Expected and Unexpected OFF Episodes in Parkinson’s Disease

EP: 1.OFF Episodes in Parkinson’s Disease

EP: 2.Parkinson’s Disease: Why do OFF Episodes Occur?

EP: 3.Impact of Parkinson’s Disease OFF Episodes on Quality of Life

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EP: 4.Expected and Unexpected OFF Episodes in Parkinson’s Disease

EP: 5.Parkinson’s Disease: Evaluating Patients for OFF Episodes

EP: 6.Motor and Non-Motor Symptoms in Parkinson’s Disease

EP: 7.The Relationship Between the Gut and Parkinson’s Disease

EP: 8.Important Attributes of On-Demand Therapies for Parkinson’s Disease

EP: 9.When to Use On-Demand Therapies in Parkinson’s Disease

EP: 10.Levodopa Inhalation Powder for Parkinson’s Disease

EP: 11.Apomorphine Subcutaneous Injections for Parkinson’s Disease

EP: 12.Side Effects of Apomorphine Usage in Parkinson’s Disease

EP: 13.Sublingual Apomorphine for Parkinson’s Disease

EP: 14.Parkinson’s Disease: Advice for Community Neurologists

Stuart Isaacson, MD: The OFF episodes could be expected or unexpected. Patients at an FDA meeting a few years back pointed out how difficult it can be to have these unexpected disruptions during the day. What do you think about those?

Laxman Bahroo, DO: There is a little bit of a bias recall when we ask our patients about OFFs. They may be only telling us a portion of the story, and sometimes they’re not able to tell a story, and I don’t view that as a negative. I ask for patterns like, “Is it occurring after you take a dose and the dose doesn’t take effect?” That’s one pattern. “Is it occurring consistently before a dose ends? Is it occurring as a surprise to you for no rhyme or reason? Have you missed a dose, have you taken a dose close to food?” About 50% of the time, I get a typical pattern. I’m assuming that’s the most common type of OFF. I’m sure there are other lingering OFFs that they also have.

If I don’t get a clear history, I don’t view it as a negative. I use this as an opportunity for the patient to give me a journal or diary of things. I’ll give them information and a diary. Folks can download this from the internet as well. They’re available if you simply look for a Parkinson diary. I ask them to mark off 3 things: when they take their medications, when they eat food, and when they experience OFF. I ask them to keep it for 3 or 4 random days. I don’t want them to be affected by 1 day or something else going on. They bring it to our office in about 2 weeks, and with virtual visits, it’s actually even easier because I can review it while they put it up in front of the camera.

I look for a pattern. Either I’m able to identify a pattern or I am not, and we can talk about that. Many times you’ll see the pattern occurs after a meal. They take the medication, an hour later they take a meal, and then an hour later, they’re OFF and they have an extended OFF. Sometimes we look for trying to quantify how many they have. Sometimes people will say there are only 1 or 2 OFFs. But in reality, some days they will have 3 or 4 OFFs. There’s a little bit of bias recall. They might only tell me the last few days’ worth of information, but there’s more lingering underneath.

Sometimes the most interesting thing is compliance or adherence. We tell our patients to take medications on time. Now that they’re forced to mark off an X when they take the medication, many times you’ll see an X marked off at 2 o’clock with an arrow saying, “Oops, that was my 12 o’clock that I missed and I actually took it at 2.” And you can see that from 12 to 2 they had an OFF; that OFF continued till about 3. I tell them, “There are 2 types of OFFs here. One, you took your medication late, turning yourself OFF, and then it took longer to get into your system.” I say, “Look, this is self-inflicted, this is something you could have avoided with better adherence to time.” We talk about alarms.

There are a lot of different strategies, and the diaries are good as long as we use them appropriately, keeping a couple of days of diary to get a good sample size of what types of OFFs they’re having, how frequent, if there’s a pattern. If there’s a pattern, good. If there’s generally no pattern, then we work from there as well.

Daniel E. Kremens, MD, JD: You raised an interesting point that we haven’t touched on about what OFF is. Because it’s not just the wearing OFF, it’s also time to ON, and a lot of people don’t think about that when they’re talking about OFF. That really expands the OFF episode for the person. We now have therapies that can rapidly turn patients back ON, but if you just take another levodopa that has to sit in the gut and metabolize and get up to the brain, that can be awhile, and that time to turn ON is part of that full OFF episode.

Laxman Bahroo, DO: Absolutely, and you see that in diaries much more. Somebody who should have taken their dose at 12, they start to turn OFF at 10:30, and here they are still OFF at 12:30. I say, “Look, this dose never kicked in. You started to turn OFF before your next dose is due, and your next dose didn’t kick in.” You can see that and I can look at it much more neatly, whereas patients may not be able to vocalize that this was 1 combined episode from our point-of-view made up of 2 separate components.

Daniel E. Kremens, MD, JD: Diaries are great, but diaries also rely on the patient to accurately fill them out, and we now have some evidence emerging with wearables. With respect to at least kinetic or motor type OFFs, the future is to use some type of wearable to more reliably correlate potentially with the diary. It’s the old “trust but verify.”

Laxman Bahroo, DO: I completely agree.

Stuart Isaacson, MD: Thank you all for joining me and for watching this NeurologyLive® Peer Exchange; I hope that you enjoyed the content. Please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.