Repetitive Nerve Stimulation in Amyotrophic Lateral Sclerosis

Abstract

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 of decremental 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.

Can the Large-Scale Decrement in Repetitive Nerve Stimulation Be Used as an Exclusion Criterion for Amyotrophic Lateral Sclerosis?

“…Moreover, this study showed that the onset of ALS did not affect the RNS decrement responses, which was consistent with previous research (8,18). However, some studies have shown that patients with upper limb onset had higher decremental percentages compared with those with other sites of onset (7,17). The underlying reason for these differences is unclear.…”

“…The patients in the positive decrement group had lower ALSFRS-R scores compared with those in the decremental negative group, suggesting that the former were worse. Some studies have shown that the disease progressed more rapidly in ALS patients with a positive decrement (4,8,13,14), but others contradicted this (5,7,(15)(16)(17). If the RNS decrement responses were not related to the disease progression, the interpretation of the mechanism of decrement responses, the early neural reinnervation, may need to be corrected (5).…”

“…Another possible explanation is that the disease arises from distal axons or NMJs and proceeds to the cell body in reverse. This is the "dying back" hypothesis (17). Fischer et al performed a good deal of pathological experimentation on the SOD1-G93A mice model and found that NMJ destruction and axon degeneration occurred before motor neurons degenerated.…”

“…The mechanism of "dying back" remains unclear. A possible explanation is energy deficiency resulting from the hypermetabolism and malnutrition of ALS, which could lead to NMJ dysfunction (17).…”

Low Frequency-Repetitive Nerve Stimulation and Factors Affecting Decremental Response in Amyotrophic Lateral Sclerosis: A Retrospective Study of 449 Cases

“…That's why we think multicenter retrospective studies are needed in the future. Secondly, present statistic analysis shows the positivity rate of 3Hz RNS test delivered to the accessory nerve in upper-limb-onset group is 60.6%, leading all the others and followed by bulbar group (45.0%) and lower limb group (32.9%), which is in line with some previous study (Sun et al, 2018;Hatanaka et al, 2017;Hu et al, 2018;Miyaji et al, 2018;Clark et al, 2016). The probable reason for this obviously high positivity rate in the upper-limb-onset group may be ALS's preference for spreading around its onset site.…”