大学医院的核医学科．神经内科。对象：2001-04／10第二军医大学长海医院神经内科帕金森病专病门诊筛选的25例未经任何药物治疗的早期帕金森病患者。干预：25例患者随机分为安慰剂组和司来吉兰治疗组，安慰剂组13例，司来吉兰治疗组12例。联合帕金森病量表(Unified Parkinson’s disease rating scale，UPDRS)评分后，按照逐渐增量的原则，分别给予安慰剂和司来吉兰治疗(起始剂量均为0．05mg)。每周增加0．05mg，经过4周的加量期，剂量均达到0．2mg，此后维持剂量恒定。于入组时、治疗13个月后分别行多巴胺转运蛋白(^99Tc^m-TRODAT-1)单光子发射型计算机体层扫描(single photon emission-cnmputered tomography，SPECT)检查，半定量法分析起病肢体对侧、同侧纹状体放射计数。于入组时、治疗6个月、治疗13个月后分别进行UPDRS评分。主要观察指标：①主要结局：两组治疗13个月后起病肢体对侧、同侧纹状体^99Tc^m-TRODAT-1特异性摄取降低百分率的比较。②次要结局：两组UPDRS评分的变化。结果：治疗13个月后起病肢体对侧、同侧纹状体^99Tc^m-TRODAT-1特异性摄取降低百分率分别为：安慰剂组(28．9&;#177;13．0)％、(31．8&;#177;15．6)％；司来吉兰治疗组(30．39&;#177;14．7)％、(32．6&;#177;166)％，两组之间比较差异无显著性意义(P&;gt;0．05)。UPDRS评分：治疗6个月后，安慰剂组(23．7&;#177;4．3)分，司来吉兰治疗组(13．1&;#177;5．5)分；治疗13个月后，安慰剂组(27．0&;#177;4．3)分，司来吉兰治疗组(9．8&;#177;4．8)分，司来吉兰治疗组明显优于安慰剂组(P&;lt;0．05)。结论：司来吉兰对早期帕金森病的I临床效果较好，而且不加重纹状体多巴胺能神经元的凋亡。     

早期未经替代治疗帕金森病患者脑多巴胺的单光子发射计算机断层扫描显像特点

目的:探讨脑多巴胺转运体99Tcm-TRODAT-1与多巴胺D2受体131I- epidepride单光子发射计算机断层扫描显像在早期帕金森病中的临床应用价值。方法:选择2002/2004长海医院门诊收治的46例早期未经替代治疗的帕金森病患者(H-Y Ⅰ级22例,Ⅱ级24例),分别接受脑多巴胺转运体 99Tcm-TRODAT-1 与多巴胺D2受体131I-epidepride单光子发射计算机断层扫描断层显像,利用感兴趣区技术计算纹状体与枕叶、额叶的放射性比值。结果:46例全部进入结果分析。①脑多巴胺转运体99Tcm-TRODAT-1 单光子发射计算机断层扫描显像结果:Ⅰ,Ⅱ级患者起病肢体对侧纹状体-枕叶／枕叶和纹状体-额叶／额叶放射性比值较同侧明显降低 (P<0．05,0．001);Ⅱ级患者起病肢体对侧纹状体-枕叶／枕叶放射性比值明显低于Ⅰ级患者(0.33±9．99,0．75+0．18 F=4．121,P<0．05)。②脑D2 受体131I-epidepride单光子发射计算机断层扫描显像分析结果:Ⅰ,Ⅱ级患者起病肢体对侧纹状体-枕叶／枕叶和纹状体-额叶／额叶放射性比值较同侧明显增高(P<0．05,0．01);Ⅱ级患者起病肢体对侧纹状体-枕叶／枕叶放射性比值明显高于Ⅰ级(1．33±0．70,0．69±0.37,F=5.493,P<0．05)。结论:①多巴胺神经元突触前多巴胺转运体与H-Y分期呈负相关。②早期未经替代治疗的帕金森病患者突触前多巴胺转运体与突触后D2 受体呈明显负相关。③人脑多巴胺转运体99Tcm-TRODAT-1与D2受体 131I-epidepride单光子发射计算机断层扫描显像结合将有助于帕金森病的早期诊断及病情临测。     

培高利特对早期帕金森病患者纹状体多巴胺能神经元自然变性率及其运动能力的影响：一项双盲、随机、平行、安慰剂对照实

目的：探讨培高利特对早期帕金森病患者纹状体多巴胺能神经元的影响以及改善患者肢体运动能力的作用。方法：选择2001-04／2001-12在上海长海医院神经内科帕金森病专病门诊就诊、未经抗帕金森病药物治疗、具有单侧肢体运动徐缓、震颤、强直、特殊姿势的早期帕金森病患者22例为研究对象；男14例，女8例；年龄55～70岁。所有患者均书面同意参加该试验，整个试验过程中能坚持服用单一药物治疗，未经同意不能改动治疗方案。将患者随机分为安慰剂组11例和培高利特组11例。安慰剂组给予苯海索治疗，培高利特组给予培高利特治疗。苯海索、培高利特起始日剂量均为0．05mg。入组第l周时，每日服用1次；以后每周增加1粒，经过1个月左右达到日剂量0．25mg，此后维持剂量恒定(该剂量苯海索抗帕金森病作用不明显，故安慰剂组可称为帕金森病自然变性组)。①观察两组治疗前及治疗后13个月纹状体^99Tc^m-2β-[N’双(2-硫乙基)乙撑二胺基]甲基，3β-(4氯苯基)托烷单光子发射计算机断层扫描特异性摄取值百分率的变化，评估纹状体多巴胺神经元的变性数量。②观察治疗前，治疗后6，13个月时帕金森病评定量表变化，评估培高利特对肢体运动功能障碍的改善作用。结果：最终进入结果分析的帕金森病患者22例。①治疗13个月后，安慰剂组和培高利特组患者起病肢体对侧纹状体^99Tc^m-2β-[N’双(2-硫乙基)乙撑二胺基]甲基，3β-(4氯苯基)托烷特异性摄取下降值百分率分别为(31．8&;#177;15．6)％，(33．8&;#177;17．2)％，两组比较，无明显差异(P&;gt;0．05)；起病肢体同侧纹状体^99Tc^m-2β-[N’双(2-硫乙基)乙撑二胺基]甲基，3β-(4氯苯基)托烷特异性摄取下降值百分率分别为(28．9&;#177;13．0)％，(34．4&;#177;18．1)％，两组比较，无明显差异(P&;gt;0．05)。②培高利特组治疗后6，13个月帕金森病评定量表评分[(13．0&;#177;6．0)，(10．O&;#177;5．9)分]明显低于安慰剂组评分[(23．7&;#177;4．3)，(27．0&;#177;4．3)分](t=4．69，5．87，P&;lt;0．01)。培高利特组治疗13个月时帕金森病评分量表评分明显低于治疗前(t=2．13，P&;lt;0．05)。结论：早期帕金森病患者经培高利特治疗13个月后，起病肢体同侧和对侧纹状体多巴胺能神经元的变性率与应用苯海索大致相同，说明培高利特治疗不增加该区域多巴胺能神经元的自然变性率；而培高利特治疗后帕金森病评定量表评分的下降表明该药具有提高早期帕金森病患者运动能力的作用。     

99Tcm-TRODAT-1 SPECT脑显像对早期帕金森病患者纹状体及多巴胺转运蛋白功能变化的评估价值

目的探讨99Tcm-TRODAT-1 SPECT脑显像在早期帕金森病(Parkinson disease,PD)评估中的价值,为实施有效的神经保护治疗提供理论依据.方法对10例早期PD患者(Hoehn-YahrⅠ级)和10例年龄匹配正常对照者分别进行99Tcm-TRODAT-1 SPECT脑显像,应用计算机感兴趣技术分别计算早期PD患者和正常对照者双侧纹状体/小脑的放射性计数比值,并对结果进行比较分析.结果早期PD患者的患侧肢体对侧纹状体/小脑的放射性计数比值(1.53±0.09)较正常对照者(双侧均值为1.74±0.05)明显降低,差异有显著性意义(t=6.802,P=0.000),较同侧(1.67±0.07)也有降低,差异有显著性意义(t=4.035,P=0.000 8),并且患侧肢体同侧纹状体/小脑的放射性计数比值较正常对照者也有降低,差异有显著性意义(t=2.896,P=0.0096).结论早期PD患者患侧肢体对侧纹状体DAT的功能明显降低,同侧纹状体的功能也有降低,99Tcm-TRODAT-1 SPECT脑显像有助于PD的早期诊断.     

培高利特、美多巴起始治疗对早期帕金森病患者预后的影响

背景:培高利特与美多巴都是治疗帕金森病的有效药物,但对于帕金森病患者愈后的影响尚有争议,神经影像学的进展使得定量评价药物治疗对帕金森病的预后影响成为可能。目的:采用99Tcm-TRODAT-1多巴胺能转运体单光子发射型计算机体层扫描成像结合联合帕金森病量表评分,观察培高利特、美多巴作为起始治疗对早期帕金森病患者预后及对纹状体多巴胺能神经元的影响。设计:随机分组、平行对照、安慰剂对照实验。单位:解放军第八一医院神经内科,解放军第二军医大学长海医院神经内科与核医学科。对象:选择2002-02/07上海长海医院神经内科帕金森病专病门诊收治的未经任何药物治疗的早期帕金森病患者36例,随机分为安坦对照组、培高利特组、美多巴组,12例/组。所有入选患者均书面同意参加试验,诊断符合英国帕金森病协会制定的临床诊断标准,本实验经过长海医院伦理委员会批准实施。干预措施:安坦对照组、培高利特组、美多巴组患者接受联合帕金森病量表评分、多巴胺转运体行单光子发射型计算机体层扫描显像检查后,分别服用各自药物,每粒安坦、培高利特、美多巴胶囊含药物分别为0.05,0.05,125mg。第1周时1粒/次,1次/d;以后每周的日剂量较上周日剂量增加1粒,治疗1个月使日剂量分别达到0.2,0.2,500mg。此后维持剂量恒定,治疗6,10个月分别用联合帕金森病量表进行疗效评定。所有患者治疗10个月后,分别进行脑纹状体多巴胺转运体单光子发射型计算机体层扫描成像,半定量法分析受累肢体同侧或对侧纹状体99Tcm-TRODAT-1的特异性摄取值。主要观察指标:①比较3组治疗10个月后受累肢体同侧、对侧99Tcm-TRODAT-1特异性摄取值降低百分率的变化。②比较3组治疗前后联合帕金森病量表评分的变化。结果:实验纳入患者36例,治疗10个月后3组各脱落1例,最终33例患者进入结果分析。①各组治疗10个月后受累肢体同侧、对侧99Tcm-TRODAT-1特异性摄取值降低百分率的变化:治疗10个月后,美多巴组受累肢体同侧、对侧99Tcm-TRODAT-1特异性摄取值降低百分率均明显高于安坦对照组、培高利特组[(46.3±19.4)%,(28.9±13.0)%,(34.4±18.1)%;(47.5±20.8)%,(31.8±15.6)%,(33.8±17.2)%;P均<0.05]。②各组治疗前后联合帕金森病量表评分的变化:与治疗前比较,治疗10个月后安坦对照组无明显变化,但美多巴组、培高利特组均明显下降[(15.5±8.68),(6.4±9.05)分;(15.8±6.75),(10.36±8.30)分;P均<0.05]。结论:美多巴、培高利特虽都能对早期帕金森病起到有效治疗,但对于帕金森病患者的预后影响不同。美多巴可能会加速多巴胺能神经元的凋亡而使病情恶化,培高利特则不影响帕金森病的预后,更适合作为早期帕金森病治疗的选择药物。     

99Tcm-TRODAT-1 SPECT DAT显像与帕金森病UPDRS评分关系的研究

目的:探讨帕金森病(PD)患者双侧纹状体对99Tcm-TRODAT-1特异性摄取浓度与统一帕金森病评分量表(UPDRS)评分的关系,从影像学上对PD病情严重程度进行评价。方法:对51例PD患者以及15例正常对照组分别行99Tcm-TRODAT-1 SPECT多巴胺转运体(DAT)显像,利用感兴趣区技术计算双侧纹状体与小脑的特异性放射性比值(ST/CB)及两侧纹状体特异性放射性摄取比值的不对称指数(AIPD、AICON),同时对PD患者进行UPDRS评分和Hoehn-Yahr分级。结果:PD患者双侧ST/CB值与UPDRS日常生活能力、运动功能评分以及Hoehn-Yahr分级呈显著负相关,PD患者两侧纹状体特异性放射性摄取比值的不对称指数与PD病情呈负相关。结论:PD患者双侧纹状体对99Tcm-TRODAT-1特异性摄取浓度与UPDRS评分以及Hoehn-Yahr分级存在良好的相关性,能够监测PD的病情,反映PD病情的严重程度。     

99Tcm-TRODAT-1多巴胺转运蛋白SPECT脑显像在亚临床期和临床期帕金森病模型猴诊断中的研究

目的探讨99Tcm-TRODAT-1多巴胺转运蛋白SPECT脑显像在帕金森病亚临床期诊断中的价值.方法对4只食蟹猴静脉注射多巴胺转运蛋白显像剂99Tcm-TRODAT-1,观察99Tcm-TRODAT-1在不同时间点正常猴体内分布并进行纹状体DAT功能分析.用MPTP分别制备无症状亚临床期和临床期PD猴模型,利用计算机感兴趣区(ROI)技术进行纹状体DAT功能半定量分析.结果99Tcm-TRODAT-1最佳SPECT脑显像时间为注射99Tcm-TRODAT-1后3～4 h.PD猴毁损侧(右侧)纹状体在亚临床期就已存在DAT功能的降低,并随着损伤的加重毁损侧纹状体DAT功能进一步降低,对侧纹状体的DAT也受损.结论99Tcm-TRODAT-1 SPECT脑显像可用于PD的亚临床期诊断和病情监测.     

99Tcm-TRODAT-1单光子发射计算机断层脑显像对早期帕金森病与原发性震颤的评估与鉴别

目的探讨应用99Tcm-TRODAT-1进行单光子发射计算机断层扫描(SPECT)脑多巴胺转运蛋白(dopaminetransporter,DAT)显像鉴别诊断早期帕金森病与原发性震颤(essential tremor,ET)的临床应用价值.方法对江苏省原子医学研究所收治的30例帕金森病患者(Ⅰ级),17例ET患者和9例健康志愿者行99Tcm-TRODAT-1 SPECT DAT显像,并应用ROI技术测定纹状体与小脑部位的放射性比值.结果与正常对照组相比,ET患者纹状体区对99Tcm-TRODAT-1的摄取仅有轻微降低,并无明显差别;帕金森病患者双侧纹状体区对99Tcm-TRODAT-1的摄取均明显减少(P＜0.01).帕金森病患者与ET患者相比也表现为降低(P＜0.01),且帕金森病患者双侧纹状体不对称,而ET患者却非如此.结论99Tcm-TRODAT-1SPECT DAT显像对鉴别帕金森病与ET是一种可靠的方法.     

运用单光子发射计算机断层扫描显像研究培补肝肾中药治疗帕金森病的疗效机制

目的:运用99Tcm-TRODAT-1的单光发射计算机断层扫描(SPECT)显像研究培补肝肾中药治疗帕金森病疗效机制。方法:制备偏侧猴模型,造模前后及服用培补肝肾中药2个月后分别进行脑99Tcm-TRODAT-1的SPECT检查,观察纹状体对多巴胺转运体(DAT)特异性放射性摄取率的变化,并观察行为学改变。结果:偏侧帕金森病模型猴1-甲基-4-苯基1,2,3,6-四氢吡啶(MPTP)注射侧和对侧纹状体DAT的特异性放射性摄取率均显著低于正常猴,中药治疗2个月后,偏侧帕金森病模型猴的主要症状有所改善,MPTP注射侧和对侧纹状体DAT的特异性放射性摄取率较治疗前明显增加。结论:培补肝肾中药对多巴胺能神经元有一定的保护作用。     

培高利特对早期帕金森病患者纹状体多巴胺能神经元自然变性率及其运动能力的影响:一项双盲、随机、平行、安慰剂对照实验

目的:探讨培高利特对早期帕金森病患者纹状体多巴胺能神经元的影响以及改善患者肢体运动能力的作用。方法:选择2001-04/2001-12在上海长海医院神经内科帕金森病专病门诊就诊、未经抗帕金森病药物治疗、具有单侧肢体运动徐缓、震颤、强直、特殊姿势的早期帕金森病患者22例为研究对象;男14例,女8例;年龄55～70岁。所有患者均书面同意参加该试验,整个试验过程中能坚持服用单一药物治疗,未经同意不能改动治疗方案。将患者随机分为安慰剂组11例和培高利特组11例。安慰剂组给予苯海索治疗,培高利特组给予培高利特治疗。苯海索、培高利特起始日剂量均为0.05mg。入组第1周时,每日服用1次;以后每周增加1粒,经过1个月左右达到日剂量0.25mg,此后维持剂量恒定(该剂量苯海索抗帕金森病作用不明显,故安慰剂组可称为帕金森病自然变性组)。①观察两组治疗前及治疗后13个月纹状体99Tcm-2β-犤N'双(2-硫乙基)乙撑二胺基犦甲基,3β-(4氯苯基)托烷单光子发射计算机断层扫描特异性摄取值百分率的变化,评估纹状体多巴胺神经元的变性数量。②观察治疗前,治疗后6,13个月时帕金森病评定量表变化,评估培高利特对肢体运动功能障碍的改善作用。结果:最终进入结果分析的帕金森病患者22例。①治疗13个月后,安慰剂组和培高利特组患者起     

司来吉兰治疗早期帕金森病睡眠障碍的临床研究

目的 研究司来吉兰治疗早期帕金森病（Parkinson disease ,PD）睡眠障碍的临床疗效和安全性。方法 将90例已用安坦、金刚烷胺、维生素E联合治疗的早期PD患者随机分为司来吉兰组和艾司唑仑组,前者在原用药物剂量不变的基础上添加司来吉兰片,5 mg／d ,后者添加艾司唑仑1 mg／d。疗程均为4周。90例患者在治疗前后分别进行匹兹堡睡眠质量指数（PSQI）问卷调查,分析两组患者在治疗前后的睡眠情况。同时在加药前后进行常规实验室指标检测,分析比较不良反应发生情况。结果 两组在治疗后PS Q I评分均明显好转,与治疗前相比较差异均有显著性（ P ＜0．01）。司来吉兰组和艾司唑仑组治疗后的 PSQI评分相比较差异无显著性（ P ＞0．05）。在PSQI中睡眠质量、日间功能、催眠药物三个因子的评分,两组在治疗后相比较差异有显著性（ P＜0．05）。司来吉兰组的总不良反应发生率为17．8％,艾司唑仑组为36．9％,两组间相比较差异有显著性（ P ＜0．05） ,其中治疗后嗜睡和直立性低血压不良反应发生率比较,司来吉兰组显著低于艾司唑仑组（ P ＜0．01）。结论 司来吉兰治疗早期帕金森病睡眠障碍安全、有效,并且在减少催眠药物的使用以及改善PD患者睡眠质量和日间功能方面明显优于艾司唑仑,值得推广应用。     

左旋多巴治疗对帕金森病大鼠纹状体强啡肽原表达的影响

目的 :观察左旋多巴 (L dopa)治疗对帕金森病 (PD )大鼠纹状体强啡肽原表达的影响 ,探讨L dopa诱发异动症 (LID)的机制。方法 :SD大鼠 36只 ,随机分为PD组、LID组和正常组。PD组及LID组大鼠以 6 OHDA损毁单侧黑质致密部建立PD模型 ,LID组 2周后腹腔注射L dopa甲酯 苄丝肼 ,每日 2次 ,持续 4周 ,制备LID大鼠模型。分别取各组大鼠纹状体组织检测强啡肽原 (Prodynorphin ,PDyn)mRNA的表达水平。结果 :LID组大鼠L dopa治疗过程中 ,大多数出现继发异常不自主运动障碍 ,累及损毁对侧头、躯干、前肢和口面部肌肉。PD大鼠损毁侧纹状体内PDynmRNA水平较正常组大鼠减低 (P <0 .0 1) ,而反复L dopa治疗导致其表达水平明显高于其它 2组 (P <0 .0 1)。结论 :长期间断应用L dopa导致多巴胺缺失的纹状体区表达D1受体γ 氨基丁酸 (GABA)神经元选择性活化 ,纹状体区PDynmRNA表达增加参与了LID的发生     

Selegiline in the treatment of mild to moderate Alzheimer-type dementia

Selegiline, an inhibitor of monoamine oxidase B, was tested on patients with mild to moderate dementia of the Alzheimer type. Its efficacy and tolerability were compared with that of phosphatidylserine in a randomized, single-blind, parallel fashion. Forty patients (24 men and 16 women) entered the trial. Selegiline was administered in 10-mg tablets once daily and phosphatidylserine in 100-mg capsules twice daily, both treatments lasting three months. Drug efficacy was assessed at baseline and then each month by means of an extensive battery of neuropsychological tests. The assessment of drug safety was based on monitoring for adverse drug reactions and on routine laboratory tests performed before and after treatment. At the end of the study the selegiline group showed improvements statistically significantly superior to those obtained in the phosphatidylserine group on most of the cognitive areas examined. Furthermore, of particular interest was the discovery, found only in the selegiline group, of an increased degree of autonomy in day-to-day activities. Tolerability was good, the only side effect reported in both groups being slight or moderate nausea, which was severe enough to warrant withdrawal from treatment only in one case, a patient in the selegiline group with a history of gastroduodenitis.     

Rotigotine transdermal system for the treatment of Parkinson's disease

BACKGROUND: Levodopa has been the cornerstone of the treatment of Parkinson's disease (PD) for >30 years, but long-term levodopa therapy is associated with development of such motor complications as motor fluctuations, dyskinesias, and drug-induced involuntary movements. Rotigotine is a dopamine agonist with high affinity for the D(2) receptor. Rotigotine transdermal system, the first such system approved by the US Food and Drug Administration for the management of PD, has been formulated to deliver a consistent concentration of drug to the bloodstream with the goal of minimizing the complications associated with pulsatile dosing. OBJECTIVE: This article reviews the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and efficacy of rotigotine transdermal system in the treatment of PD. METHODS: MEDLINE (1966-April 2008) and International Pharmaceutical Abstracts (1971-April 2008) were searched using the term rotigotine. All prospective, randomized clinical efficacy trials in humans were included. The reference lists of the identified articles were reviewed for additional publications. RESULTS: In clinical trials, rotigotine transdermal system at doses ranging from 4.5 to 67 mg/d was associated with significant clinical benefit in patients with early and advanced PD. In 4 randomized, doubleblind, placebo-controlled trials of 6 months' duration, patients receiving rotigotine transdermal system had significant improvements on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) that ranged from -0.3 to -4.2, compared with +0.92 to -2 for placebo (P < 0.001, rotigotine transdermal system vs placebo). In one trial that included pramipexole as an active comparator, the change in UPDRS II at 6 months was -4.2 in the rotigotine transdermal system group and -4.6 in the pramipexole group (P = NS, rotigotine transdermal system vs pramipexole). Changes on the UPDRS III (motor examination) at 6 months ranged from -3.58 to -8.7 with rotigotine transdermal system, compared with +0.38 to -4.3 in the placebo group and -10.3 in the pramipexole group (P < 0.001 vs placebo; P = NS vs pramipexole). The change in "off" time at 6 months ranged from -2.1 to -2.7 hours with rotigotine transdermal system, compared with -0.9 hour with placebo and -2.8 hours with pramipexole (P < 0.001 vs placebo; P = NS vs pramipexole). The proportion of patients achieving a >30% reduction in "off" time ranged from 55.1% to 59.7% of patients receiving rotigotine transdermal system, compared with 34.5% to 35.0% of patients receiving placebo and 67.0% of patients receiving pramipexole (P<0.001 vs placebo; P = NS vs pramipexole). The most commonly reported adverse event was application-site reaction, occurring in 9% to 46% of patients receiving rotigotine transdermal system, compared with 5% to 13% of patients receiving placebo. Other adverse events occurring in >20% of patients receiving rotigotine transdermal system were somnolence(8%\2-33%)and nausea(12%-49%). Less than 5% of patients assigned to rotigotine transdermal system discontinued study medication because of an adverse drug event. CONCLUSIONS: The available evidence suggests that rotigotine transdermal system was effective compared with placebo in decreasing morbidity in patients with early and advanced PD. The most commonly reported adverse events associated with rotigotine transdermal system were application-site reaction, nausea, and somnolence. Additional clinical trials are needed to determine the long-term tolerability profile of rotigotine transdermal system and its clinical efficacy and tolerability compared with oral dopamine agonists.     

帕金森患者丘脑区磁共振波谱研究价值

目的利用多体素磁共振波谱技术(magnetic resonance spectroscopy,MRS)研究帕金森病(Parkinson’s disease,PD)患者丘脑区代谢物质的变化,探讨PD患者丘脑区MRS比值与临床Hoehn&Yahr分级评分量表(H-Y分级)和帕金森病统一评分量表(unified Parkinson’s disease rating scale,UPDRS)之间的相关性。材料与方法对30例确诊的PD患者和24名年龄、性别等相匹配的志愿者为研究对象,将其分为PD组和对照组,并对PD组30例患者进行H-Y分级和UPDRS评分。使用Philips Achieva TX 3.0 T MR成像系统多体素1H-MRS技术对研究对象的双侧丘脑区进行检测,获取相应代谢物比值及谱线信息。探讨PD组丘脑区MRS比值与临床H-Y分级的关系,并比较其与UPDRS量表之间的相关性。结果 (1)对照组左、右侧丘脑NAA/Cr、Cho/Cr、NAA/Cho值差异无统计学意义(P>0.05);PD组症状严重侧与对侧丘脑NAA/Cr、Cho/Cr值表现出统计学差异(P<0.05)。(2)PD组症状重侧丘脑区NAA/Cr值与NAA/Cho值,以及对侧的NAA/Cr值较对照组明显减低,差异具有统计学意义(P<0.05)。(3)对照组、早、中、晚期帕金森患者的症状重侧NAA/Cr、NAA/Cho及对侧NAA/Cr比值整体比较有统计学差异,进一步进行多重比较,发现PD患者症状重侧NAA/Cr值在病情进展中存在统计学差异。Spearman相关性分析显示PD患者症状重侧丘脑区NAA/Cr值与H-Y分级存在极强的负相关性,症状重侧丘脑区NAA/Cho值、对侧丘脑区的NAA/Cr值及Cho/Cr值与H-Y分级存在中等强度负相关性。(4) Pearson相关分析显示,PD患者的症状重侧丘脑区NAA/Cr值与UPDRS评分存在极强的负相关性,NAA/Cho值与UPDRS评分存在中等强度的负相关性。对侧的NAA/Cr值与Cho/Cr值与UPDRS评分存在中等强度的负相关性。结论 1H-MRS能够无创性检测出丘脑区神经功能的减低,并与帕金森病症状体征的不对称性进展具有密切关系,能够为帕金森病的诊断提供一定的依据。MRS相关代谢物比值与H-Y分级和UPDRS评分之间存在一定的相关性,在反映病情程度及分期上具有一定辅助作用。     

Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease

Regenerative medicine for the treatment of motor features in Parkinson's disease (PD) is a promising therapeutic option. Donor cells can simultaneously address multiple pathological mechanisms while responding to the needs of the host tissue. Previous studies have demonstrated that mesenchymal stromal cells (MSCs) promote recovery using various animal models of PD. SanBio Inc. has developed a novel cell type designated SB623, which are adult bone marrow‐derived MSCs transfected with Notch intracellular domain. In this preclinical study, SB623 cells protected against 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced nigrostriatal injury when transplanted unilaterally into C57BL/6 mouse striatum 3 days prior to toxin exposure. Specifically, mice with the SB623 cell transplants revealed significantly higher levels of striatal dopamine, tyrosine hydroxylase immunoreactivity and stereological nigral cell counts in the ipsilateral hemisphere vs vehicle‐treated mice following MPTP administration. Interestingly, improvement in markers of striatal dopaminergic integrity was also noted in the contralateral hemisphere. These data indicate that MSCs transplantation, specifically SB623 cells, may represent a novel therapeutic option to ameliorate damage related to PD, not only at the level of striatal terminals (i.e. the site of implantation) but also at the level of the nigral cell body. Copyright © 2015 John Wiley & Sons, Ltd.     

还原型谷胱甘肽治疗帕金森病

目的:探讨还原型谷胱甘肽(GSH)治疗帕金森病(PD)的价值。方法:38例原发性PD患者随机分为2 组,均予抗PD药物治疗,GSH组联合静脉注射还原型GSH600mg。治疗前后分别采用PD评分量表(UPDRS)进 行临床评价和血清总抗氧化能力(TRAP)、谷胱甘肽过氧化物酶(GSH Px)和脂质过氧化物含量(LPO)测定。结 果:与对照组比较,GSH组UPDRS评分无显著改善,而TRAP、GSH Px活性显著增高,LPO含量显著降低(P<0. 05),疗效持续时间>4个月。结论:GSH能够发挥辅助性治疗作用,提高机体抗氧化能力。     

Effect of subcutaneous apomorphine on tremor in idiopathic Parkinson's disease.

Among the cardinal symptoms of Parkinson's disease (PD) rest tremor is the least responsive to dopaminergic treatment, raising the assumption that it may not be directly related to the loss of dopaminergic neurons. Apomorphine is a potent short-acting dopamine agonist that rapidly ameliorates symptoms of PD. The aim of this study was to evaluate the extent to which apomorphine can suppress tremor in patients with idiopathic PD compared to other symptoms. The study group included 18 patients with Parkinson's disease. Increasing doses of 1mg, 2mg, and 4 mg of subcutaneous apomorphine were used. Treatment response was assessed with the motor section of the unified Parkinson's disease rating scale (UPDRS). Tremor, rigidity and bradykinesia were scored using specific items of the UPDRS. UPDRS motor score improved from 31.5+/-9 at baseline to 20.0+/-6.4 after treatment. The scores for tremor, bradykinesia and rigidity improved after administration of apomorphine. The improvement in each of these scores for each individual patient was not significantly different, i.e., the magnitude of improvement was similar for all symptoms. These results indicate that subcutaneous apomorphine appears to be as effective in the treatment of tremor in Parkinson's disease as compared to the other symptoms.     

清晨关期对早期帕金森病患者生活质量的影响

目的探讨清晨关期(early-morning off, EMO)对早期帕金森病(Parkinson’s disease, PD)患者生活质量的影响。方法 60例原发性早期PD患者,根据是否出现EMO分为EMO组30例和无EMO组30例。采用PD统一评分量表(Unified Parkinson’s Disease Rating Scale, UPDRS)、Hoehn-Yahr(H-Y)分级评估病情严重程度,采用PD生活质量量表(39-Item-Parkinson’s Disease Questionnaire, PDQ-39)评测患者生活质量,采用简易精神状态检查量表(Mini-mental State Examination, MMSE)评估患者精神状态,采用汉密尔顿焦虑量表(14-Item Hamilton Anxiety Rating Scale, HAMA-14)、汉密尔顿抑郁量表(24-Item Hamilton Depression Rating Scale, HAMD-24, HAMD-24)、帕金森病睡眠量表(Parkinson’s Disease Sleep Scale, PDSS)、帕金森病非运动症状评价量表(Non-motor Symptoms Scale, NMSS)、Epworth思睡量表(Epworth Sleepiness Scale, ESS)等对其非运动症状进行评估。比较2组患者一般临床资料,采用多元线性回归分析影响早期PD患者生活质量的相关因素。结果 EMO组H-Y分级[1.5(1.0,2.0)级]高于无EMO组[1.0(1.0,1.5)级](P>0.05),患者PDQ-39评分[(40.8±20.7)分]、UPDRSⅠ评分[(5.1±2.2)分]、UPDRSⅡ评分[(12.8±6.1)分]、UPDRS总分[(34.1±16.8)分]、NMSS评分[(61.8±38.1)分]、ESS评分[(8.3±5.0)分]和左旋多巴每日等效剂量[(701.4±438.2)mg]均明显高于无EMO组[(14.4±11.0)、(2.9±2.2)、(8.8±3.4)、(25.3±9.0)、(35.4±25.6)、(4.6±4.5)分、(466.8±344.3)mg],PDSS评分[(108.0±21.3)分]低于无EMO组[(128.6±24.8)分](P<0.05),UPDRSⅢ、UPDRSⅣ、HAMA-14、HAMD-24、MMSE评分与无EMO组比较差异均无统计学意义(P>0.05);对PDQ-39影响程度最大的为H-Y 2.5级,其次依次为EMO、H-Y 1级、UPDRSⅣ和PDSS(P<0.05)。结论 EMO明显影响早期PD患者的生活质量。