What is dyskinesia in Parkinson's disease?

Dyskinesia in Parkinson's Disease

Dyskinesia in Parkinson's disease refers to involuntary movements—most commonly chorea, but also dystonia, stereotypies, or myoclonus—that develop as a complication of long-term levodopa therapy, occurring when levodopa-derived dopamine peaks in the brain. 1, 2

What Dyskinesia Is

• Dyskinesia represents involuntary movements that are distinct from the tremor of Parkinson's disease itself. 1
• The movements typically manifest as chorea (dance-like, flowing movements), but can also present as dystonia (sustained muscle contractions causing twisting postures) or myoclonus (sudden muscle jerks). 1, 2
• These movements are a direct consequence of dopamine replacement therapy, not the underlying Parkinson's disease. 1

Types Based on Timing

Dyskinesias are classified by when they occur relative to levodopa dosing:

• Peak-dose dyskinesia is the most common type, occurring when levodopa levels are highest in the brain and antiparkinsonian benefit is maximal. 1, 2, 3
• Diphasic dyskinesia occurs during the rise and fall of levodopa levels (beginning and end of dose), particularly affecting younger-onset Parkinson's patients. 2, 3
• Off-period dystonia (also called "wearing off" dyskinesia) emerges when levodopa levels are low, often manifesting as painful foot dystonia in early morning. 2, 3

Why Dyskinesia Develops

• The fundamental cause is abnormal pulsatile stimulation of dopamine receptors due to the short half-life of levodopa combined with progressive loss of dopaminergic neurons that normally buffer dopamine levels. 1, 4, 5
• As Parkinson's disease progresses and fewer dopaminergic neurons remain, the brain loses its ability to store and release dopamine smoothly, resulting in non-physiologic fluctuations. 4, 5
• Levodopa itself permits more dopamine to reach the brain, which means dyskinesias may occur at lower doses and sooner when carbidopa-levodopa combinations are used compared to levodopa alone. 6

Impact on Patients

• Dyskinesias significantly decrease quality of life and become a major complicating factor in Parkinson's treatment. 4, 5
• The FDA warns that dyskinesias may require dosage reduction of levodopa therapy. 6
• Patients face a therapeutic dilemma: reducing levodopa to control dyskinesia worsens parkinsonian symptoms, while increasing levodopa to control parkinsonism worsens dyskinesia. 4, 2

Critical Distinction from Other Movement Disorders

• Do not confuse levodopa-induced dyskinesia with paroxysmal kinesigenic dyskinesia (PKD), which is a separate condition triggered by sudden movements and responds dramatically to sodium channel blockers like carbamazepine. 7, 8
• PKD affects approximately 70% of patients with facial involvement and is treated completely differently than levodopa-induced dyskinesia. 8

Treatment Approach by Type

For peak-dose dyskinesia:

• Reduce individual levodopa doses while increasing dosing frequency. 2
• Add amantadine, which is the only medication with demonstrated ability to reduce established dyskinesia without reducing antiparkinsonian benefit. 1, 2
• Add dopamine agonists to smooth dopamine stimulation. 2

For off-period dystonia:

• Increase levodopa dosing or add longer-acting dopaminergic medications. 2
• Consider baclofen or botulinum toxin injections for focal dystonia. 2

For diphasic dyskinesia (most difficult to treat):

• Fractionate levodopa dosage into smaller, more frequent doses. 2
• Many patients ultimately require deep brain stimulation for control. 2

Surgical Options

• Deep brain stimulation of the subthalamic nucleus (STN DBS) is highly effective for treating levodopa-induced dyskinesias by allowing significant reduction in dopaminergic medications. 7, 1
• When reduction of "on" medication dyskinesias is the primary goal without medication reduction, globus pallidus internus (GPi) DBS should be targeted instead. 7

Common Pitfall

The FDA specifically warns that carbidopa does not decrease adverse reactions due to central effects of levodopa—it only reduces peripheral side effects like nausea. Because carbidopa allows more levodopa to reach the brain, dyskinesias may actually occur at lower doses and sooner than with levodopa alone. 6 This is a critical concept: adding carbidopa makes levodopa more effective but does not protect against dyskinesia.