A 26-year-old woman is evaluated in the clinic due to absence of her last 3 menstrual periods. The patient has also developed bilateral milky nipple discharge. Menarche was at age 13. Until now, she has had regular menses, lasting 4-5 days, every 28 days. The patient says she takes acetaminophen for occasional headaches and a medication that "stops the voices" in her head. BMI is 29 kg/m². Pelvic examination is unremarkable. Urine β-hCG testing is negative. Interruption of which of the following central nervous system pathways is the most likely cause of this patient's presenting symptoms?

Question

Quizplus · Accepted Answer

11ec160b_35d8_45cd_9249_e3732b241ca9_MD0001_00 This patient likely has developed amenorrhea and galactorrhea as an adverse effect of dopamine-2 (D2) receptor blockade from treatment with antipsychotics. There are 4 major dopaminergic pathways in the brain (eg, mesolimbic, mesocortical, tuberoinfundibular, nigrostriatal); dopamine hyperactivity in the mesolimbic pathway is associated with positive psychotic symptoms (eg hallucinations, delusions). The side effects of antipsychotic therapy are largely caused by D2 receptor blockade in other dopaminergic pathways. The tuberoinfundibular pathway connects the hypothalamus to the pituitary gland and is responsible for the tonic inhibition of prolactin secretion. Neurons in the arcuate nucleus of the hypothalamus secrete dopamine, which binds to D2 receptors on pituitary lactotrophs, resulting in decreased prolactin secretion from the anterior pituitary gland. Antipsychotics can interrupt the tuberoinfundibular pathway, causing increased blood prolactin levels (hyperprolactinemia), which may lead to galactorrhea (milky nipple discharge unrelated to pregnancy/breastfeeding) and menstrual irregularities (eg, amenorrhea). (Choice A) The arcuate fasciculus is a neural pathway that connects the Broca and Wernicke areas, which are responsible for expressive and receptive language, respectively. Disruption of the arcuate fasciculus classically results in conduction aphasia, characterized by fluent speech, intact comprehension, and impaired repetition. (Choice B) The hypothalamospinal tract projects from the hypothalamus to the ciliospinal center of the intermediolateral cell column (T1-L2), providing sympathetic innervation to the ipsilateral eye and face. Disruption of this tract typically results in ipsilateral Horner syndrome (eg, ptosis, miosis, anhidrosis). (Choice C) The lateral medullary spinothalamic tract transmits pain and temperature signals from the contralateral body to the thalamus. Lateral medullary infarction (Wallenberg syndrome) presents with loss of pain and temperature sensation on the contralateral body and ipsilateral face as well as vertigo, hoarseness, dysphagia, and abnormal eye movements. (Choice D) The therapeutic effect of antipsychotics arises from blockade D2 receptors in the mesolimbic pathway. (Choice E) The nigrostriatal pathway projects from the substantia nigra to the caudate nucleus and putamen and primarily regulates the coordination of voluntary movements. D2 receptor blockade in this pathway results in extrapyramidal effects (eg, dystonia, akathisia, tardive dyskinesia) and drug-induced parkinsonism. Educational objective: Antipsychotic medications work by blocking dopamine-2 receptors in the mesolimbic dopamine pathway. Dopamine-2 receptor blockade in the tuberoinfundibular pathway can result in galactorrhea and amenorrhea. __________ References: A real-world analysis of healthcare costs and relative risk of hyperprolactinemia associated with antipsychotic treatments in the United States. (http://www.ncbi.nlm.nih.gov/pubmed/30188234) The effects of antipsychotics on prolactin levels and women's menstruation. (http://www.ncbi.nlm.nih.gov/pubmed/24490071)

A 26-Year-Old Woman Is Evaluated in the Clinic Due to Absence