Differentiating Off Episodes in Parkinson Disease

Fernando L. Pagan, MD: An off episode is a return of the Parkinson’s disease symptoms. When somebody is “on,” you reduce the Parkinson’s disease symptoms, mainly the motor symptoms are what we talk about: There is a reduction in the tremor, there is an improvement in the slowness of movements, an improvement in the bradykinesia, and an improvement in the rigidity. There are also some nonmotor features as well that can be seen in Parkinson’s disease that do improve with on, when the medicines are working and do worsen with off. Sometimes you can see anxiety, you can see sweating, and you can see a shortness of breath. People just don’t feel good. They feel like a brain fog or a feeling of impending doom sometimes. It’s very different from person to person.

Off can be seen very early in Parkinson’s disease: about a quarter of patients within the first 4 to 5 years start to have these off episodes or these off periods. As the disease progresses, you start to see a higher percentage of patients with Parkinson’s disease having these off episodes.

You’ll see about 50% of patients within 5 to 10 years. After 10 years, 11 years, you’re going to see at least 75% of patients having off episodes. It’s very variable from person to person how common they are.

There are a lot of factors that go into it. It’s not only progression of the disease, but there are a lot of gastrointestinal problems that can be seen in Parkinson’s disease. Our most effective medication is levodopa. Levodopa is absorbed through the gastrointestinal tract, so if you have a lot of gastroparesis or you have a lot of constipation, there can be a delayed gastric emptying. It’s really within the first part of the small intestine that you see the levodopa is going to be absorbed, so a lot of gastrointestinal problems can also lead to having more off time and off episodes. It is a multifactorial problem that we see in patients who have more off episodes, but it definitely goes more with the progression of the disease as well as the gastrointestinal problems.

Off episodes can occur because of various reasons. Not only is it because of progression of disease, but also the gastrointestinal issues that occur in Parkinson’s disease, namely the gastroparesis, the constipation. Using a medicine can break these off episodes, like the levodopa inhalation that can be used up to 5 times a day. You inhale the contents of what is virtually pure levodopa. It comes in 2 capsules, so you have to inhale 2 capsules, and it can be used up to 5 times a day. Within 10 minutes, you can see a resolution of these off episodes, decreasing the return of those Parkinson’s disease symptoms. That is what an off episode is.

This is very important for neurologists: not only do we sometimes have to increase the overall dose, but we also need to give these on-demand therapies, and on-demand therapies that bypass the gastrointestinal system can be very effective in reducing these off episodes.