本文關鍵詞： 左旋多巴試驗 帕金森病 繼發(fā)性帕金森綜合征 變性性帕金森綜合征鑒別診斷 顱腦MRI 帕金森病 帕金森綜合征 多系統(tǒng)萎縮 進行性核上性麻痹鑒別診斷　出處：《安徽中醫(yī)藥大學》2014年碩士論文　論文類型：學位論文

【摘要】：第一部分：左旋多巴試驗在帕金森病與帕金森綜合征鑒別診斷的意義 研究背景 帕金森綜合征通常包括：原發(fā)性帕金森病(Parkinson’s disease, PD)、繼發(fā)性帕金森綜合(Parkinsonism，PS)、變性性帕金森綜合征(Degenerative parkinsonism，DP)、遺傳變性性帕金森綜合征（Hereditary degenerative parkinsonism，HDP）。 原發(fā)性帕金森病(Parkinson’s disease, PD)是中老年人常見的神經(jīng)系統(tǒng)變性疾病，神經(jīng)病理典型表現(xiàn)是：黑質多巴胺能神經(jīng)元變性、壞死，殘余神經(jīng)元出現(xiàn)路易小體（Lewy-body，LB），黑質多巴胺能(DA)神經(jīng)元減少，造成黑質-紋狀體通路的多巴胺減少，與之功能相互拮抗的乙酰膽堿（Acetylcholine，Ach）相對增高，導致患者出現(xiàn)運動障礙。 繼發(fā)性帕金森綜合征(Parkinsonism，，PS)是由感染、藥物、中毒、腦動脈硬化、外傷等引起以基底節(jié)區(qū)為主的神經(jīng)核團變性、脫失，白質的脫髓鞘、變性等，引起的以運動遲緩、姿勢、步態(tài)異常、肌張力改變等臨床表現(xiàn)的一組綜合征。包括血管性帕金森綜合征（Vascular Parkinsonism，VP）、外傷性帕金森綜合征（Traumatic parkinsonism，TP）、藥物性帕金森綜合征（Drug-induce parkinsonism，DIP）、中毒性帕金森綜合征（Toxic parkinsonism，TP）、感染性帕金森綜合征（Infection parkinsonism，IP）等。 變性性帕金森綜合征(Degenerative parkinsonism，DP)屬于神經(jīng)系統(tǒng)變性疾病，通常包括多系統(tǒng)萎縮（Multiple system atrophy，MSA），進行性核上性麻痹(Progressive supranuclear palsy，PSP)，皮質基底節(jié)變性(Corticobasal degeneration，CBD)，路易體癡呆(Dementia with Lewy bodies，DLB)，正常顱壓腦積水(Normalpressure hydrocephalus，NPH)等。 多系統(tǒng)萎縮（Multiple system atrophy，MSA）是DP家族中的主要疾病之一，是一組病因不明，表現(xiàn)為神經(jīng)系統(tǒng)多部位進行性萎縮的疾病。多系統(tǒng)萎縮分為MSA-P型和MSA-C型。MSA-P型主要是以紋狀體病理改變?yōu)橹�，臨床表現(xiàn)是進行性肌強直、運動遲緩、步態(tài)障礙等。MSA-C型主要病理改變以小腦為主，臨床表現(xiàn)是進行性步態(tài)和肢體共濟失調、構音障礙、眼球震顫等，隨著病情發(fā)展，晚期可以出現(xiàn)運動遲緩、姿勢障礙等類帕金森樣癥狀。 進行性核上性麻痹(Progressive supranuclear palsy，PSP)是DP家族中的另外一種主要疾病。PSP發(fā)病原因目前不明，可能與遺傳、中毒、Tau基因突變等因素，導致細胞線粒體的代謝功能障礙等有關。病理表現(xiàn)為以中腦、腦橋、間腦病變?yōu)橹鳌SP主要臨床表現(xiàn)是軀體中軸肌強直、動作減少、運動遲緩等類帕金森樣癥狀，早期可以出現(xiàn)垂直性眼外肌麻痹、假性球麻痹、癡呆等表現(xiàn)。 PD和DP、PS在臨床上都表現(xiàn)為運動遲緩、肌強直、姿勢步態(tài)異常等，癥狀互相重疊。PD、DP、PS患者目前以臨床診斷為主，雖然PD和DP、PS均有各自診斷標準，但在疾病早期，鑒別診斷非常困難，三者經(jīng)常相互誤診。 既往學者研究認為，左旋多巴試驗是評價原發(fā)性帕金森病與變性性帕金森綜合癥及繼發(fā)性帕金森綜合征的一種簡單易行的方法，根據(jù)對左旋多巴反應性的不同，可作為PD與DP及PS之間鑒別診斷依據(jù)之一。研究對象與方法 選擇我院2005年1月-2013年12月期間住院，左旋多巴試驗的PD、YOPD、PS、DP患者共73例，試驗前詳細詢問患者姓名、性別、年齡、職業(yè)等相關資料。試驗前所有患者均抽血化驗血常規(guī)、肝腎功能等相關檢查。 本文采用的試驗方法是改良左旋多巴試驗，具體試驗方法是： 1.病人在24小時內停用所有與帕金森病治療有關的藥物； 2.在服藥前30min服10mg嗎丁啉； 3.在服藥前進行一次帕金森病的改良Weber’s分級量表評分； 4.口服500mg美多巴； 5.從服藥后10min開始，每20min對病人進行一次帕金森病的改良Weber’s分級量表評分，測至150min； 6.從服藥后開始監(jiān)測心率，血壓，及其它不適，每30min監(jiān)測記錄一次； 7.最大改善率=（服藥前基線評分-服藥后最低評分）/服藥前基線評分，病情改善30%者為陽性。 結果 1.1PD組和YOPD組分病程＜5年和≥5年，試驗后帕金森病的改良Weber’s分級量表評分比較，10min-150min，兩組均無明顯差異； 1.2PD和YOPD組分性別，試驗后帕金森病的改良Weber’s分級量表評分比較，10min-150min，男女兩組均無明顯差異； 1.3PD組和PS組試驗后帕金森病的改良Weber’s分級量表評分比較，服藥后120min，兩組差異有統(tǒng)計學意義，（t=2.615，P=0.012，P＜0.05）；服藥后150min，兩組差異極有統(tǒng)計學意義（t=2.856，P=0.007，P＜0.01），PD組最大改善率52.23%，明顯高于PS組最大改善18.87%； 1.4PD組和VP組試驗后帕金森病的改良Weber’s分級量表評分比較，120min和150min有極明顯差異（120min：t=2.779，P=0.009＜0.01；150min：t=2.970，P=0.006＜0.01）。PD組最大改善率52.23%，明顯高于VP組最大改善率16.15%； 1.5YOPD組和PS組試驗后帕金森病的改良Weber’s分級量表評分比較，90min兩組有明顯有差異（t=2.645，P=0.012＜0.05）；120min和150min，兩組有極明顯差異（120min：t=3.072，P=0.004＜0.01；150min：t=3.053，P=0.004＜0.01）。YOPD組最大改善率63.85%，明顯高于PS組最大改善率18.87%。 2. PD組和DP組試驗后帕金森病的改良Weber’s分級量表評分比較120min和150min兩組均有明顯差異（120min：t=2.232，P=0.033＜0.05）（150min，t=2.280，P=0.030＜0.05）。PD組最大改善率52.32%，明顯高DP組最大改善率12.06%。 結論 1.改良左旋多巴試驗，根據(jù)對左旋多巴不同的反應性，可作為PD與PS、PD與VP、YOPD與PS鑒別診斷依據(jù)之一； 本次試驗中，病程＜60月與≥60月PD患者，對左旋多巴的反應性無明顯差異，但前者最大改善率稍高于后者； 本次試驗中，性別不同的PD患者，對左旋多巴的反應性無明顯差異。 2.改良左旋多巴試驗，根據(jù)對左旋多巴的不同反應性，可作為PD與DP鑒別診斷依據(jù)之一； 改良左旋多巴試驗，根據(jù)對左旋多巴的不同反應性，可以用來指導，不同亞型的MSA患者和不同病變部位引起的VP患者，是否可以使用左旋多巴類藥物進行治療。 第二部分：顱腦MRI在帕金森病與帕金森綜合征、多系統(tǒng)萎縮、進行性核上性麻痹鑒別診斷的意義 研究背景 最近，國內外研究者經(jīng)過研究發(fā)現(xiàn)，顱腦MRI常規(guī)檢查，觀察基底節(jié)區(qū)、小腦、腦干等形態(tài)結構的改變，根據(jù)不同形態(tài)變化的特點，對PD和PS、MSA、PSP進行診斷與鑒別。另外，通過測量中腦面積、橋腦面積、及中腦面積與橋腦面積比值大小，亦能對PD和PS、MSA、PSP的診斷與鑒別診斷提供一定的診斷依據(jù)。本文把我院2012年1月-2013年12期間住院， PD和PS、MSA和PSP四組患者的顱腦MRI常規(guī)檢查圖像資料進行分析研究。 研究對象與方法 選擇我院2012年1月—2013年12月期間住院，PD、PS、MSA-C、MSA-P和PSP患者共56人，另外選則年齡、性別相匹配的20名健康者作為對照。以上所有研究對象均有MRI常規(guī)檢查圖像資料。 詳細詢問患者的姓名、性別、年齡、發(fā)病日期、診斷日期等一般資料。并收集記錄。 所有患者均抽血化驗血常規(guī)、肝腎功能、電解質、血糖、血脂等常規(guī)檢查并收集記錄。 收集研究對象的顱腦MRI圖像資料，并詳細記錄。具體研究方法 1.目測所有入組患者顱腦MRI圖像資料，觀察基底節(jié)區(qū)殼核低信號、殼核外側高信號“裂隙征”、小腦萎縮、橋腦基底部“十”字征、中腦萎縮變小呈“蜂鳥征”及大腦萎縮、腦池擴大等。 2.使用SIEMENS SYMPHONY1.5T超導MRI，測量不規(guī)則形面積軟件系統(tǒng)，T1加權像正中矢狀位測量中腦面積(M)和橋腦面積(P)，并計算中腦面積與橋腦面積比值(M/P)。 研究結果 1. MRI圖像目測結果 1.1MSA-C型組橋腦基底部“十”字征、橋腦、小腦明顯萎縮發(fā)生率100%，高于其他各組，與其他各組比較，均有明顯差異； 1.2MSA-P型組殼核“裂隙征”發(fā)生率100%，高于其他各組，與其他各組比較，均有明顯差異； 1.3PSP組“蜂鳥征”發(fā)生率100%，高于其他各組各組，與其他各組比較，均有明顯差異； 1.4PD組、PS組顱腦MRI無特征性圖像改變。 2. MRI圖像測量結果 2.1中腦面積測量，PSP組中腦面積平均值最�。�94.52±5.47mm2）,與其各組比較，均有極明顯差異（P＜0.01）； 2.2橋腦面積測量，MSA-C型組橋腦面積平均值最�。�376.98±4.49mm2），與其他各組比較，均有極明顯差異（P＜0.01）。MSA-P型組橋腦面積平均值(504.98±39.52mm2），與PS組比較，有明顯差異，MSA-P型組小于PS組。MSA-P型組與其他各組比較，雖然無明顯差異，但MSA-P型橋腦面積平均值均小于其他各組； 2.3中腦面積與橋腦面積比值(M/P)，PSP組M/P值（0.181±0.010）最小，與其他各組比較，均有極明顯差異（P＜0.01）。MSA-C型組M/P值（0.374±0.008）最大，與其他各組比較，均有極明顯差異（P＜0.01）。 結論 1.顱腦MRI圖像目測 1.1顱腦MRI常規(guī)掃描，T2WI殼核裂隙征有助于MSA-P型患者的診斷與鑒別，T2WI腦橋基底部“十”字征有助于MSA-C型患者的診斷與鑒別，T1WI中腦明顯萎縮變小呈“蜂鳥征”，有助于PSP患者的診斷與鑒別； 1.2帕金森病和帕金森綜合征患者顱腦MRI常規(guī)掃描，圖像無特征性改變。 2.顱腦MRI圖像測量 橋腦面積測量及中腦面積與橋腦面積比值(M/P)有助于MSA-C型患者的診斷與鑒別；中腦面積測量及中腦面積與橋腦面積的比值有助于PSP患者的診斷與鑒別。
[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.

【學位授予單位】：安徽中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R742.5

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