McCall AL et al, Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis. Respir Physiol Neurobiol. 2020 Nov
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no current cure. Patients with ALS commonly die 3-5 years after diagnosis from respiratory failure. However, if the bulbar muscles (muscles of the mouth and throat responsible for speech and swallowing) and motor neurons are affected first, death may occur within 2-3 years. Bulbar involvement results in speaking and swallowing difficulties leading to recurrent aspiration, choking and aggravation of breathing problems. The most severely affected bulbar muscle is the tongue.
In addition to tongue involvement, all individuals afflicted with ALS ultimately succumb to inadequate breathing and respiratory failure secondary to respiratory muscle weakness (diaphragm and intercostal weakness). The diaphragm and intercostal muscles are essential for breathing. Initial symptoms and signs of respiratory involvement include nighttime carbon dioxide retention, inadequate oxygenation and ultimately decreased daytime ventilation and oxygenation. Clinically, patients present with decreased exercise tolerance, shortness of breath, early morning headaches, and excessive daytime sleepiness. The rate of decline in respiratory function is related to mortality. Non-invasive ventilation with bi-level intermittent positive air pressure (BiPAP) prolongs survival significantly. The next step in respiratory support is invasive mechanical ventilation which becomes necessary for survival – however, few patients agree to the use of invasive mechanical ventilation since it places a heavy burden on their families and can lead to prolonged immobility and limited communication.
