Diphasic Dyskinesia and OFF-State Dystonia: Two Types of Dyskinesia Associated with Parkinson’s

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Dyskinesia is one of the most challenging aspects of Parkinson's to understand and treat. One significant aspect of this challenge is that there are similarities between an OFF state and a dyskinetic state, which can delay the recognition and treatment of dyskinesia.

A broader challenge with dyskinesia in Parkinson's is that the exact causes of it are not entirely understood. At a basic level, the current understanding of dyskinesia in Parkinson's is that as Parkinson's progresses, it becomes more difficult to maintain stable levels of dopamine in the body using the available medication, and this instability can cause dyskinetic movements. More specifically, dyskinesia in Parkinson's is often called levodopa-induced dyskinesia because it is typically associated with using levodopa, especially over an extended period.

Diphasic dyskinesia and OFF state dystonia

One common misunderstanding of dyskinesia is to think that it only occurs as a dose of levodopa reaches its most effective level. This is called peak-dose dyskinesia, but there are other types of dyskinesia. The two most common dyskinesias besides peak-dose dyskinesia are diphasic dyskinesia and OFF-state dystonia. There is also yo-yo dyskinesia, which follows a more erratic pattern, and, more rarely, ON-state dystonia.

Diphasic dyskinesia is sometimes called D-I-D, which stands for "dyskinesia-improvement-dyskinesia." This type of dyskinesia occurs at the beginning of an ON state, improves as your medication is in effect, and then returns at the beginning of an OFF state. Diphasic dyskinesia often involves large, uncontrolled movements of one or both legs and is more common in young onset Parkinson's.

OFF-state dystonia is a type of dystonia that occurs in or as you begin to enter an OFF state. OFF-state dystonia most often occurs on waking in the morning, before the day's first dose of medication takes effect. This dyskinesia is often experienced as a sustained muscle contraction or muscle spasm. It occurs most often in the lower limbs and initially in one foot. Recognizing OFF-state dystonia can be challenging because dystonia can occur independently of dopamine therapy. Keeping a record of the timing of your medication and when dystonia occurs can help determine if your dystonia experience is a levodopa-induced dyskinesia or a different type of dystonia.

OFF-state dystonia can also be confusing because dystonia and dyskinesia are frequently considered separate things. However, dyskinesia means abnormal movement, which is why dystonia (uncontrolled, sustained contraction of muscles) is considered a type of dyskinesia.

Treatment of Diphasic Dyskinesia and OFF-State Dystonia

As with peak-dose dyskinesia, effective treatment of diphasic dyskinesia and OFF-state dystonia is difficult to come by. It's essential to talk with your care team about any changes to your treatment regimen, especially related to a complicated issue like dyskinesia.

Diphasic dyskinesia

A typical initial treatment for diphasic dyskinesia is to take more frequent but smaller doses of levodopa. This strategy can help avoid the transitions between ON and OFF times, but it can contribute to the development of peak-dose dyskinesia. Lowering the overall dosage of levodopa and adding a dopamine agonist may also help, but dopamine agonists can have complicated side effects and may not be appropriate for some people, such as those who experience impulse control disorders as a side effect. Sometimes, the best management of diphasic dyskinesia can be achieved through deep brain stimulation (DBS) or continuous subcutaneous apomorphine injection. Note that continuous subcutaneous apomorphine injection is currently being reviewed for approval in the United States.

There have been mixed results with amantadine, currently available apomorphine formulations, and the duopa system in treating diphasic dyskinesia. For example, in one study involving the duopa system, 10-15% of participants developed diphasic dyskinesia after beginning to use the system, and as levels of the medication increased, up to 50% of participants began to experience diphasic dyskinesia. Using controlled-release levodopa may also negatively affect the management of diphasic dyskinesia. The delayed onset of treatment effectiveness can complicate the timing of doses and contribute to worsened afternoon and evening onset dyskinesia.

OFF-State Dystonia

For OFF-state dystonia, an effective treatment may be increasing your levodopa dose. Additionally, if you are experiencing OFF-state dystonia when you wake up, a controlled or extended-release formulation of levodopa can be helpful when taken at bedtime. Alternatively, you might take a dose of levodopa in the middle of the night. Rescue formulations like Inbrija™, Apokyn®, or Kynmobi™ may also be helpful.

The Importance of a Parkinson's care Team

When managing dyskinesia, the need for a strong care team can't be overstated. Dyskinesias can be extraordinarily challenging to live with and treat, so it's essential to have a knowledgeable Parkinson's specialist involved in your care. A mental health provider can also help you manage the psychological and social aspects of living with dyskinesia.

Fortitude and Practical Reasons for Hope

Treatment of complex dyskinesia can take a long time to optimize. Finding effective relief may involve an advanced therapy like a duopa system, DBS, or a continuous apomorphine or levodopa infusion formulation--both of which are currently in the late stages of development.

There are treatment strategies for complex dyskinesias today, and as our understanding of dyskinesias increases, more treatments are on the horizon!

Additional Resources

The Pathophysiology of Parkinson's

Impulse Control Disorders in Parkinson's

Building a YOPD Care Team

Early Morning Off-Medication Dyskinesias

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