Neuromuscular junction in amyotrophic lateral sclerosis. Is there more to follow?

Abstract

Background. Amyotrophic lateral sclerosis (ALS) causes progressive degeneration of upper motor neurons in the cortex, and lower motor neurons in the spine. In addition, it is unclear where motor neuron dysfunction begins and what causes motor neuron degeneration: whether it is the dying forward process or the dying back phenomenon where motor neuron degeneration begins distally at the nerve terminal or at the neuromuscular junction and progresses toward the cell body, is still a matter of debate. Materials and methods. Are there neuromuscular junction disorders in the early stages of ALS? To answer this, we described 5 patients with ALS presented at Petre Sarajishvili Institute of Neurology in 2018–2022, 3 males and 2 females aged 50–61 years. ALS diagnosis was based on clinical signs, the Gold Coast criteria, electromyography (Awaji), neuroimaging, blood and urine tests. At the early stage of the disease, only asymmetric ptosis and diplopia were noted, which did not improve on pyridostigmine or steroids. Results. We studied patients’ anamnesis, physical data, evaluated their mental, cognitive functions and neurological status. We have also interviewed family members, as it was often difficult for the patient to accurately describe the symptoms. Acetylcholine receptor antibodies were mildly positive only in one patient. Thymoma was excluded. The neurophysiological study showed only marked neuromuscular transmission failure in orbicularis oculi, there were no clinical and electromyographic signs of motor neuron damage. Conclusions. Approximately 2 years later, all five patients developed clinical and electromyographic signs of ALS. In the present study, neuromuscular junction disorders are found to play an important role in the pathogenesis of ALS and may serve as a useful early diagnostic marker.