A 68-year-old man presents to his primary care physician for a follow up visit to discuss increased falls over the last eight months. Prior work-up demonstrated no abnormalities on complete blood count, complete metabolic panel, or computed tomography of the head. Prior physical examinations have demonstrated a bilateral pill rolling tremor, cogwheel rigidity, and shuffling gait, all of which are slightly progressed at this visit from the patient’s last visit two months ago. The physician suggests a trial of levodopa-carbidopa therapy.
Based on the patient’s most likely diagnosis, which of the following neurotransmitter derangements is most likely present?
The correct answer is:
C) Increased acetylcholine in the basal nucleus of Meynert
This patient’s pill rolling tremor, cogwheel rigidity, shuffling gait, and the suggestion to begin levodopa-carbidopa therapy suggest a primary diagnosis of Parkinson disease. The primary neurotransmitter disturbance of Parkinson disease (decreased dopamine in the ventral tegmentum/substantia nigra) relieves autoinhibition of acetylcholine release, thus increasing acetylcholine in the basal nucleus of Meynert.
Answer choice A: Decreased acetylcholine in the basal nucleus of Meynert, is incorrect. This is a characteristic of Huntington disease, which is due to expansion of the CAG trinucleotide repeat, resulting in loss of GABA neurons in the striatum and progressive onset of chorea, athetosis, aggression, and dementia.
Answer choice B: Decreased norepinephrine in the locus ceruleus, is incorrect. This is a characteristic of depression. Other neurotransmitter changes seen in depression may include decreased serotonin in the raphe nuclei.
Answer choice D: Increased dopamine in the ventral tegmentum/substantia nigra, is incorrect. This is another characteristic of Huntington disease. Dopamine in the ventral tegmentum/substantia nigra is decreased in Parkinson disease.
Answer choice E: Increased norepinephrine in the locus ceruleus, is incorrect. This is a neurotransmitter change commonly seen in anxiety. Other characteristic changes include decreased serotonin in the raphe nuclei (as in depression) and decreased GABA activity in the nucleus accumbens (as in Huntington disease).
Key Learning Point
In addition to decreased dopamine activity in the substantia nigra, Parkinson disease is also characterized by an increase in acetylcholine in the basal nucleus of Meynert. Classic physical examination findings include a pill rolling tremor, cogwheel rigidity, and shuffling gait.
