A 65-year-old man comes to the office for evaluation of slowly progressive right-hand weakness for the past 3 months. The patient has no pain or numbness. Medical history is significant for degenerative joint disease in both his hips and hypertension. Vital signs are normal. Physical examination shows atrophy of right thenar eminence and first and second web spaces. Muscle strength testing reveals decreased right grip strength and moderate weakness of the finger abduction. Tendon reflexes are 3+ in the right arm and 1+ in the left arm and lower limbs. Sensory examination shows no abnormalities. Electrophysiologic studies reveal widespread fibrillations and positive sharp waves in bilateral upper and lower extremity muscle groups. The underlying mechanism of this patient's disease most likely involves an abnormality in which of the following?

Question

A 65-year-old man comes to the office for evaluation of slowly progressive right-hand weakness for the past 3 months.  The patient has no pain or numbness.  Medical history is significant for degenerative joint disease in both his hips and hypertension.  Vital signs are normal.  Physical examination shows atrophy of right thenar eminence and first and second web spaces.  Muscle strength testing reveals decreased right grip strength and moderate weakness of the finger abduction.  Tendon reflexes are 3+ in the right arm and 1+ in the left arm and lower limbs.  Sensory examination shows no abnormalities.  Electrophysiologic studies reveal widespread fibrillations and positive sharp waves in bilateral upper and lower extremity muscle groups.  The underlying mechanism of this patient's disease most likely involves an abnormality in which of the following?

Quizplus · Accepted Answer

11ec25c8_d56e_11ab_bc81_43e4ee167451_MD0003_00 This patient has hand weakness associated with hyperreflexia, an upper motor neuron (UMN) sign, and atrophy, a lower motor neuron (LMN) sign. This presentation is strongly suggestive of amyotrophic lateral sclerosis (ALS), a progressive, fatal neurodegenerative disease. Symptoms result from deterioration of UMNs (eg, corticospinal neurons located in the primary motor cortex) and LMNs (eg, cranial nerves, anterior horn cells). The diagnosis of ALS is typically made clinically in a patient who displays both UMN and LMN signs. However, early in the disease process, only a few muscle groups may be affected (as in this patient), and electrodiagnostic studies can be helpful to rule out other neuromuscular diseases. Electrodiagnostic studies typically demonstrate signs of LMN dysfunction, with denervation in multiple muscle groups (even asymptomatic muscle groups). The denervated fibers upregulate acetylcholine receptors (as they no longer receive input from the neuromuscular junction), leading them to become hypersensitive to acetylcholine and spontaneously discharge; this manifests as widespread fibrillations and positive sharp waves (reflecting spontaneous depolarization) on electrophysiologic studies. Classically, sensory nerve testing is normal. (Choice B) Degeneration of dorsal spinal roots would lead to sensory dysfunctions, not motor dysfunctions, as seen in this patient. (Choice C) Diseases of the neuromuscular junction such as myasthenia gravis (MG) or Lambert-Eaton myasthenic syndrome (LEMS) are characterized by weakness that either worsens (MG) or improves (LEMS) with repetition; UMN signs are unexpected. Repetitive nerve stimulation tests demonstrate progressive decline (or improvement) in the amplitude of complex motor action potentials. (Choice D) Although peripheral nerve disorders (eg, hereditary motor and sensor neuropathy) may present with weakness and widespread electrodiagnostic changes consistent with denervation, patients would not have hyperreflexia (an UMN sign). (Choice E) Diseases affecting the skeletal muscle include dermatomyositis and polymyositis. Although fibrillation potentials can be seen on insertion of the needles for electromyography (EMG), inflammatory myopathies typically affect symmetric proximal skeletal muscles, and EMG changes are limited to muscles that are affected rather than the widespread changes seen in this patient. In addition, these myopathies do not cause UMN signs. Educational objective: Amyotrophic lateral sclerosis leads to degeneration of cells in the anterior horn of the spinal cord. It is characterized by often asymmetric weakness with upper and lower motor neuron signs. Electrodiagnostic studies often show characteristics of both acute and chronic denervation. References: Electrodiagnosis in persons with amyotrophic lateral sclerosis. (http://www.ncbi.nlm.nih.gov/pubmed/23523708)

A 65-Year-Old Man Comes to the Office for Evaluation of Slowly