How pot products affect the brain and body; long COVID's effects on the nervous system: Upstate Medical University's HealthLink on Air for Sunday, June 19, 2022

Hesham Masoud, MD: Up next on Upstate's "HealthLink on Air," an overview of the different effects someone might experience from products containing marijuana... ... that relative concentration of THC versus CBD is really what's going to predict for you if you're getting more of a psychoactive component versus one that doesn't have that and has CBD's effect, which are thought to have anti-inflammatory, antioxidant effects. ...

Host Amber Smith: And we'll hear about the neurological deficits some people experience long after recovering from COVID and what to expect if you undergo autonomic testing.

Ahmed Eldokla, MD: ... All the autonomic symptoms, or most of the autonomic symptoms, can be worsened with COVID infections. And we see this all the time. ...

Host Amber Smith: All that. And a visit from The Healing Muse. Coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine, with the experts from Central New York's only academic medical center. I'm your host, Amber Smith. On this week's show, we'll learn about autonomic testing and how it's helping people who have neurological deficits long after they've recovered from COVID. But first, with recreational marijuana now legal for adults in New York state, we'll hear what's important to know about the effects these products may create and what to consider before you begin experimenting.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." Recreational marijuana is now legal for adults in New York state, and a variety of cannabis products will soon be available in dispensaries. Before you start experimenting, let's understand what you might be getting into. My guest today is Dr. Hesham Masoud. He's an associate professor of neurology and neurosurgery at Upstate. He specializes in endovascular surgical neuroradiology, and he's a member of the stroke team at Upstate. Welcome back to "HealthLink on Air, Dr. Masoud."

Hesham Masoud, MD: Thank you. Thank you for having me.

Host Amber Smith: Let me first ask you about the basics. Cannabis contains a bunch of ingredients. The two I think we'll be focusing on are CBD and THC. Can you differentiate those for us?

Hesham Masoud, MD: Yeah. So CBD stands for cannabidiol, and THC stands for tetrahydrocannabinol. So those are the major components, like you had said, and the difference is, the CBD is non-psychoactive, and the THC is psychoactive. I'd say that that's the biggest difference between those two major ingredients in in cannabis.

Host Amber Smith: What does psychoactive mean?

Hesham Masoud, MD: Essentially what it does is, cannabis, it works on these two receptors that we have called CB-1 and CB-2. And, you know, we have this endogenous so an internal system, that we use of endo-cannabinoids that utilize these receptors. But when we're using exogenous cannabinoids from from a flowering product -- plant, I should say -- it's acting on those two receptors, and those receptors are located in areas that have to do with executive function and memory. When we say psychoactive effect, we mean essentially really applying a lot of the effect on those systems. So, you would have differences that would have to do with those realms, and specifically what they would be, would be, typically, some change in behavior and inhibition, disinhibition, I would say, and memory impairment.

Host Amber Smith: Is it true that different cannabis products have different amounts of CBD and/or THC?

Hesham Masoud, MD: Yes. Yes. So, cannabinoids, exogenous cannabinoids, and cannabinoids that we're getting from these plants, they have lots of ingredients that are called just sort of phyto-cannabinoids. Now the most common ones are the -- in terms of their frequency -- is the THC and CBD. And that relative concentration of THC versus CBD is really what's going to predict for you if you're getting more of a psychoactive component versus one that doesn't have that and has maybe the CBD's effect, which are thought to have anti-inflammatory, antioxidant effects. And so, if you're looking at the ratio between those two -- and that's essentially what they use to sort of classify the the ratios. You know, they call them "chemo types," and if 1 is if you're THC rich, and all the way down to 5 is if you don't have any cannabinoids at all in it. So, it is a marker of how to sort of predict, also, the effect of the product is by paying attention to those two concentrations or the ratio, I should say, between the two.

Host Amber Smith: Are there other components of marijuana that have important effects on the body? Or is it mostly we need to be concerned with CBD and THC?

Hesham Masoud, MD: There are over a hundred of these phytocannabinoids, which are these exogenous cannabinoids that we're getting from the flowering plants that can be extracted. But I'd say, yeah, THC and CBD are the most abundant. And so that's the focus and primary understanding of its effect and modulation. You know, CBD is interesting because it signals through different pathways, and it doesn't activate CB-1 and CB-2. So that's why you don't get that psychoactive effect. So CBD is a cannabinoid that doesn't act on those two receptors, and that's why we think it doesn't have those impairments associated. And then you see its use in a broad field, almost like a cure-all. Now CBD at low concentration blocks certain receptors, and in a higher concentration may activate others. And so these are sort of the ideas of its effect, but it does not include the CB-1 and CB-2, and that's why people are not having those, behavioral disinhibitions and memory losses associated.

Host Amber Smith: You specialize in taking care of patients who have had strokes. I wonder, is there an association between marijuana use and strokes?

Hesham Masoud, MD: I will say just as a blanket statement, anecdotally in my own practice, over 10 years now, I would say it's exceedingly rare that I've seen marijuana be the culprit that is directly associated with a stroke. And this seems to be born out in the literature when we're looking at population studies. And so there's a lot of differences when we're trying to interpret population studies. Because you know, populations are a little bit different, obviously. And so, there are Swedish trials out there. There are nationwide inpatient sampling that we do of different age groups. And for the most part, there is not a clear association across the board between marijuana and strokes. And so, preparing for this, I tried to pick out sort of the highest risk stuff that I've found. And then for every one that you find an association, you may find something that doesn't have that association. And so it makes it a little bit more difficult. And I think to start, it would be sort of pertinent to understand, OK, what is this doing to my risk factors for stroke in general and kind of start from there. Because I think one thing that might be lost in population studies is essentially the specificity of someone's own circumstances. That kind of gets washed out when you're looking at a large population.

So someone may have an individual risk that is maybe modulated by the THC use. So for instance, it's thought that THC may have effects on blood pressure, may have effects on heart rhythm. And so if I'm someone who's tenuous in that regard, then maybe it may tip me over into a bad state, a pathological condition, as opposed to just, oh, a symptom. That's the thing about marijuana, I would say, sort of the overarching theme.

But if we look at some of the data, the effect that marijuana has on blood pressure is typically a lowering of the blood pressure, not a highering of the blood pressure. And high blood pressure is the thing I worry about the most for strokes.

However, if you have a certain scenario where your blood vessels are narrow, and you lower your blood pressure suddenly, then maybe that narrowing and that low blood pressure can equal a stroke. So you can see how a specific scenario is lost when I make these blanket statements. So I don't want a listener to be like, "Oh, yeah, I listened to this, and they just said, oh, population studies." No. Well, in general, yes, it seems like the risk is lower, and really what seems to be the issue is how you're ingesting this thing. So if you're mixing it with tobacco, and tobacco inhalation and smoke is part of this, it's certainly more inflammatory an agent to your system and detrimental potentially than it would be, for instance, if you were using it in a way where you're not combusting it.

So not combusting it means vaporizing where you can pass hot air through it. Or, ingesting it, which has its own special considerations between those two, but just to kind of understand the risk profile. There are things about how one is using the marijuana that we're seeing. A population study will find a risk associated with marijuana and then say, oh, but if we control for smoking, that risk goes away. And then another observation that it has a synergistic effect potentially. So marijuana and smoking -- bigger risk for stroke. These are the things that I think we have to pay attention to.

Now there is a study that I found about heart attacks -- which I thought was interesting and of relevance here -- that found that within about an hour of smoking marijuana, this observation that there was an elevated, up to five times almost -- short of an, a 4.8 -- so almost five-timeelevated risk of having a heart attack within an hour of smoking. So compared to a period of nonuse. And so that maybe signals that it could sort of trigger an acute illness, right? An acute condition. Does it do that for everybody? It doesn't seem like it, but when it does, it seems like there's an elevated risk in certain situations.

Now, interestingly, in another study over 25 years of follow-ups, so we're talking about around 5,000 patients followed for around 25 years, they found that marijuana wasn't associated with heart disease. So you can see how it's difficult to interpret this in a black-and-white fashion. And that held true for other risk of death from cardiovascular disease and stroke. And then again, on the flip side, maybe an increased risk in a three-year study of cumulative incidents, which is maybe a difference of around 0.5%. So 1.37 and 0.54% was the difference, so you can see how these risks are not huge differences when they're being quoted or observed. And they're also not consistent. But that doesn't necessarily convey a universal low risk for everyone who's using the recreational marijuana.

You know, this is a long answer to a short question, but I think it's important that it kind of extend it out to include things that, were specific to stroke risk and found that patients who had heavy use -- meaning more than 10 days out of the month -- may be at an elevated risk for TIA (trans ischemic attack) and stroke. And like I said, there might be vulnerable populations. So, you know, in one Canadian study, pregnant patients, who really shouldn't be smoking marijuana, obviously, because that has a risk to the baby in certain development, but they may have even higher risk of certain types of strokes, like a bleeding stroke. So again, speaking to this, it's all a combination of its effect and how that has its unique consequences, depending on what the risk profile is, which is individual.

Host Amber Smith: So there might be a risk of, like you said, heart disease or stroke, but I'm also curious about if someone is experiencing symptoms after they've taken a cannabis product and it feels like they're having a stroke. Have you seen cases where the side effects of cannabis use make a person feel as if they're having a stroke?

Hesham Masoud, MD: You know, this is really a great question to ask because anything that gets commercialized is automatically going to get more intense flavor and higher effect and more potency, right? That's essentially what happens with products that are sold in that way. And so we're seeing that. A study found that the THC component, the potency, has increased from 4% in 1995 to around 15% in 2018. So it's important that we know that we're also maybe getting some more potent recreational use here. And so it is important to distinguish between the two things. So going back to what does it essentially do? So we talked about behavioral disinhibition. We talked about memory. And then, some of the cardiovascular effects which may have to do with the rhythm of the heart and lowering the blood pressure.

And so essentially what I would say is it really goes down to the symptom to me. So if someone smokes or uses marijuana and then has a prolonged palpitation of the heart, I wonder did that then precipitate this patient to going into atrial fibrillation, which is an irregular heart rhythm that may be stimulated. Now again, in the literature, is this a consistent observation? No, but it would be something that I would worry about, something that is now triggering an underlying condition, and it's come now and bubbled up to the surface. If someone is hypotensive, and they feel like they're going to pass out, and essentially they're just an overall feeling of malaise or whatever, I'd say, come in, you may need to get some fluids.

Host Amber Smith: Are there symptoms that would prompt someone, a cannabis user, to seek medical care?

Hesham Masoud, MD: So looking at symptoms that can happen from acute use of marijuana, I kind of reviewed poison center calls in Colorado, from a period of time of over a couple of years and found that most symptoms seem to be things like being agitated or irritable, confused, and for the most part, people just got IV (intravenous) fluids when they got to the hospital, and a couple got maybe an anti-anxiety medication because they were having maybe too much anxiety related to what I would presume is a higher THC content in a specific product. Those are the kinds of things that I would expect to see. Now in my practice, have I really been called a lot for patients who've had a marijuana intoxication that have had a stroke? Only once in the emergency room. An older patient presented to me, and I examined him, and really, it's key that you don't try to make a lot of decisions on your own. Because you want an evaluation. And like I said, something like this can precipitate a real deficit. And so I would go back to the symptoms.

If the symptoms are, from a neurologic standpoint, are a subtraction of neurologic function. So suddenly I can't do something, then I want you to get evaluated. And then the evaluation is really going to be, is this something that could be attributed to a vascular territory in the brain versus just an overall drug effect? And then it's important to know, what is this person's blood pressure? What is their heart rhythm? Do I need to support that? In some very small instances -- you know, obviously children have a more sensitive; they may need to get respiratory support. There is a condition that has been linked with marijuana use that's called RCVS. Marijuana products have a vasoactive component in terms of its effect, meaning that it can exert an effect on our blood vessels in the brain, in terms of their size maybe they can spasm down as a relation tomarijuana, and that has been described in a condition called reversible cerebral vasoconstriction syndrome, (RCVS.) It's a descriptive term, which essentially means that the blood vessels of the brain, they clamp down, but it was reversible. It went away after a while. And this is linked with certain medications and has been associated with marijuana use, presumably because of this vasoactive effect of the cannabinoids. And so that's something to be aware of.

How does it manifest? Well, a sudden-onset, really severe headache. And so it can mimic an aneurism rupture. And in some instances you may even see leaking of blood on the surface of the brain. Now the good news is, is the prognosis of it is very different and favorable in comparison to an aneurysm that's ruptured, but you can see how it can be a pretty seriouscondition. And so that is something that I think people should be aware of that if you do have a sudden, severe-onset headache, you should get that checked out.

Host Amber Smith: Upstate's "HealthLink on Air" has to take a short break, but we'll be back soon with more information about cannabis from neurologist Dr. Hesham Masoud.

This is Upstate's "HealthLink on Air," with your host, amber Smith. I'm talking with Dr. Hesham Masoud. He's a neurologist at Upstate, and we've been talking about marijuana since recreational marijuana is now legal for adults in New York state.

Now, people may not want to damage their lungs by smoking. So edibles are maybe gaining favor -- gummies, chocolates, teas. Are edibles more potent in terms of THC than smoking marijuana would be?

Hesham Masoud, MD: People are more health conscious now, and this is a good thing, and so other methods of ingesting marijuana are becoming pretty common. So you had mentioned edibles. Another one is vaporizing, and that could be vaporizing the dry flower product or vaporizing a concentrate where essentially you're not combusting but using some sort of material to heat and provide air and pass it through. And it's important to know that eating versus vaporizing has a different effect, slightly, that is not as easy to predict in terms of comparing it to smoking it using a conventional lighter. And so the reason for that is because these cannabinoids, so for instance, for vaporizing, they can have different vaporizing points in terms of temperature. And therefore you can have different ratios between your THC and your CBD than if you had smoked it. And so, essentially, people have a conversion factor of say, well, you know, 0.3 of the dose smoked is the same as the dose vaporized. But you can see how there is a consideration with that.

Now the other thing about an edible to consider besides its effects, so its effect is a little bit different because it's metabolized, and when it's metabolized through the liver and in our system, it gives us a product that has maybe a little bit of a different psychoactive effect that can be a little bit more, have a slightly different flavor to it and be a little bit more potent in a way that is different than smoking it. And so that can be difficult to predict as well because the dose response has to do with, obviously, the time from ingestion, and it's not as quick an absorption as it would be if one were inhaling it through smoking or a vapor. And then it's also important to know that this THC or these cannabinoids, if you're ingesting it, are really enhanced by foods that have fat in them. And so if you eat something that's greasy, it may potentiate the effect even more. So it can be a little bit difficult with edibles. And a lot of times you'll see scenarios where, or you're hear about scenarios where, people don't wait enough time to know what their effect is going to be. And so they keep eating a little bit more, and then it potentiates. So, I would say it's a little bit more psychoactive when it's with an edible, so it can have a slightly different, almost a little bit more of a potential effect on there. And then, it's difficult for the prediction of response. I would say at least a 90-minute period, and start really slow.

Host Amber Smith: Now marijuana was used medicinally before it was legalized for recreational use. What did doctors prescribe it for?

Hesham Masoud, MD: So historically things like pain management, anxiety coming back up again. CBD is something that's being touted as an antioxidant and anti-inflammatory agent. And so people are trying to utilize it in conditions where there may be inflammatory nerve pain, or arthritic pain or so on and so forth. Other than that, there has been some business about its use in seizures. It hasn't really been born out that much in data, but that might be something that listeners may have heard about. Essentially, it's just about this THC CBD profile and that ratio and trying to figure out, well, what would be helpful if I did a lot of this, or if I had more of this in the ratio? You know, the plants are different, right? So if you were to split the two plants and say, okay, what's a plant that's going to give me more body and less of a head effect, then I would say would be something that would be indica. Indica plants sort of tend to do that sort of effect. And then a sativa is something that's going to maybe make you more anxious or have more of a psychoactive effect. And so that's a basic marker between the two. But again, it's important to note that indica will have THC in it, right? It's just about the ratios. So I think looking at those ratios, one can sort of predict where these things are being used as therapeutic agents, but, you know, clinical trials are forthcoming.

Host Amber Smith: Are there cannabis products that could be used legitimately to help with sleeping, for instance?

Hesham Masoud, MD: Well, the indica products tend to be ones that have more of a body effect that will make people sleepy. I just think essentially utilizing something like a recreational drug for a sort of basic housekeeping, sleeping, things like that, is probably not a great idea, in the same way that it would be not a great idea to be taking sleeping pills as your way to sleep because it's indicative of something else here. Why can't we sleep? Is it because of poor sleep hygiene? Is it because I have a sleep condition? You know, it's sort of a symptom and not something that needs some attention. So essentially, yeah, it would be higher up on that indica content or indica flavor, which would essentially make people more sleepy. People have used it specifically for that. But I would say, in terms of medicinal use, I think it's important to understand why these things are happening to us before we start trying to figure out how to solve them.

Host Amber Smith: Are there long-term neurological effects from cannabis use?

Hesham Masoud, MD: There is a consideration about the timing of marijuana use in terms of adolescents, which can sort of put a cap on some cognitive abilities, seems to be the observation. And then it seems to be that people who have long-term use may have some structural changes on their MRI, so certain areas related to memory can be a little bit smaller. And so there is a concern that it can have long-term cognitive effects if we're using those structural changes as a surrogate for cognitive impairment. So yeah, I think it's very clearly bad for adolescents, and I think there is a suggestion that long-term -- I mean, it makes sense, you know -- if long-term, I'm using something that is inhibiting my memory center, then maybe longterm that memory center is going to be smaller than one that's not constantly being inhibited. You know what I mean? That would be, my interpretation of it as well. But in terms of, are we seeing long-term cannabis users are now going to nursing homes because of cognitive impairment? No, but there is a signal here of its effect in that direction.

Host Amber Smith: Interesting. Do you have any advice for adults who want to try cannabis products now that the state has made them legal? I'm thinking about you just mentioned two different types of plants that are grown differently that have different concentrations of CBD versus THC. How would a person know that when they go to a dispensary?

Hesham Masoud, MD: If you were to enter into a dispensary and have to be tasked with making this decision, I would say 1. Be aware that you're dealing with more potent products now. So if you had used recreational marijuana in the past, then maybe now you're entering into a commercialized space now, and so you need to be aware that things are significantly more potent. Be aware that essentially THC is what's going to have that psychoactive alkaloid that's going to have those behavioral disinhibitions, maybe anxiety, so on and so forth. That's going to be in a higher concentration in sativa plants. So if it says sativa, if it comes from a sativa plant, or they say, "sativa dominant," expect that that means it's going to have more THC, so potentially more psychoactive versus CBD. And CBD is the one that has the anti-inflammatory, antioxidant effect and sort of the body type stuff. And thatmay have a higher component or higher concentration in a plant called indica. So if it says "indica dominant" or indica, then I would expect not to get as cerebral, but maybe more body. Are you never going to have the cerebral? No. Unless it's like zero THC and all CBD, expect to have some sort of psychoactive component. So that would be something to be aware of. It's this ratio though, of how much between THC and CBD and using sativa as your surrogate for THC and indica as your surrogate for CBD with the knowledge that indica still has THC in it.

I would say another thing to be aware of is the people behind the counter for the most part, if you're going to a dispensary that has some regulation to it, are going to know a little bit about things. So I would share maybe your history of use because potency is modulated, obviously, by your own intrinsic tolerance. And you can't really say, "Oh, well, when I use alcohol, I am fine, so I'm going to be OK with marijuana." There is really no conversion there that I've seen. But, just sort of sharing that, "yes, I'm a heavy cannabis user," or "I'm a very light user," so on and so forth. And then that general awareness of that ratio in those two plants, I think one would do well to, as much as one can, sort of predict a little bit how things are going to go. And then when deciding on the way to ingest it, understanding that a vaporizer may be more potent, an ingestible may have a little bit more of a different behavioral effect than what you were used to when you had tried marijuana in the past. That can be in a very delayed fashion, so really give yourself time and plan your day accordingly. I think those are the basic considerations.

Host Amber Smith: Can a person predict how their body's going to react to cannabis?

Hesham Masoud, MD: Like I said, I think it really has to do with your tolerance level. And I would say it's really just about understanding when you would notice the effect. So if I've smoked within 15, 20 minutes, I sort of know what my dose was and what I would expect and then maybe stop, or someone wants to modulate beyond that point. But for ingestion, it's different because you may forget that you took something or time passes in a different way, and you maybe get a little bit of a psychoactive effect and then your understanding of time gets more expansive, and then you sort of forget, and then you re-dose. And so I would say maybe setting a timer for an edible so you understand when to expect, sort of an alarm like, "OK, by now it would have worked." And if it didn't, then I know where my general tolerance is.

Host Amber Smith: Do you think a person who's never tried cannabis before, will they experience symptoms the first time they try it, or is this something that you have to use over time?

Hesham Masoud, MD: It depends. I mean, the thing that's interesting is, you'll hear anecdotally, I'm sure people have conversations with friends and family members or whatever about like, oh, different tolerance levels, just inherent to the first time they tried it. "Oh, I tried it, I didn't feel anything." And so, really there's a big variable here, which is, we don't really know what we've tried, because we don't have that information. Now, with the legalization, the advantage is now I know what this stuff is, right? I know if it's sativa. I know if it's indica. I know if it has a THC component, that's higher CBD component. So I really, I can predict almost, based on my understanding of that ratio, right? And then how it's affected me specifically, I would start with a really low dose, and then wait for the effect. That's how we do it with pain medications in the hospital, interoperatively. I start with a very small dose. I see how it works. I wait enough time to expect that effect. And then I re-dose. I don't do cumulative dosing because I don't want to have a snowball effect at the end. And I think that that makes sense for anything. So yeah, the good news is, is if one has a basic understanding of the ratios, one can predict more than they could ever in the past. And I think it's important to know what we're using. There are synthetic cannabis out there, and that's dangerous and has a different effect and is very clearly linked to stroke and seizures and things, so it's important that if people are going to get these products, you get them from a very reputable source that's been verified. And I think that's an advantage behind legalization at the very least.

Host Amber Smith: If someone ingests marijuana and then starts having troubling symptoms, can they do anything to get it out of their system?

Hesham Masoud, MD: I did look into this and found for the most part, it seems to be waiting it out, having awareness that this is a drug effect in a big sense can sort of calm one down. Changing the sensory experience, so taking a shower. I would be mindful if you take a hot shower and you're having low blood pressure, then you may feel even worse and want to pass out, but maybe using something cold on the face. If you change the sensory experience, that tends to assist. Like we went over the poison control calls and when it got really bad, patients may have gotten an anti-anxiety drug in a controlled fashion in the emergency room. So what could be a search surrogate for that? Well, it seems like you can take CBD, so if you have a CBD -- no THC, just CBD -- product, apparently that might help. And then there is some interesting business about terpenes. And so I looked into this, and so terpenes are essentially like these essential oils of plants and are these aromatic, organic hydrocarbon class of these natural sort of unsaturated hydrocarbons that these plants produce. And they're classified by the number of carbons: mono, di, terpene, whatever. And the research seems to suggest that terpenes can modulate the effect of the cannabinoid at the receptor. So it can either assist its effect or inhibit its effect. And so, there are these "cure-all's," and in pop culture, I guess Neil Young is famous for recommending peppercorn if one has a little bit of an adverse effect to the recreational use, or lemon. And I think the idea here is to sort of evoke those terpenes that can inhibit the cannabinoid. And I've heard that in relation to just eating, that I'll maybe eat something, I think, oh, perhaps if they're eating something with a high terpene content.

So I think for the most part wait it out. Be aware that this is a drug effect and not something more sinister than that. If there is symptoms of actual organic disease, God forbid, like a sudden neurologic deficit, a prolonged heart rate rhythm, then come in and get it evaluated. If it's nothing, it's a quick turnaround. But be aware that maybe marijuana can be the straw that breaks the camel's back for someone specific, with a specific set of circumstances. And then, maybe take some CBD or use this terpene hypothesis.

Host Amber Smith: Well Dr. Masoud, I thank you so much for making time for this interview.

Hesham Masoud, MD: Oh, my pleasure.

Host Amber Smith: My guest has been Dr. Hesham Masoud. He's an associate professor of neurology and neurosurgery at Upstate, where he specializes in endovascular surgical neuroradiology, and he's a member of the stroke team. I'm Amber Smith for Upstate's HealthLink on Air."

Who may need autonomic testing? Next, on "Upstate's HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." A number of patients who survive COVID infections struggle with a variety of symptoms long after they've recovered from the infection, and some of those symptoms are related to the body's autonomic system. Here with me to talk about his research on this subject is Dr. Ahmed Eldokla. He's a neurologist at Upstate who specializes in neuromuscular medicine and autonomic disorders. Welcome back to "HealthLink on Air," Dr. Eldokla.

Ahmed Eldokla, MD: Hi, Amber. How are you doing?

Host Amber Smith: Great. Now you and your colleagues have examined the association between long COVID syndrome and autonomic dysfunction. But before I asked you more about that, can you explain dysautonomia, what that is?

Ahmed Eldokla, MD: So, simply it means dysfunction, or a problem in the autonomic nervous system. The autonomic nervous system is a part of the peripheral nervous system that regulates involuntary -- without a person's conscious effort -- regulates many parts of the human body, blood pressure, heart rate, body temperature, digestion, metabolism, production of body fluids, like saliva, sweat, tears, urination, defecation and sexual response.

Host Amber Smith: So these are all things that happen without us controlling or even knowing?

Ahmed Eldokla, MD: Absolutely.

Host Amber Smith: OK. And then by long COVID, we're talking about people who've recovered from COVID, but then they're still having symptoms more than a month after they've recovered, is that right?

Ahmed Eldokla, MD: Absolutely. Yes. So long COVID is defined as or refers to symptoms that developed or persisted at least four weeks after the onset of acute COVID-19 infection. Long COVID symptom encompasses many symptoms, including shortness of breath, headache, memory changes, nausea, abnormal sweating, palpitation, anxiety, depression, fatigue, chest pain and also orthostatic intolerance. Many of those symptoms are seen in patients with autonomic dysfunction.

Host Amber Smith: You said "orthostatic..."

Ahmed Eldokla, MD: intolerance... which means, simply, lightheadedness when you stand up, dizziness when you stand up.

Host Amber Smith: Well, now, if I understand correctly, for the study that you were involved in, there was a questionnaire for patients who came to a post-COVID clinic at a hospital in Egypt. What did that questionnaire ask?

Ahmed Eldokla, MD: So the questionnaire is called Composite Autonomic Symptom Score 31. We usually referred to as COMPASS-31 questionnaire. It is validated and widely used the questionnaire to quantify autonomic symptom severity. It consists of 31 questions regarding different parts of autonomic nervous system. And answers are scored anywhere between zero to a point, which would be 1, 2 or 3, and a score was obtained by adding together points to give a total score ranging from zero to a hundred. I'll give you examples: In the past year, have you ever felt faint, dizzy or had trouble thinking soon after standing up from a sitting or lying position? When standing up, how frequently do you get these feelings or symptoms? Does your mouth feel dry? Have you had trouble focusing your eyes? And so on, and so on. 31 questions.

Host Amber Smith: What can you tell me about the 320 patients who participated?

Ahmed Eldokla, MD: So patients were included in this study if they were above 18 years old, symptomatic at COVID-19 acute phase, regardless of the severity of the symptom or the need for oxygen or ICU support, and had a confirmed diagnosis by PCR (polymerase chain reaction testing) or antibody testing, and they should have symptoms for long COVID that developed or persisted at least four weeks after the onset of the illness.

Host Amber Smith: So were they men or women in the study?

Ahmed Eldokla, MD: About 73% were female, and 27% were male. Age ranges from 18 to 74 years, with a mean of 35.9 years. Most patients, 90%, had a diagnosis of covered for more than 12 weeks, with a mean duration of 42 weeks.

Host Amber Smith: So with three quarters, roughly, of your sample being female, do you think that means that more women are affected by long COVID?

Ahmed Eldokla, MD: It seems like more women affected by long COVID, yes.

Host Amber Smith: Do you have any idea why the virus affects some people one way and other people another way, because patients are not having all of those symptoms. You've got some patients with these symptoms and some patients with these other symptoms is that right?

Ahmed Eldokla, MD: That's that's correct. That's absolutely correct. I think no one knows for sure, but I think people's immune response to infection, rather than the virus itself, that determines who is at the greatest risk from COVID-19. I also think that genetics play a role, as does gender, too.

Host Amber Smith: Genetics and gender, in what way? What symptoms affect women versus what symptoms affect men?

Ahmed Eldokla, MD: It's not clear, but there is some research that estrogen may help women against the severe disease.

Host Amber Smith: So would that protection apply only to premenopausal women? In other words, after the estrogen starts to decline, after menopause, do those rates change?

No. It is really female, no matter what age. And actually you see this also in autoimmune disease. So like people who have lupus, you see most of them are female. So any autoimmune disease, or most autoimmune diseases, affect the female more than male. Now, what dysautonomia symptoms were most common among the participants in the study?

Ahmed Eldokla, MD: So, many symptoms, I'm going to mention some of those: bloated feeling after a meal, vomiting, cramping, colicky, abdominal pain, bouts of diarrhea, a change in the skin color, dry eyes or dry mouth, feeling dizzy soon after standing up from a seating or lying position, trouble focusing your eyes, and sensitivity to bright light. Those symptoms are just an example.

Host Amber Smith: Do you have any prediction for whether these symptoms will get better with time?

Ahmed Eldokla, MD: That's a good question. This study doesn't address that question specifically. However, in our practice, we see these symptoms improve with time, but not necessarily resolve completely.

Host Amber Smith: What is the treatment, or is there a treatment? Is there a way to accelerate getting rid of these symptoms?

Ahmed Eldokla, MD: The treatment usually is directed to the symptom itself. We call it symptomatic treatment, meaning we mainly treat the symptoms. For example, if the patient has lightheadedness or dizziness when he stands up, we encourage him or her to drink enough fluid, exercise, and if it didn't work, we start medications that improve the blood pressure upon standing. Same thing with nausea. Same thing with the vomiting.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Ahmed Eldokla. He's a neurologist at Upstate who specializes in neuromuscular medicine and autonomic disorders.

Do researchers understand why some people are plagued by these symptoms and some people aren't, long after the active disease has gone? Do we have a feel for why these people are affected?

Ahmed Eldokla, MD: That's a very important question. So there is not much literature that discusses etiology (the causes of disease) and the rationale of autonomic dysfunction associated with COVID. In our paper, we discussed a possible mechanism. Let me give you some examples. COVID-19 infection in mice down-regulate the angiotensin converting enzyme two, or we call it ACE-2. The changes in ACE-2 expression or function can lead to blood pressure changes, resulting in lowering the blood pressure, which can give you lightheadedness when you stand up. Scans of the brain have suggested possible COVID-19 impairment of areas of the brain that control the autonomic nervous system. For example, the hypothalamus and the brain stem, which are important parts of the autonomic nervous system. COVID-19 also leads to release of a large number of inflammatory cytokines, which is a material that makes you fight the infections or inflammations. These materials can affect various body organs. For example, sympathetic nervous system is a part of the autonomic nervous system. When sympathetic hyperactivation occurs, it can cause arrhythmia, which is irregular heart rhythm, hypertension, increased sweating, reduced intestinal motility, and it can lead to serious complications, including injury to the heart.

Host Amber Smith: Do we know if vaccination status has any impact on whether someone develops long COVID?

Ahmed Eldokla, MD: We didn't look into that in this study, but I'm sure there will be more studies to discuss this question.

Host Amber Smith: Now, this particular study was focused on patients in Egypt. Is there any reason to believe you would find something vastly different among the people in the United States?

Ahmed Eldokla, MD: No, I don't think so.

Host Amber Smith: Well, I'd like to ask you about the autonomic testing that you're doing here in Syracuse for patients with long COVID who are struggling with symptoms. What does autonomic testing consist of?

Ahmed Eldokla, MD: The autonomic testing we are doing here in Syracuse consists of four parts. One -- Tilt-table testing. We tilt the patient up and down and measure the blood pressure and heart rate. Two -- we measure the sweating from the legs and arms, a test called QSART or Q sweat. Three -- we ask the patient to breathe in and out, and we measure the variability of the heart rate. Four -- we ask the patient to blow in a closed tube and measure the changes in the blood pressure and heart rate.

Host Amber Smith: So, do you do all of this in one visit?

Ahmed Eldokla, MD: Yes. Yes we do.

Host Amber Smith: How long is the visit? It seems like it's pretty comprehensive.

Ahmed Eldokla, MD: It is. And actually it involves a lot of technical factors and training, but usually it takes anywhere between 60 to 90 minutes.

Host Amber Smith: So, are you able to determine, based on the results of those four tests, whether someone's symptoms are caused by COVID or, I mean, how do you tell if it's something else?

Ahmed Eldokla, MD: That's an interesting question, but to a certain degree, yes. If the symptoms started after COVID-19 infection or in association with the onset of the COVID-19, it makes sense to say that it is most likely associated with COVID. But if the symptoms started well before COVID-19, we can conclude that it is unlikely to be caused by COVID, but I have to say that all the autonomic symptoms, or most of the autonomic symptoms, can be worsened with COVID infections. And we see this all the time.

But not all the people who have symptoms really have the disease. So there is another study that is going to be published in a few weeks. We find only 25% of the patients who have symptoms actually have a real autonomic disease.

Host Amber Smith: Meaning autonomic disease caused by long COVID, or any sort of autonomic disease?

Ahmed Eldokla, MD: Autonomic disease caused by long COVID. So they have symptoms, but they do not necessarily have the autonomic disease. So, it could be they are bedridden for a long time. It could be they're anxious. It could be they are deconditioned. But only 25% of those have a real autonomic disease.

Host Amber Smith: So among the other 75%, if they don't have the disease, is it some kind of psychosomatic manifestation that they think they have it? Or are these symptoms that just pop up, and then they go away and there's nothing ever really there?

Ahmed Eldokla, MD: I think they are real. They have symptoms, but the problem is how you act with those symptoms. I will give you an example. When we are sitting down we have at least millions of receptors at work, so you'll feel the chair under you, right? But your brain ignores that. You might feel it now, when I told you you feel the chair under you, but you didn't think about it, you know? So those people who are somatic, or have more response to the symptom, it is the same thing. Their brains are not turned off. Their brains react to any small thing. So they are hyper-excitable. We believe them. They have symptoms. But this could be because of the disease itself. You are in the ICU for a long time. You know, you are thinking about everything. You're anxious. You are not moving. Imagine that you are lying in bed for a week, how you will feel. So it's not necessarily that they have autonomic disease per se, but they have symptoms that need physical therapy, deconditioning, psychotherapy, stuff like that.

Host Amber Smith: So with the 25% who it is autonomic disease, once they recover and the symptoms abate, have they got lasting damage to their autonomic nervous system?

Ahmed Eldokla, MD: So the damage can be functional. Or the damage can be anatomical, like, for example, when you have a stroke. It's anatomical damage. You have damaged certain parts of the brain because you don't have enough blood supply to that part of the brain. But with the autonomic nervous system, mostly it's a functional problem. So they are not working as they used to work, not anatomical damage. So just to answer this question simply, most of the patients will have dysfunction or abnormal function of the autonomic nervous system that can resolve with time, but some of them will not resolve with time.

Host Amber Smith: Interesting. Now this specialized testing is not available from every neurologist. So the patients who come to you for the testing, do you see them continually, or do they go back to their other doctor after the testing?

Ahmed Eldokla, MD: Mostly they go back to their doctor after the testing. The patients who are severely affected, they continue to see us.

Host Amber Smith: OK, well, this has been very informative, and I appreciate you making time for this interview.

Ahmed Eldokla, MD: Thank you, Amber. Thank you very much.

Host Amber Smith: My guest has been Dr. Ahmed Eldokla. He's a neurologist at Upstate with expertise in neuromuscular medicine and autonomic disorders. I'm Amber Smith for Upstate's "HealthLink on Air."

And now, Deirdre Neilen, editor of Upstate's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: David Radavich's most recent lyric collection eloquently praises the astounding miracle of organ donation.

"Gift"

It's not something

I ever expected.

Casually wrapped

in hospital blue,

wires and monitors,

nametag askew.,

nothing asked for

from no body I knew.

But here is the vital

up on the charts.

this heart of hearts

pumping to parts

of every cell

without thinking

without counting

without any flash --

a red bloom of flesh

wrapped in what

used to be a tight husk

now singing

its arteries

a psalm at dusk.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York. Next week on "HealthLink on Air," an initiative to recruit more people of color into medical research. If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org. Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Stephen Shaw. This is your host, Amber Smith, thanking you for listening.