Decremental responses in patients with motor neuron disease

Abstract

ObjectiveInvolvement of the neuromuscular junction (NMJ) in amyotrophic lateral sclerosis (ALS) has been reported and is increasingly recognized as an important pathophysiological aspect. The relationship between decrement and clinical measures for possible application as a biomarker has not been comprehensively explored.MethodsWe performed routine repetitive nerve stimulation (RNS) of three nerves on patients with ALS. We captured measures of muscle strength, grip strength, fatigability, and calculated slow vital capacity (SVC) rates of change assessing for associations.ResultsIn 42 subjects, 210 muscles were studied. Negative correlation was found between the percentage of decrement and compound muscle action potential (CMAP) amplitude. Approximately half of the patients with hand weakness did not have decrement. There was no significant correlation between decrement and handgrip fatigue, SVC < 80% predicted, or more rapid worsening of SVC over time.ConclusionsAbnormal decremental responses are well described in ALS. We report that the degree of decremental response does not correlate with the degree of weakness. Abnormal decrement is only rarely present in nerve–muscle pairs with normal motor power. Our findings did not support a correlation between abnormal decrement and clinical measures suggesting that RNS may not be useful as a biomarker to monitor ALS progression.

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).…”

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

“…Previous research has presented conflicting results concerning the relationship between RNS and disease progression. Some authors have suggested that there is no correlation between RNS and disease progression (Henderson et al, 2009;Yamashita et al, 2012;Alanazy et al, 2017;Zheng et al, 2017a;Hu et al, 2018). However, others have stated that a higher RNS decremental percentage indicates rapid disease progression (Bernstein and Antel, 1981;Wang et al, 2001).…”

“…RNS was performed in the following muscles: upper TRAP, representing the bulbar regions; middle deltoid (DEL) and APB, representing the cervical regions; and tibialis anterior (TA), representing the lumbar regions. We selected these muscles because of abnormal decremental responses to RNS that had been frequently observed in previous studies (Iwanami et al, 2011;Alanazy et al, 2017;Hatanaka et al, 2017;Wang et al, 2017;Zheng et al, 2017a;Sun et al, 2018). Researchers have also compared different stimulus frequencies and found that the decrements reached a maximum at 3 Hz (Iwanami et al, 2011;Wang et al, 2017).…”

“…Subsequent studies discussed the characteristics of decremental response in different nerve/muscle pairs (Iwanami et al, 2011;Yamashita et al, 2012;Alanazy et al, 2017;Hatanaka et al, 2017;Wang et al, 2017;Zheng et al, 2017a, b;Hu et al, 2018;Sun et al, 2018;Fu et al, 2019). The decremental response was more frequently observed in proximal muscles than distal muscles, in upper limbs than lower limbs, and most commonly, in trapezius and deltoid muscles (Iwanami et al, 2011;Alanazy et al, 2017;Hatanaka et al, 2017;Wang et al, 2017;Zheng et al, 2017a;Sun et al, 2018).…”

Neuromuscular transmission defects in myopathies: Rare but worth searching for

“…Generally, a decrease in compound muscle action potential (CMAP) amplitude or area greater than 10% between the first and the last of 4 to 6 stimuli at low frequency (2–3 H z )is regarded as a significant decrement . Physiologically, decrement of this degree supports a failure of neuromuscular transmission which can be a primary process, as seen in neuromuscular junction disorders or a secondary process, as observed in 40–70% of patients with motor neuron diseases (MNDs) …”