【作者】 马晓伟；

【导师】 王铭维；

【作者基本信息】 河北医科大学 ， 神经病学， 2010， 硕士

【摘要】 目的:帕金森病(Parkinson Disease,PD)是一种中老年常见的神经系统变性疾病,临床上以进行性加重的运动缓慢、肌强直、静止性震颤、姿势步态异常等为特征,目前机制尚不清楚,至今尚无完善的治疗方案。本研究从运动功能、电生理检测方面观察PD患者皮质兴奋性的改变及其影响因素;利用低频重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)技术对帕金森病患者进行治疗,明确rTMS对PD患者的皮质兴奋性、运动障碍和情感障碍的疗效,并从电生理角度进一步探索PD的发病机制。方法:①根据入选标准和排除标准选择本科门诊和住院68例PD患者,另选择30名性别、年龄相匹配的健康者作为对照组。采用统一帕金森病评定量表(Unified Parkinson’s Disease Rating Scale,UPDRS)、运动诱发电位(motion evoked potential,MEP)作为评定指标,观察PD患者皮质兴奋性的改变及其影响因素。②采用丹麦维迪公司磁刺激器MagPro X100和MC-B70 Butterfly“8”字形线圈对28例PD患者进行低频rTMS技术治疗,刺激部位为入选者双侧的第一运动皮质手代表区M1Hand,频率为1Hz,磁场强度为120%静息阈值,每序列20次脉冲,每天3个序列,序列间隔60s,共60次脉冲,1次连续给予,共15 d。通过磁刺激治疗前后比较MEP、UPDRS、汉密顿抑郁量表(Hamilton Depression Scale,HAMD)、汉密顿焦虑量表(Hamilton Anxiety Scale,HAMA)的变化,以观察低频rTMS对PD患者的皮质兴奋性、运动障碍和情感障碍的治疗作用。所有数据以均数±标准差(x±s)表示,用SPSS11.5统计学软件分析,所有统计结果均以P<0.05作为判断差异有统计学意义的标准。结果:①PD患者的MEP改变: PD患者MEP的静息阈值(relaxed motor threshold,RMT()41.99±4.72)、中枢运动传导时间(central motor conduction time,CMCT)(7.55±1.07)较正常对照组RMT(48.87±5.59)、CMCT(8.12±0.89)明显降低或缩短(P<0.01)。其中强直型患者的RMT(40.92±5.28)比震颤型患者的RMT(42.93±3.97)缩短,同时强直型患者的UPDRS评分(50.66±16.28)高于震颤型患者(31.56±14.98),均存在统计学差异(P<0.05或P<0.01);病程>5年患者的RMT(40.70±4.74)比≤5年患者的RMT(42.60±4.61)缩短,存在统计学差异(P<0.05)。②低频rTMS后,MEP改变:PD患者RMT(42.70±5.70)增加至(45.65±4.53),CMCT(7.53±0.89)延长至(7.88±0.88),存在统计学差异(P<0.01)。其中Hoehn-Yahr分级≤2.5级和>2.5级PD患者rTMS后均RMT增加,CMCT延长,存在统计学差异(P<0.01或P<0.05);震颤型和强直型PD患者rTMS后均RMT增加,CMCT延长,存在统计学差异(P<0.01或P<0.05)。③低频rTMS后,UPDRS评分改变:PD患者UPDRS总分(44.96±18.22)降低至(35.04±17.26),分量表UPDRSⅠ评分(2.68±1.83)降低至(1.71±1.54),UPDRSⅡ评分(17.07±8.21)降低至(13.29±7.43),UPDRSⅢ评分(24.93±10.18)降低至(20.11±9.68),存在统计学差异(P<0.01)。其中≤2.5期和>2.5期的PD患者rTMS后UPDRS总分及分量表评分均降低,存在统计学差异(P<0.01或P<0.05);震颤型和强直型PD患者rTMS后UPDRS总分及分量表评分均降低,存在统计学差异(P<0.01或P<0.05);强直型比震颤型患者UPDRS总分降低更为明显,存在统计学差异(P<0.05)。④低频rTMS后,情感障碍改变:PD患者HAMD评分(12.53±7.68)降至(10.25±7.84) (P<0.01),其中HAMD躯体化评分(2.75±1.67)降至(2.29±1.94),阻滞评分(1.86±1.69)降至(1.03±1.45),睡眠因子评分(1.64±1.83)降至(1.11±1.50),存在统计学差异(P<0.05)。HAMA评分无明显改变(P>0.05)。结论:○1 PD患者存在运动功能障碍,大脑皮质兴奋性升高;强直型和病程长的患者病情较重,大脑皮质兴奋性升高更加明显。②低频rTMS可以改善PD患者运动功能障碍,可部分抑制大脑皮质兴奋性升高的改变。而且低频rTMS对PD病情严重程度不同的患者均有效,对强直和震颤症状均有治疗作用,且对强直型的效果优于震颤型。③低频rTMS可以改善PD患者抑郁症状,对焦虑无明显作用。更多还原

【Abstract】 Objective: Parkinson’s disease (PD) is a major neurodegenerative disease in elderly people characterized by bradykinesia, resting tremor, muscular rigidity, and gait disturbance. Up to date, the unknown etiology of PD has made it difficult to develop a perfect therapeutic strategy. This study was to reveal the MEP and its influential factors in Parkinson’s disease from motor function and electrophysiology. To investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on motor functions , the excitability of the motor cortex and affective disorder in PD and to study mechanism of PD from the eletrophysiology.Methods:①According to inclusion criteria and exclusion criteria, 68 PD patients were selected. Motor evoked potential (MEP) was observed in 68 PD patients and 30 gender-age matched normal control subjects and the difference between two groups were recorded. Adoption of Unified Parkinson’s Disease Rating Scale (UPDRS) and MEP as assessment indicators. Excitability of the motor cortex were assessed by rest motor threshold (RMT) , central motor conduction time (CMCT) and amplitude of MEP.②28 patients with PD were performed by 1Hz rTMS therapy to 15 days. (the rTMS protocol : stimulation site was the first motor cortex hand area M1Hand, and the magnetic field strength was 120% resting threshold, each sequence has 20 pulses, and sequence interval was 60 s, three sequences, a total of 60 second pulses were given every day). Adoption of UPDRS, Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and MEP as assessment indicators. Excitability of the motor cortex were assessed by RMT, CMCT and amplitude of MEP. All data (x±s) indicated by the mean value±standard deviation that with the SPSS11.5 statistics software analysis, all statistical result has statistics significance standard by P<0.05 as the judgment difference. Results:①MEP changes in PD patients: RMT (41.99±4.72) and CMCT (7.55±1.07) of PD patients were significantly reduced or shortened compared with normal control group RMT (48.87±5.59), CMCT (8.12±0.89) (P<0.01).Among them, RMT(40.92±5.28) of rigidity-group was shorter than RMT (42.93±3.97) of tremor-group in PD patients, while UPDRS(50.66±16.28) of rigidity-group was higher than UPDRS (31.56±14.98) of tremor-group, which exist in statistically significant difference (P<0.05 or P<0.01).RMT(40.70±4.74) of duration>5 years was shorter than RMT (42.60±4.61) of duration≤5 years in PD patients, which exist in statistically significant difference(P<0.05).②MEP changes in PD patients after being treated by rTMS: RMT (42.70±5.70) of PD patients increased to (45.65±4.53), CMCT (7.53±0.89) be extended to (7.88±0.88), the difference was statistically significant (P <0.01). This changes also exist in different Hoehn-Yahr stages, rigidity-group and tremor-group.③UPDRS changes in PD patients after being treated by rTMS: motor function have improved. UPDRS total score of PD patients was decreased from (44.96±18.22) to (35.04±17.26), UPDRSⅠscore (2.68±1.83) reduced to (1.71±1.54), UPDRSⅡscore (17.07±8.21) reduced to (13.29±7.43), UPDRSⅢscore (24.93±10.18) reduced to (20.11±9.68). Differences were statistically significant (P<0.01). The rigidity-group had more obvious improvement. Reduce of UPDRS total score (44.96±18.22) of rigidity-group was more significant than the lower of tremor-group, the difference was statistically significant (P <0.05).④HAMD and HAMA changes in PD patients after being treated by rTMS: HAMD score was decreased from (12.53±7.68) to (10.25±7.84) (P<0.01). The rigidity PD patients had more obvious improvement. In which the Somatization of HAMD score (2.75±1.67) reduced to (2.29±1.94), block score (1.86±1.69) reduced to (1.03±1.45), sleep factor score (1.64±1.83) reduced to (1.11±1.50), the difference was statistically significant. (P<0.05).HAMA score had no significant change in in PD patients after being treated by rTMS(P>0.05).Conclusion:①PD patients had motor dysfunction, and their cerebral cortex excitability increased; rigidity-group and longer course of illness in patients had more serious illness, and the brain cortex excitability increased more apparent.②Low-frequency rTMS can improve motor dysfunction in PD patients, and it could partly inhibit the increase in the cerebral cortex excitability changes. And the low-frequency rTMS to the severity of the different PD patients were effective, the symptoms of rigidity and tremor have therapeutic effect, and the type of rigidity is better than the tremor type.③Low-frequency rTMS can improve depressive symptoms in patients with PD, no significant effect on anxiety.更多还原