A 58-year-old woman with newly diagnosed Parkinson disease is being counselled about motor complications. Her neurologist explains the difference between early-stage motor fluctuations and levodopa-induced dyskinesias. Which finding best distinguishes peak-dose dyskinesia from diphasic dyskinesia?

Explanation

## Motor Complications in Parkinson Disease: Dyskinesias ### Classification of Levodopa-Induced Dyskinesias (LID) **Key Point:** Peak-dose dyskinesia occurs at the time of **maximum plasma levodopa concentration** (peak effect), whereas diphasic dyskinesia occurs during the **rising and falling phases** of levodopa absorption. ### Comparison Table: Peak-Dose vs Diphasic Dyskinesia | Feature | Peak-Dose Dyskinesia | Diphasic Dyskinesia | | --- | --- | --- | | **Timing** | At peak levodopa plasma level | During rising and falling phases | | **Dose relationship** | Occurs at optimal therapeutic dose | Occurs at suboptimal and supraoptimal doses | | **Choreiform pattern** | Smooth, flowing movements | Ballistic, dystonic, or stereotyped | | **Frequency** | 40–50% of patients on levodopa >5 yrs | 10–15% of patients | | **Management** | Reduce dose or shorten intervals | Increase dose frequency or add amantadine | | **Mechanism** | Pulsatile dopamine stimulation | Non-physiologic dopamine receptor cycling | ### Pathophysiology **High-Yield:** Peak-dose dyskinesia reflects the **pulsatile (on-off) dopamine stimulation** that occurs when levodopa levels peak and trough. The denervated striatum loses capacity for tonic dopamine buffering and becomes hypersensitive to fluctuating dopamine levels. **Mnemonic:** **PEAK = Plasma Elevation At Kainate-like (maximal) concentration** ### Clinical Pearls **Clinical Pearl:** Peak-dose dyskinesia typically manifests as **smooth, flowing choreiform movements** (limb chorea, trunk writhing), whereas diphasic dyskinesia is more **dystonic and ballistic**—the distinction helps localize the problem in the levodopa dosing cycle. **Clinical Pearl:** Diphasic dyskinesia is more difficult to manage and often requires dose restructuring (more frequent, smaller doses) or addition of amantadine, whereas peak-dose dyskinesia may respond to dose reduction. ### Management Strategy 1. Confirm timing of dyskinesia relative to levodopa dose 2. If peak-dose: reduce individual dose or extend intervals 3. If diphasic: increase dose frequency or add amantadine 4. Consider long-acting dopamine agonists or COMT inhibitors to smooth levodopa levels [cite:Harrison 21e Ch 429; Robbins 10e Ch 28]