A 43-year-old right-handed man presents to the clinic with gradual onset of right hand and arm…

A 43-year-old right-handed man presents to the clinic with
gradual onset of right hand and arm weakness. He had been in good health and an
avid golfer until a few weeks ago when he noted that he was having trouble
keeping his club steady during his swing. His driving distance had markedly
decreased, and he had begun to drop things that he was holding with his right
hand. He had no numbness or other sensory symptoms. On physical examination, he
appears well and has normal vital signs. He has mild wasting and fasciculations
along his right brachioradialis muscle. His grip strength is 4 out of
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A 43-year-old right-handed man presents to the clinic with
gradual onset of right hand and arm weakness. He had been in good health and an
avid golfer until a few weeks ago when he noted that he was having trouble
keeping his club steady during his swing. His driving distance had markedly
decreased, and he had begun to drop things that he was holding with his right
hand. He had no numbness or other sensory symptoms. On physical examination, he
appears well and has normal vital signs. He has mild wasting and fasciculations
along his right brachioradialis muscle. His grip strength is 4 out of 5 on the
right and 5 out of 5 on the left. He has absent reflexes in his right arm and
1+ reflexes on the left. An electromyelogram shows features of denervation,
including increased numbers of spontaneous discharges in resting muscle, and a
reduction in the number of motor units detected during voluntary contraction. A
diagnosis of amyotrophic lateral sclerosis (ALS) is entertained.

Questions

A. What are the presenting clinical symptoms and progression
of the clinical course in ALS?

B. Which cells are affected in ALS?

C. What are some possible molecular mechanisms responsible
for the pathologic changes?

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