左旋多巴试验和颅脑MRI在帕金森病与帕金森综合征鉴别诊断的意义

发布时间：2018-02-27 12:05

本文关键词： 左旋多巴试验帕金森病继发性帕金森综合征变性性帕金森综合征鉴别诊断颅脑MRI 帕金森病帕金森综合征多系统萎缩进行性核上性麻痹鉴别诊断　出处：《安徽中医药大学》2014年硕士论文　论文类型：学位论文

【摘要】：第一部分：左旋多巴试验在帕金森病与帕金森综合征鉴别诊断的意义研究背景帕金森综合征通常包括：原发性帕金森病(Parkinson’s disease, PD)、继发性帕金森综合(Parkinsonism，PS)、变性性帕金森综合征(Degenerative parkinsonism，DP)、遗传变性性帕金森综合征（Hereditary degenerative parkinsonism，HDP）。原发性帕金森病(Parkinson’s disease, PD)是中老年人常见的神经系统变性疾病，神经病理典型表现是：黑质多巴胺能神经元变性、坏死，残余神经元出现路易小体（Lewy-body，LB），黑质多巴胺能(DA)神经元减少，造成黑质-纹状体通路的多巴胺减少，与之功能相互拮抗的乙酰胆碱（Acetylcholine，Ach）相对增高，导致患者出现运动障碍。继发性帕金森综合征(Parkinsonism，，PS)是由感染、药物、中毒、脑动脉硬化、外伤等引起以基底节区为主的神经核团变性、脱失，白质的脱髓鞘、变性等，引起的以运动迟缓、姿势、步态异常、肌张力改变等临床表现的一组综合征。包括血管性帕金森综合征（Vascular Parkinsonism，VP）、外伤性帕金森综合征（Traumatic parkinsonism，TP）、药物性帕金森综合征（Drug-induce parkinsonism，DIP）、中毒性帕金森综合征（Toxic parkinsonism，TP）、感染性帕金森综合征（Infection parkinsonism，IP）等。变性性帕金森综合征(Degenerative parkinsonism，DP)属于神经系统变性疾病，通常包括多系统萎缩（Multiple system atrophy，MSA），进行性核上性麻痹(Progressive supranuclear palsy，PSP)，皮质基底节变性(Corticobasal degeneration，CBD)，路易体痴呆(Dementia with Lewy bodies，DLB)，正常颅压脑积水(Normalpressure hydrocephalus，NPH)等。多系统萎缩（Multiple system atrophy，MSA）是DP家族中的主要疾病之一，是一组病因不明，表现为神经系统多部位进行性萎缩的疾病。多系统萎缩分为MSA-P型和MSA-C型。MSA-P型主要是以纹状体病理改变为主，临床表现是进行性肌强直、运动迟缓、步态障碍等。MSA-C型主要病理改变以小脑为主，临床表现是进行性步态和肢体共济失调、构音障碍、眼球震颤等，随着病情发展，晚期可以出现运动迟缓、姿势障碍等类帕金森样症状。进行性核上性麻痹(Progressive supranuclear palsy，PSP)是DP家族中的另外一种主要疾病。PSP发病原因目前不明，可能与遗传、中毒、Tau基因突变等因素，导致细胞线粒体的代谢功能障碍等有关。病理表现为以中脑、脑桥、间脑病变为主。PSP主要临床表现是躯体中轴肌强直、动作减少、运动迟缓等类帕金森样症状，早期可以出现垂直性眼外肌麻痹、假性球麻痹、痴呆等表现。 PD和DP、PS在临床上都表现为运动迟缓、肌强直、姿势步态异常等，症状互相重叠。PD、DP、PS患者目前以临床诊断为主，虽然PD和DP、PS均有各自诊断标准，但在疾病早期，鉴别诊断非常困难，三者经常相互误诊。既往学者研究认为，左旋多巴试验是评价原发性帕金森病与变性性帕金森综合症及继发性帕金森综合征的一种简单易行的方法，根据对左旋多巴反应性的不同，可作为PD与DP及PS之间鉴别诊断依据之一。研究对象与方法选择我院2005年1月-2013年12月期间住院，左旋多巴试验的PD、YOPD、PS、DP患者共73例，试验前详细询问患者姓名、性别、年龄、职业等相关资料。试验前所有患者均抽血化验血常规、肝肾功能等相关检查。本文采用的试验方法是改良左旋多巴试验，具体试验方法是： 1.病人在24小时内停用所有与帕金森病治疗有关的药物； 2.在服药前30min服10mg吗丁啉； 3.在服药前进行一次帕金森病的改良Weber’s分级量表评分； 4.口服500mg美多巴； 5.从服药后10min开始，每20min对病人进行一次帕金森病的改良Weber’s分级量表评分，测至150min； 6.从服药后开始监测心率，血压，及其它不适，每30min监测记录一次； 7.最大改善率=（服药前基线评分-服药后最低评分）/服药前基线评分，病情改善30%者为阳性。结果 1.1PD组和YOPD组分病程＜5年和≥5年，试验后帕金森病的改良Weber’s分级量表评分比较，10min-150min，两组均无明显差异； 1.2PD和YOPD组分性别，试验后帕金森病的改良Weber’s分级量表评分比较，10min-150min，男女两组均无明显差异； 1.3PD组和PS组试验后帕金森病的改良Weber’s分级量表评分比较，服药后120min，两组差异有统计学意义，（t=2.615，P=0.012，P＜0.05）；服药后150min，两组差异极有统计学意义（t=2.856，P=0.007，P＜0.01），PD组最大改善率52.23%，明显高于PS组最大改善18.87%； 1.4PD组和VP组试验后帕金森病的改良Weber’s分级量表评分比较，120min和150min有极明显差异（120min：t=2.779，P=0.009＜0.01；150min：t=2.970，P=0.006＜0.01）。PD组最大改善率52.23%，明显高于VP组最大改善率16.15%； 1.5YOPD组和PS组试验后帕金森病的改良Weber’s分级量表评分比较，90min两组有明显有差异（t=2.645，P=0.012＜0.05）；120min和150min，两组有极明显差异（120min：t=3.072，P=0.004＜0.01；150min：t=3.053，P=0.004＜0.01）。YOPD组最大改善率63.85%，明显高于PS组最大改善率18.87%。 2. PD组和DP组试验后帕金森病的改良Weber’s分级量表评分比较120min和150min两组均有明显差异（120min：t=2.232，P=0.033＜0.05）（150min，t=2.280，P=0.030＜0.05）。PD组最大改善率52.32%，明显高DP组最大改善率12.06%。结论 1.改良左旋多巴试验，根据对左旋多巴不同的反应性，可作为PD与PS、PD与VP、YOPD与PS鉴别诊断依据之一；本次试验中，病程＜60月与≥60月PD患者，对左旋多巴的反应性无明显差异，但前者最大改善率稍高于后者；本次试验中，性别不同的PD患者，对左旋多巴的反应性无明显差异。 2.改良左旋多巴试验，根据对左旋多巴的不同反应性，可作为PD与DP鉴别诊断依据之一；改良左旋多巴试验，根据对左旋多巴的不同反应性，可以用来指导，不同亚型的MSA患者和不同病变部位引起的VP患者，是否可以使用左旋多巴类药物进行治疗。第二部分：颅脑MRI在帕金森病与帕金森综合征、多系统萎缩、进行性核上性麻痹鉴别诊断的意义研究背景最近，国内外研究者经过研究发现，颅脑MRI常规检查，观察基底节区、小脑、脑干等形态结构的改变，根据不同形态变化的特点，对PD和PS、MSA、PSP进行诊断与鉴别。另外，通过测量中脑面积、桥脑面积、及中脑面积与桥脑面积比值大小，亦能对PD和PS、MSA、PSP的诊断与鉴别诊断提供一定的诊断依据。本文把我院2012年1月-2013年12期间住院， PD和PS、MSA和PSP四组患者的颅脑MRI常规检查图像资料进行分析研究。研究对象与方法选择我院2012年1月—2013年12月期间住院，PD、PS、MSA-C、MSA-P和PSP患者共56人，另外选则年龄、性别相匹配的20名健康者作为对照。以上所有研究对象均有MRI常规检查图像资料。详细询问患者的姓名、性别、年龄、发病日期、诊断日期等一般资料。并收集记录。所有患者均抽血化验血常规、肝肾功能、电解质、血糖、血脂等常规检查并收集记录。收集研究对象的颅脑MRI图像资料，并详细记录。具体研究方法 1.目测所有入组患者颅脑MRI图像资料，观察基底节区壳核低信号、壳核外侧高信号“裂隙征”、小脑萎缩、桥脑基底部“十”字征、中脑萎缩变小呈“蜂鸟征”及大脑萎缩、脑池扩大等。 2.使用SIEMENS SYMPHONY1.5T超导MRI，测量不规则形面积软件系统，T1加权像正中矢状位测量中脑面积(M)和桥脑面积(P)，并计算中脑面积与桥脑面积比值(M/P)。研究结果 1. MRI图像目测结果 1.1MSA-C型组桥脑基底部“十”字征、桥脑、小脑明显萎缩发生率100%，高于其他各组，与其他各组比较，均有明显差异； 1.2MSA-P型组壳核“裂隙征”发生率100%，高于其他各组，与其他各组比较，均有明显差异； 1.3PSP组“蜂鸟征”发生率100%，高于其他各组各组，与其他各组比较，均有明显差异； 1.4PD组、PS组颅脑MRI无特征性图像改变。 2. MRI图像测量结果 2.1中脑面积测量，PSP组中脑面积平均值最小（94.52±5.47mm2）,与其各组比较，均有极明显差异（P＜0.01）； 2.2桥脑面积测量，MSA-C型组桥脑面积平均值最小（376.98±4.49mm2），与其他各组比较，均有极明显差异（P＜0.01）。MSA-P型组桥脑面积平均值(504.98±39.52mm2），与PS组比较，有明显差异，MSA-P型组小于PS组。MSA-P型组与其他各组比较，虽然无明显差异，但MSA-P型桥脑面积平均值均小于其他各组； 2.3中脑面积与桥脑面积比值(M/P)，PSP组M/P值（0.181±0.010）最小，与其他各组比较，均有极明显差异（P＜0.01）。MSA-C型组M/P值（0.374±0.008）最大，与其他各组比较，均有极明显差异（P＜0.01）。结论 1.颅脑MRI图像目测 1.1颅脑MRI常规扫描，T2WI壳核裂隙征有助于MSA-P型患者的诊断与鉴别，T2WI脑桥基底部“十”字征有助于MSA-C型患者的诊断与鉴别，T1WI中脑明显萎缩变小呈“蜂鸟征”，有助于PSP患者的诊断与鉴别； 1.2帕金森病和帕金森综合征患者颅脑MRI常规扫描，图像无特征性改变。 2.颅脑MRI图像测量桥脑面积测量及中脑面积与桥脑面积比值(M/P)有助于MSA-C型患者的诊断与鉴别；中脑面积测量及中脑面积与桥脑面积的比值有助于PSP患者的诊断与鉴别。
[Abstract]:The first part: the significance of levodopa test in the differential diagnosis of Parkinson's disease and Parkinson's syndrome
Research background
Parkinson syndrome usually includes: idiopathic Parkinson's disease (Parkinson 's disease, PD), secondary (Parkinsonism, PS) Parkinson, degenerative Parkinson syndrome (Degenerative, parkinsonism, DP) genetic degenerative Parkinson syndrome (Hereditary degenerative, parkinsonism, HDP).
Idiopathic Parkinson's disease (Parkinson 's disease, PD) is a common neurodegenerative disease in the elderly, typical neuropathological manifestations are: dopaminergic neuron degeneration, necrosis, residual neurons appeared Louis bodies (Lewy-body, LB), dopamine (DA) neurons in substantia nigra, cause the nigrostriatal pathway decrease of dopamine and acetylcholine antagonism function (Acetylcholine, Ach) is relatively higher, resulting in patients with dyskinesia.
Secondary Parkinson syndrome (Parkinsonism, PS) by infection, drug poisoning, cerebral arteriosclerosis, trauma caused by basal ganglia mainly nucleus degeneration, demyelination, white matter demyelination and degeneration, caused by the slow movement, posture, gait abnormalities, muscle tension changes and clinical manifestations a group of syndrome, including vascular Parkinson syndrome (Vascular Parkinsonism, VP), traumatic Parkinson syndrome (Traumatic parkinsonism, TP), drug-induced Parkinson syndrome (Drug-induce parkinsonism, DIP), toxic Parkinson syndrome (Toxic parkinsonism, TP), infectious Parkinson syndrome (Infection parkinsonism, IP).
Degenerative Parkinson syndrome (Degenerative parkinsonism DP) belongs to neurodegenerative diseases, often including multiple system atrophy (Multiple system, atrophy, MSA), progressive supranuclear palsy (Progressive supranuclear, palsy, PSP), corticobasal degeneration (Corticobasal degeneration CBD), Louis (Dementia with Lewy's bodies. DLB), normal pressure hydrocephalus (Normalpressure hydrocephalus, NPH).
Multiple system atrophy (Multiple system, atrophy, MSA) is one of the main diseases of the DP family, is a group of unknown etiology, manifestations of nervous system in many parts of atrophy disease. Multiple system atrophy is divided into MSA-P type and MSA-C type.MSA-P type is mainly because of the change of striatal pathology, clinical manifestations of myotonia. The slow movement, the main pathological change in.MSA-C gait disorder type cerebellar, clinical manifestations of gait and limb ataxia, dysarthria, nystagmus, with the progression of the disease can occur late bradykinesia, postural disorders such as Parkinson like symptoms.
Progressive supranuclear palsy (Progressive supranuclear, palsy, PSP) of the DP family is also a major disease of.PSP pathogenesis is unknown, may be related to genetic mutations in the Tau gene, poisoning, and other factors, resulting in mitochondrial dysfunction and so on. The pathological in the midbrain, pons, diencephalic lesions.PSP the clinical manifestation is the body movement decrease, axial rigidity, bradykinesia and other types of Parkinson like symptoms, early vertical ophthalmoplegia, pseudobulbar paralysis, dementia and other symptoms.
PD and DP, PS in clinical myotonia showed bradykinesia, gait abnormalities, symptoms of overlapping.PD, DP, PS in patients with the clinical diagnosis, while PD and DP, PS has its own diagnostic criteria, but early in the disease, the differential diagnosis is very difficult, the three are often misdiagnosed.
Previous scholars believe that levodopa test is the primary method to evaluate a simple Parkinson disease and degenerative Parkinson syndrome and secondary Parkinson syndrome, according to the different reaction of levodopa, as between PD and DP and PS differential diagnosis. One of the research objects and methods
A total of 73 cases of PD, YOPD, PS and DP hospitalized in our hospital during January 2005 -2013 December were selected. The names, gender, age and occupation related data were inquired before the experiment. All the patients were tested for blood routine, liver and kidney function and other related tests before the test.
The experimental method used in this paper is to improve the levodopa test. The specific test method is:
1. patients were discontinued for all drugs associated with Parkinson's disease within 24 hours.
2. before taking the medicine 30min 10mg domperidone;
3. a modified Weber 's rating scale for Parkinson's disease was performed before taking the drug.
4. oral 500mg;
5. from 10min after taking the medicine, a modified Weber 's rating scale for Parkinson's disease was performed per 20min for patients, and 150min was measured.
6. the heart rate, blood pressure, and other discomfort were monitored after taking the medicine, and each 30min monitoring record was recorded.
7. the maximum improvement rate = (the baseline score before taking the medicine - the lowest score after taking the medicine) / the baseline score of the medicine before taking the medicine, and the positive condition of the improvement of the 30%.
Result
1.1PD group and YOPD group divided the course less than 5 years and more than 5 years, the modified Weber test after s in Parkinson's Disease Rating Scale score, 10min-150min, the two groups had no significant difference;
1.2PD and YOPD groups were sexed, and the improved Weber 's rating scale of Parkinson's disease was compared, and there was no significant difference in 10min-150min between the two groups of men and women.
The modified Weber '1.3PD group and PS group after the test of s in Parkinson's Disease Rating Scale score, 120min after treatment, there was significant difference between two groups (t=2.615, P=0.012, P, 150min < 0.05); after the treatment, the difference between the two groups had statistical significance (t=2.856, P=0.007, P < 0.01), PD group the maximum improvement rate of 52.23%, significantly higher than that of group PS the maximum improvement of 18.87%;
In group 1.4PD and group VP, the scores of modified Weber 's scale for Parkinson's disease were significantly different from those of group Weber (120min:t=2.779, P=0.009 < 0.01), 150min:t=2.970 (P=0.006 < 0.01), and the maximal improvement rate of.PD group was 52.23%, which was significantly higher than that of the group with a maximum improvement rate of 16.15%.
The modified Weber '1.5YOPD group and PS group after the test of s in Parkinson's Disease Rating Scale score, 90min two was significantly different (t=2.645, P=0.012 < 0.05); 120min and 150min, the two groups have significant differences (120min:t=3.072, P=0.004 < 0.01; 150min:t=3.053, P=0.004 < 0.01) in.YOPD group the maximum improvement rate of 63.85% the largest group, was significantly higher than that of PS to improve the rate of 18.87%.
2. there was a significant difference between the PD group and the DP group in the scores of the improved Weber 's scale for Parkinson's disease compared with those in the two groups of 120min and 150min (120min:t=2.232, P=0.033 < 0.05) (150min, t=2.280, P=0.030 < 0.05). The maximal improvement rate of the group was 52.32%, significantly higher than that of the latter group.
conclusion
1. modified levodopa test, according to the different responsiveness to levodopa, can be used as one of the diagnostic criteria for the differential diagnosis of PD and PS, PD and VP, YOPD and PS.
In this test, the duration of 60 months and 60 months "or PD patients, no significant difference in response to levodopa, but the maximum improvement rate was slightly higher than that of the latter;
In this trial, there was no significant difference in responsiveness to levodopa in the PD patients with different sex.
2. the modified levodopa test, according to the different reactivity of levodopa, can be used as one of the diagnostic criteria for the differential diagnosis of PD and DP.
The modified levodopa test can be used to guide VP patients with different subtypes of MSA and different lesion sites, depending on the different reactivity of levodopa, and whether they can be treated with levodopa.
The second part: the significance of the differential diagnosis of craniocerebral MRI in Parkinson's disease and Parkinson's syndrome, multi system atrophy and progressive supranuclear paralysis
Research background
Recently, researchers at home and abroad after the study found that the brain MRI routine examination, observation of basal ganglia, cerebellum, brain stem morphological structure changes, according to the different characteristics of morphological changes, PD and PS, MSA, PSP diagnosis and differential diagnosis. In addition, by measuring the area of midbrain, pons and midbrain area and the area. Pons area ratio of size, can also for PD and PS, MSA, and provide diagnostic basis in the diagnosis and differential diagnosis of PSP. The inpatients in our hospital during January 2012 -2013 12, PD and PS, analysis of brain MRI image data of MSA and routine PSP of the four groups.
Research objects and methods
A total of 56 PD, PS, MSA-C, MSA-P and PSP patients were selected in our hospital from January 2012 to December 2013. In addition, 20 healthy persons with age and gender matched were selected as controls. All of the above subjects had image data of routine MRI examination.
General information about the patient's name, sex, age, date of onset, date of diagnosis, and so on.
All patients were tested for routine blood test, liver and kidney function, electrolytes, blood sugar, blood lipid and other routine examinations and collected records.
The brain MRI images of the subjects were collected and recorded in detail.
1. brain MRI images were observed in all the patients. We observed low signal in the basal ganglia putamen, "high fissure sign" on the lateral part of the putamen, cerebellar atrophy, "ten" sign on the base of the pons, atrophy of midbrain, "hummingbird sign", atrophy of the brain and enlargement of the cisterna.
2., we used SIEMENS SYMPHONY1.5T superconducting MRI to measure irregular area software system, T1 weighted image median sagittal measurement of midbrain area (M) and pons area (P), and calculate the ratio of midbrain area to pons area (M/P).
Research results
Visual results of 1. MRI images
The "ten" sign on the base of the bridge brain base in type 1.1MSA-C group, the incidence of obvious atrophy of the pontine and cerebellum was 100%, which was higher than that of the other groups, and there were significant differences compared with the other groups.
The incidence of "fissure sign" in group 1.2MSA-P putamen was 100%, which was higher than that in other groups, and there were significant differences compared with other groups.
The incidence of "hummingbird sign" in group 1.3PSP was 100%, which was higher than that in other groups, and there were significant differences compared with other groups.
In group 1.4PD and group PS, there was no characteristic image change in brain MRI.
2. MRI image measurement results
2.1 the mean area of the middle brain area of group PSP was least (94.52 + 5.47mm2), and there was a significant difference between the two groups (P < 0.01).
2.2 pontine area measurement, MSA-C group of pons area average minimum (376.98 + 4.49mm2), compared with other groups, there were very significant difference (P < 0.01) type.MSA-P group pons area average (504.98 + 39.52mm2), compared with the PS group, there was significant difference, MSA-P group than PS group.MSA-P group compared with other groups, while no significant difference, but the MSA-P pontine area average is less than the other groups;
2.3, the ratio of mesencephalon area to pons area (M/P), and PSP group M/P value (0.181 + 0.010) is the smallest. Compared with other groups, there is a very significant difference (P < 0.01). The M/P value of.MSA-C group is the largest (0.374 + 0.008), and there is a very significant difference compared with other groups (P < 0.01).
conclusion
1. visual MRI images of craniocerebral
1.1 cranial MRI routine scan, T2WI putamen cleft sign is helpful for diagnosis and differentiation of MSA-P type patients. T2WI pons basal part "ten" sign is helpful for diagnosis and differentiation of MSA-C type patients. T1WI mesencephalon obviously atrophy and decrease is "hummingbird sign", which is helpful for diagnosis and identification of PSP patients.
1.2 the patients with Parkinson's disease and Parkinson's syndrome were scanned with MRI routine, and the images were not changed.
2. MRI image measurement of craniocerebral
The area measurement of pons and the ratio of midbrain area to pons area (M/P) are helpful for the diagnosis and differentiation of MSA-C patients. The ratio of midbrain area and the area of midbrain to pons contributes to the diagnosis and differentiation of PSP patients.

【学位授予单位】：安徽中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

【参考文献】