Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Marra C, Daniele A, Ghirlanda S, Gainotti G, Tonali P A
Institute of Neurology, Università Cattolica, Largo A. Gemelli 8, 00168 Rome, Italy.
J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):555-9. doi: 10.1136/jnnp.2003.018127.
Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits.
We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals.
The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine.
The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.
近期的经颅磁刺激（TMS）研究表明，阿尔茨海默病（AD）患者的运动皮质兴奋性增加，且皮质内抑制现象受损。本研究的目的是确定这种兴奋性过高是由于皮质内抑制回路受损还是兴奋性回路的独立异常所致。
我们使用多种TMS范式，对28例AD患者的运动皮质兴奋性进行了评估，并将皮质兴奋性数据（通过测量静息运动阈值进行评估）与使用运动皮质胆碱能抑制试验（短潜伏期传入抑制）和GABA能抑制试验（短潜伏期皮质内抑制）评估的运动皮质去抑制量进行了比较。AD患者的数据还与12名年龄匹配的健康个体的数据进行了比较。
AD患者的平均静息运动阈值显著低于对照组。AD患者的短潜伏期传入抑制量显著低于正常对照组。AD患者的短潜伏期皮质内抑制也有比对照组不明显的趋势，但这种差异不显著。静息运动阈值与短潜伏期传入或皮质内抑制的测量值之间均无相关性（r分别为-0.19和0.18，无统计学意义）。在14例AD患者中，单次口服胆碱酯酶抑制剂卡巴拉汀后重复进行了电生理研究。卡巴拉汀给药后静息运动阈值无显著改变。相比之下，卡巴拉汀给药后正中神经的短潜伏期传入抑制显著增加。
阈值变化似乎与皮质内胆碱能和GABA能抑制回路功能障碍无关，也与中枢胆碱能活性无关。我们认为运动皮质的兴奋性过高是由皮质内兴奋性回路异常引起的。
