A 37-year-old woman comes to the office due to frequent tearfulness. The patient describes herself as "a happy person" at baseline but says that "about 6 months ago, I began to have more sad days than happy days." She frequently goes a week without leaving home and has to force herself to eat and clean. The patient's father committed suicide at age 41, and her paternal grandfather is said to have died of a "mental disease" at age 49. The patient tearfully admits to thoughts of suicide but has no plans or intent. Temperature is 36.9 C (98.4 F), blood pressure is 121/77 mm Hg, pulse is 68/min, and respirations are 14/min. The patient has no subjective memory issues. She scores 25/30 on the Montreal Cognitive Assessment (normal: ≥26), losing points on measures of executive function. She appears restless during the examination, shifting frequently in her chair. The patient repeatedly raises her right arm in an abrupt, twisting motion that ends with smoothing her hair. Extraocular movement testing shows delayed initiation of voluntary saccades. Deep tendon reflexes are 3+ in both upper and lower extremities. The patient's disease is primarily associated with degeneration of which of the following neuronal cell groups?

Question

A 37-year-old woman comes to the office due to frequent tearfulness.  The patient describes herself as "a happy person" at baseline but says that "about 6 months ago, I began to have more sad days than happy days."  She frequently goes a week without leaving home and has to force herself to eat and clean.  The patient's father committed suicide at age 41, and her paternal grandfather is said to have died of a "mental disease" at age 49.  The patient tearfully admits to thoughts of suicide but has no plans or intent.  Temperature is 36.9 C (98.4 F), blood pressure is 121/77 mm Hg, pulse is 68/min, and respirations are 14/min.  The patient has no subjective memory issues.  She scores 25/30 on the Montreal Cognitive Assessment (normal: ≥26), losing points on measures of executive function.  She appears restless during the examination, shifting frequently in her chair.  The patient repeatedly raises her right arm in an abrupt, twisting motion that ends with smoothing her hair.  Extraocular movement testing shows delayed initiation of voluntary saccades.  Deep tendon reflexes are 3+ in both upper and lower extremities.  The patient's disease is primarily associated with degeneration of which of the following neuronal cell groups?

Quizplus · Accepted Answer

11ec25c8_d57e_174f_bc81_518db81640d0_MD0003_00 This patient's psychiatric symptoms, cognitive impairment, family history, and neurological findings are consistent with Huntington disease (HD), an autosomal dominant disease of CAG trinucleotide repeat expansion. This trinucleotide expansion results in the formation of an abnormal huntingtin protein that is particularly toxic to the caudate nucleus and putamen (ie, neostriatum). The neostriatum is rich in GABA-producing neurons that are preferentially destroyed due to HD. Because trinucleotide repeats may expand between generations (particularly with paternal transmission), HD is often associated with an anticipation effect in which consecutive generations develop symptoms of the disease at progressively younger ages. HD is classically associated with chorea (ie, involuntary contractions that seem to flow from one muscle group to the next). Early in the disease course, chorea may be mild and mistaken for restlessness, and patients may unconsciously assimilate mild chorea into purposeful movements (eg, smoothing one's hair). Other neurological findings include hyperreflexia and delayed initiation of voluntary saccades. Cognitive impairment is most evident in the domain of executive function. (Choice A) Loss of dopamine-producing neurons in the substantia nigra is associated with Parkinson disease, which causes a resting tremor, bradykinesia, and rigidity. (Choice B) Endorphins are a group of neurotransmitters that are primarily produced in the hypothalamus and pituitary gland; they provide pain-relieving effects through their actions at opioid receptors. Degeneration of endorphin-producing neurons is not seen in HD. (Choice D) Glutamate is the major excitatory neurotransmitter in the central nervous system. Excess glutamate is implicated in numerous neurodegenerative conditions (ie, glutamate excitotoxicity), but degeneration of glutamate-producing neurons is not associated with HD. (Choice E) Histamine is produced in the tuberomammillary nucleus in the hypothalamus and is involved in maintenance of arousal, among other functions. Degeneration of histamine-producing neurons is not seen in HD. (Choice F) Norepinephrine is primarily produced in neurons that make up the locus coeruleus. Degeneration of the locus coeruleus may be seen in Alzheimer disease and Parkinson disease. (Choice G) Serotonin is primarily produced in neurons that form the raphe nuclei in the brainstem. Although serotonin is thought to be involved in many disease processes, selective degeneration of serotonergic neurons is not seen in HD. Educational objective: Huntington disease is an autosomal dominant disease of CAG trinucleotide repeat expansion characterized by psychiatric symptoms, cognitive impairment, and chorea. It is associated with preferential degeneration of GABA-producing neurons in the caudate nucleus and putamen. References: Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons. (http://www.ncbi.nlm.nih.gov/pubmed/27080129)

A 37-Year-Old Woman Comes to the Office Due to Frequent