Amyotrophic lateral sclerosis

A 53-year-old male presents to his primary care physician with worsening hand and leg weakness. He often feels as if his left leg is “dragging” and experiences “spasms” while running. He additionally has difficulty holding a pen as firmly as he used to. Past medical history is notable for Graves disease. The patient does not smoke, use alcohol or other illicit substances. His temperature is 37.0°C (98.6°F), pulse is 65/min, respirations are 14/min, blood pressure is 125/64 mmHg, and O2 saturation is 98% on room air. Physical exam is notable for 4/5 strength in the right hand, with thenar muscle atrophy, as well as 4/5 strength in the left lower extremity. He has upgoing toes when the inner sole of the left foot is stroked. Which of the following best describes the pathophysiology of this disease?