**1. Introduction**

Given the effect of neuromuscular disease on respiratory muscle strength (including the diaphragm, upper airway and accessory muscles), it is an undeniable fact, that neuromuscular disease can cause disruption of sleep. In general, sleep disorders are underrecognized in this population, as their secondary effects can mimic symptoms of the underlying disease. Recognizing sleep-related disorders in patients with neuromuscular disease such as Amyotrophic Lateral Sclerosis (ALS) is of utmost importance, as they are potentially treatable problems and their correction can improve quality of life and even increase survival time [1].

ALS is an incurable neurodegenerative disorder of upper and lower motor neurons, which is characterized by degeneration of the corticospinal tracts, resulting in loss of motor neurons in the brain, brainstem and anterior horn cells of the spinal cord. Age of onset of disease is in the sixth decade of life and is usually

sporadic, though a minority of patients have familial disease. Numerous abnormalities exist in cellular and molecular function in ALS, including protein aggregation, mitochondrial dysfunction, DNA and RNA processing and central nervous system inflammation [2].

The hallmark of clinical disease is the presence of both upper and lower motor neuron signs. Weakness in ALS starts as asymmetrical or focal, and then progresses to generalized weakness, ultimately affecting all skeletal muscles. Loss of motor neurons in the brainstem and spinal cord causes weakness of the pharyngeal, laryngeal, intercostal and diaphragmatic muscles. This predisposes patients with ALS to respiratory dysfunction (the physiology behind this to be detailed below). When respiratory dysfunction becomes severe, tracheostomy and permanent ventilation are required. From the time of the diagnosis the median survival time is 3 to 5 years. The most common cause of death in ALS is respiratory failure [3, 4].

There are two FDA approved medications for ALS. Riluzole was approved in 1997 and provides a modest survival benefit of 3 months. A second medication, Edaravone, a free radical scavenger, was approved in 2017, but is only approved for use in ALS patients without respiratory insufficiency, and is controversial for clinical use due to its burdensome administration schedule and questionable clinical efficacy [5]. Numerous clinical drug trials have failed to demonstrate marked clinical benefit in ALS. However, provision of non-invasive ventilation has shown survival benefit in some ALS patients [6]. The dearth of effective treatment options for ALS underscores the importance of modifying those factors that optimize quality of life and extension of survival, particularly sleep and respiration.
