Ultra-early amplitude decrement after repetitive nerve stimulation supports early neuromuscular junction injury in amyotrophic lateral sclerosis:a prospective cross-sectional study

The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease.Previous basic studies have confirmed early damage to neuromuscular junctions,but it is difficult to obtain such evidence directly in clinical practice.In this prospective cross-sectional study,we recruited 22 patients with early amyotrophic lateral sclerosis with disease duration < 12 months and with clinical symptoms limited to the upper limbs.We also recruited 32 healthy controls.Repetitive nerve stimulation was performed,and patients were followed for 12 months.We found a significant change in the response to repetitive nerve stimulation in amyotrophic lateral sclerosis patients without spontaneous electromyographic activity.Patients that were prone to denervation had an increased decrement response of target muscles after repetitive nerve stimulation.These results suggest that changes in response to repetitive nerve stimulation may occur before denervation in amyotrophic lateral sclerosis patients.The damage to lower motor neurons is more obvious in patients with a higher percentage of repetitive never stimulation-related amplitude decrements.This study was approved by the Institutional Ethics Committee of Peking University Third Hospital(approval No.M2017198) on August 24,2017.

Repetitive Nerve Stimulation in Amyotrophic Lateral Sclerosis

Background： Nowadays, it is widely known that decremental responses in low-frequency repetitive nerve stimulation （LF-RNS） are frequently observed in patients with amyotrophic lateral sclerosis （ALS）. The pathological mechanism of this phenomenon remains unknown. This study aimed to illuminate the features of RNS in Chinese patients with ALS. Methods： Clinical and electrophysiological data of 146 probable and definite ALS patients who underwent RNS were retrospectively enrolled and analyzed. LF-RNS （3 Hz） was performed in trapezius, deltoid, abductor digiti minimi （ADM）, quadriceps femoris, and tibialis anterior. High-frequency RNS （HF-RNS, 10 Hz） was performed only in ADM. The two-sample t-test and Chi-squared test were used for statistical analysis.Results： Decremental responses to LF-RNS （≥ 10%） in at least one muscle were detected in 83 （56.8%） of the cases and were most commonly seen in trapezius and deltoid. The incidence ofdecremental response was higher in patients with upper limb onset. Incremental responses to HF-RNS （≥60%） in ADM were observed in 6 （5.6%） of the cases. In 106 muscles with decremental response, 62 （57.4%） muscles had a continuous decremental pattern, more than a U-shape pattern （37 cases, 34.3%）. Nineteen cases showed definite decrements in LF-RNS tests in trapezius, while no abnormalities were found in the electromyography and neurological examination of the sternocleidomastoid muscle, supplied by the accessory nerve as well.Conclusions： Decremental responses in the RNS are commonly observed in ALS patients. The findings regarding the trapezius indicated that some ALS onsets could be initiated by a ＂dying back＂ process, with destruction of neuromuscular junctions （NMJs） before motor neurons. Incremental responses in the ADM implied damage of the NMJs involved both the post and presynaptic membranes.