低频重复经颅磁刺激治疗帕金森病的疗效研究
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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。
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.
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。
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.
引文
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28 Ohnishi T,Hayashi T,Okaba S,et al.Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex:an raclopride positron emission tomography study in anesthetized macaque monkrys.Biol Psychiatry,2004,55:(5)484-489
29 Keck ME,Welt T,Müller MB,et al.Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system.Neuropharmacology,2002,43(1):101-109
30 Ohnishi T, Hayashi T, Okaba S, et al. Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an raclopride positron emission tomography study in anesthetized macaque monkrys. Biol Psychiatry,2004, 55(5):484-489
31 Helmich RC,Siebner HR,Bakker M,et al.Repetitive transcranial magnetic stimulation to improve mood and motor function in parkinson's disease.J Neurol Sci,2006,248(1-2):84-96
32 Kolosova LI, Akoev GN, Ryabchikova OV, Avelev VD. etal. Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats. Neurosci Behav physiol, 1998,28(1):26-30
33刘传玉,梅元武,张小乔,等.经颅磁刺激对脑缺血大鼠功能恢复和健侧突触结构的影响.中华物理医学与康复杂志,2005,27 (12): 210-314
34 Ben-Shachar D.Belmaker RH, Grisaru N, et al. Transcranial magnetic stimulation induces alterations in brain monoamines. J Neural Transm, 1997.104(2-3):191-197
35许涛,饶耀剑,郭风劲等.磁刺激对大鼠神经干细胞CDK5基因表达的影响,中国康复,2006,21(5):294-296
36刘传玉,梅元武,张小乔.经颅磁刺激对局灶性脑缺血大鼠梗死周边区GAP-43和Syp表达的影响,卒中与神经疾病,2006,13(1):15-18
37王全懂,顾平,董巧云,等。重复经颅磁刺激对帕金森病鼠纹状体生长相关蛋白和突触素表达的影响,中国老年学杂志,2008,28(19):1885-1888
38 McDonald WM, Richard IH, DeLong MR. Prevalence, Etiology, and Treatment of Depression in Parkinsonps Disease. Biol Psychiatry, 2003, 54(10):363-375
39 Mayberg HS,Starkstein SE,Sadzot B,et al.Selective hypometabolism in the inferior frontal lobe in depressed patient s with Parkinson's disease. Ann Neuro1, 1990, 28(2):57-64
40 Slaughter JR, Slaughter KA. Prevalence, clinical manifestations. Etiology and treatment of depression in Parkinson’s disease. J Neuropsychiaty clin Neurosci,2001, 13(2):187-196
41陆菁菁,龙洁.帕金森病伴发抑郁症状的研究近况.中国神经精神疾病杂志,2003,29(2):153
42 Helmich RC, Siebner HR, Bakker M, et al. Repetitive transcranial magnetic stimulation to improve mood and motor function in parkinson's disease. J Neurol Sci,2006,248(1-2):84-96
43 Strafella AP, Paus T, Fraraccio M, et al. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain, 2003,126(12):2609-2615
44 Strafella AP, Pans T, Barrett J, et al. Repetitive transcranial magnetic stimulation of the human p refrontal cortex induces dopamine release in the caudate nucleus. J Neurosci,2001,21(15):RC57
45崔冬生,顾平,刘力,等.低频磁刺激对PC12细胞分化的影响.中华物理医学与康复杂志,2005,27(12):728-731
46叶青,李巍,王正荣,等.不同频率的重复经颅磁刺激的抗抑郁作用.西部医学,2007,19(4):516-518
47 Keck ME, et al. Acute transcranial magnetic stimulation of frontal brain regions selectively modulates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur J Neurosci, 2000. 12(10): 3713-3720
48王全懂,董巧云,王铭维,等.重复经颅磁刺激帕金森模型鼠纹状体vmat-2和syn表达的影响.第三军医大学学报,2008,30(4):322-325
49董巧云,顾平,王铭维,等.经颅磁刺激对帕金森病小鼠黑质多巴胺能神经元及脑源性神经营养因子的影响.第二军医大学学报,2008,29(3):245-249
50董巧云,王全懂,王铭维等.磁刺激对帕金森病鼠黑质多巴胺能神经元的保护及其机制.中华物理医学与康复杂志,2008,30(4):227-230
1 Liu LX,Chen WF,Xie JX,et al.Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson's disease.Neurosci Res,2008,60(2):156-161
2 Faherty CJ,Raviie Shepherd K,Herasimtschuk A,et al.Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism.Brain Res Mol Brain Res,2005,134(1):170-179
3 Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex.Lancet,1985,1(8437): 1106-1107
4陈昭燃,张蔚婷,韩济生.经颅磁刺激:生理、心理、脑成像及其临床应用.生理科学进展,2004,35(2):102-106
5 Maeda F,Keenan JP,Tormos JM,et al.Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.Exp Brain Res,2000,133(4):425-430
6 Wassermann EM.Risk and safety of repetitive transcranial magnetic stimulation : report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation,June 5-7,1996.Electroencephalogr Clin Neurophysiol,1998,108(1):1-16
7 Lefaucheur JP.Motor cortex dysfunction revealed by cortical excitability studies in Parkinson's disease:influence of antiparkinsonian treatment and cortical stimulation.Clin Neurophysiol,2005,116(2):244-253
8 Soysal A,Sobe I,Atay T,et al.Effect of therapy on motor cortical excitability in Parkinson's disease.Can J Neurol Sci,2008,35(2):166-172
9 Gorsler A,Baumer T,Weiller C,et al.Interhemispheric effects of high and low frequency rTMS in healthy humans.Clin Neurophysiol,2003,114(10):1800-1807
10 Obeso JA,Rodriguez-Oroz M,Marin C,et al.The origin of motor fluctuations in Parkinson's disease : importance of dopaminergic innervation and basal ganglia circuits.Neurology,2004,62(1 suppl 1): 17-30
11 Kim DK,Hoyt J,Bacchi C,et al.Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins.Neurosurgery,1993,33(4):619-626
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17 Keck ME,Welt T,Müller MB,et al.Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system.Neuropharmacology,2002,43(1):101-109
18 Helmich RC,Siebner HR,Bakker M,et al.Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease.J Neurol Sci,2006,248(1-2):84-96
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31王全懂,董巧云,王铭维,等.重复经颅磁刺激帕金森模型鼠纹状体vmat-2和syn表达的影响.第三军医大学学报,2008,30(40):322-325
32董巧云,王全懂,王铭维,等.磁刺激对帕金森病鼠黑质多巴胺能神经元的保护及其机制.中华物理医学与康复杂志,2008,30(4):227-230
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44 Kolosova LI, Akoev GN, Ryabchikova OV, Avelev VD. etal. Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats. Neurosci Behav physiol,1998,28(1):26-30
45崔冬生,顾平,刘力,等.低频磁刺激对PC12细胞分化的影响.中华物理医学与康复杂志,2005,27(2):728-73
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8 Khedr EM, Farweez HM, Islam H. Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson's disease patients. Eur J Neurol, 2003, 10(5): 567-572
9 Kim DK, Hoyt J, Bacchi C, et al. Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins. Neurosurgery, 1993, 33(4): 619-626
10 Cantello R, Gianelli M, Civardi C, et al. Focal subcortical reflex myoclonus. A clinical and neurophysiological Study. Arch Neurol, 1997, 54(2):187-196
11丁则呈,崔丽英.经颅重复磁刺激技术在治疗中的应用进展.国外医学神经病学神经外科学分册,2004, 31(6):508-511
12 Sabatini U, Boulanouar K, Fabre N, et al. Cortical motor reorganization in akinetic patients with Parkinson's disease: a functional MRI study. Brain , 2000;123( Pt 2):394-403
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18 Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex.Lancet,1985,1(8437): 1106-1107
19吕浩,唐劲天.经颅磁刺激技术的研究和进展,中国医疗器械信息,2006;12(5):28-32
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22 Levit-Binnun N, Handzy NZ, Moses E, et al., Transcranial Magnetic Stimulation at M1 disrupts cognitive networks in schizophrenia. Schizophr Res, 2007. 93(1-3): 334-344
23 Chouinard PA, Leonard G, Paus T. Changes in effective connectivity of the primary motor cortex in stroke patients after rehabilitative therapy. Exp Neurol, 2006. 201(2): 375-387
24 Schneider SA, Pleger B, Draganski B, et al. Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia-an fMRI-TMS study. Mov Disord. 2010,25(1):76-83
25 Fregni F, Simon DK, Wu A, et al.Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature.J Neurol Neurosurg Psychiatry, 2005, 76(12):1614-1623
26 Haslinger B, Erhard P, Kampfe N, et al.Event-related functional magnetic resonance imaging in Parkinson disease before and after levodopa.Brain,2001,124(Pt3):558-570
27 Wassermann EM,Grafman J,Berry C,et al.Use and safety of a new repetitive transcranial magnetic stimulator. Electroenceph clin Neurophysiol, 1996,101(5):412-417
28 Ohnishi T,Hayashi T,Okaba S,et al.Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex:an raclopride positron emission tomography study in anesthetized macaque monkrys.Biol Psychiatry,2004,55:(5)484-489
29 Keck ME,Welt T,Müller MB,et al.Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system.Neuropharmacology,2002,43(1):101-109
30 Ohnishi T, Hayashi T, Okaba S, et al. Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an raclopride positron emission tomography study in anesthetized macaque monkrys. Biol Psychiatry,2004, 55(5):484-489
31 Helmich RC,Siebner HR,Bakker M,et al.Repetitive transcranial magnetic stimulation to improve mood and motor function in parkinson's disease.J Neurol Sci,2006,248(1-2):84-96
32 Kolosova LI, Akoev GN, Ryabchikova OV, Avelev VD. etal. Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats. Neurosci Behav physiol, 1998,28(1):26-30
33刘传玉,梅元武,张小乔,等.经颅磁刺激对脑缺血大鼠功能恢复和健侧突触结构的影响.中华物理医学与康复杂志,2005,27 (12): 210-314
34 Ben-Shachar D.Belmaker RH, Grisaru N, et al. Transcranial magnetic stimulation induces alterations in brain monoamines. J Neural Transm, 1997.104(2-3):191-197
35许涛,饶耀剑,郭风劲等.磁刺激对大鼠神经干细胞CDK5基因表达的影响,中国康复,2006,21(5):294-296
36刘传玉,梅元武,张小乔.经颅磁刺激对局灶性脑缺血大鼠梗死周边区GAP-43和Syp表达的影响,卒中与神经疾病,2006,13(1):15-18
37王全懂,顾平,董巧云,等。重复经颅磁刺激对帕金森病鼠纹状体生长相关蛋白和突触素表达的影响,中国老年学杂志,2008,28(19):1885-1888
38 McDonald WM, Richard IH, DeLong MR. Prevalence, Etiology, and Treatment of Depression in Parkinsonps Disease. Biol Psychiatry, 2003, 54(10):363-375
39 Mayberg HS,Starkstein SE,Sadzot B,et al.Selective hypometabolism in the inferior frontal lobe in depressed patient s with Parkinson's disease. Ann Neuro1, 1990, 28(2):57-64
40 Slaughter JR, Slaughter KA. Prevalence, clinical manifestations. Etiology and treatment of depression in Parkinson’s disease. J Neuropsychiaty clin Neurosci,2001, 13(2):187-196
41陆菁菁,龙洁.帕金森病伴发抑郁症状的研究近况.中国神经精神疾病杂志,2003,29(2):153
42 Helmich RC, Siebner HR, Bakker M, et al. Repetitive transcranial magnetic stimulation to improve mood and motor function in parkinson's disease. J Neurol Sci,2006,248(1-2):84-96
43 Strafella AP, Paus T, Fraraccio M, et al. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain, 2003,126(12):2609-2615
44 Strafella AP, Pans T, Barrett J, et al. Repetitive transcranial magnetic stimulation of the human p refrontal cortex induces dopamine release in the caudate nucleus. J Neurosci,2001,21(15):RC57
45崔冬生,顾平,刘力,等.低频磁刺激对PC12细胞分化的影响.中华物理医学与康复杂志,2005,27(12):728-731
46叶青,李巍,王正荣,等.不同频率的重复经颅磁刺激的抗抑郁作用.西部医学,2007,19(4):516-518
47 Keck ME, et al. Acute transcranial magnetic stimulation of frontal brain regions selectively modulates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur J Neurosci, 2000. 12(10): 3713-3720
48王全懂,董巧云,王铭维,等.重复经颅磁刺激帕金森模型鼠纹状体vmat-2和syn表达的影响.第三军医大学学报,2008,30(4):322-325
49董巧云,顾平,王铭维,等.经颅磁刺激对帕金森病小鼠黑质多巴胺能神经元及脑源性神经营养因子的影响.第二军医大学学报,2008,29(3):245-249
50董巧云,王全懂,王铭维等.磁刺激对帕金森病鼠黑质多巴胺能神经元的保护及其机制.中华物理医学与康复杂志,2008,30(4):227-230
1 Liu LX,Chen WF,Xie JX,et al.Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson's disease.Neurosci Res,2008,60(2):156-161
2 Faherty CJ,Raviie Shepherd K,Herasimtschuk A,et al.Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism.Brain Res Mol Brain Res,2005,134(1):170-179
3 Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex.Lancet,1985,1(8437): 1106-1107
4陈昭燃,张蔚婷,韩济生.经颅磁刺激:生理、心理、脑成像及其临床应用.生理科学进展,2004,35(2):102-106
5 Maeda F,Keenan JP,Tormos JM,et al.Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.Exp Brain Res,2000,133(4):425-430
6 Wassermann EM.Risk and safety of repetitive transcranial magnetic stimulation : report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation,June 5-7,1996.Electroencephalogr Clin Neurophysiol,1998,108(1):1-16
7 Lefaucheur JP.Motor cortex dysfunction revealed by cortical excitability studies in Parkinson's disease:influence of antiparkinsonian treatment and cortical stimulation.Clin Neurophysiol,2005,116(2):244-253
8 Soysal A,Sobe I,Atay T,et al.Effect of therapy on motor cortical excitability in Parkinson's disease.Can J Neurol Sci,2008,35(2):166-172
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