A discussion on how patients are evaluated for OFF episodes, by expert neurologists.
Stuart Isaacson, MD: How do you evaluate your patients for OFF, and how do you evaluate patients from morning OFF? Patients don’t always come in and say that they have a morning OFF. How do you look for it, and what questions do you ask? Which patients do you ask?
William G. Ondo, MD: After asking about how they’re doing, typically my next question is, “Tell me the exact times you’re taking your levodopa”—7:11, 3:08, whatever. “At any point in between these doses, are your symptoms changing? Is anything worse?” I often say, “Around the time you’re taking a pill,” because some patients think that when they take the pill, in 2 seconds the pill is going to have its effect, but it’s typically at least 30 minutes.
“Is anything worse? Are there any changes through the day?” We try to ask, “Is there any pattern that you can come up with this?”
Sometimes you get these nice stories with a straightforward pattern. Other times it’s much more inconsistent. It’s like, “Usually I’m doing well, but every now and then, at 11 PM, I’m freezing up.” I keep it open-ended because OFFs can be quite a few types of symptoms. There are the obvious OFFs, where the tremor comes back or they can’t walk, but there’s this whole spectrum of nonmotor OFF symptoms. They break down into 2 groups, which are opposite in some way.
The first group of nonmotor OFF is this anxiety, sometimes palpitations, or even breaking out into a drenching sweat, called “the drenching paroxysmal sweat,” or Parkinson disease. These patients can look like they’re having an MI [myocardial infarction], and I’ve had plenty of patients with this sort of wearing OFF that have been evaluated with ECGs [electrocardiograms] and gone to the emergency department.
The other general nonmotor wearing OFF is the opposite, where people get fatigue or anhedonia. They don’t want to do anything, but they may be physically able to do that. I keep it very open-ended when I’m looking for anything that’s changing through their day, then looking for a pattern or not a pattern with these changes.
In the morning, some patients expect to take a little while for that first dose to kick in. We try to quantify that, and it largely comes down to how it impacts their life. This often comes down to whether they’re working or retired, and those sorts of things.
There is a small subgroup of people who do very well in the morning. Historically, in the literature this was called the sleep-sparing effect. I don’t think it has anything to do with sleep-sparing effect, but it’s more just natural circadian patterns. Our own natural dopamine levels peak, maybe 4:30 to 5 AM, or maybe 6:37 AM, and then they start to come down. This occurs in 5% of patients who have this nice time when they first wake up. Those are the ones telling you, “I’m doing fine until I take my levodopa, and then I’m doing worse.” You especially see this if they wake up very early, but that’s a minority. In most patients, the problem is the other way around: they’re taking a little while to get going in the morning. How aggressive you are with this depends on how aggressive the patient needs to be in addressing that.
Daniel E. Kremens, MD, JD: One thing that happens is that the patients accommodate it, and that’s not necessarily a good thing. They take their medicine and lie around in bed for a long time waiting for it to kick in. They delay activities in the morning or they change their social situation because they’re not going to turn ON.
They accept it. I tend to be a little more aggressive with questioning about that, like how much is it really impacting their day? If they say it’s not, I push them a little and ask, “Tell me about your morning.” When they tell me, “Well, I’m lying around in bed until 10 o’clock because my levodopa takes an hour or more to kick in, so I’m not going out to walk with my friends who take their 9 o’clock walk,” or things like that. They’ve gotten used to it, and the patients don’t appreciate necessarily the impact it may be having on their lives if we don’t explore it.
What does the conversation sound like in California? How do your patients feel in the morning? Is that a problem on the West Coast?
Khashayar Dashtipour, MD: I start with education because I can get important information from my patient if I educate them about why I’m asking the question. It usually starts with when I look at the status of my patient, if my patient is ON or if my patient is OFF. When the patient is OFF, I tell them that I’m asking because I don’t want you to feel like this the rest of the day, and I ask them, “Are you having this condition the rest of the day?”
Also, a patient can come to the clinic ON condition, and I ask them, “Is this the way you are 24-7?” All of us get this response: “Doctor, you’re so lucky. This is the only time he’s doing that well. The majority of the time, he is not like this.” Correct? Therefore, I always bring this to the front of their face. But I say, “If you can be this good, like speaking nicely, having the body language, and you can walk well, there’s no reason I cannot extend this and you’d be continuously ON.”
When they understand the importance of what I’m asking them, then I start to ask them about how they are doing from 1 dose to the other. The conversation doesn’t go the way we want, or they’re not the best historian to tell you exactly what happened during the day. I ask them chronologically, “Can you tell me how do you in the morning when you wake up? Based on what I told you what is OFF and ON, do you wake up OFF or not?” Then they tell me, step by step. I say, “If you take your first dose in 7 AM, how do you do after you take your 7 AM until your next dose?”
They walk me through that. How many times we heard from our own colleagues, “I don’t see that much unpredictable OFF time.” Patients teach us that it’s more than we expected. The first thing the patient says is, “Doctor, that’s not the way you’re asking me. It’s not the regular matter. One day my dad is doing good, the other time he’s not.” They’re telling us that these OFF times are unpredictable and not always in a regular fashion.
That’s the best way that I found to educate them about ON and OFF. Second, I emphasize that it’s important for me to know that because that’s the goal that they’re going to achieve. You’re going to achieve that if a patient is ON continuously during the day.
Stuart Isaacson, MD: Thank you all for joining me and for watching this NeurologyLive® Peer Exchange. I hope you enjoyed the content. Please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box.
Transcript edited for clarity.