What is Parkinson’s Disease Dyskinesia?

What is Parkinson's Disease Dyskinesia?

Written by Dr. J. William Langston

What is Parkinson’s Disease Dyskinesia?

Dyskinesia literally means abnormal movement. Parkinson’s Disease (PD) Dyskinesia, often referred to as levodopa-induced dyskinesia, can be described as uncontrolled jerking, dance-like or wriggling movements. Symptoms range from minor tics to full-body movements. It can be a stand-alone condition; however, in people with Parkinson’s, it is most often associated with long-term use of levodopa, a drug that increases levels of dopamine in the brain.

What’s the cause of Parkinson’s Disease Dyskinesia?

Parkinson’s Disease Dyskinesia is generally believed to be caused by disease progression and the use of levodopa medications. As Parkinson’s progresses, deteriorating dopamine brain cells have increasing difficulty in managing normal movement. Levodopa medications replace normal dopamine allowing good movement control which is less “OFF” time (or slow movement) and more “ON” time (normal movement).

Over time it may be necessary to take more frequent doses of levodopa to manage movement problems. When levodopa is administered in frequent doses (e.g., 100 mg every four hours during the day), the levels in the blood vary between doses, creating “peak” and “troughs” rather than continuously replacing dopamine. This has the potential to damage dopamine receptors over the years, eventually causing Parkinson’s Disease Dyskinesia.  

How do I know if it’s Parkinson’s Disease Dyskinesia or a Parkinson’s tremor?

At times, it can be difficult to distinguish between Parkinson’s Disease Dyskinesia and parkinsonian tremor, particularly when the information is based primarily on history. Making the correct diagnosis is critically important, as it can profoundly alter treatment decisions. If a person with Parkinson’s is having dyskinesias that are bothersome and/or present most of the time, one option would be to reduce the levodopa dose. On the other hand, if a person with Parkinson’s is experiencing a parkinsonian tremor, one would do the exact opposite (i.e., increase dopaminergic therapy using levodopa or a dopamine agonist such ropinirole or pramipexole).  

In short, making the wrong decision such as increasing levodopa when the person with Parkinson’s actually has bothersome dyskinesias or decreasing the dose when the person with Parkinson’s actually has tremor, can significantly compromise normal movement and quality of life.

First and foremost, your doctor must take the time to educate him/herself on your condition before making this distinction. As noted above, dyskinesias are highly irregular and cause a variety of types of movements. Parkinsonian tremor is quite different. It can affect one or more parts of the body (hands or legs) and is characterized by regular back and forth oscillations of movement with a frequency of 5-7 cycles per second. If recorded, one would see rhythmic sinusoidal waves of to and fro movements.

If your doctor is unable to make a determination of what kind of movement you’re experiencing, your doctor may suggest that you video yourself when you’re at home. “Wearables” (wearable devices that can detect movements overtime) are becoming better at identifying Parkinson’s Disease Dyskinesia as opposed to parkinsonian tremor and may one day be able to confirm diagnosis more objectively.

How is Parkinson’s Disease Dyskinesia diagnosed?

Contrary to many disorders in modern medicine, where sophisticated medical tests are required, in most instances, diagnosis of this is almost purely based on the clinical history and most importantly a physical examination. It can best be made by the well-trained eye of a movement disorder specialist.  

The movements can include (1) chorea (dancing – think of choreography, quick, restless and/or twisting movements), (2) athetosis (sinuous, slower writhing movements) or (3) dystonia (rigidity and posturing of the limbs or trunk). They are typically random in occurrence rather than rhythmically repetitive and can range from very mild to severe. In milder cases, they can be mistaken for normal restlessness, and it’s not unusual for a person with Parkinson’s to be totally unaware of them.  

At the other end of the spectrum, Parkinson’s Disease Dyskinesia can be quite severe (so-called “troublesome dyskinesias”) and can significantly interfere with activities of daily living, even affecting gait and balance. The critical point is that these dyskinesias can occur when a person with Parkinson’s needs more, not less, levodopa.

How can Parkinson’s Disease Dyskinesia be managed?

Because Parkinson’s Disease Dyskinesia can become such a problem in the management of Parkinson’s and is still so poorly understood, much of the effort to deal with its complication has centered on delaying, if not actually preventing the dyskinesia altogether.  

One approach has been to delay the start of levodopa for as long as possible in an attempt to delay the onset of dyskinesias. However not taking, or limiting the dose of levodopa may not allow for greater movement control in early disease and throughout treatment. Another approach to forestall starting levodopa has been to use a dopamine agonist (e.g., pramipexole and ropinirole) as a first line of treatment, particularly as these agents rarely cause dyskinesia on their own.

A number of large studies have shown that early agonist therapy can delay the need for levodopa by a number of years. However, this approach has gradually become less attractive for two reasons. First, dopamine agonists carry a significant burden of side-effects on their own, including excessive daytime sleepiness, impulse control disorder and pedal edema (swelling of the lower legs and feet) to name a few. These side-effects can be carefully monitored, and are dose dependent, so they can be dealt with when both the person with Parkinson’s and physician are on the lookout for them.

Secondly, it has been reported that when a person with Parkinson’s is started on dopamine agonists, Parkinson’s Disease Dyskinesia is just as severe as it would have been if they were started on levodopa in the first place. Stated another way, it has been shown that pre-treatment with agonists was in no way protective against Parkinson’s Disease Dyskinesia when levodopa was eventually necessary.  

Finally, while one often hears the argument that the incidence of severe and bothersome Parkinson’s Disease Dyskinesia has declined over the years, which I have observed myself in my own practice, this is most likely due to the fact that many movement disorders specialists undertreat their patients to lessen the incidence of bothersome dyskinesias. Unfortunately, when a person with Parkinson’s is undertreated, they experience less “ON” time and more “OFF” time.

There are options out there for people with Parkinson’s who do not want to be undertreated. Deep brain stimulation can be tried for appropriate patients willing to undergo surgery. Or, oral medications can be added on to levodopa to reduce dyskinesias. Over the past two years, there have been extended-release oral medications developed that offer convenient once-daily dosing.

As with everything, the only way to get a full understanding of what you’re dealing with and the potential solutions that may help is by speaking to your movement disorder specialist or neurologist. I encourage people with Parkinson’s to proactively start the conversation about dyskinesias with their doctors.

This blog article was sponsored by Adamas Pharmaceuticals, Inc.

Dr. J. William Langston has been at the forefront of the Parkinson’s field for over 30 years.  During that time, he has become known for his work in both clinical and basic research in Parkinson’s disease, as well as in day-to-day patient care. He has published nearly 400 scientific papers in a wide variety of areas, including disease-modifying therapies for disease, ways to treat the side-effects of chronic levodopa therapy (in particular levodopa-induced dyskinesias or Parkinson’s Disease Dyskinesia), the genetics of Parkinson’s disease and related disorders and the epidemiology of the disease.

Dr. Langston has received many awards for his work, including the Pritzker Prize for Leadership in Parkinson’s Research for the Michael J Fox Foundation, and most recently the Van Andel Prize for Outstanding Achievement in Parkinson’s disease. He originally gained national and international recognition when he discovered the cause of parkinsonism in a group of young heroin addicts in Northern California who suddenly developed severe parkinsonism after using a new “synthetic heroin”.  The offending agent proved to be a substance known as MPTP. This discovery provided a new tool to study degeneration of the substantia nigra (a key affected area of the brain in Parkinson’s), led to the first good animal model for disease and inspired a renaissance in the epidemiology of Parkinson’s.  MPTP continues to be widely used as a research tool to study parkinsonism.

Dr. Langston is currently focused on redefining the nature of Parkinson’s, ways to identify it much earlier (before patients actually develop parkinsonism clinically) and to better understand the cause(s) and pathways to the prevention of Parkinson’s Disease Dyskinesia. Dr. Langston is a paid consultant of Adamas Pharmaceuticals, Inc. 

 

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Comments (4)

Karyl Campbell

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Could you please include some information on diphasic dyskinesia?

Hi Karyl – Thank you for the suggestion. We may address this at some point in the future.

Experiencing severe dyskinesia in off times before medication. Reduced levodopa to 100mg at night seeems to be helping. Now taking200mg every 4hrs and reducing last to doses to 150 and 100 at night. Any suggestions.

Hi Dana, this is a question we encourage you to discuss with a movement disorder specialist or your doctor. They will have the best insight into treating your dyskinesia based on your unique experience and a more comprehensive understanding of your symptoms.

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