A 62-year-old man with Parkinson disease for 8 years presents with motor fluctuations and dyskinesias despite optimal levodopa dosing. Regarding the motor complications of Parkinson disease, all of the following statements are true EXCEPT:

Explanation

## Motor Complications in Parkinson Disease ### Understanding the Correct Answer **Key Point:** On-off fluctuations cannot be completely prevented, even with continuous dopaminergic stimulation. While continuous dopaminergic strategies (transdermal rotigotine, apomorphine infusion, levodopa-carbidopa intestinal gel) significantly reduce the severity and frequency of on-off fluctuations, they do not eliminate them entirely. Some degree of motor variability typically persists. ### Why the Other Options Are Correct #### Wearing-Off Phenomenon **High-Yield:** As Parkinson disease progresses, the striatum loses its capacity to store dopamine. Early in the disease, oral levodopa doses lasting 4–6 hours are smoothed out by striatal buffering. By 5–10 years, this buffering is lost, and motor benefit directly tracks plasma levodopa levels, causing predictable end-of-dose deterioration [cite:Harrison 21e Ch 435]. #### Peak-Dose Dyskinesias **Clinical Pearl:** Peak-dose dyskinesias are involuntary movements (choreiform or dystonic) that occur when plasma levodopa is highest. They are dose-dependent and often improve with dose reduction or more frequent smaller doses. This is a hallmark of long-term levodopa therapy. #### Diphasic Dyskinesias **Key Point:** Diphasic dyskinesias occur in a biphasic pattern — at the beginning of the dosing interval (as plasma levels rise) and at the end (as levels fall). They are distinct from peak-dose dyskinesias and are thought to reflect non-physiologic dopaminergic stimulation at the edges of the therapeutic window. ### Continuous Dopaminergic Stimulation Strategy | Strategy | Mechanism | Effect on On-Off | Residual Fluctuation | | --- | --- | --- | --- | | Transdermal rotigotine | Continuous D~2~/D~3~ agonist delivery | Marked reduction | Still present (20–30%) | | Apomorphine infusion | Continuous subcutaneous dopamine agonist | Marked reduction | Still present (10–20%) | | Levodopa-carbidopa intestinal gel | Continuous duodenal levodopa infusion | Marked reduction | Still present (15–25%) | | Oral pulsatile dosing | Intermittent stimulation | Minimal benefit | Persists | **Warning:** Clinicians often overestimate the benefit of continuous dopaminergic therapies. While they substantially improve quality of life, complete abolition of on-off fluctuations is unrealistic and should not be promised to patients. ## Summary **Mnemonic: WOPD** — **W**earing-off (striatal buffering loss), **O**n-off (cannot be fully prevented), **P**eak-dose dyskinesias (dose-dependent), **D**iphasic dyskinesias (biphasic pattern). The key insight is that on-off fluctuations are a fundamental consequence of pulsatile dopaminergic replacement in a denervated striatum. Even the most sophisticated continuous delivery systems cannot completely normalize dopaminergic signaling.