GEY 3601 Lecture Notes - Lecture 8: Osteopenia, Muscular System, Neuromuscular Disease

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.

11. Which type of immunityoccurs as a response to illness or vaccination?

12. What are the uniquecharacteristics of the immune system?

13. Which of the followingis not one of the three unique characteristics ofthe immune system?

14. Which of the followingis an age related change associated with the immune system?

15. A decrease in ________secretion causes a lowering of blood volume and blood pressure andan increase is body osmotic pressure.

16. Which of the followingstatements regarding antibodies is true?

17. Which condition causesautoimmune damage to receptors for acetylcholine at theneuromuscular junction?

18. Which is true inregards to Immune memory?

19. All of the followingare ways to minimize the undesirable effects of aging on our immunesystem, except what?

20. Which type of immunesystem cell is formed from an unspecialized lymphocyte because ofthe influence of the thymus on the lymphocyte?

Consider the following abstracts about intervention to improve memory, one real, and one fictitious:

Memory enhancement in healthy older adults using a brain plasticity-based training program: A randomized, controlled study
Mahncke HW et al. PNAS August 15, 2006 vol. 103 no. 33 12523-12528
Normal aging is associated with progressive functional losses in perception, cognition, and memory. Although the root causes of age-related cognitive decline are incompletely understood, psychophysical and neuropsychological evidence suggests that a significant contribution stems from poorer signal-to-noise conditions and down-regulated neuromodulatory system function in older brains. Because the brain retains a lifelong capacity for plasticity and adaptive reorganization, dimensions of negative reorganization should be at least partially reversible through the use of an appropriately designed training program. We report here results from such a training program targeting age-related cognitive decline. Data from a randomized, controlled trial using standardized measures of neuropsychological function as outcomes are presented. Significant improvements in assessments directly related to the training tasks and significant generalization of improvements to nonrelated standardized neuropsychological measures of memory (effect size of 0.25) were documented in the group using the training program. Memory enhancement appeared to be sustained after a 3- month no-contact follow-up period. Matched active control and no-contact control groups showed no significant change in memory function after training or at the 3-month follow-up. This study demonstrates that intensive, plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults.

Memory enhancement in healthy older adults using genetic modification also protects against Alzheimer’s Disease.1
I M Genius, Prestigious Journal 1 (1): 1-10
Inserting extra copies of the gene NR2B, which encodes the NMDA receptor, leads to improved memory and also prevents onset of Alzheimer’s Disease. Two chemical signals are needed to trigger this nerve cell receptor, which means that it plays a key role in forming associations. For instance, if you touch a flame, the visual signal and pain signal arrive to the brain at roughly the same time, activating NMDA receptors and creating a memory. Healthy adults were given extra copies of the gene and these were rigged so that genes’ activity would increase over time as the adults aged. Earlier studies had revealed that in young animals, NMDA receptors are activated even by signals that arrive somewhat far apart, facilitating learning. As an animal ages, though, the signals must travel more in step to trip NMDA receptors and cement memories. Adults treated with the NR2B gene had significant improvements in assessments directly related to the training tasks and significant generalization of improvements to nonrelated standardized neuropsychological measures of memory (effect size of 0.25). In addition, adults treated with the genes showed lower levels of onset of Alzheimer’s Disease compared with matched controls.

For discussion

Are these interventions therapy or enhancement? (Is age-related loss of memory a disease?)

Are there morally significant differences between the methods (cognitive training versus genetic

modification)?

What are the potential harms and benefits from using these interventions?

What are your views on the moral permissibility of the interventions?

How would your responses change if the interventions were for increasing muscle mass and performance in elite athletes?