可乐定生长激素刺激试验在鉴别多系统萎缩和原发性帕金森病的临床应用研究

目的:探讨可乐定生长激素刺激试(CGHST)在鉴别多系统萎缩(MSA)和原发性帕金森病(IPD)的应用价值.方法:对11例MSA-P和14例IPD患者清晨空腹仰卧安静状态下静脉采血,测定患者基础生长激素(GH)浓度,15 min以后口服盐酸可乐定300 ug,以后每隔30 min连续采血4次测定血清GH浓度.根据ROC曲线确立最佳的截断值,计算其敏感度和特异度.结果:IPD患者口服可乐定后血清GH浓度显著增加,60 min时最为明显,平均值达(5.4±0.9)ng.μL-1(P<0.001);而MSA-P患者服用可乐定以后血清GH基本保持稳定,最大增加值仅为(2.1±0.5)ng·μL-1(>0.05);比较两组间服用可乐定后30、60、90 min血清GH水平,MSA-p患者血清GH增加值均显著低于IPD组(P<0.05);CGHST 对MSA-P的敏感度和特异度分别是81.8%和85.7%.结论:CGHST可以作为MSA-p和IPD鉴别诊断的一种有效手段.     

多系统萎缩与帕金森病的早期鉴别诊断

目的　为多系统萎缩 (m ultiple system atrophy,MSA)与帕金森病 (Parkinson disease,PD)的鉴别诊断提供依据。方法　对 12名首发锥体外系症状的 MSA患者和 40名 PD患者的临床症状及主要辅助检查行比较分析。MSA诊断依据 Quinn(1994)提出的临床诊断标准。PD诊断参考英国帕金森病协会 1997年提出的诊断标准。结果　与 PD患者比较 ,MSA患者发病年龄较小 (5 4.3 2± 9.5 0 vs 61.5 6± 9.5 5 ,P<0 .0 5 ) ,主要以行动困难或僵硬为首发症状 (66.7% vs 2 5 % ,P<0 .0 5 ) ;少数以震颤为首发症状 (3 3 .3 % vs 75 % ,P<0 .0 5 ) ,也可以单侧症状发病(5 8.3 % vs 80 % ,P>0 .0 5 ) ,多数对多巴胺反应不良 (66.7% vs 2 0 % ,P<0 .0 5 ) ,植物神经症状、语言障碍比 PD患者显著多见 (分别为 83 .3 % vs 2 5 % ;5 0 % vs12 .5 % ;P<0 .0 5 )。辅助检查 :MRI:大部分 MSA患者有阳性表现 ,橄榄体、脑桥和小脑部位有萎缩 ,PD患者未发现特征性病变。 PET:3例 MSA患者均呈阳性表现。神经心理 :MSA患者未出现智能障碍的情况 (0 % ) ,少数 PD(10 % )患者出现智能障碍 ,但两者比较无统计学意义 (P>0 .0 5 )。结论　依据详细的病史和全面的神经系统查体 ,并结合临床辅助检查 ,可提高 MSA和 PD早期鉴别诊断的准确性     

磁敏感加权成像在帕金森病和多系统萎缩的诊断及鉴别诊断中的应用研究

目的 探讨磁敏感加权成像(SWI)对帕金森病(PD)和多系统萎缩(MSA)的诊断及鉴别诊断价值。方法 选择PD患者76例为PD组和MSA患者42例为MSA组,另选择25例非PD患者为对照组,采用SWI显示黑质背外侧和基底节区图像。根据临床症状相对应侧的中脑黑质部“燕尾征”消失结合基底节区“壳核后外侧低信号”特征表现鉴别PD和MSA,并与临床诊断进行比较,评价其诊断的灵敏度、特异度、约登指数、阳性预测值和阴性预测值。结果 PD组、MSA组和对照组中脑黑质“燕尾征”消失分别为96.05%、90.47%和12.00%,组间差异均有统计学意义(均P<0.05);但PD组与MSA组比较(P>0.05)。“壳核后外侧低信号”改变在PD、MSA和对照组患者中分别为7.89%、76.19%和4.00%,组间差异均有统计学意义(均P<0.01);MSA组发生率与PD和对照组比较(均P<0.05),但PD与对照组比较差异无显著性(P>0.05)。采用SWI上“燕尾征”消失诊断PD的灵敏度为96.05%、特异度为88.00%,约登指数为84.05%,阳性预测值为96.05%、阴...     

磁共振测量小脑中脚宽度在多系统萎缩与帕金森病鉴别诊断中的价值

目的探讨多系统萎缩(MSA)患者小脑中脚宽度改变的意义,以及它对MSA与帕金森病(PD)鉴别诊断的价值。方法对23例临床诊断的MSA患者(MSA组)、同时选取年龄及性别相匹配28例PD患者(PD组)行MRI扫描。观察桥脑十字征,并测量分析各受试组的小脑中脚(MCP)宽度。结果 MSA组13例(56.5%)可见桥脑十字征,PD组未见桥脑十字征;MSA组MCP宽度(6.5±1.3)mm明显小于PD组(9.4±1.1)mm(P0.01)。结论磁共振测量MCP宽度大小对MSA的诊断临床意义重大,同时也可用于MSA与PD的鉴别。     

多系统萎缩和帕金森病患者执行功能障碍研究

目的探讨多系统萎缩和帕金森病患者执行功能障碍特点。方法采用简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(Mo CA),以及Stroop色词测验(SCWT)、数字符号转换测验(DSST)/图形符号转换测验(GSST)、画钟测验(CDT)和连线测验(TMT)评价34例多系统萎缩患者[以小脑共济失调为主要表现型(MSA-C型)21例、以帕金森病综合征为主要表现型(MSA-P型)13例]和18例原发性帕金森病患者的整体认知功能和执行功能。结果各组受试者Mo CA评分差异有统计学意义(P=0.019),其中PD组和MSA-C型组患者评分低于对照组(P=0.015,0.002)。各组受试者SCWT测验各部分评分(P=0.035,0.013,0.012,0.037)、DSST评分(P=0.000)、GSST评分(P=0.000)、TMT评分(P=0.035)差异均有统计学意义,其中,MSA-C型组和MSA-P型组患者SCWT-A(P=0.004,0.045)、SCWT-B(P=0.001,0.036)和SCWT-D(P=0.023,0.010)评分均高于对照组,PD组、MSA-C型组和MSA-P型组患者SCWT-C评分(P=0.005,0.014,0.003)、DSST评分(P=0.003,0.000,0.000)和GSST评分(P=0.001,0.000,0.000)均高于对照组,仅MSA-P型组患者TMT评分高于对照组(P=0.006)。结论多系统萎缩和帕金森病患者均存在不同程度的执行功能障碍,SCWT和DSST/GSST测验有助于评价此类患者的执行功能障碍。     

眼动功能检查在帕金森病与多系统萎缩P型鉴别诊断的价值

目的 评价眼动功能检查在鉴别帕金森病(PD)与多系统萎缩P(MSA-P)型的价值.方法 纳入陕西省人民医院39例PD患者和11例MSA-P型患者,行前庭眼动功能和视觉眼动功能检查并记录.结果 前庭眼动功能结果发现PD组患者均未出现自发眼震,而MSA-P型患者中仅有1例出现垂直下跳眼震.视觉眼动功能检查包括扫视试验(ST...     

帕金森病和多系统萎缩的异常眼球运动研究进展

帕金森病(PD)是一类主要累及基底神经节的一种神经退行性疾病,其典型的临床表现有静止性震颤、运动迟缓、肌强直.多系统萎缩(MSA)的临床表现主要是帕金森症状、共济失调及自主神经症状的结合.由于临床表现重叠性强、缺乏具有特异性的检查手段及生物学标志物,PD与MSA患者在早期鉴别诊断非常困难,但如果存在眼球运动异常,它们可...     

帕金森病和多系统萎缩患者脑脊液阿片肽含量变化的研究

采用放射免疫法检测８例帕金森病（ＰＤ）和１３例具帕金森综合征的多系统萎缩（ＭＳＤ）患者脑脊液（ＣＳＦ）中β－内啡肽（β－ＥＰ）、亮脑啡肽（ＬＥＫ）、强啡肽Ａ_（１－１３）（ＤｙｎＡ_（１－１３））含量。发现患者组ＣＳＦ中β－ＥＰ和ＬＥＫ含量显著高于对照组，ＤｙｎＡ_（１－１３）含量变化不显著。帕金森病和多系统萎缩两组间ＣＳＦ中三种阿片肽含量相差不明显。提示且ＥＰ、ＬＥＫ含量增高可能与ＰＤ和ＭＳＤ患者所共有的肌张力增高和肌强直等锥体外系症状产生有关。     

MRI、EAS-EMG和TCS鉴别多系统萎缩P型和帕金森病的价值

目的探讨头部磁共振成像(MRI)、肛门括约肌肌电图(EAS-EMG)和经颅超声成像(TCS)三种辅助检查对多系统萎缩P型(MSA-P型)和帕金森病(PD)的鉴别诊断价值。方法选取临床确诊的21例MSA-P型和33例PD患者,均行MRI、EAS-EMG、TCS检查且病历资料全面并保存完整。采用ROC曲线对其MRI、EASEMG、TCS结果进行对比分析。结果 MSA-P型组的壳核裂隙征、MUP平均时限、平均波幅、多相波百分比、自发电位发生率、卫星电位发生率均高于PD组,但黑质高回声面积、黑质高回声总面积与中脑总面积比值均低于PD组(均P<0.01)。ROC曲线显示,在两者的鉴别诊断方面,壳核裂隙征的特异度最高(97.0%),黑质高回声面积的敏感度最高(81.0%),MUP平均时限的曲线下面积(AUC)最高(0.781);三种指标联合对两者鉴别诊断的敏感度为95.2%,AUC为0.939,鉴别诊断价值极高。结论 MRI、EAS-EMG、TCS对鉴别MSA-P型和PD的价值各不相同,互为补充,且三种指标联合具有良好的鉴别诊断价值。     

帕金森病及多系统萎缩患者执行功能差异性的随机对照研究

目的 探讨帕金森病(PD)患者与多系统萎缩(MSA)患者在认知功能损害,尤其是执行功能障碍的异同.方法 连续选择帕金森患者26例,多系统萎缩患者18例,正常对照患者20例.详细收集年龄、教育程度、病程等资料,给予MOCA评分(总体认知)、TMT测验、Stroop色词测验、画钟试验(CDT)、Rey-Osterrich复...     

Subcortical atrophy and perfusion patterns in Parkinson disease and multiple system atrophy

BackgroundThe clinical differentiation between Parkinson disease (PD) and multiple system atrophy (MSA) is difficult.ObjectivesArterial spin labeling (ASL) is an advanced MRI technique that obviates the use of an exogenous contrast agent for the estimation of cerebral perfusion. We explored the value of ASL in combination with structural MRI for the differentiation between PD and MSA.MethodsNinety-four subjects (30 PD, 30 MSA and 34 healthy controls) performed a morphometric and ASL-MRI to measure volume and perfusion values within basal ganglia and cerebellum. A region-of-interest analysis was performed to test for structural atrophy and regional blood flow differences between groups.ResultsMSA patients showed higher subcortical atrophy than both PD patients and HC, while no differences were observed between the latter. MSA and PD showed lower volume-corrected perfusion values than HC in several cerebellar areas (Crus I, Crus II, right VIIb, right VIIIa, right VIIIb), right caudate and both thalami. MSA and PD patients displayed similar perfusion values in all aforementioned areas, but the right cerebellar area VIIIb (lower in MSA) and right caudate and both thalami (lower in PD). Similar results were obtained when comparing PD and MSA patients with the parkinsonian variant.ConclusionsA perfusion reduction was equally observed in both MSA and PD patients in cerebellar areas that are putatively linked to cognitive (i.e., executive) rather than motor functions. The observed hypo-perfusion could not be explained by atrophy, suggesting the involvement of the cerebellum in the pathophysiology of both MSA and PD.     

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

ObjectiveBiomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).MethodsIn 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2 h after 6-[¹⁸F]fluorodopa injection, septal myocardial radioactivity measured 8 min after 6-[¹⁸F]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities.ResultsPUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[¹⁸F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p < 0.0001, p < 0.0001, p = 0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p < 0.0001, each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p = 0.004; p = 0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r = 0.61, p < 0.0001). Myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity).ConclusionsPD and MSA feature low PUT:OCC ratios of 6-[¹⁸F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU ratios of 6-[¹⁸F]fluorodopa-derived radioactivity, cardiac 6-[¹⁸F]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA.     

Multiple system atrophy masking multiple sclerosis

Multiple system atrophy (MSA) and multiple sclerosis (MS) are progressive neurological disorders with overlapping clinical signs and symptoms. However, due to the course of the disease and the age of onset both disorders are rarely differential diagnosis for each other. We here report the remarkable association of the two diseases in one patient. As MSA dominated the clinical presentation, diagnosis and therapy of MS were delayed. We discuss the clinical symptoms in our patient and highlight the features that allow to differentiate both diseases.     

Heart rate circadian profile in the differential diagnosis between Parkinson disease and multiple system atrophy

Clinical diagnostic criteria indicate presence of autonomic features as the primary hallmark of Multiple System Atrophy (MSA). However involvement of the autonomic system is also a recognized feature of Parkinson's Disease (PD), yielding a broad clinical overlap between the two diseases. Laboratory assessments may help in the differential diagnosis between PD and MSA. Ambulatory Monitoring of Blood Pressure (AMBP) is a suitable tool to study the circadian rhythm of blood pressure (BP) and heart rate (HR). Different studies reported a reduction of physiological BP nocturnal dipping in PD and MSA patients, but failed to identify a distinctive pattern discriminating the two diseases. On the other hand, HR nocturnal behavior has not been exhaustively analyzed. In the present study we compared the profiles of HR circadian rhythm in 61 PD and 19 MSA patients who underwent 24 h AMBP.We found higher nocturnal HR (nHR) (71.5 beats/min ± 7.4) in MSA compared with PD (63.8 beats/min ± 9.6) as well as significantly lower nocturnal decline of HR (ndHR) in MSA (7.3% ± 8.2) vs. PD (14% ± 7.5). At a Receiver Operating Curve analysis nHR and ndHR significantly discriminated MSA from PD. nHR showed a sensitivity of 84.2% and a specificity of 62.3% (AUC 0.76; 95% IC 0.65–0.85); ndHR showed a sensitivity of 68% of and a specificity of 77% (AUC 0.72; 95% IC 0.61–0.82).According to our findings, nHR is increased and ndHR is reduced in MSA compared to PD. Moreover, these two indices discriminate between the two diseases with acceptable accuracy.     

GBA variation and susceptibility to multiple system atrophy

IntroductionGenetic variants in the glucocerebrosidase (GBA) gene have been previously associated with susceptibility to synucleinopathies. The risk is well-established in Lewy body disease but is not as confirmed for multiple system atrophy (MSA). We aim to evaluate associations between exonic variants in GBA and risk of neuropathologically-confirmed multiple system atrophy (MSA).MethodsSanger gene sequencing of GBA was performed on 167 pathologically confirmed MSA patients collected at Mayo Clinic Florida Brain Bank, and data were extracted from whole-genome sequencing of 834 clinical controls. Common GBA variants were assessed for association with MSA. Rare GBA variants (and also all GBA variants) were collapsed together and evaluated for association with MSA risk using a gene-burden test.ResultsA total of 17 exonic GBA variants were observed, including a novel p.Q112X variant that is likely pathogenic in a patient with mixed parkinsonism-cerebellar subtype MSA. The more common p.N409S and p.L483P variants that recessively cause Gaucher's disease (GD), and are associated with risk of Lewy body disease, were not observed. When collapsing across all GBA variants, the presence of any GBA variant was significantly more frequent in MSA patients than in controls (OR = 1.90, P = 0.031). However, this association was driven by p.T408M, which had a significantly higher frequency in MSA patients compared to controls (OR = 4.21, P = 0.002). There was no significant association with risk of MSA for the p.E365K variant (OR = 0.79, P = 0.72).ConclusionsOther than the specific GBA p.T408M variant, coding GBA variants are not associated with risk of MSA.     

Pain in multiple system atrophy

Pain is a recognized feature of idiopathic Parkinson’s disease (IPD) but has never been studied in multiple system atrophy (MSA), the commonest cause of atypical parkinsonism. We retrospectively analysed histories of pain in 100 consecutive cases of clinically probable MSA. Details were obtained from the medical records of 100 patients with MSA, comprising 82 with the striatonigral degeneration (SND) type and 18 with the olivopontocerebellar atrophy (OPCA) type of MSA. Pain was reported in 47% of the MSA patients. It was classified as rheumatic in 64% of MSA patients reporting pain, sensory in 28%, dystonic in 21%, and levodopa-related in 16%, mostly related to off-period or diphasic dystonias. There was a mixed pain syndrome in 19% of these patients. Pain was significantly more commonly reported by females (P=0.02), and by patients with levodopa-induced dyskinesias (P=0.02). No other clinical feature differentiated MSA patients who reported pain from those who did not. The mean delay between disease onset and onset of pain was 2.9 years, but pain was reported at the time of, or before, disease onset in about 30% of patients. The overall prevalence of pain in MSA was similar to that reported in IPD, but the distribution of pain categories was different.