The Impact Of Abnormality In Repetitive Nerve Stimulation On The Prognosis Of Amyotrophic Lateral Sclerosis

Background:Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease,though its pathogenesis remains elusive and no specific treatment is available so far.ALS not only involves both upper and lower motor neurons,but also the Neuromuscular Junction(NMJ),according to recent studies.It has been observed that ALS patients may show decrement in Compound Muscle Action Potential(CMAP)during Low Frequency Repetitive Nerve Stimulation(LF-RNS).Objectives:The current study aimed to identify the association between the clinical and Electromyography(EMG)features of ALS patients and their LF-RNS results,and explored the impact of LF-RNS abnormalities on patients’ survival.Methods:We retrospectively analyzed the clinical and electrophysiologic data of ALS patients diagnosed by Peking Union Medical College Hospital from March 2014 to December 2018.LF-RNS were conducted in the Orbicularis Oculi(00),Trapezius(TRAP)and Abductor Digiti Minimi(ADM)in all patients to obtain LF-RNS decrement(a decrement≥10%was considered to be LF-RNS+).EMG was also performed and documented.Baseline data collected at diagnosis included gender,age of onset,diagnostic delay,site of onset,diagnostic categories,the Revised ALS Functional Rating Scale(ALSFRS-r),respiratory functional score,disease progression rate.Body Mass Index(BMI),muscle strength,presence of atrophy and complications of important comorbidities.All patients were followed up every half to one year for clinical outcomes and administration of Riruzole.Results:72 ALS patients were enrolled in this study,with an overall LF-RNS+incidence of 40.3%.The positive rate of LF-RNS in TRAP,ADM and 00 were 38.9%,5.6%and 0.0%,respectively.In univariate analysis,muscle strength(P=0.037)and presence of atrophy(P=0.003)were found to be significantly related to incidence of LF-RNS aberrance,though only atrophy in proximal upper limbs was the independent risk factor for positive TRAP LF-RNS in multivariate Logistic regression model(OR=6.5,95%CI 1.7～24.7,P=0.006).In terms of EMG,the more segments were involved(1～4),the higher the overall LF-RNS positive rate(0.0%,0.0%,17.6%,53.1%,P=0.006).The clinical outcomes of a total of 61 ALS patients were investigated,and though diagnostic delay and disease progression rate were significantly associated with survival in univariate analysis,multivariate Cox regression model showed that a higher diagnostic category and a shorter diagnostic delay were independent risk factors for death in ALS(P<0.05).The LF-RNS result at diagnosis had little influence on survival in ALS.Conclusions:LF-RNS abnormality could occur in a significant proportion of ALS patients,and NMJ involvement seemed to be particular in distribution.Analysis of clinical and EMG features,survival data and LF-RNS results showed that LF-RNS was closely related to atrophy and lower motor neuron injury,but it had limited prognostic values in ALS.This was the first study in China to investigate the correlation of LF-RNS and survival in ALS by multivariate analysis.It also assessed systematic clinical parameters and their association with LF-RNS result using multivariate analysis.