A single motor unit study of spinal cmd brainstem motor neuron in ALS

为探讨肌萎缩侧索硬化症(ALS)皮质脊髓束退行性变的病理生理学机制，研究了经颅磁刺激对自发激活时单个运动单位放电特性的影响。在刺激前时间直方图(PSTH)中描绘第一骨间背肌(FDI)运动单位放电的发生，并评估运动神经元的兴奋性。为了进行分析，我们开发了新的计算机程序。接下来，我们用同样的分析方法研究了三叉神经电刺激对面神经核的突触功能障碍。在ALS有上运动神经元征象的16个运动单位中，有6个(38%)来自FDI肌肉的PSTH显示出双峰(PPS)，而在多发性硬化症或脑血管疾病有上运动神经元征象的16个运动单位中，只有2个(13%)出现了双峰(PPS)。下运动神经元病或无上运动神经元征的ALS患者均无上述异常。这些发现表明，典型的ALS具有慢速或多突触皮质脊髓神经元的异常过度兴奋状态。三叉神经电刺激产生三叉神经-面反射。正常人反射的PSTH表现为早期短兴奋(P1：10毫秒)和晚期离散性兴奋(P2：30毫秒)，持续时间较长。10例ALS患者的P1峰高度同步化，潜伏期正常。提示ALS面神经核具有异常的兴奋性，运动神经元的过度兴奋状态是ALS病理生理学的基本特征。

The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The occurrence of motor unit discharges from first dorsal interosseus muscle (FDI) was plotted in a peristimulus time histogram (PSTH) and evaluated the excitability of the motor neurons. For the analyses, we developed new computer programs. Next, we investigated the synaptic dysfunction of facial nucleus by trigeminal electrical stimulation using the same analysis method.PSTHs from FDI muscle revealed double primary peaks (PPs) in 6 out of 16 motor units (38%) in ALS with upper motor neuron sign as compared to only 2 out of 16 (13%) motor units in multiple sclerosis or cerebrovascular disease with upper motor neuron sign. None of the patients with lower motor neuron diseases or ALS without upper motor neuron sign had these abnormalities. These findings suggest typical ALS has abnormal hyperexcitable state of slow or polysynaptic corticospinal neurons.Trigeminal electrical stimulation produced trigemino-facial reflex. PSTH of the reflex from normal subjects showed an early short excitation (P1 : 10 msec) and a late dispersed one (P2 : 30 msec) with prolonged duration. That from 10 ALS patients revealed highly synchronized P1 peak with normal latency. These findings indicated facial nucleus of ALS had the abnormal hyperexcitability.Both of these findings suggest that the hyperexcitable state of motoneuron is a cardinal feature in the pathopysiology of ALS.