WBR0611

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 62-year-old man presents with complaints of a tremor in both hands. The tremor initially started in his right hand and has recently progressed over the past 4 weeks to involve his lips and his left hand. The patient also reports the tremor intensity decreases when he intentionally moves his hands, and it disappears when he sleeps. Physical examination is remarkbale for a resting tremor, bradykinesia, rigidity, and shuffling gait. Which of the following is the most likely pathological mechanism responsible for this this patient’s condition?]]
Answer A	AnswerA::Depletion of dopamine leading to less stimulation of the direct pathway via D1 receptors
Answer A Explanation	[[AnswerAExp::Dopamine, released from substantia nigra compacta, binds to D1 receptors and stimulates the direct pathway leading to increased motion. In Parkinson's disease, dopamine depletion causes less stimulation of the direct pathway via D1 receptors.]]
Answer B	AnswerB::Depletion of dopamine leading to less stimulation of the indirect pathway via D1 receptors
Answer B Explanation	[[AnswerBExp::Dopamine, released from substantia nigra compacta, binds to D2 receptors and inhibits the indirect pathway leading to increased motion. In Parkinson's disease, dopamine depletion causes less inhibition of the indirect pathway via D2 receptors.]]
Answer C	AnswerC::Depletion of dopamine leading to less stimulation of the direct pathway via D2 receptors
Answer C Explanation	[[AnswerCExp::Dopamine, released from substantia nigra compacta, binds to D1 receptors and stimulates the direct pathway leading to increased motion. In Parkinson's disease, dopamine depletion causes less stimulation of the direct pathway via D1 receptors.]]
Answer D	AnswerD::Depletion of dopamine leading to less inhibition of the direct pathway via D1 receptors
Answer D Explanation	[[AnswerDExp::Dopamine, released from substantia nigra compacta, binds to D1 receptors and stimulates the direct pathway leading to increased motion. In Parkinson's disease, dopamine depletion causes less stimulation of the direct pathway via D1 receptors.]]
Answer E	AnswerE::Depletion of dopamine leading to more inhibition of the indirect pathway via D2 receptors
Answer E Explanation	[[AnswerEExp::Dopamine, released from substantia nigra compacta, binds to D2 receptors and inhibits the indirect pathway leading to increased motion. In Parkinson's disease, dopamine depletion causes less inhibition of the indirect pathway via D2 receptors.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient in this vignette is most likely diagnosed with Parkinson's disease, a neurodegenerative disease characterized by depletion of dopamine-producing cells. His age, progressive tremor that involves both extremities and his lips and improves with intentional movement and sleep, and the signs on physical examination (resting tremor, bradykinesia, rigidity, and shuffling gait) are all features of Parkinson's disease. There are two pathways in the basal ganglia that control the fine tuning of voluntary motor activities: the direct excitatory pathway and the indirect inhibitory pathway. Dopamine, released from the substantia nigra compacta (SNC), binds to D1 receptors and stimulates the direct pathway while also binding to D2 receptors and inhibiting the indirect pathway. The outcome is increasing motor activity through both pathways. The patient presents with pill-rolling tremor present at rest and absent upon motion and sleep, which is characteristic of Parkinson's disease. Parkinson's disease presents with resting tremor, rigidity, bradykinesia and postural instability that result from the depletion of dopamine in the SNC. When dopamine decreases, there will be less activation of the direct pathway through D1 receptors and less inhibition of the indirect pathway through D2 receptors which result in decreased motion and symptoms of Parkinson's disease. Shown below is an image depicting the direct and indirect pathways in the basal ganglia. Educational Objective: Dopamine is normally released from the substantia nigra compacta and then binds to D1 receptors to stimulate the direct pathway, thereby leading to increased motion. This mechanism is perturbed in Parkinson's disease. References: First Aid 2014 page 596]]
Approved	Approved::No
Keyword	WBRKeyword::Resting tremor, WBRKeyword::Parkinson's disease, WBRKeyword::Basal ganglia, WBRKeyword::Dopamine
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::