Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis

Abstract

Background:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily.Methods:A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude.Results:The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave.Conclusions:Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.

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

“…Before the new NMJ structures are fully mature, the motor neurons have degenerated and lost. Along with the repeated cycles, these highly immature reinnervations cause an intermittent conduction block in the newly formed nerve endings, eventually leading to a decremental response (4,19). Another possible explanation is that the disease arises from distal axons or NMJs and proceeds to the cell body in reverse.…”

Persistent neuromuscular junction transmission defects in adults with spinal muscular atrophy treated with nusinersen

“…In support of the possibility of secondary process, prior studies in other motor neuron disorders including amyotrophic lateral sclerosis, poliomyelitis/postpolio syndrome and Kennedy disease have shown striking NMJ transmission defects in each of these disorders. [36][37][38] It is possible that an individual's ability to maintain connectivity (via compensation/sprouting) at the NMJ irrespective of SMA severity is an SMN independent modifier of phenotype related to other intrinsic factors within individuals. In other words, the ability of an individual's neuromuscular system to maintain NMJ transmission in the face of motor neuron loss may be a modifier of SMA severity.…”

Diagnosis of Myasthenia Gravis

“…A decremental response may be seen in denervating/reinnervating muscles, particularly with ALS, but differs from the typical postsynaptic decrement in distribution and pattern [55]. In a large cohort of 85 ALS patients, none had a significant decrement in a facial muscle; besides, the typical "U" shape, with some reversal of decrement at the fifth and sixth responses, was not observed in ALS [49,55].…”

“…The hand muscles are easier to test and are better tolerated, but less sensitive [10,52]. Proximal muscles (like deltoid) give a high yield but require adequate immobilization and excellent cooperation [10,49,55]; among them, the trapezoid seems easier to test [56]. The anconeus muscle at the elbow is rated among the most sensitive in ocular MG [54] and in oculobulbar MG in some studies [57].…”