Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease
Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease
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DOI：
10.1093/brain/awl172
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发表时间：
2006-09-01
期刊：
影响因子：
14.5
通讯作者：
Kiernan, Matthew C.
中科院分区：
文献类型：
--
作者：
Vucic, Steve;Kiernan, Matthew C.
运动神经元病（MND）的死亡前向假说表明，皮质运动神经元诱导兴奋性毒性前角细胞死亡，并参与了多巴胺能神经递质系统。本研究的目的是应用新的阈值跟踪经颅磁刺激（TMS）技术与周围神经兴奋性研究在MND患者进一步调查死亡的前向假说，并可能确定疾病发作的部位。在23名MND患者中进行了研究，使用90 mm圆形线圈连接到BiStim磁刺激器进行皮质研究和电刺激进行外周神经兴奋性研究。在同一条件下记录右侧拇短展肌的运动诱发电位和复合肌肉动作电位（CMAP）。皮质和周围神经兴奋性的测量与疾病严重程度的临床和神经生理学参数相关。与对照组相比，MND患者的短间期皮质内抑制（SICI）显著降低（MND组= 3.6 +/- 0.8%;对照组= 8.5 +/-1.0%，P < 0.001），在肢体起病的MND患者中最为显著。皮质内抑制的变化伴随着磁刺激-反应曲线、皮质沉默期持续时间和静息运动阈值的改变，所有这些都表明皮质过度兴奋。虽然SICI的降低在疾病不太严重的MND患者中更明显，但根据CMAP振幅评估，即使在疾病晚期的MND患者中也仍然明显。外周疾病负荷的测量，即CMAP振幅（r = -0.6）和神经生理学指数（r = -0.6），与皮质过度兴奋性变化相关，强度持续时间常数（r = -0.6），轴突兴奋性的外周标志物。中枢和外周神经兴奋性的同时评估已经建立了共存的上，下运动神经元功能障碍的存在下，皮质过度兴奋的早期功能在MND。
The dying forward hypothesis of motor neuron disease (MND) suggests that corticomotoneurons induce excitotoxic anterior horn cell death, with involvement of the glutamatergic neurotransmitter system. The aim of the present study was to apply novel threshold tracking transcranial magnetic stimulation (TMS) techniques in conjunction with peripheral nerve excitability studies in MND patients to further investigate the dying forward hypothesis and possibly determine the site of disease onset. Studies were undertaken in 23 MND patients using a 90-mm circular coil connected to a BiStim magnetic stimulator for cortical studies and electrical stimulation for peripheral nerve excitability studies. Motor-evoked potentials and compound muscle action potentials (CMAPs) were recorded from the right abductor pollicis brevis in the same setting. Measures of cortical and peripheral nerve excitability were correlated with clinical and neurophysiological parameters of disease severity. Short-interval intracortical inhibition (SICI) was significantly reduced in MND patients compared with controls (MND group = 3.6 +/- 0.8%; controls = 8.5 +/- 1.0%, P < 0.001), most prominently in MND patients with limb-onset disease. Changes in intracortical inhibition were accompanied by alterations in the magnetic stimulus-response curve, cortical silent period duration and resting motor threshold, all indicative of cortical hyperexcitability. Although the reduction in SICI was more pronounced in MND patients with less severe disease, as assessed by the CMAP amplitude, it remained evident even in MND patients with advanced disease. Measures of peripheral disease burden, namely the CMAP amplitude (r = -0.6) and neurophysiological index (r = -0.6), correlated with cortical hyperexcitability changes, as did the strength-duration time constant (r = -0.6), a peripheral marker of axonal excitability. Simultaneous assessment of central and peripheral nerve excitability has established the presence of co-existent upper and lower motor neuron dysfunction, with cortical hyperexcitability an early feature in MND.