The history of cyclic vomiting

Steve Wartenberg: Welcome back. This is our ongoing series on cyclic vomiting syndrome with Dr. V. I'm Steve Wartenberg, and this is Dr. Thangam Venkatesan. Today, we're going to talk about the history of CVS.

We'll be hearing from Dr. B Li, a pioneer in this field, and an emeritus professor at the Medical College of Wisconsin in the division of Pediatric Gastroenterology, Hepatology and Nutrition. And later we'll hear from Kathleen Adams, president Emeritus of the CVS and her daughter, Molly. Dr. V., why don't you introduce your friend and mentor?

Thangam Venkatesan, MD: It's really a great honor and pleasure for me to introduce B U. Li. If I had to talk about him, I can actually talk the entire day, but I won't take up the entire day. And so B. Li is emeritus professor at the Medical College of Wisconsin in the division of Pediatric Gastroenterology, Hepatology and Nutrition.

He was really instrumental in increasing awareness about cyclic vomiting syndrome and he has worked tirelessly for the past three decades with Kathleen Adams, who we meet later, and he actually sat with me in my CVS clinic the first time I saw a CVS patient.

B U.K. Li, MD: Fond memories.

Thangam Venkatesan, MD: That is true, and I'm really deeply honored and it's a great pleasure to have you here today.

B U.K. Li, MD: Thank you. Thank you, Thangam.

Steve Wartenberg: Wow. When and what drew you to CVS and what were some of your early experiences with patients?

B U.K. Li, MD: I think I like medical mysteries and I think this was one, and when I saw them during my fellowship and during my first few years, I was amazed at how sick they could be and then I'd see them back in clinic and they were totally normal.
So there's this on and off pattern that I really didn't understand and I wrote an abstract and I thought pretty much that was the end of it. But how serendipity happens with Thangam and myself, Kathleen Adams invited me to a conference in Milwaukee, and-

Steve Wartenberg:
What year are we talking about, roughly?

B U.K. Li, MD: This is 1993, so this is really 31 years ago. What was fascinating is that I learned a lot from the patients. I listened to it from their point of view.

Steve Wartenberg: But it wasn't just you who didn't know across the board. What was sort of the knowledge at the time that you were having to overcome and add to?

B U.K. Li, MD: That's an excellent question. At that point, it didn't even have a name, and therefore nobody really knew what it was and exactly how to make a diagnosis; so really the dark ages at that point.

Steve Wartenberg: Yeah, and there was no research going on.

B U.K. Li, MD: No research, maybe zero papers a year, maybe one over the last a hundred years.

Steve Wartenberg: Wow. So you were starting from scratch with no research foundation to guide you.

Dr. B U.K. Li: Essentially. And I think I would add that when I talked to my colleagues about potentially getting interested in it, I became more intrigued. And then I think Kathleen was so inspiring with trying to care for her daughter that I thought maybe I should get involved.

But I would say that many of my colleagues were very pessimistic. Well, you'll never make a career because there's no test for it. There's no name for it, there's no way to diagnose it. You're going to be lost in the swamp.

Steve Wartenberg: So talk about some of the early challenges and how you figured out how to treat and diagnose this.

B U.K. Li, MD: I thought that the first step was to have a conference and really a high level conference where people gave talks and we came to some agreement on what the disorder was and how to diagnose it and where the next research steps were.

And so that happened in 1994, and we had the honor of actually going to the hospital where it was first described by Dr. Samuel Gee in 1882, which is Saint Bartholomew's Hospital in Central London. And at that point, the goal was to get everybody who had published on it, and we literally gathered almost everybody who was living who had published on the disorder and came together for two days' symposium and eventually published the proceedings with some general criteria on how to diagnose it. And from that point on, it became known as cyclic vomiting syndrome.

Thangam Venkatesan, MD: And I do want to mention that like B said, it was not even a validated disorder, and in pediatrics they started recognizing it. And when I started it and I met B, some of the premium institutions even in this country didn't believe in this disorder. And here I was sitting there and saying, "No, it exists."
And so it does take some time to make people understand that this is a real disease, that it exists, and it's not a figment of anybody's imagination.

Steve Wartenberg: Wow. So talk a little bit about how YouTube connected, and some of the challenges you each faced in educating and treating people.

B U.K. Li, MD: It clearly has been an uphill battle. And I will say even through the publication of the first pediatric guidelines, it was called a consensus statement in 2008. There's still people in my field who feel it's not a real disorder.

Steve Wartenberg: Even today?

B U.K. Li, MD: Well, that was through 2008.

Steve Wartenberg: Okay, through 2008. Okay.

B U.K. Li, MD: And I still feel there are skeptics. This is a disorder that you have to listen to the story very carefully and you diagnose it by pattern, by what has happened, but there's no test you can run. So when you don't have a defined cause or pathway mechanism, I think doctors tend to say it must be psychological, and then they put it off to the side because-

Steve Wartenberg: Is it also because they're a little hesitant to make a diagnosis when they don't have that test to back them up? I don't know if scared is the right word, but they're hesitant.

Thangam Venkatesan, MD: No, but it requires finesse and it requires actually... You don't recognize something until you see that pattern, right?

Steve Wartenberg: And if you've never seen it before, yeah.

Thangam Venkatesan, MD: So it's difficult. And I guess going back to your question about how we met, B U. Li actually happened to come to the Medical College of Wisconsin. I was a very junior, young faculty member and we were introduced to each other and I said, "I'm interested in this disorder." And I said, "Will you help me?" He actually came and sat in my clinic physically for the first two clinics because I think it takes some degree of nuance and experience to really know what is happening.

Steve Wartenberg: Well, it's interesting how I've seen this in the medical profession that doctors, physicians like yourself have a family tree of people you mentor, including you, and now you have a family tree of people you're mentoring and it keeps spreading all over the country and beyond. And that's how you educate and train people.

What are some of the new research areas and findings and even hopefully breakthroughs that you're both finding and that you and your collaborators are finding?

B U.K. Li, MD: One is an area that Thangum has pioneered, which is the endocannabinoid system. I think you've heard about that before. I think the interest became stimulated in 2004 by the report that young, mostly, I think they were all young-

Thangam Venkatesan, MD: Men.

B U.K. Li, MD: ... adult, Australian men, were developing cyclic vomiting syndrome by description, but triggered by too much cannabis. And by too much I meant almost daily for, I think, between six and sometimes 10 years.

Thangum has subsequently shown that there are some mutations that actually seem to predispose one to develop cyclic vomiting syndrome. So cyclic vomiting syndrome, and what has now been called sick cannabinoid hyperemesis syndrome, there seems to be some overlap. And I think by understanding the system, we're going to shed light on both disorders.

I would say the second one is autonomic nervous dysfunction. And the autonomic nervous system controls obviously things you don't think about like your heart, but also your stress response. So when you get nervous and your blood pressure goes up, what has been shown is that it looks like that you are revved up in a flight or fight mode too often, chronically all the time, instead of up and down back to normal, that you're always revved up like this.
But now it looks like our last symposium, it looks like the calming system called a parasympathetic system, which is the calming, so it should dampen down, is actually what is more defective. It doesn't dampen down the sympathetic to get it back to rest.

But there's some ways to restore it. And that is one of the breakthroughs that just came recently and that if you can restore it, and some of it can be without medication, that you can use this ear stimulator and stimulate the vagus nerve, it can actually calm the system back down, can help re-regulate the system.

Steve Wartenberg: So someone would wear something on the ear similar-

B U.K. Li, MD: Yes, almost like a hearing aid. Yeah.

Steve Wartenberg: And they activate it and it stimulates that vagus nerve-

B U.K. Li, MD: Right, little electric pulses.

Steve Wartenberg: ... and that calms them down.

Thangam Venkatesan, MD: Correct.

Steve Wartenberg: Thank you, Dr. Li for that excellent overview and history. And now we have two new guests and can you introduce your friends to us?

B U.K. Li, MD: Yes, I'm delighted to welcome Kathleen Adams and Molly. I've known Molly since she was 13 when I came to the first conference organized by Kathleen, who was then elected as the president of the Cyclic Vomiting Syndrome Association, and I think was president for at least 25 years and really the heart, soul of the organization.

Steve Wartenberg: Molly, what's it been like to live with CVS all these years?

Molly Adams: It was very challenging. I didn't like going in the hospital, just didn't want to get sick a lot. And then when I got older, I felt outgrown it, but I do get it sometimes with headaches. I hate headaches. Yeah, it was really difficult when I was little. Yeah.

Steve Wartenberg: What was the toughest part about it?

Molly Adams: I don't like saying the word, but yeah.

Kathleen Adams: The V word. We call it the V word.

Steve Wartenberg: Yeah, I don't blame you. And you've also become someone who's helped other people with CVS.

Molly Adams: I like to be an advocate for people that have it when they were younger and yeah, it's just great.

Thangam Venkatesan, MD: And Molly has always been at all of these conferences. She accompanies Kathleen Adams and I think she really interacts with patients like herself, children, and of course Molly is an adult. And I think just listening to her story, she continues to advocate for these patients.

Steve Wartenberg: Molly, thank you very much for sharing your story with us and the best of luck in the years to come. Kathleen, can you talk about how and why you became involved with CVS and then founded the CVSA?

Kathleen Adams: Molly had an episode of vomiting when we were on a trip at one point, at age one and a half. Then it progressed to episodes that were happening about once every six months, then once every four, then two, then one. And so she ended up with 11 years of very severe vomiting episodes that lasted about two and a half days.

So those 11 years she was undiagnosed and I thought Molly cannot be the only one.
We ended up connecting through my pediatrician who actually read a letter in Contemporary Pediatrics, which is one of the pediatric journals, a letter from another physician who had a child with very similar symptoms. And so from there we ended up seeing Dr. Fleischer. A year and a half later, I ended up pulling together a team of people who I had, had contact with through Dr. Fleischer, and that was the beginning of what's now about 31 years of CVSA.

Steve Wartenberg: So first, before we talk a little more about what you accomplished at the CVSA, what was it like after 11 years with no diagnosis, no doctors who knew anything about this, to finally find Dr. Fleischer to realize here's someone who understood it. There are other people with this. There are some things maybe that he could do to help you.

Kathleen Adams: It really cannot be expressed. It's so valuable and important on a journey like this.

B U.K. Li, MD: I wanted to add something, Kathleen, to give a deeper sense of your commitment and leadership to this whole process that I think I've told you before that what I think the physicians recognized who were there was your profound commitment to try to solve this and engage physicians to help you and to partner and collaborate.

I think that is the spirit that you brought with deep commitment that really inspired us. And I think as I told you at the time, I probably would have looked at this disorder for a couple of years and just moved on, but your persistence and your collaboration was what kept many of us in for this 30 years.

Steve Wartenberg: Yeah, it's amazing how much one person can accomplish when they set their mind to it. So thank you, Kathleen. And I'm curious, it's been 30 years, what would you consider some of the top accomplishments of the CVSA that you helped lead?

Kathleen Adams: There've been so many that have been involved, enormous amount of people and background and coordination and all, and there've been some that have been more momentary. I think that the most obvious probably had to do with the development, and this was an ongoing situation, the development of our advisory board.

And every time when Dr. Li and Dr. Fleischer were together at that first meeting, the bud of the whole thing, and when Dr. Venkatesan joined us, again, it was an explosion of delight and relief and joy in the collaboration that Dr. B mentioned. So I feel like that constant connection with our advisory board was critical. In the process of planning different events over the years, the three that turned out or were the three that to be the most memorable for me and probably the most effective as far as number of people connected with were the three symposiums.
So those are the main things that come to mind.

Steve Wartenberg: Kathleen, what advice would you give to families and patients who are newly diagnosed with CVS?

Kathleen Adams: To seek expert care and then somehow figure out a way to become partners with the team?

Steve Wartenberg: For our last question, I thought it's important to kind of look at and ask all three of you: Look ahead into your crystal balls and what do you see in terms of support and treatment and research and in the next five, 10 or more years?

Kathleen Adams: There's a strong need for ongoing financial support, strong connection with NIH. We've already been funded once by an NIH grant, and that's critical.

B U.K. Li, MD: We have now come to a much broader picture. As I said in the beginning, we thought this is this weird vomiting syndrome, and they just vomit and then they're normal vomit. And we now know that one, they have many other symptoms in between that affect their quality of life. For example, fatigue, sleep disorders, anxiety, and other GI complaints such as irritable bowel syndrome, cramps and diarrhea.
So it is no longer just a vomiting disorder. It's a complex disorder, and now we see developmental delay in a subset. The other thing is that there seems to be various subtypes, and one of them is associated with hypertension. One of them only occurs with menses. And so part of the broader picture is that hopefully in the future we will understand that CVS is not just one pot, but it's actually a number of different pots, all of which end up with vomiting, but they're actually slightly different.

They may have a different genetic pattern. They actually may have a different clinical course and require different types of treatment. And so as we are trying to do it with other diseases like Crohn's disease, we're trying to ultimately be able to subtype them and stratify them and then apply very specific. So I'm thinking 10 to 15 years out that this will be the broader view that we'll have, and we have I think, the right team in place to help do this.

Thangam Venkatesan, MD: When I think about CVS, I think there are three facets, and one is clinical care, education and research. As far as research, I think it's very important to have specific targeted therapies and to have specific targeted therapies, you need to understand the pathophysiology of CVS. So it's very, very important, like Kathleen said, to have both public funding and pharmaceutical support to really drive the research forward.

But before I finish, and like Molly said, there should be a cure for this disease, and I think that would be something that should happen, and I do think it will happen, and I'm very optimistic about it.

The second thing is we all want to come together and pretty much put all our heads together to try and crack this puzzle because I think it's very important that we have not just a U.S. registry, but a world registry of patients so that we can create a bio-bank and really a world registry to understand this better and drive the research.

Steve Wartenberg: Wow. Well, thank you everyone. This has been fascinating. And Kathleen and Molly, thank you and good luck as you continue your role as a caregiver. And thank you Dr. Li and Dr. V for all you do for CVS patients, all over the world.
 
The Ohio State University Wexner Medical Center logo

For more information, visit wexnermedical.osu.edu/CVS

YouTube link: