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 remarkable for a resting tremor, bradykinesia, rigidity, and shuffling gait. Which of the following is the most likely pathological mechanism responsible for this patient’s condition?]]
Answer A	AnswerA::Reduced stimulation of the direct pathway via D1 receptors
Answer A Explanation	[[AnswerAExp::Dopamine is released from the substantia nigra compacta and binds to D1 receptors of the striatum to stimulate the direct pathway of the basal ganglia. In Parkinson's disease, dopamine depletion results in a reduced stimulation of the direct pathway via D1 receptors.]]
Answer B	AnswerB::Reduced stimulation of the indirect pathway via D1 receptors
Answer B Explanation	[[AnswerBExp::Dopamine is released from the substantia nigra compacta and binds to D2 receptors of the striatum to inhibit the indirect pathway of the basal ganglia. In Parkinson's disease, dopamine depletion results in a reduced inhibition of the indirect pathway via D2 receptors.]]
Answer C	AnswerC::Reduced stimulation of the direct pathway via D2 receptors
Answer C Explanation	AnswerCExp::The activity of the direct pathway is reduced due to a reduced release of D1, which normally bind to D1 receptors of the striatum.
Answer D	AnswerD::Reduced inhibition of the direct pathway via D1 receptors
Answer D Explanation	AnswerDExp::Depletion of dopamine results in reduced inhibition of the indirect pathway via D2 receptors.
Answer E	AnswerE::Greater inhibition of the indirect pathway via D2 receptors
Answer E Explanation	AnswerEExp::In Parkinson's disease, depletion of dopamine results in a reduced 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 in the substantia nigra compacta (SNc). The patient's age, progressive tremor that involves both extremities and his lips and improves with intentional movement and sleep, and the signs on physical examination (resting pill-rolling 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. These pathways have antagonistic net effects. Stimulation of the direct pathway results in activation of the motor cortex, whereas stimulation of the indirect pathway results in the inhibition of the motor cortex. Dopamine is released from the substantia nigra compacta (SNc), binds to D1 receptors of the striatum, and stimulates the direct pathway. At the same time, D2 is released from the SNc and binds to D2 receptors of the striatum to inhibit the indirect pathway. The activity from both pathways aims to stimulate the motor cortex. In patients with Parkinson's disease, the reduction in dopamine results in a reduced activation of the direct pathway through D1 receptors and reduced inhibition of the indirect pathway through D2 receptors. Accordingly, the activity of the motor cortex is reduced, resulting in the characteristic rigidity. Shown below is an illustration of the direct and indirect pathways in the basal ganglia. Educational Objective: Dopamine is released from the substantia nigra compacta and binds to D1 receptors of the striatum to stimulate the direct pathway of the basal ganglia. In Parkinson's disease, dopamine depletion results in a reduced stimulation of the direct pathway, which normally occurs via D1 receptors. References: First Aid 2014 page 596]]
Approved	Approved::Yes
Keyword	WBRKeyword::Resting tremor, WBRKeyword::Parkinson's disease, WBRKeyword::Basal ganglia, WBRKeyword::Dopamine, WBRKeyword::Rigidity, WBRKeyword::Direct pathway, WBRKeyword::Indirect pathway, WBRKeyword::Bradykinesia, WBRKeyword::Shuffling gait, WBRKeyword::Tremor
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::