What are dyskinesias and how are they treated?

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What are dyskinesias and how are they treated?

Dyskinesias are involuntary, erratic, and often excessive movements that can occur in people with Parkinson’s disease (PD) as a side effect of long-term use of levodopa, a medication commonly used to manage Parkinson’s symptoms. These movements are typically most prominent when the medication is at its peak effectiveness. Dyskinesias can range from mild to severe and may affect different parts of the body, including the arms, legs, torso, or face.

Dyskinesias are not a symptom of Parkinson’s disease itself but are a complication of the treatment. They are often seen after several years of using levodopa and are more likely to occur in people who started levodopa at a younger age.

Types of Dyskinesias

Peak-dose Dyskinesias: These occur when the levels of levodopa in the bloodstream are highest, usually when the medication is most effective in controlling Parkinson’s symptoms.
Diphasic Dyskinesias: These occur as levodopa levels rise or fall, typically appearing during the transition periods when the medication is “wearing on” or “wearing off.”
Off-period Dystonia: This type of dyskinesia happens during the “off” periods when the medication is not effective, and the patient experiences Parkinson’s symptoms as well as muscle cramps or painful spasms.

Causes of Dyskinesias

Dyskinesias are primarily caused by long-term use of levodopa, the most effective medication for treating Parkinson’s disease. Over time, the brain’s response to levodopa becomes less predictable, and fluctuations in dopamine levels can trigger involuntary movements. Risk factors for developing dyskinesias include:

Younger age at onset of Parkinson’s disease: Younger patients are more likely to experience dyskinesias due to the longer duration of levodopa use.
Higher doses of levodopa: Larger doses can increase the risk of developing dyskinesias.
Duration of levodopa use: The risk increases with prolonged use of the medication.

Treatment of Dyskinesias

Managing dyskinesias requires a careful balance between controlling Parkinson’s symptoms and minimizing the side effects of medication. Here are the main approaches to treating dyskinesias:

1. Adjusting Levodopa Dosing

One of the first steps in managing dyskinesias is adjusting the dosage or timing of levodopa. Reducing the individual dose of levodopa or dividing it into smaller, more frequent doses (fractionating the doses) can help smooth out dopamine levels and reduce the occurrence of peak-dose dyskinesias.

Strategy: Split levodopa into smaller, more frequent doses or reduce the total daily dose.

2. Adding Medications to Smooth Dopamine Levels

Other medications can be added to help smooth out dopamine fluctuations and reduce dyskinesias. These include:

Amantadine: Amantadine is one of the most effective medications for managing dyskinesias. It is thought to work by blocking glutamate receptors in the brain, reducing involuntary movements. An extended-release version of amantadine (Gocovri) has been developed specifically to treat dyskinesias.
- Effectiveness: Amantadine is often well-tolerated and can reduce both dyskinesias and “off” time, but it may cause side effects like confusion, hallucinations, or swelling in the legs.
COMT Inhibitors: Drugs like entacapone and tolcapone prevent the breakdown of levodopa, allowing for a smoother and more prolonged effect. By helping stabilize levodopa levels, they can reduce the need for large doses, which may help decrease dyskinesias.
- Use: These drugs are often combined with levodopa to enhance its duration and smooth out dopamine fluctuations.
MAO-B Inhibitors: Medications like rasagiline and selegiline inhibit the breakdown of dopamine in the brain, allowing more stable dopamine levels and reducing the need for higher doses of levodopa.
- Use: They may be added to help manage motor fluctuations and, in some cases, reduce dyskinesias.

3. Using Dopamine Agonists

Dopamine agonists (e.g., pramipexole, ropinirole) stimulate dopamine receptors in the brain and can be used as a substitute for levodopa or in combination with it. They may allow for a lower dose of levodopa, which can reduce dyskinesias.

Benefit: Reducing the reliance on levodopa by adding dopamine agonists can help lower the risk of dyskinesias, but these drugs also have their own side effects, such as drowsiness, hallucinations, and impulse control disorders.

4. Continuous Dopaminergic Stimulation

The concept of continuous dopaminergic stimulation (CDS) aims to maintain more consistent levels of dopamine in the brain, reducing fluctuations that can lead to dyskinesias. This approach can be achieved through:

Duodopa: Involves the delivery of a gel form of levodopa and carbidopa directly into the small intestine via a pump. This provides a continuous infusion, helping to stabilize dopamine levels and reduce dyskinesias.
- Benefit: Continuous levodopa delivery can reduce “off” periods and dyskinesias by maintaining more stable dopamine levels.
Apomorphine Infusion: Apomorphine is a dopamine agonist that can be delivered via continuous subcutaneous infusion. It provides a more constant stimulation of dopamine receptors, reducing motor fluctuations and dyskinesias.
- Use: Typically used in advanced Parkinson’s patients who experience significant motor fluctuations and dyskinesias.

5. Deep Brain Stimulation (DBS)

Deep brain stimulation is a surgical treatment option for people with advanced Parkinson’s disease who have significant motor fluctuations or dyskinesias that cannot be controlled with medication. DBS involves implanting electrodes in specific areas of the brain (usually the subthalamic nucleus or globus pallidus) to modulate abnormal brain activity.

Effectiveness: DBS can significantly reduce dyskinesias by allowing for lower doses of levodopa and stabilizing dopamine fluctuations. It can also improve overall motor function.
Consideration: DBS is typically considered when medication adjustments are no longer effective, and the patient’s quality of life is significantly impacted by dyskinesias or motor fluctuations.

6. Lifestyle and Dietary Adjustments

In some cases, lifestyle changes can help manage dyskinesias. Strategies include:

Dietary Adjustments: As mentioned earlier, timing protein intake separately from levodopa can help optimize medication effectiveness and potentially reduce dyskinesias.
Exercise: Regular physical activity, such as walking, stretching, yoga, or swimming, can improve overall motor function and may help alleviate dyskinesias.

7. Careful Monitoring of Medications

It’s essential for people with Parkinson’s disease to work closely with their healthcare provider to adjust their medications as needed. Levodopa dosage, the addition of other medications, or even surgical options like DBS should be carefully monitored to achieve the best possible balance between managing symptoms and reducing dyskinesias.

Conclusion

Dyskinesias are a common side effect of long-term levodopa use in Parkinson’s disease, and their treatment requires a careful balance of medication adjustments. By modifying levodopa dosing, adding other medications (such as amantadine), using advanced therapies like continuous dopaminergic stimulation, or considering surgical options like deep brain stimulation, dyskinesias can often be managed effectively. Each patient’s treatment plan should be individualized, and close communication with healthcare providers is key to finding the right approach for managing dyskinesias while maintaining good control of Parkinson’s symptoms.

Jodi Knapp