A 52-year-old man is brought to the office due to social withdrawal and inability to care for himself. The patient is divorced and lives alone, and he was found to be living in disarray by his daughter, who is visiting from out of state. His neighbors and friends say the patient rarely comes out of the house or contacts them. During previous visits, his daughter noticed fidgety movements of his hands, but now he has marked jerky movements of his extremities with frequent facial grimaces. He has a history of depression with frequent angry outbursts that led to his divorce several years ago. The patient has no other medical conditions and does not use tobacco, alcohol, or illicit drugs. He was adopted and his family history is unknown. On physical examination, the patient is forgetful and has slowed mental processing. Involuntary, spasmodic movements of the hands and facial muscles are present. Deep tendon reflexes and sensation are normal. The loss of neurons supplying which of the following neurotransmitters is most specific for this patient's disease process?

Question

A 52-year-old man is brought to the office due to social withdrawal and inability to care for himself.  The patient is divorced and lives alone, and he was found to be living in disarray by his daughter, who is visiting from out of state.  His neighbors and friends say the patient rarely comes out of the house or contacts them.  During previous visits, his daughter noticed fidgety movements of his hands, but now he has marked jerky movements of his extremities with frequent facial grimaces.  He has a history of depression with frequent angry outbursts that led to his divorce several years ago.  The patient has no other medical conditions and does not use tobacco, alcohol, or illicit drugs.  He was adopted and his family history is unknown.  On physical examination, the patient is forgetful and has slowed mental processing.  Involuntary, spasmodic movements of the hands and facial muscles are present.  Deep tendon reflexes and sensation are normal.  The loss of neurons supplying which of the following neurotransmitters is most specific for this patient's disease process?

Quizplus · Accepted Answer

This patient with behavioral abnormalities (eg, mood changes, withdrawal), cognitive impairment, and chorea (eg, jerky, fidgety, involuntary movements) most likely has Huntington disease (HD). HD is a neurodegenerative disorder inherited as an autosomal dominant trait and classically manifests between ages 30 and 50. Excessive CAG trinucleotide repeats cause a gain-of-function mutation that leads to the accumulation of abnormal huntingtin protein in neural cells. The inhibitory GABAergic neurons in the caudate nuclei (striatum) are especially vulnerable and atrophy early in the course of the disease. These neurons play an important role in regulating both emotional and motor impulses from the cerebral cortex, and their loss is central to the behavioral and movement changes in HD. As HD progresses, neuronal atrophy becomes more widespread. Patients display features of advanced dementia (eg, memory loss, facial agnosia, incontinence) with bradykinesia and near-total absence of voluntary movement. (Choice A) The largest concentration of acetylcholine-producing neurons in the brain is found in the amygdala (eg, nucleus basalis of Meynert). Although there are lower levels of acetylcholine in the amygdalas of patients with HD, this change is not specific to the disease (it also occurs in Alzheimer and Lewy body dementia), and atrophy of these neurons does not occur until late in the clinical course. (Choice B) In HD, dopamine is typically increased, likely due to the loss of regulation by inhibitory GABA-producing neurons. Loss of dopaminergic neurons in the substantia nigra and striatum is found in Parkinson disease. (Choices D and E) Reduced concentrations of norepinephrine and serotonin in the CNS are associated with depression, which can be treated with agents (eg, SSRIs, SNRIs) that block the reuptake or degradation of these neurotransmitters. Educational objective: Huntington disease is an autosomal dominant neurodegenerative disease that leads to the accumulation of abnormal, toxic huntingtin protein in neural cells. Inhibitory GABAergic neurons in the caudate nuclei are most susceptible, and their loss is responsible for the characteristic manifestations of Huntington disease (eg, chorea, behavioral abnormalities).

A 52-Year-Old Man Is Brought to the Office Due to Social