Motor fluctuations can erode function in advanced Parkinson’s disease. Take this clinical challenge to test recognition, mechanisms, and management strategy—when to optimize pharmacologic regimens versus evaluate for advanced therapeutic approaches.
5 questions
A 68-year-old patient with Parkinson’s disease reports that benefit from each dose now lasts ~2 hours, with predictable end-of-dose “off” and morning akinesia. Which concept best explains why motor fluctuations intensify over time?
Correct Answer: B
As Parkinson’s disease progresses, loss of nigrostriatal neurons reduces the brain’s capacity to buffer dopaminergic input. This increases reliance on short-term pharmacokinetics and contributes to greater variability between “on” and “off” states.
https://link.springer.com/article/10.1007/s00702-025-02990-4
Which patient description most strongly suggests unpredictable “off” rather than predictable wearing-off?
Correct Answer: C
Unpredictable “off” episodes are characterized by abrupt transitions that are not clearly linked to dosing intervals and may reflect variable absorption and diminished physiologic buffering in advanced disease.
In advanced Parkinson’s disease with motor fluctuations, which strategy is most aligned with minimizing variability in dopaminergic stimulation?
A widely accepted management principle for motor fluctuations is reducing exposure variability to improve stability of “on” time. The concept of more continuous dopaminergic stimulation remains an area of active discussion in recent literature.
https://www.sciencedirect.com/science/article/pii/S1353802025000951
A patient experiences ≥3 hours per day of “off” time despite frequent oral dosing and adjunct therapies; dyskinesia is present but not the primary concern. What is the most appropriate next step conceptually?
Correct Answer: D
When clinically meaningful “off” time persists despite optimized oral and adjunctive strategies, contemporary evidence supports structured evaluation for advanced approaches guided by symptom burden and functional impact.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1725248/full
Which factor should weigh most heavily when determining the timing of referral for advanced management of motor fluctuations?
Recent literature emphasizes that decisions regarding escalation should be driven primarily by functional burden—particularly persistent “off” time affecting daily activities—rather than disease duration or chronological age alone.
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1622283/full
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