Study On Repeated Electrical Stimulation Of Amyotrophic Lateral Sclerosis

Background:Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, mainly involves cortical pyramidal cells, brainstem motor neurons, pyramidal tract and spinal cord anterior horn cells. However, ALS could also lead to impairment of neuromuscular junction (NMJ). The first evidence was provided in 1959 by Mulder, who discovered that ALS patient with muscle fati gable phenomena appeared a decremental response in low-frequency repetitive nerve stimulation (RNS). After that, related studies focused on the RNS positive rate of ALS patients and the relationship between RNS results and clinical features. However, there is no research focusing on the decremental pattern of amplitude curve or area curve in ALS patients with low-frequency RNS positive. Myasthenia gravis (MG), a classical NMJ disorders, mainly involves postsynaptic membrane. MG always exhibits a decremental response in low-frequency RNS. Both ALS and MG present low-frequency RNS decrement, but their pathophysiological mechanisms are different.Objectives:This study aimed to discover the differences in patterns of decrement in low-frequency RNS between ALS and Generalized MG (GMG), and to investigate the clinical features related to RNS results in ALS patients.Methods:The ALS patients and GMG patients with RNS results in Beijing Union Medical College Hospital were analyzed retrospectively from 2012-7-1 to 2015-2-28. In all included patients, RNS were performed on ulnar nerve, accessory nerve and facial nerve at 3HZ and 5HZ frequency with 10 stimulations. The compound muscle action potential (CMAP) amplitude and area for ten waves, the decrement ratio of amplitude and area were collected. Demographic and clinical data were also collected to analysis. The decrement ratio>=15% of 4th wave was defined as positive for low-frequency RNS.Results:85 ALS patients and 41 GMG patients were included. In ALS patients, the decrement of low-frequency RNS dropped to the nadir at 4th or 5th CMAP, without significant recovery followed in all tested nerves. In GMG patients, the decrement of low-frequency RNS also dropped to the nadir at 4th or 5th CMAP, but recovered significantly since the 6th CMAP in all tested nerves. For the ulnar nerve of GMG patients, the CMAP amplitudes of 8th to 10th all exceeded that of 3rd but were not higher than 2nd. In the ALS patients or GMG patients, the decremental patterns of amplitude curve and area curve were similar under the same stimulation frequency of the same nerve. For ulnar and accessory nerves under the same stimulation frequency, the 4th amplitude decrement ratio,1st CMAP amplitude size,4th area decrement ratio and 1st CMAP area size in ALS patients were all lower than that of GMG patients.In ALS patients, the low-frequency RNS positive rates for accessary, ulnar and facial nerves were 54.1%,8.2% and 0.0% respectively, which were significantly different. There was no correlation between low-frequency RNS positive rate and sex, age, duration or tendon reflexes of upper limb. RNS positive rate was higher in limb onset group and muscle strength of 0-â…¢ level group. Reduced CMAP amplitude was negatively correlated with CMAP decrement in accessory nerve and ulnar nerve (P<0.05).Conclusions:The decrement of low-frequency RNS in GMGs was a typical "U-shaped" decrement. But in ALSs, there was no significant recovery after the nadir of decrement. The difference in the trends of amplitude or area curve of low-frequency RNS between ALS and GMG is related to their different mechanisms resulting in NMJ dysfunction.This study compared the patterns of low-frequency RNS decrement curve between ALS and GMG for the first time and indicated that characteristics of decrement curves were significantly different between these two diseases.