帕金森病多巴胺转运体代谢和葡萄糖代谢相关性研究

目的 研究帕金森病(PD)患者脑内多巴胺转运体(DAT)代谢和葡萄糖代谢特征的相关性.方法 选择2006年7月至2008年7月在北京天坛医院神经内科住院,临床诊断为原发性PD患者11例和原发性震颤(ET)患者3例.分别接受了18氟-脱氧葡萄糖(18F-FDG)和DAT示踪剂11C-CFT 2种示踪剂的正电子发射扫描检查.应用半定量法计算壳核前部、壳核后部、尾状核头、丘脑、额叶后部、项叶前部和枕叶皮层等脑部感兴趣区的18F-FDG和11C-CFT的摄取强度.以感兴趣区与枕叶皮层的局灶性示踪剂摄取强度比值作为主要参数进行比较和相关性分析.结果 PD患者壳核后部可见18F-FDG和11C-CFT等示踪剂摄取信号缺如.其中首发症状肢体对侧壳核后部示踪剂摄取缺如更显著,低于首发症状肢体同侧(P<0.01);首发症状对侧壳核后部、壳核前部18F-FDG和11C-CFT代谢有显著相关性(P<0.01和P<0.05).首发症状同侧壳核后部18F-FDG和11C-CFT代谢有显著相关性(P<0.05).ET患者纹状体区18F-FDG和11C-CFT等示踪剂摄取信号未见缺如.结论 PD纹状体区的DAT代谢和葡萄糖代谢障碍具有相关性,可用于PD的诊断、鉴别诊断和判断病情进展等.     

血管性帕金森综合征的多巴反应性研究

目的观察血管性帕金森综合征(VP)对复方多巴的反应性以及多巴反应性与病变部位的相关性。方法临床诊断VP的患者共61例(VP组)进行急性阶梯性左旋多巴治疗试验,计算服用左旋多巴-苄丝肼后统一帕金森病(PD)评分量表(UPDRS)运动部分评分最大改善率。同期146例PD患者(PD组)作为对照。根据头颅MRI所示缺血性病灶部位,将VP组再分组,第1种分组:基底节区病变组(25例);白质病变组(21例);黑质病变组(3例);混合病变组(12例)。第2种分组:黑质纹状体通路病变组(28例);白质病变组(21例)。经t检验比较各组间UPDRS运动部分最大改善率。结果VP组和PD组的UPDRS运动部分平均最大改善率依次为(10.4±7.4)%和(40.1±14.9)%,两组差异有显著性意义(P<0.01)。VP各分组:基底节区病变组UPDRS改善率(23.2±11.3)%,高于白质病变组的(6.5±4.3)%,低于PD组(P<0.01)。黑质病变组UPDRS改善率为(35.4±8.7)%,但例数少无法进行统计学分析。黑质纹状体通路病变组UPDRS改善率(26.3±10.6)%,高于白质病变组,但低于PD组(P<0.01)。结论VP组由于不同的病变部位,对复方多巴有不同的反应性;以累及黑质、基底节等黑质纹状体通路病变为主的VP对复方多巴有一定的反应性,而以白质病变为主的对复方多巴反应较差。可根据MRI提示的病变部位决定是否应用复方多巴治疗VP患者。     

不对称静止性震颤患者脑多巴胺转运体代谢分析

目的本研究拟通过脑多巴胺转运体的正电子发射断层显像(PET)对不对称静止性震颤患者进行脑多巴胺转运体代谢特点进行分析,以指导临床诊断。方法筛选出不对称静止性震颤患者40例,每例受试者均进行脑~(11)C-甲基-N-2β-甲基酯-3β-(4 F-苯基)托烷(~(11)C-β-CFT)PET。根据PET结果 ,分为2组,无多巴胺能系统功能缺失的分子影像学证据(SWEDD)组6例,非SWEDD组34例。比较2组间临床特征的差异,分析不对称静止性震颤患者脑多巴胺转运体代谢的特点。结果 SWEDD组双侧纹状体对脑多巴胺转运体对比剂~(11)C-β-CFT摄取对称完整。非SWEDD组11例表现为纹状体对~(11)C-β-CFT不对称性摄取下降,23例表现为纹状体对~(11)Cβ-CFT对称性摄取下降。SWEDD组患者平均病程明显高于非SWEDD组[(9.42±11.40)年vs(3.64±2.70)年,P<0.05]。结论不对称静止性震颤患者的脑多巴胺转运体代谢存在异质性,部分患者扫描为SWEDD。进行脑多巴胺转运体分子影像学检查有助于鉴别SWEDD和帕金森病患者。     

多巴胺转运体基因多态性与帕金森病的易感性及PET/CT显像

目的探讨多巴胺转运体(DAT)基因3'非翻译区可变串联重复序列(VNTR)多态性与内蒙古地区帕金森病(PD)的相关性并分析其机制。方法选取PD患者52例为PD组,健康体检人员60例为对照组。对DAT基因的3'非翻译区VNTR进行基因分型;对20例PD患者和10例对照者进行11C-甲基-N-2β-甲基酯-3β-(4-F-苯基)托烷(11C-β-CFT) DAT正电子发射计算机断层显像(PET)-CT脑显像。结果 VNTR有9R和10R两个等位基因,VNTR的基因型频率和等位基因频率在对照组和PD组差异无统计学意义(P0. 05)。对照组DAT显像清晰,双侧尾状核、前壳核和后壳核11C-β-CFT放射性摄取均匀对称。PD组尾状核、前壳核和后壳核11C-β-CFT放射性摄取指数与对照组比较显著下降,差异有统计学意义(P0. 05)。结论 DAT基因VNTR多态性与内蒙古地区PD无明显相关性,VNTR多态性与PD患者纹状体11C-β-CFT放射性摄取无明显相关性。     

不同临床类型、分期帕金森病患者99mTc-TRODAT-1DAT显像特征分析

目的 对帕金森病(PD)患者进行99mTc-TRODAT-1多巴胺转运蛋白SPECT显像,半定量分析纹状体/小脑、尾状核/小脑和壳核/小脑放射性计数比值,结合UPDRS评分,分析探讨不同临床类型、分期PD患者的特征.方法 58例临床确诊PD患者和10例对照组,在空腹6 h后,口服KClO4 400 mg以封闭甲状腺、脉络丛和鼻黏膜,1 h后经肘静脉注射99mTc-TRODAT-1 30 mCi.3 h后进行99mTc-TRODAT-1多巴胺转运蛋白显像,取SPECT图像中基底节最清晰的1帧横断层图像勾画左右纹状体、尾状核和壳核感兴趣区(ROI),利用半定量分析法,分别计算纹状体与小脑、尾状核与小脑及壳核与小脑放射性计数比值.比较PD患者和对照组纹状体及主要区域DAT功能差异.并应用统一PD评定量表(UPDRS)对患者的运动功能进行评分,分析其UPDRS Ⅲ评分与起病肢体对侧、同侧及双侧纹状体/小脑放射性计数的相关性.分析不同分期纹状体/小脑,壳核/小脑,尾状核/小脑放射性比值.结果 与正常对照组比较,不同分期的PD患者纹状体DAT功能均明显减低.在三组不同类型的PD患者中,强直为主与运动迟缓为主型PD患者的评分与纹状体、尾状核、壳核摄取值呈负相关(P<0.05),混合型PD患者的评分与纹状体、尾状核、壳核摄取值也呈负相关(P<0.05).而震颤为主型PD患者的评分与纹状体、尾状核、壳核摄取值无明显相关性(P＞0.05).结论 99mTc-TRODAT-lDAT显像可作为评价PD严重程度的可靠指标,与PD患者UPDRS临床量表结合,能更好对PD患者进行诊断、分级和病情监测.     

头部MRI及PET检查对进行性核上性麻痹与帕金森病的诊断价值

目的探讨头部磁共振成像(MRI)及以18F-脱氧葡萄糖(18F-FDG)为示踪剂的正电子发射计算机断层扫描(PET)两种影像学检查对进行性核上性麻痹(PSP)及帕金森病(PD)的诊断价值。方法对2004年8月至2006年11月在首都医科大学附属北京天坛医院神经内科就诊的11例PSP和178例PD患者进行常规头部MRI检查,并对其中5例PSP和48例PD患者进行18F-FDGPET检查。结果(1)MRI检查:11例PSP患者均可见矢状位T1加权像有中脑上缘平坦或者凹陷表现,PD组未见上述表现;正中矢状位T1加权像上计算中脑截面面积,PSP组低于PD组,差异有显著性意义(P<0.01)。(2)18F-FDGPET检查:PSP组主要表现为对称性额叶低代谢,纹状体代谢基本对称。PD组主要表现为顶叶代谢略低于额叶前部,首发症状肢体对侧顶叶代谢降低明显;纹状体呈不对称表现,首发症状肢体同侧纹状体代谢降低,对侧纹状体后部代谢降低;纹状体代谢高于同侧丘脑。结论MRI及18F-FDGPET检查对诊断PSP在中脑形态学改变(中脑萎缩)及脑葡萄糖低代谢方面有特异性,与PD组比较差异有显著性意义。     

脑深部电刺激器对帕金森病多巴反应性和左旋多巴等效剂量的影响

目的本研究拟探讨慢性双侧丘脑底核脑深部电刺激器(STN-DBS)对患者多巴反应性以及所需多巴胺能药物剂量的影响。方法选择在我院行双侧STN-DBS的帕金森病患者共37例。术后持续开机,随访期1年。分别在术前1周、术后12个月进行急性左旋多巴试验观察左旋多巴的短时程反应。进行国际统一的帕金森病评分量表(UPDRS)运动部分评分,改善率、进入开期的潜伏期、开期持续时间为指标进行术前和术后的比较。在术后12个月分别在开机和关机的情况下观察达到术前UPDRS评分改善率所需多巴胺能药物的剂量。结果在开机情况下,服用左旋多巴-苄丝肼后左旋多巴反应的潜伏期缩短,持续时间延长,UPDRS运动部分评分改善率增加,与术前比较差异显著(P<0.05)。但在关机30 min后,急性左旋多巴试验短时程效应的潜伏期、持续时间和UPDRS最大改善率等与术前相似,无显著差异。开机时,达到术前UPDRS改善率所需的左旋多巴等效剂量比术前降低,差异显著(P<0.01)。关机时达到术前UPDRS改善率所需的左旋多巴等效剂量比术前略增加,但差异无统计学意义(P>0.05)。结论持续性双侧STN-DBS在术后1年内并不改善帕金森病患者对多巴胺能药物的反应性,而可以与多巴胺能药物产生叠加效应,改善帕金森病症状。     

帕金森病不同临床阶段静态脱氧葡萄糖代谢模式的正电子发射断层扫描

目的研究帕金森病(PD)在不同临床阶段脱氧葡萄糖(FDG)代谢特征和变化过程。方法对33例PD患者(PD组)以及8例无神经系统疾病患者(正常对照组)进行了18F-FDG-正电子发射断层扫描(PET)检查。PD患者中H-Y分期:Ⅰ期3例,Ⅱ期18例,Ⅲ期10例,Ⅳ期2例。分别取豆状核、尾状核、丘脑、小脑、双侧额叶、双侧顶叶、双侧颞叶和双侧枕叶为感兴趣区(ROI)进行放射性显像强度比较。结果与正常对照组比较,PD组不同临床阶段FDG代谢的共同点是:颅内结构FDG脑代谢呈现不对称性,以豆状核代谢不对称为主;丘脑、尾状核、额顶叶交界区FDG代谢降低;豆状核代谢高于尾状核以及丘脑。随着病情进展FDG脑代谢逐渐变化:H-YⅠ期时症状首发肢体对侧豆状核代谢高于同侧豆状核,H-YⅡ~Ⅳ期时症状首发肢体同侧豆状核代谢也逐渐增高接近于对侧的豆状核;H-YⅠ期的额顶交界区皮质代谢降低,Ⅱ、Ⅲ期低代谢范围逐渐扩大,Ⅳ期则发展到额、顶、颞叶广泛低代谢。结论PD的FDG代谢随着病情进展既有共性,也有不同的特征性改变。这种FDG代谢的变化有助于PD的诊断和鉴别诊断。     

99Tcm-TRODAT-1多巴胺转运体SPECT显像在帕金森病中的临床应用

目的 观察99Tcm-TRODAT-1多巴胺转运体（DAT）SPECT显像在帕金森病（PD）中的临床应用.方法 53例确诊PD患者及10例正常对照者行99Tcm-TRODAT-1显像,利用感兴趣区技术计算双侧纹状体/小脑、尾状核/小脑、壳核/小脑放射性比值,并与帕金森病统一量表（UPDRS）评分进行相关性分析;根据Hoehn＆Yahr分级,分析不同病程PD患者纹状体放射性比值;以UPDRSⅢ评分标准分组,分析不同临床症状PD患者纹状体放射性比值;53例PD患者显像后正规内科治疗1 a并再次显像,分析治疗前后纹状体放射性比值的变化.结果 PD患者纹状体摄取99Tcm-TRODAT-1随病情严重程度增加而逐渐减少;纹状体DAT摄取比值与UPDRSⅡ、Ⅲ、Ⅴ和Ⅵ评分存在负相关（P均＜0.01）;强直与运动迟缓评分与DAT摄取比值呈负相关,震颤评分与DAT摄取比值不相关.治疗后PD患者纹状体摄取比值明显增高33例,未见明显变化15例,摄取降低5例.结论 99Tcm-TRODAT-1 DAT SPECT 显像可用于PD的早期诊断及病程分期;与UPDRS量表结合,能更好地对PD患者进行诊断、分级和病情监测;在一定程度上,该显像方法还可作为药物疗效评价的客观指标.     

帕金森病~(99m)TC-TRODAT-1多巴胺转运体单光子计算机断层摄影脑显像研究

目的应用~(99m)Tc-TRODAT-1多巴胺转运体(DAT)单光子计算机断层摄影(SPECT)脑显像,研究不同运动障碍亚型帕金森病(Parkinson's diseas e,PD)纹状体生化改变。方法选择不同运动障碍亚型PD患者68例,其中震颤为主型PD患者36例(震颤PD组),姿势异常步态障碍(PIGD)为主型PD患者32例(PIGD PD组),分别行~(99m)Tc-TRODAT-1 DAT SPECT脑显像,利用感兴趣区技术计算首发症状对侧纹状体与小脑的特异性放射性比值。结果 PIGD PD组患者首发症状对侧纹状体、小脑较震颤PD组患者明显降低(1.43±0.92) vs (1.49±0.10),P0.05]。纹状体、小脑下降与PIGD评分呈负相关(r=-0.73,P0.05),而与震颤评分无明显相关性(r=-0.21,P0.05)。结论不同运动障碍亚型PD患者~(99m)Tc-TRODAT-1 DAT SPECT脑显像存在明显的异质性,PIGD为主型PD患者纹状体DAT的功能降低更明显,提示不同运动障碍亚型PD有不同的生化病理基础。     

脑多巴胺转运蛋白SPECT显像在帕金森病临床诊断中的研究

目的　探讨脑99mTc TRODAT 1SPECT多巴胺转运蛋白 (dopaminetransporter,DAT)显像对帕金森病 (PD)临床诊断的价值。 方法　选择PD患者 2 2例 ,健康对照组 5例 ,口服过氯酸钾 40 0mg ,30min后静脉注射99mTc TRODAT 1 ,2 5mCi,放射化学纯度 >93 % ,注射后 4h行SPECT显像。结果　健康对照组SPECT扫描示双侧基底节DAT显像结果正常 ,即DAT核素密度集中于双侧基底节呈红色 ,尾状核头部密度更高 ,呈“八”字形 ,左右基本对称。PD组SPECT扫描示双侧基底节DAT分布、位点、形态变异 ,数量减少 ,体积变小 ,以PD症状对侧为著。结论　DAT数量减少是PD发病的重要环节之一 ,DAT显像是PD实验室早期诊断依据之一     

Intrasubject relationship between striatal 18F-FP-CIT uptake and cardiac 123I-MIBG uptake differs by motor subtype in early Parkinson disease

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder. Dopamine transporter imaging using ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (FP-CIT) and noradrenergic cardiac imaging using ¹²³I-meta-iodobenzylguanidine (MIBG) have been used in combination or separately to study PD patients. Published results regarding uptake of the 2 tracers in each motor subtype are fairly abundant and mostly in agreement. However, data on the intrasubject association between dopaminergic and noradrenergic systems in PD patients are relatively scant and vary. We aimed to assess the intrasubject relationship between striatal dopamine transporter density using a PET tracer and cardiac sympathetic innervation in tremor-dominant subtype (TD) and akinetic-rigid subtype (AR) of PD.This study has a cross-sectional design. Thirty-one patients with early PD (17 TD/14 AR) who underwent both ¹²³I-MIBG cardiac scintigraphy and ¹⁸F-FP-CIT PET/CT were retrospectively selected. We assessed the relationship between heart-to-mediastinum ratio (H/M) of ¹²³I-MIBG and specific (striatal)-to-nonspecific (cerebellar) dopamine transporter binding ratio (S/N) measured from 4 separate regions-of-interest (bilateral caudate nuclei and lentiform nuclei) of ¹⁸F-FP-CIT in each motor subtype.S/N of all 4 striatal regions were significantly lower in the AR subgroup than in the TD subgroup. H/M was not significantly different. There was a significant intrasubject correlation between H/M and S/N of the lentiform nucleus in AR-PD but no correlation between H/M and any of 4 S/N in TD-PD.Our data suggest a coupled degeneration of nigrostriatal dopaminergic and myocardial sympathetic denervation in AR subtype, but not in TD subtype, of early PD patients. These different results between the 2 motor subtypes likely reflects the heterogeneous pathophysiology of PD.     

多巴胺转运体SPECT显像鉴别老年ET和早期PD

目的证实99m锝-2β-[N,N’双(2巯乙基)乙撑二胺基]甲基-3β(4氯苯基)托烷(99mTc-TRODAT-1)单光子发射型计算机断层摄影术(SPECT)多巴胺转运蛋白(DAT)显像在老年人原发性震颤(ET)及早期帕金森病(PD)的鉴别诊断价值。方法对12例ET,15例早期PD,15例年龄、性别相匹配的正常人进行99mTc-TRODAT-1SPECTDAT显像。计算纹状体(ST)/小脑(CB)比值来反映纹状体内DAT特异性结合TRODAT-1的量。结果ET患者ST与CBDAT的特异性放射性摄取比值(ST/CB)双侧对称,双侧均数与正常组比较无显著性差异(P>0·05)。PD患者ST/CB双侧不对称,双侧均数与正常组比较有显著差异(P<0·01)。结论99mTc-TRODAT-1SPECTDAT显像可以鉴别ET和PD。     

Comparison of perfusion 18F-FP-CIT PET and 99mTc-ECD SPECT in parkinsonian disorders

Early and accurate identification of various conditions that can cause parkinsonian symptoms is important for determining treatment policies. Currently dopamine transporter (DAT) imaging using FP-CIT, glucose metabolism imaging using fluorodeoxyglucose, cerebral blood flow image using ethyl cysteinate dimer (ECD), and others are used for differentiation. However, the use of multiple modalities is inconvenient and costly. In the present retrospective study, we evaluated the correlation between regional brain uptake ratios (URs) in perfusion FP-CIT PET and ECD SPECT images.Twenty patients with Parkinson''s symptoms underwent perfusion DAT positron emission tomography (¹⁸F-FP-CIT PET/CT) and cerebral blood flow tomography (^99mTc-ECD SPECT) within a 2-week period. Perfusion ¹⁸F-FP-CIT PET/CT and ^99mTc-ECD SPECT URs of 19 brain regions (bilateral frontal, temporal, parietal and occipital lobes, bilateral caudate nucleus, bilateral putamen, bilateral insula, bilateral cingulate gyrus, bilateral thalamus, and brainstem) were directly compared and correlations were analyzed.Average ¹⁸F-FP-CIT PET/CT regional perfusion URs were higher than ^99mTc-ECD SPECT URs. Uptake ratios were well correlated in all 19 regions (except right putamen), and especially in dopamine poor regions (cerebral cortex). In left putamen, URs were significantly correlated, but the correlation coefficient was lower than those of other regions.A single tracer dual phase N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane test seems to be helpful for differential diagnosis of parkinsonian disorders. Large-scale, longitudinal studies on complementary diseases with parkinsonian patterns are required to investigate differences in correlations between perfusion ¹⁸F-FP-CIT PET/CT and ^99mTc-ECD SPECT over time.     

Striatal phosphoproteins in Parkinson disease and progressive supranuclear palsy.

This study was undertaken to evaluate the levels of cAMP-regulated phosphoproteins in the striatum of patients with neurodegenerative diseases of the dopaminergic system. Postmortem samples of caudate nucleus and putamen from 24 control subjects, 23 patients with Parkinson disease, and 13 patients with progressive supranuclear palsy were studied with immunoblotting techniques. The levels of tyrosine hydroxylase were reduced in patients with Parkinson disease (levels were 24% and 10% of controls in caudate nucleus and putamen, respectively) and with progressive supranuclear palsy (levels were 11% and 6% of controls in caudate nucleus and putamen, respectively). Five phosphoproteins, which are present in striatal neurons and are likely to play a role in the postsynaptic actions of dopamine, were measured. These included ARPP-16, ARPP-19, ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively), DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), and phosphatase inhibitor I. The levels of these phosphoproteins were inversely correlated with postmortem delay. In brains of patients with Parkinson disease or progressive supranuclear palsy with postmortem delays comparable to those of controls, the levels of these proteins as well as those of synaptic (synapsin I and synaptophysin) and glial (glial fibrillary acidic protein and myelin basic protein) markers were not significantly modified. We conclude that the levels of several phosphoproteins involved in signal transduction in striatal neurons are not altered in Parkinson disease and progressive supranuclear palsy. This observation supports the view that the striatal output neurons are intact in both diseases.     

Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.

Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders.     

Quantitative T1 mapping of hepatic encephalopathy using magnetic resonance imaging

Changes are shown in the spin-lattice (T1) relaxation time caused by the putative deposition of manganese in various brain regions of hepatic encephalopathy (HE) patients using a novel and fast magnetic resonance imaging (MRI) method for quantitative relaxation time mapping. A new method, T1 mapping with partial inversion recovery (TAPIR), was used to obtain a series of T1-weighted images to produce T1 maps. Imaging of 15 control subjects and 11 patients was performed on a 1.5T MRI scanner. The measurement time per patient with this technique, including adjustments, was approximately 5 minutes. Regions of interest in the globus pallidus, the caudate nucleus, the posterior and anterior limbs of the internal capsule, the putamen, the frontal and occipital white matter, the white matter of the corona radiata, the occipital visual and frontal cortices, and the thalamus were interactively defined in the left hemisphere and analyzed with respect to their T1 values. T1 changes in the brains of HE patients can be determined quantitatively with TAPIR in short, clinically relevant measurement times. Significant correlations between the change in T1 and HE severity have been shown in the globus pallidus, the caudate nucleus, and the posterior limb of the internal capsule. No significant correlation of T1 with grade of HE was found in the putamen, frontal white matter, white matter of the corona radiata, white matter in the occipital lobe, the anterior limb of the internal capsule, visual cortex, thalamus, or frontal cortex. In conclusion, these measurements show that T1 mapping is feasible in short, clinically relevant acquisition times.     

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders.     

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using ¹²³I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects’ Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.     

原发性进行性冻结步态

目的提高临床医师对原发性进行性冻结步态的认识。方法对1例79岁的原发性进行性冻结步态的患者随访2年8个月,并对临床资料进行总结分析。结果患者主要表现为间断性的冻结步态,未发现其他神经系统的阳性体征。对多巴胺能药物无反应。实验室检查未见异常。头颅MRI提示多发性腔隙性脑梗死,多巴胺转运体检查提示:两侧尾状核放射性分布略低,双侧壳核CFT显影剂放射性分布明显降低。结论此患者的临床表现符合原发性进行性冻结步态的诊断标准,多巴胺转运体检查结果为阳性,需进一步随访观察。