利用配对关联刺激检测帕金森病患者感觉运动整合功能的变化

Changes of sensorimotor integration detected by paired associative stimulus in patients with Parkinson's disease

目的:研究早期和中晚期帕金森病(Parkinson’s disease,PD)患者运动皮层兴奋性以及感觉运动整合功能变化情况,早期和中晚期PD患者感觉运动整合功能是否存在差异。方法:研究对象为PD患者16例,分为早期PD组(PD-E,n=10)、中晚期PD组(PD-L,n=6)和正常对照组(n=10)。采用经颅磁刺激(transcranial magnetic stimulation,TMS)刺激运动皮层,在对侧拇短展肌产生运动诱发电位(motor evoked potential,MEP),记录静息运动阈值(resting motor threshold,RMT)、静息期(silent period,SP)、强度反应曲线比较3组背景运动皮层兴奋性。运用配对关联刺激(paired associative stimulation,PAS)技术观察外周正中神经感觉传入对TMS诱发的拇短展肌MEP幅度影响,分析感觉运动整合功能变化。将正中神经电刺激与对侧运动皮层TMS组成PAS作为条件刺激(PAS间隔16、20、24、28、100、200 ms),将单一TMS刺激作为非条件刺激。分别记录不同刺激间隔条件刺激和非条件刺激拇短展肌MEP,以条件刺激MEP幅度与非条件刺激MEP幅度比值(MEP’)表示外周感觉传入对MEP幅度影响。结果:PD-E组及PD-L组RMT均低于正常对照组且差异具有统计学意义(P<0.05),PD-E组与PD-L组2组之间RMT无统计学差异(P>0.05);PD-L组SP小于正常对照组(P<0.05),PD-E组SP与正常对照组比较差异无统计学意义(P>0.05)。3组强度反应曲线均表现为MEP波幅随刺激强度递增而递增,TMS刺激强度自130%RMT增长至150%RMT时,PD-L组MEP波幅均小于其余2组且差异具有统计学意义(均P<0.05)。PAS实验显示3组MEP’随着PAS的ISI值不同而变化(MEP’>1或MEP’<1)。ISI为24 ms时,PAS对PD-L组则呈现易化效应[MEP’:(1.71±0.67)],正常对照组MEP波幅无明显影响[MEP’:(0.98±0.40)],在PD-E组呈现轻度抑制效应[MEP’:(0.75±0.44)],PD-L组MEP’与其余2组比较具有统计学差异(均P<0.05),提示ISI为24 ms时中晚期PD患者外周感觉传入对运动皮层抑制效应减弱并发生反转。ISI为200 ms时,正常对照组和PD-E组PAS对MEP波幅呈现易化效应[MEP’分别为(1.37±0.66)、(1.35±0.64)],PD-L组则呈现抑制效应[MEP’:(0.84±0.35)],但MEP’3组间无统计学差异(P>0.05)。PD-E组与正常对照组PAS对MEP波幅的影响类似,各ISI对应MEP’无统计学差异。结论:配对关联刺激随刺激间隔不同对诱发运动电位波幅有易化或抑制效应,早期PD患者外周感觉传入对运动皮层兴奋性的影响与正常人比较差异不显著,中晚期PD患者24 ms短潜伏期传入抑制效应减弱并反转为兴奋效应,提示其感觉运动整合功能存在紊乱。

Objective：To study whether the motor cortex excitability and the sensorimotor integration function are differentially affected in patients with Parkinson＇s disease（PD）in early stage in relative to mid-late stage. Methods ：Sixteen patients with PD were divided into early course group（PD-E,n=10） and middle-late course（PD-L,n=6） according to Hoen/Yahr scale;10 normal healthy volunteers were included as the normal control group. Transcranial magnetic stimulation（TMS）was applied on the hand area of the cerebral motor cortex,and motor evoked potentials（MEPs）on the contralateral were recorded by surface electrodes. The resting motor threshold（RMT）,silent period（SP）and intensity-response of MEP were measured in each group to assess the background excitability of motor cortex. Paired associative stimulation（PAS）,which comprised of electrical stimulation of contralateral median nerve and TMS at defined interstimulus interval（ISI）,was used to analyze the influence of sensory input to motor cortex output and the sensorimotor integration function.PAS at serial ISI（16,20,24,28,100,200 ms）were delivered at contralateral median nerve and motor cortex and the amplitudes of MEPs on abductor pollicis brevis were measured as the conditioned-stimulus MEPs,and the amplitudes of MEPs induced by TMS without associative sensory input were also measured as the unconditioned-stimulus MEPs. The ratio of MEPs of conditioned-stimulus and unconditioned-stimulus,defined as MEP＇,was used to analyze the effects of sensory input to motor cortex excitability and sensorimotor integration. Results：Both PD-E group and PD-L group showed lower RTMs than the control group（P〈 0.05）,while the RTMs between PD-E group and PD-L group were not significantly different（P0.05）. The SP of PD-L group,not PD-E group was significantly shorter than that of the control group（P〉0.05）;SP between PD-E group and PD-L group was not significantly different（P〉0.05）. In intensity-response study of TMS-MEP,the MEP amplitudes were increased with the escalation of the magnetic stimulation intensity in all the groups,however,the TMS-MEP amplitude was significantly less in PD-L group than in PD-E group and normal control group when the TMS intensity increased from 130% RMT to 150% RMT（P〉0.05）. In PAS test,the MEP＇fluctuated in response to PAS of various ISI（MEP＇1 or1）. PAS with ISI of 24 ms has no obvious effect in normal control group[MEP＇：（0.98±0.40）],slight inhibitory effect in PD-E group[MEP＇：（0.75±0.44）],facilitative effect in PD-L group [MEP＇：（1.71±0.67）];MEP＇of PD-L group was significantly higher than that of the other two groups（both P〈0.05）,suggesting that the inhibitory effect of sensory input on motor cortex was reduced and even reversed in late stage PD patients. PAS with ISI of 200 ms showed facilitative effects on amplitude of MEP in both normal control group[MEP＇：（1.37±0.66）] and PD-E group[MEP＇：（1.35±0.64）] and inhibitory effects on amplitude of MEP in PD-L group [MEP＇：（0.84 ±0.35）],however,the differences of MEP＇were not statistically significant among the three groups（P〈0.05）. Effects of PAS on the amplitudes of MEP were similar between PD-E group and normal control group,the MEP＇related to serial ISI PAS was not statistically different between the two groups（P0.05）. Conclusion：PAS with various ISI may have facilitative or inhibitory effects on the amplitudes of MEP. The impacts of peripheral sensory input on motor cortex excitability are not significantly affected in early stage PD patients compared to normal controls,the short latency afferent inhibition at ISI of 24 ms observed in early stage PD patients was remarkably reduced and even reversed in mid-late stage PD patients,indicating that the sensorimotor integration function is disrupted in mid-late stage PD.