Question

To investigate Neil’s symptoms further, doctors referred him to a neurologist, Dr. Bonasera, that specialized in motor disorders. Dr. Bonasera noted that Neil exhibited diminished right dorsalis pedis and posterior tibial pulses. His cognitive tests were normal. Tests of the cranial nerves were normal, with the exception of occasional slurred speech. His motor tests revealed generally slowed movements. Neil was experiencing pain and stiffness in the shoulder joints, which could explain his restricted range motion. Dr. Bonasera tested the motor strength of his finger extensors (4+/5), hip flexors (4/5), and various muscle groups in his arms and legs (5/5). There were tests for dysmetria (i.e., lack of coordination) and dexterity, which were normal yet slowed. Neil did have difficulty lifting his legs for some of the examinations, and he walked with a shuffling gate, often keeping both feet close together for a narrow base of support. He took very small steps and often stooped over while walking. When placing one foot in front of the other in a tandem walking stance, he would fall to either side and was unable to regain his balance. Sensory examination was normal, deep tendon reflexes were normal, and the Babinski sign was absent bilaterally. There were no Parkinsons-like symptoms, increased motor tone, or muscle fasciculations observed in testing.

Just one day later, another neurologist noted brisk reflexes and bilateral Babinski signs. Doctors performed magnetic resonance imaging (MRI) of the brain to reveal an infarct in the right caudate nucleus and an infarct in the right cerebellum. Doctors prescribed intense physical therapy. Neil saw some improvements for articulation, but he continued to struggle with the speed of speech and began to experience weakness of the tongue on his left side. CT angiograms revealed an aneurysm of the infrarenal aorta extending into the right common iliac artery. A spinal MRI revealed degenerative disease of the cervical spine (C4-C5) with a mild central canal stenosis. No such degeneration was present in the thoracic or lumbar spine. However, Neil did have mild impingement of the right L3-L5 nerve roots. A lumbar puncture revealed normal CSF pressures, cell counts, and composition. Neil continued physical therapy and experienced significant improvements in speech, walking, and balance. He also commented that his muscle soreness and fatigue had improved.

Neil continued his physical therapy while recovering at home. However, his symptoms worsened over the following weeks. Neil grew progressively weaker, occasionally falling. He required assistance for walking, and he was experiencing some numbness in both hands. He was admitted to a hospital, where he underwent a neurological examination. Cognitive and cranial nerve tests were normal. There were no fasciculations of the neck or tongue muscles. He was able to rotate and extend the neck with normal strength, however neck flexion seemed to be compromised. Neil exhibited widespread fasciculations in his arms and legs, and the muscles of these limbs had mildly atrophied. Motor tests were conducted for the arms and legs (4/5), and wrist extensors and intrinsic muscles of the hand (3+/ 5). Neil exhibited hyperactive deep-tendon reflexes and positive Babinski signs bilaterally. Sensory examinations were unchanged.

Based on the compounding symptoms and rapid progression of the disease, doctors suspected that Neil was suffering from amyotrophic lateral sclerosis (ALS), a disease that results in the destruction of upper and lower motor neurons. To confirm this diagnosis, neurologists conducted a series of tests., including nerve conduction tests and needle EMG. Nerve conduction tests of the motor and sensory nerves revealed normal conduction velocities with low amplitude compound motor action potentials, and normal sensory nerve potentials. There were abundant fasciculations and characteristics that suggested remodeling of motor units following denervation. Furthermore, EMG suggested net motor unit loss. There was no evidence of demyelination. Based on these results, doctors confirmed the diagnosis of ALS. For the following weeks, Neil experienced physical therapy aimed to help him preserve his strength and energy. He soon began to experience difficulty swallowing, and his cough progressed. Soon thereafter he developed pneumonia, was placed on a feeding tube, and ultimately died just 15 weeks after his initial hospitalization.

5. Electromyography involves recording electrical activity from muscle fibers. Justify Neil's low amplitude compound motor action potentials given his diagnosis of ALS. Be sure to describe how a muscle fiber initiates and propagates action potentials, and state how that process differs in the case of ALS.

6. Motor unit remodeling includes a reduction in the number of motor units, atrophy of muscle fibers, and an increased number of fibers per motor unit. Describe how motor unit remodeling may be indicative of ALS. Be sure to describe the typical structure and function of a motor unit, a typical distribution of motor unit (and fiber types) within a muscle, and how motor unit remodeling could contribute to Neil's weakness.

7. Based on the etiology of the disease, justify the finding of hyperactive deep-tendon reflexes and positive Babinski signs bilaterally in a patient suffering from ALS. Be sure to describe a typical reflex, and describe how descending inhibition may modulate a reflex response.

8. Justify why Neil's motor tests progressively worsened, whereas sensory, and cognitive tests remained unchanged. Be sure to describe the central and peripheral nervous system structures required for perception versus movement, and identify where deficits may be found in a patient with ALS.