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Video Library

Ask the Experts Open Forum – Breakout Session – 2018 NMO Patient Day

Audience:

Hello, right. First. I want to say thank you for everything that you do. And my question is, is someone on Immigran more susceptible to infection than Rituxan or should, or are they both equally immunosuppressant? So I’m asking because I’ve never been on Immigran, I went from being diagnosed to Plex, to Rituxan, but I’m concerned because I work. I’m a teacher, so I work in the back of germ every day. So I’m wondering, should I switch career because I’m immuno suppressed and it’s only been a year, so I don’t want to, if I have to change my job to stay healthy, I will. So I don’t know if I’m less immuno suppressed than others.

Dr. Michael Levy:

I mean, I would say that you are partially immune- suppressed. That’s how the drug helps in NMO. But I wouldn’t say you’re to the point where you need to be worried about career, or flying, or cruises or anything like that. Generally, what I suggest is to keep Purell in your purse, so that after a kid comes and interacts with you, then- don’t Purell the kid because, that person, that kid, needs to become immunized, but you should Purell yourself. ‘Cause most of the infections are caught when you touch your face after touching something the kid’s touched.

Audience:

Hi.

Audience:

So my next question is, with respect to MRIs, how often should a person have an MRI or does it just depend on the doctor? ‘Cause I know some people say they have them once a year. Some people only if they feel like they’re having a relapse-

Dr. Nancy Sicotte:

So I’ll take them. I do a lot of research in imaging and MS, which is a really different story. So, in MS, there’s silent inflammation that goes on. And so we definitely do more frequent imaging because we can’t rely on the clinical symptomatology. Although the studies haven’t been done systematically, the generalist assessment is that an NMO is a disease of relapses. So normally we are not doing serial imaging in… As routine management, certainly when there’s new symptoms, I will get new imaging. Now the only caveat to that is there are some people that have kind of combination or unusual brain lesions, for example. Sometimes I will do more frequent imaging in people like that because those were probably not associated with a symptom. But, in general, this is not a disease where routine imaging is done on all patients, all the time. I don’t know if my colleagues have other practice.

Dr. Michael Levy:

Yeah, I would say the only time I ask my patients to get an MRI and not them telling me there’s something wrong, but me saying, “hey, let’s go get an MRI”, is if there’s something that I think is wrong, that’s out of the ordinary and a new symptom or a new… A change on the exam or something like that. But if it… If everything is stable and you’re using your Rituxan, or whatever you’re using, you’re coming in for follow-up and everything is the same old, same old, then there’s no reason to re scan.

Maureen Mealy, R.N.:

I’ll also mention that patients who are aquaporin-4 negative, who maybe don’t have a very classic presentation of NMO, and it could still be within the spectrum of them having MS or another type of autoimmune disease of the central nervous system, we might be more prone to MRI.

Audience:

Hi, my question relates to something that was mentioned in the morning and the Rituximab causing the hypogammaglobulinanemia. And I guess my question is one is it dose-related, is the length of treatment-related, is an allergic response? And do you have to monitor it on a regular basis?

Dr. Jeff Bennett:

So it’s a… It’s a treatment-related adverse event. So it’s not due to allergies, but it is a mechanism that happens in some individuals. Generally… Probably duration and independent of duration event. That is, some people as we may or may not understand it right now may be more susceptible to it. It may be dependent on where they start in terms of their levels of immunoglobulins or IgG to begin with. And so now I’ve started, beginning several years ago, to get a baseline on immunoglobulins before they start to know how soon I might want to look again. But it is a fraction of patients, not all patients. It’s less common than it is more common in those who are treated with it. And keeping an eye on it is important, but it’s not an allergy, but just a result of the mechanism of treatment and that individual’s make-up in terms of not only how they respond to Rituxan, but how their immune system works.

Audience:

Is there a percentage drop that you’re concerned about?

Dr. Jeff Bennett:

No, it’s an absolute level drop. And still, I have some patients who are hypogammaglob- that is, the lab will report back, “this is your IgG level, this is the normal range”, and, are you below the normal range? Are you within the normal range? That’s purely the cut-off. And if you’re below that normal range, then you are hypogammaglobulinemic. The next issue becomes, do you need to be treated? And if I have a Rituxan patient who’s marginally low on the IgG and not having any side effects, that is, recurrent infections, I don’t bother to treat it. I will watch it closely and make sure it’s not drifting lower and lower, but I’m not going to treat a number in terms of that issue. But if they have infections, yes, they get treated for it and we make changes in their dosing regimen or therapies. If we… If it’s not going to restore itself.

Audience:

What have you seen successful, in terms of, in your patients and managing pain, maybe outside of normal medications like Gabapentin? Have you seen patients use medical marijuana or other treatments to help manage pain?

Maureen Mealy, R.N.:

So, I know some people stayed around from the first session and some people are new and I think you might be one of the new ones. So we did have a little bit of discussion about this. I’m a big advocate of combining nonmedical and medical interventions, because I think both work, but neither of them work as completely as they might work together, which we don’t know that for a fact, but that’s why we do research, right? So in addition… So you asked about cannabis specifically. I have very little experience, but I’ve at least done the-

Dr. Michael Levy:

Personal experience? Professional experience.

Maureen Mealy, R.N.:

I have very little professional experience.

Dr. Michael Levy:

Yeah.

Maureen Mealy, R.N.:

But just because of how slow it’s been for the program to be implemented in Maryland, despite the fact that it’s approved. And so… But, I’ve done enough of these talks that I’ve gotten wonderful feedback from people that it’s very effective. In addition to that, a lot of patients temperature application helps. We talked about there’s a new interventional trial that we launched at Hopkins using a type of transcutaneous electrical nerve stimulation… Requires visits to Hopkins, but you don’t have to change whatever regimen you’re on now. And TENS is something, a technology that’s been around for dozens and decades of years. But this one in particular, is supposed to… The idea of it is that it targets chronic pain better than traditional TENS does.

Maureen Mealy, R.N.:

So, anyone who’s interested in that trial, we’re actively recruiting. Now, as far as I know, it’s the only interventional trial for pain and NMO in the United States. So you have to come to Baltimore. But, in addition, it’s so variable. And so I say that it’s a lot of trial and error. A lot of patients will say therapeutic massage, acupuncture, physical therapy and exercise. Some say, each of these things help tremendously. Others say that it was just a waste of all my money. And so it’s, it’s really got to be tailored to you. And there’s a lot of frustrating trial and error involved along that way.

Dr. Nancy Sicotte:

I could make a comment, living here in California where it’s a lot easier and we have a lot more experience. I’d probably, I’d say probably 50% of the patients I see with MS are using some sort of cannabinoid product. And some people find it very helpful, in particular, if you’re having pain, that’s keeping you awake at night. I think we were talking about how managing pain requires a lot of energy, and so if you can use something to help with sleep… So CBD oil is something that folks have been using that has less of the psychogenic effects, psychoactive effects. And some people find really beneficial. That said, there isn’t a lot of great data out there to guide our recommendations. So some of it is just very individual in terms of how responsive you are to it. So I don’t know if other-

Dr. May Han:

Patients come and teach us, like what they have tried and anecdotal experience at least, spasticity seems to work really well with the CBD oil, but then, the sources also… It’s not well-regulated. So we don’t really know how much of what edible cannabinoid product has the active component, so that you have to do your research on your own. We would love to know much about it because that way we can give you better advice, but then these research are not well done. So, we can share what we have from our experience that patients have shared with us, it works for some.

Audience:

Hi, first of all, thank you, all of you, for being so dedicated to this, my question is about pediatric onset. There’s a very small population of us here today that have children and what’s the… I don’t know how to say it. My daughter hasn’t experienced what all these adults have and she’s on the treatments, so she’s doing great. But what about the kids? What can we do to get them the best care? And there’s no research trials for them, I guess just what about the kids that have this? My daughter sees a pediatric neurologist, who’s phenomenal. So I trust him, but just in general for these little ones that are experiencing all these issues, what’s being done for them?

Dr. Nancy Sicotte:

So through the foundation, there’s another researcher. Who’s not with us today, but Tanuja Chitnis, thank you, your last name, who is a pediatric also does pediatric MS. So they have a center where they’re focused more on pediatrics. So we’re taking a very rare disorder and then a rarer manifestation of it, that, again, I’m speaking very generally ’cause it’s not my area of expertise, but there are some seem to be some differences in terms of the autoimmune process, the amount of MOG positivity and some other features that make it a little different. There’s a little twist on it. I think it’s really important, even if you have the ability to travel, to go to a center where they have more experience, because it is relatively unusual and then be able to take part in research or at least connect your practitioner with the expertise. And I think the foundation is really good about that, of getting people connected. So I don’t know if other folks have other ideas or input?

Dr. May Han:

UCSF has one. So Emmanuelle Waubant also has a cohort of NMO cases. And I think Penn also has a cohort. So these pediatric… pediatricians who specialize in NMO, they’re also connected to each other and they share information. So it would be a good way to connect with them-

Dr. Jeff Bennett:

In the middle of the country there actually are medical centers. One in Colorado, Terry Shiner has a pediatric cohort of NMO. But I think the most important part is if you’re solidly diagnosed, that is, we’ve talked about aquaporin-4, obviously for a number of years. And if you now are able to be clinically tested and know that you’re MOG IgG positive, obviously we have a little better feeling knowing perhaps what to expect, maybe a little less for MOG, but if you’re have meet the clinical criteria for Neuromyelitis Optica and are seronegative, that’s more of a puzzle in children and it’s more of a mixture of potential disorders. And that’s where I think it’s really important to see a pediatric specialist to get a good look at what’s going on in the case, because I’ve seen it go in many different directions, including many children who are seronegative and then finally present with an aquaporin-4 antibody, a little bit puzzling in terms of how the disease was being driven without it, I’ve seen it go to MOG and I’ve seen it never have seropositivity and the responses can be quite distinct.

Dr. Jeff Bennett:

And we… Hopefully will get more information in the future because, as is always mentioned, treating children as if they’re just small adults is not quite how it works. And their immune systems are less mature in many different ways. And treating with some of the medications we do such as even Rituximab in a young individual, the the B cells, if you look at the distribution, what types of B cells there at different age groups is quite different until it gets to the mature adult form. And so we don’t know what the consequences for longterm treatments are in these young populations. And until we get more information, it’s best to have a good idea of what you’re dealing with.

Audience:

So there are people that are studying the children?

Dr. Jeff Bennett:

Yep.

Dr. Michael Levy:

Of course all of the trials that are going on now with Chugai, there’s a kid’s group in that trial. And then if Alexion gets approval, they’ll have a post-marketing trial in children. And I think same with MedImmune depending on whether or not they get FDA approval, because if they do then they’ll have the next phase with kids involved as well.

Audience:

Okay, good. Thank you.

Audience:

Okay. Hi, I just wanted to ask, have you seen anyone with NMO with being treated with Rituximab, I’ve actually been treated with multiple of IVIG, Rituximab, develop a bleeding disorder or blood issues, platelet aggregation or anything like that. ‘Cause I’ve recently discovered that’s why I didn’t have my surgery that I spoke to you about a little earlier it’s because I’ve developed some kind of a bleeding disorder so they wouldn’t clear me for the surgery.

Dr. Jeff Bennett:

Not as a result of Rituximab, have I seen that as a significant side effect, but you also mentioned from the earlier things that you have other auto immunities, including Lupus, which has various clotting and blood disorders with it. So what I can say is that a fraction of NMO patients have other auto immunities. That’s one of the things we recognize. And sometimes it could be a clue in terms of diagnosis and given your history of multiple other auto immunities, there are many other mechanisms by which that could be affecting you without having any relationship to Rituximab itself.

Audience:

I just wanted to say I’ve been, I’ve been doing cryotherapy because I can’t take medications for the past two weeks for the pain that I had. And it’s pretty significant. The relief I’ve gotten is incredible. So… If that helps anybody that’s suffering with pain.

Audience:

So I have a question. My daughter here, Michelle, she’s 22 now. When she was 14 months old she was paralyzed from the waist down. All I got told was she had transverse myelitis, go home, she’ll walk eventually one day. Then when she was 13 years old, she’s running track at school, passes out, go to the hospital, told she had a brain tumor. Then they’ve retracted that and said, no, it’s not a brain tumor. She had optic neuritis, she’ll go blind one day, go home. Then last year, March 13, she goes to the hospital. We were told MS, NMO, two months later, they finally diagnosed her NMO. She had no medications from the time she was a baby all the way up until recently with getting Rituximab in June and then again in December. And then she has had the steroids, infusions and whatnot. Is there possibly a way that my kid possibly might not have to do medication because she went 20 years with no medication? Weird question, but just pitch it out there.

Dr. May Han:

Is she positive for aquaporin-4?

Audience:

She’s… for the AQ4, whatever it is, she keeps testing negative. But every time they try to test her for it, she’s been on steroids or she’s been on Rituximab. So they’re thinking that test keeps coming back negative because of the steroids and the Rituximab

Dr. Jeff Bennett:

Was she tested for MOG?

Audience:

I don’t know. I can’t answer that.

Dr. Jeff Bennett:

She’s likely… High possibility of being MOG, from what you’re stating… Terms of her recovery from these events, in terms of the fact that they mentioned quote, brain tumor and tumefactive lesions, demyelinate lesions that look like tumors are common in MOG.

Audience:

When they gave her MRI, she has no lesions on her brain at all. It’s just all in her spine, all the way down to the-

Dr. Jeff Bennett:

No, I’m just going from your statement of, I think she has a brain… But if it was just purely optic neuritis, I’d sort of make sure that that was it. She could still be seronegative and she’s had those subsequent… Sequential events. So she met, someone’s reading the criteria of neuromyelitis optica spectrum disease. And I think you bring up a point whether it is MOG or whether it’s NMO, does the time between attacks tell us that it’s best, just not to treat you with the idea that you’re doing pretty good compared to what we might give you without any side effects, if we were not to do anything.

Dr. Jeff Bennett:

And I think that the best way to sum it up as the jury’s still out, we don’t have enough information to know that the past frequency speaks to future frequency. And we wish we had a marker to say that it’s either going to be few and infrequent, and if we had had her on therapy for the past 20 years, we’d be patting ourselves on the back saying we did such a great job. And you had one breakthrough in the past 20 years and that’s where we don’t have it. If we knew that she had, let’s say an antibody targeting a certain process, or that gave us a diagnosis, aquaporin-4, MOG, the disappearance of that antibody might be helpful in terms of thinking about risks and deciding therapy or no therapy, but without any other markers, it’s hard for us to make a decision. And I think-

Dr. Jeff Bennett:

… For us to make a decision. I think if we knew what the disease was, we could give you an idea of percentages and try to help you make a decision with us about what might be the best thing in terms of risk benefit. That’s a hard call right now without any other information.

Audience:

Her Neurologist said that she’ll probably test positive after she hasn’t been on the Rituxumab for a while. She would have positive for the AQP4 genes, I don’t know-

Dr. Jeff Bennett:

No, like we talked about before, it’s very rare that you’ll lose a significant fraction of your antibody, nor that it would serorevert for anything on Rituximab. So if you’re negative, you’re negative.

Audience:

All right. So should I possibly talk to her neurologist about the MOG?

Dr. Jeff Bennett:

Yeah.

Audience:

Okay. Thank you.

Audience:

Hi. Less of a question and a comment… I was diagnosed seven years ago, so I’ve been dealing with a lot of pain issues and pretty much, I think, tried almost everything, but on the cannabis front, what I have found is that I don’t like to take anything with THC because I’m balanced impaired already. I don’t need the help falling down, but what I found is that the low doses of edibles actually helped me of all places with, bowel and bladder issues significantly. I went through every single thing, every drug, all these different tests, nothing helped at all, except this, has helped substantially. If you’re looking for something to try for, that would be one.

Audience:

The other thing is, I found that when I do take THC at night to help me sleep and I take a low dose, longer acting low dose. That definitely helps me with spasticity in the morning. So I tend to find that my spasticity is much worse at the end of the day, but I don’t really want to take any THC during the day. The other thing we were talking about massage and making it worse, I find that, that my areas that I have specificity are worsened substantially by traditional massage where it’s compression, but I have gotten relief from cupping, which is more of a pulling. There are now massage therapists that have these machines, rather than simply just putting a cup. They actually can work up and down on the… I find, sort of the negative traction on the muscles actually gives me substantial relief.

Dr. May Han:

Thanks for sharing.

Carolyn:

Hi, my name is Carolyn. I was only diagnosed in December of 17. Starting in 2012, I started having significant cognitive issues. The year leading up to the episode, and especially the month of two before, they became extreme. Now, I know it’s not attributed to this disease as of yet, but more and more patients, I speak to seem to suffer from the cognitive issues. So mine began long before the Gabapentin fog or any of those types of medication related issues. I wound up having neuropsychological testing done on my own because I wasn’t being taken seriously. So I have severe deficits in mathematics where, it’s kind of difficult trading commodities, if you can’t do basic math. There isn’t anybody talk about treating some of the symptoms? I know we’re all looking for a cure and talking about T cells and B cells, but is there any medication on the front to help people along until there is a cure that helps with issues like this?

Dr. Nancy Sicotte:

I’ll take a stab. It’s an interesting, and really important question and understudied. There is evidence that there can be cognitive involvement. There’s a type of attack that you can get an NMO. That’s this kind of cerebral dysfunction that has to do as sort of central parts of the brain. People can almost go into a coma. It does raise the question and the possibility that there could be low levels of that going on, that would disrupt your normal cognitive processing. We know from other autoimmune disorders in particular, MS. Cognitive changes are sort of part and parcel of it. It may be driven not only by the lesions themselves in MS, but by the immune activation and having the immune system activated within the central nervous system, there’s cytokines that are released, and this could potentially contribute to dysfunction.

Dr. Nancy Sicotte:

That said, there really is not a lot of great data on this. The good news is, for our part two of the circle study, we are going to be collecting some kinds of cognitive information. I know there’s other groups in particular in Europe that have been looking at this, looking at neuropsychiatric things, including depression and anxiety and so on. People are starting to look at it.

Dr. Nancy Sicotte:

Just, in general for cognitive function, there’s kind of the usual suspects. Make sure you’re getting enough sleep, looking at your other medications, aerobic exercise, eating a good diet. These kinds of things have been shown just in general, to improve your overall quality of health. Then it may be that suppressing inflammation, whether that’s through treating your underlying NMO with immune modulators, could help with some of that other kind of mental fog that people sometimes complain about, especially we see it with MS. I guess the bottom line, at least from my perspective is we don’t really have a magic bullet, but it’s a really interesting part of the NMO picture. I don’t know if other people ever-

Dr. Michael Levy:

Are you MOG positive, or AQP4?

Carolyn:

I have not been tested for it I only became aware of it, just at this conference, but I tested for the aquapor negative. Is that the IgG?

Dr. Michael Levy:

Yep.

Carolyn:

I tested negative to that. We believe I may have the first episode in 2001 when I lost feeling in my foot. They said, “You think you have MS, but until you’re present in another way…” I didn’t have a significant episode until December, I may have had episodes in between. I thought I was allergic to a drug, but we feel it may have been other episodes, but nothing significant enough for me to go. The cognitive issues are significant. They prevent me from working and doing a lot of mental focus. So I didn’t know if there was any medications that they use, like maybe even off label.

Dr. Michael Levy:

Well, I was just going to say that with what the AQP4 folks, we don’t see that much cognitive impairment because most of the diseases, not in the brain, but with MOD, we can. We’ve seen lots of different types of presentations, some that affect brain areas that can impact memory and function. I guess it just depends more specifically on where your MRI lesions are. If there are any in the brain that could be doing this, then we would focus in on those. If the brain is pretty clear, then maybe we would target… We’d look for things like depression and sleep and other things that may be indirectly impacting your cognition.

Dr. Nancy Sicotte:

The other point I would make though, is of course the key issue, if you’re aquaporin four positive or not, but there are other autoimmune diseases that can impact your memory and can impact other encephalitis, autoimmune encephalitis. I don’t know if you’ve had a good workup to make sure there isn’t something else going on.

Laura:

My name is Laura and I’m actually a caregiver to my mother. Being a caregiver, how can I be aware of her relapses? Sorry, how can I be aware of her relapses? So that way, if she doesn’t understand that she’s having one, I can point it out to her and I can help her along those lines. I was talking to her earlier today and she was unsure of how to answer her relapse on the survey, or when you guys were talking about relapses, how she can figure out and pinpoint what those are.

Dr. Jeff Bennett:

You gave the best answer.

Dr. Michael Levy:

You like my answer?

Dr. Jeff Bennett:

Yeah, I like it.

Dr. Michael Levy:

I think the clues that we use to decide whether or not to pursue like an MRI, or further investigation, I usually ask three questions, “Is it a new symptom that you’ve never had before? Is it in a new part of the body?” So if you’ve had this symptom before, but this time it’s in a new part of the body, or if the symptom is getting worse and worse and worse over the course of days. If any of those are true, then I usually suggest an MRI.

Dr. Michael Levy:

Sometimes it’s obvious, sometimes the patient will say, “I never had any trouble with vision in my right eye. I woke up this morning and I went blind in that eye.” That’s obvious, more of the questions you’re asking are the non obvious ones, more pain or spasticity or some new discomfort. That can be a little bit tougher, so then I ask those three questions and then I also ask a series of questions, “Well, what else is going on in your life? Do you have a fever, or anything else that could bring out your old symptoms?” Then, usually I put put all those clues together and decide whether or not it’s worth dragging that patient through an MRI machine, or maybe even just treating them if it’s obvious.

Audience:

Hi, in 2006, I lost vision in my right eye, then in 2015, I started losing vision in my left eye. That’s when about a year or two, we finally found out that I had NMO, February of 2016. I feel like I’ve been pretty good physically. I’ve just had eye issues. I’ve never had pain. I can physically walk and do things. I am on Rituxan, I’ve been on it. I feel like I’ve been stable and I’ve had some fluctuation in my eyes, but I’ve been pretty stable. My concern is my spinal. Every day, I wake up thinking, “When is it? When is this relapse going to come?” I’m very concerned. Is it possible that I could be one of those patients that just have the eye issues with NMO? Or is this spinal tag eventually going to come one day?

Dr. Michael Levy:

I think on Rituxan, the chances of not having a spinal cord issue are very good. So I’m hopeful that you might not. I think if you come off of the Rituxan, then the natural courses, yes, you will eventually have spinal cord involvement, but if you’re on Rituxan and it’s working and it keeps you in remission, then hopefully never.

Julie:

Hi, my name is Julie, and I have an eight year old that was just recently diagnosed with MOG positive, at Mayo. We’ve been doing the azathioprine, talked to Dr. Lavi and thinking about after all I’ve learned here, switching to IVIg, after talking to him. My questions are, if doing the IVIg even as much as every month as we discussed, and she seems to have an attack, she seems to lose vision or something. What then, you just go to IV steroids immediately? Do you think at that point, “okay, well, the IVG isn’t working.” Or you just still keep doing it? Like if she does have an attack during…

Dr. Michael Levy:

Yeah, I think it’s sometimes can depend on how severe the attack is or what the circumstances are. If the attack occurred right before her next dose, maybe the doses are too far apart, you need to move the IVIg closer, but it really just depends on the specific attack. If it’s a bad attack, then you may want to reevaluate the approach altogether, try something different or maybe even in combination.

Julie:

Okay, second part of my question was we saved both of our daughters cord blood. Ever since all of this has happened, even back when she was three and first diagnosed with ADM and all these things in my mind, that’s always been there, “Please let there be something to do with cord blood that can cure this.” At some point, I know STEM cells were mentioned earlier, but have you guys in the research part of this heard anything on the frontier of using cord blood to help in these auto-immune or NMO or MOG or…

Dr. May Han:

Not with cord blood, but bone marrow transplant has been done in severe cases of NMO in a few centers in the world. Those are four cases that are refractory to all the conventional therapies, but so far cord blood has not been used, or implanting STEM cells to replenish the brain or spinal cord.

Julie:

Okay.

Dr. Michael Levy:

But don’t thaw those out and throw them away.

Julie:

No, I’m not. I’m going to keep paying my rent.

Dr. Michael Levy:

That cord blood contains STEM cells from early in development. One of these days we’ll be able to harvest those STEM cells, turn them into the tissues that we want and then transplant it into the damaged area. Hold onto them.

Julie:

Yeah, I will.

Moderator:

So we actually have reached time. So as you cycle in and out, just please do it quietly. We’re going to go on to the next question actually.

Corey Wolf:

Hi, I’m Corey Wolf. My daughter, Megan, she’s aquaporin four positive. Recently she had a relapse and she had a couple of brain lesions months before we noticed cognitive issues and brought it to the attention of the neurologist. It’s hard to measure and she was passing the neuro exams just fine. So they sent us for cognitive tests. We sent her for cognitive testing, but they hadn’t done that before. So it was basically just a baseline, really couldn’t compare. But we know prior to this, she was a straight A student in honors classes, winning writing competitions and things. Then, now was having difficulty doing math, and writing, and pulling words, and executive function. Several issues that were noticeable to us as her family. When she came up time for her routine MRI, that’s when they found the lesions.

Corey Wolf:

It made sense. I wasn’t surprised, but there wasn’t a quick reaction, because her physical exam still was fine. They kept saying, “Well, she doesn’t have any clinical symptoms.” But, of course we disagreed with that. The compromise was to do three days of IV steroids, and the short taper, and then do a two month followup MRI, which showed that there’s still some enhancement. It didn’t really completely stop the relapse, but there’s no follow up from that right now. This has just happened in the last couple of weeks, this followup. So my question is, if it was your patient, would you look to doing Plex? Which is what we wanted them to do when we first saw the lesions.

Corey Wolf:

And Dr Levy, thank you for being available through the Facebook page. It means a lot that we can reach you. A whole lot. That’s my question. How would you treat if it was your patient? And, and I know following up with this other cognitive things that I will be asking for them to kind of reevaluate other autoimmune issues, she does also have Hashimoto’s. So, thank you.

Dr. Nancy Sicotte:

Well, if I saw contrast enhancement that was continuing and the symptoms hadn’t resolved, I would definitely consider Plex. I’m just wondering what therapy she’s on right now?

Corey Wolf:

So she does Rituxan every… Oh, sorry. She’s doing Rituxan, she was every six months. They moved it up to do it at five months, this time. She’s also on 150 milligrams of Imuran, daily and 10 milligrams of Prednisone and Dapsone.

Dr. Nancy Sicotte:

Wow. The B cells were depleted?

Corey Wolf:

They were at zero. They were at zero the whole time.

Dr. Nancy Sicotte:

Yeah. So, very challenging-

Dr. Michael Levy:

That’s why we’re not pediatric neurologists.

Dr. Nancy Sicotte:

Yeah.

Dr. Michael Levy:

This is a very unusual presentation. This doesn’t usually-

Corey Wolf:

I asked them if they would check her for MOG, but they said, “Because she was aquaporin four positive that didn’t make any sense to check her.”

Dr. Michael Levy:

Right.

Dr. Nancy Sicotte:

Well, it’s possible multiple autoimmune diseases…

Dr. Michael Levy:

How’s the thyroid antibodies, the same? Hashimoto’s can cause encephalopathy. So, it could be independent of her activity of her NMO.

Corey Wolf:

What blood tests would, or what tests-

Dr. Michael Levy:

Could take a look at her thyroid auto antibodies to know if they’re shifting. Thyroid, not thyroid function.

Corey Wolf:

So auto antibodies, not just the TSH? Okay. Thank you

Dr. Nancy Sicotte:

The enhancing lesions or in the white matter.

Corey Wolf:

In the pons and the paraventricular… That’s the only word I can come up with right now. Yeah. There’s two, one in the pons and one in like more of the frontal lobe.

Dr. Nancy Sicotte:

I guess I’ll echo Dr. Levy that pediatric presentations are challenging. I Mean-

Corey Wolf:

We feel like we should be having Plex.

Dr. Nancy Sicotte:

My feeling is you’ve got all these options and if you can add another one, you’ve tried everything else and Plex is a relatively benign process. Then, certainly to see if it changes the enhancement pattern.

Dr. Michael Levy:

Then you have another issue after you get plasma exchange, then you have to reevaluate why she failed the Rituxan [inaudible 00:37:55] in the first place.

Corey Wolf:

Right.

Dr. Michael Levy:

So it’ll take another whole line of thinking and testing and figuring out.

Corey Wolf:

Okay. Stop.

Dr. Michael Levy:

Yeah, for the first part of this, to just put out the fire, probably do plasma exchange, consider looking for other causes like thyroid problems.

Corey Wolf:

Okay. Thank you.

Dr. Michael Levy:

Yep.

Corey Wolf:

Thank you very much.

Audience:

First, I’m very grateful that your willing to answer questions, I just wanted to say, thank you for that. Second, I have a very good doctor, who’s excellent. NMO expert. One of the things I was curious about is I am MOG positive. I’ve had more than one attack. I have permanent disability from it, and I’m on Rituxan and have multiple autoimmune conditions. So I was curious from other experts as well, what their thought is, if you’re on Rituxan and just found out that you’re MOG positive, if you would switch, or if you would stay on the same line, if you haven’t had an attack?

Dr. May Han:

Are you relapse free on Rituxan, ma’am?

Audience:

What, what was that?

Dr. May Han:

Relapse free.

Audience:

I’m relapse free, though I was just diagnosed with NMOSD in April 2017, started on Rituxan and then I started in 2009 with symptoms and not diagnosed originally, MS. I had a second episode of optic neuritis recently where I was diagnosed.

Dr. Jeff Bennett:

So you had the optic neuritis episode on Rituxan?

Audience:

No, not on Rituxan. Though, I haven’t been on Rituxan for a year yet. I’ve had two sets of treatments, and I have other multiple autoimmune conditions that also this helps them in addition to that. So I have a collection. I don’t know what the opinion is. I know that from MOG that Rituxan people say that it doesn’t work as well for most of the patient population.

Dr. Jeff Bennett:

It may not. The question is where you fall in that spectrum. Obviously you have been on for a very short time period. Normally my gestalt is if it ain’t broke, don’t fix it.

Dr. Bennett:

Normally my gestalt is, if it ain’t broke, don’t fix it. And, if you had been on Rituximab and saying, oops, we just found out I’m MOG positive, but I’ve been doing well for a number of years. I certainly would say, don’t change. At this point, I would say our body of knowledge about what is the optimal therapy for MOG positive patients is still in its infancy. And you have the option right now either to continue as you’re doing and have a very low threshold to change, should you have some evidence of activity on it, or go, as we’ve talked about on a number of agents, we feel a little bit better about in terms of the unique nature of MOG and move forward with one of those.

Audience:

Anybody else. I’m just curious if anyone else has anything.

Dr. Levy:

I wouldn’t change. I think it’s worked for you. If it fails, then switch.

Audience:

Mm-hmm (affirmative).

Dr. Levy:

But perhaps the Rituximab is helping your other autoimmune conditions, which has been driving your MOG in the past. And now, maybe you’ve kept those from driving your MOG disease. So, maybe if not, the Rituxan is not helping the MOG directly, it may be helping indirectly, so.

Audience:

Hi. I’m the caregiver of my daughter who was diagnosed with NMO last year in January. And she has just turned 24. And, prior to that, she was incredibly healthy, and in sports, and everything, and it came on very unexpectedly. And one of the questions that she asked me to ask you is, is stress a trigger? Can it be a trigger for getting NMO? Because she was undergoing a huge amount of stress during graduating and then going to work. And her question is, should that be something that you need to manage to reduce the chances of relapse in the future? Any thoughts on that?

Dr. May Han:

I can probably touch on it in the general realm of immune activation. So, we know for sure that there are two kinds of stress, acute stress and chronic stress. Acute stress is fight or flight reaction. So, it goes up when you’re faced with an obstacle, but then it goes back down right away. So, that kind of stress in general is not too harmful. However, chronic, sustained stress we know for sure is bad for the immune cells because they turn the immune cells from good immune cells into bad immune cells. So, in general, stress is considered not good for auto immune diseases or immune activation. But we don’t know for sure the direct correlation. Is it an association or direct in the case of NMO? But, regardless, if you have the disease, managing stress would be a good alternative approach to manage the disease.

Dr. Levy:

It would also help with her symptoms. Because, when you’re stressed out, your body temperature goes up and that makes all your symptoms feel worse. So, if anything, it should still help with that.

Audience:

Hello. I am 44 and I’ve been diagnosed in 2017 on April. I lost my second eyes. But I think the symptoms start in 2013 when I’m vomiting for 15 days. And then, I lost my first eye on 2015 and the second eye in 2017. So, it seems like I’m having attacks every two years. I start the Retux on July, 2017. And my doctor gave me something called Fampyra. I don’t know if you knew it.

Dr. Nancy Sicotte:

4-aminopyridine?

Dr. Michael Levy:

Yeah. It’s Fampyra in Europe.

Audience:

Yeah.

Dr. Michael Levy:

4-aminopyridine here.

Audience:

Fampyra. They say it’s usually given for the MS. It may be help get back my sight. What do you think?

Dr. Jeff Bennett:

No, unfortunately. I don’t think 4-aminopyridine has a role in restoring vision after optic neuritis. And has never been studied in that format. However, for those people who do have heat related or other stress related vision loss in an optic neuritis eye, let’s say you’ve gotten some recovery back and you have some activity that you do, either exercise, or on a hot day, or in times of stress, notice some visual detriment, and then it comes back usually on the order of 15 minutes, 30 minutes, and those are happening frequently, 4-aminopyridine may have role in reducing the frequency of those events. Again, still not directly studied, but much more consistent with its action.

Dr. Jeff Bennett:

Right now, we have only a very modicum of small studies done in terms of agents that can impact the results of optic neuritis. And none of them proven, including sodium channel drugs like Dilantin, including hormones like erythropoietin, again not commercially or proven in any way, but in terms of optic nerves damaged and restored, no evidence for that. But there are many other good to be on 4-aminopyridine with regard to fatigue and areas of demyelination, spinal cord injury, things like.

Dr. Nancy Sicotte:

So, I think the point is that this is a symptomatic treatment. It is not a therapeutic. It’s not disease modifying or remyelinating. But symptomatically might have some benefit, in particular, as Dr. Bennett was saying, if you have fluctuating symptoms, if you are heat sensitive, in those situations, sometimes there’s a benefit. But it doesn’t change the underlying pathophysiology or the underlying structural changes that are there.

Dr. Michael Levy:

Did it help you?

Audience:

No.

Dr. Michael Levy:

Okay.

Audience:

No.

Dr. Nancy Sicotte:

And anecdotally I have some patients that feel a little more symptomatic, certain symptoms that are worse, like paresthesias and sometimes other vertigo and things like that can actually be a little bit exacerbated. This is in MS patients now. So, it’s definitely something to try, see if it works, and if it doesn’t then-

Audience:

I stop.

Dr. Nancy Sicotte:

Yeah.

Audience:

So, I believe you can breastfeed while on Rituxan now. So, my question is, can you start breastfeeding right after your treatments? Or do you need to wait a few months for some of it to get out of your system and then start breastfeeding?

Audience:

I couldn’t hear the question.

Dr. Nancy Sicotte:

Is it safe to nurse after Rituxan? Did something happen that I didn’t hear about that it’s now safe to nurse after Rituxan?

Dr. Michael Levy:

We’ve always gone ahead with it. Rituximab is secreted in the breast milk. The baby will ingest it. It usually breaks down in the stomach. But the baby has no capacity to absorb it. So, IgG in the baby’s stomach never gets absorbed. So, there is essentially no risk, but I guess there’s some ways that these antibodies could get into the baby. And so, the FDA has basically just said, we don’t know. And so, there are no studies to support it. And so, they are always erring on the side of caution. But we have lots of, not lots, a handful of cases where moms will breastfeed and the babies don’t deplete.

Audience:

Okay. So, if I did, should I wait for more of it is out of my system?

Dr. Jeff Bennett:

Have they been measured?

Dr. Michael Levy:

I’m interested to hear.

Dr. Jeff Bennett:

Are they monitoring them as babies?

Dr. Michael Levy:

Not monitoring them for B cells, but monitoring them for issues.

Dr. Jeff Bennett:

So, then the answer would be we don’t know.

Dr. Michael Levy:

Yeah. The answer is, we don’t know, but it’s better than the answer is, it’s harmful and we know that it’s harmful.

Dr. Jeff Bennett:

Yeah. No. Yeah.

Dr. Michael Levy:

The answer is, we’ve never seen it.

Dr. Jeff Bennett:

I mean, for the rare instances where I’ve had that, what I’ve encouraged is it’s usually in the plan stage that is coming off of treatment at the time during pregnancy, then re instituting therapy. I usually recommend that for three half lives, which would be about the first six weeks after infusion, that they formula feed. And then, it’s okay to go back. That would get rid of any significant… just continue pumping and-

Audience:

Mm-hmm (affirmative).

Dr. May Han:

We ask our patients to wait six to eight weeks just like you do. We also tell them that, just like you have mentioned, there’s no negative effects that we know, but it’s not well studied and documented. So, to be on the safe side, even if we have to redose them, if the disease is stable, we’ll redose them after a brief period of breastfeeding. Yeah.

Audience:

Thank you.

Audience:

Hi. My 22 year old daughter was diagnosed a year ago. And I’m hearing is she seronegative, positive, MOG. And I hate to sound naive, but what is all of that? Like none of her doctors have mentioned that she is one or the other. So, is that something that we should be proactive? And, I mean, maybe it is there. I’ve just not heard anyone say yet. So I don’t know. Do we go back to them and ask them?

Dr. Jeff Bennett:

I think, yeah. It would be important for you to know just for your clarification in the future, should she switch providers and certainly that information hasn’t been relayed to you. But, in terms of the diagnosis of neuromyelitis optica, always had a clinical criterion. If you had these sorts of events and these sorts of things that were found on your imaging studies, then you would meet criteria and be diagnosed with the disease. As we learn more about it and it was first reported on the aquaporin-4 antibody, we realized that about 75% of all patients who met the clinical criteria, and the criteria evolved as we then learned about how patients with the antibody, that is the aquaporin-4 antibody, would present and we broadened out the umbrella for who would meet the clinical criteria for disease. Still appreciating that about 25% of patients who would meet the clinical criteria for neuromyelitis optica would not have these aquaporin-4 antibodies.

Dr. Jeff Bennett:

So, then we had to sort of bins you can think about, seropositive aquaporin-4 neuromyelitis optica, and then what was called seronegative aquaporin-4 negative neuromyelitis optica. Now, within this category, the 25% of patients who were negative for the aquaporin-4 antibody, further studies then found that a fraction of those patients used to be talked about as 20% of that 25% of roughly 5% of all people who qualified for the disease would be MOG positive. We now realize that might be twice as big. It might be 40% of those patients or 10% of all people who qualify are MOG positive. And, realizing that those patients, all be it that they meet clinical criteria for the disease, likely have a separate disorder that has a different responsiveness to certain therapies, as we’re starting to understand it, different presentations. That is this group of MOG positive patient to meet NMO criteria also is a bigger umbrella of many patients who don’t meet it, but are yet MOG positive.

Dr. Jeff Bennett:

And so, at this point, it’s important to know what they mean. That is obviously her physician feels that she meets the diagnostic criteria for NMO. And then, whether she’s the antibody positive aquaporin-4, that is aquaporin-4 negative, but MOG positive versus another slice that’s dual antibody negative can mean a lot of differences to how you approach it in terms of what we understand may be the best choices of therapy.

Audience:

Okay. And one additional, do you find that the patients are more susceptible to other autoimmune disorders? Because I’m finding that maybe it’ll be a skin rash, or maybe they’ve said shoguns, or lupus.

Dr. Nancy Sicotte:

Mm-hmm (affirmative).

Dr. Jeff Bennett:

Mm-hmm (affirmative).

Audience:

Like there’s several other things that have even come out of this. But unfortunately, the rheumatologist was, when we walked in, he said, well, how did you get NMO? And I thought we were going to walk out of the room. How did she get it? I don’t know.

Dr. Jeff Bennett:

You didn’t meet anybody with NMO, did you?

Audience:

You tell me.

Joe:

Hi. I’m Joe. I’m from Riverside, California. It’s not too far from here. I was diagnosed with NMO last March, a year ago this upcoming Friday. I was initially put on plasmapheresis for the first two months. I was in the hospital. I was paralyzed from the waist down. And then, I was released. Almost a week, maybe two, after getting released from the hospital I relapsed. I was put right back in with the same exact paralysis from the waist down. I was then put on Rituximab and then told, come back in six months, just like the Rituximab treatments are.

Joe:

It’s been eight months now. And I’ve been very fearful, maybe just because of my time that I spent in the hospital, but it’s just been very hard to get back. And I know it’s probably just risky not to go back, but it’s just been very scary on the thought of going back, just because everything happened. So, with that, I just wanted to get other neurologist’s opinion, because I only have one out there where I’m at, on your opinions if I should go back as soon as possible to continue those treatments. Because honestly, I’ve felt better the longer it’s been since the Rituximab. My body feels a lot healthier. I just feel less stressed in my body. Just the initial reaction Rituximab is just my body just didn’t feel great. Like I felt like it was wearing down. And the longer it’s been, the better I’ve felt. But, even with that, I’d just like to hear your guys’ opinion on whether I should be going like as soon as possible to get the next treatments or whether I should just see how it keeps going without them.

Dr. Nancy Sicotte:

Well, I’ll start, but I think all of us would probably feel the same way, that you really should be under care and you should definitely go back and see a neurologist. You should get your blood checked, see what your B cell levels are, and just to check in.

Dr. Nancy Sicotte:

So, I would offer a couple things, part of why you might’ve been feeling so awful during that time was because you were sick, and because you were getting steroids, and you were freaked out about this really scary diagnosis. And, as you felt better, from the immunological standpoint and neurological standpoint, now you’re feeling emotionally stronger. And I think getting support from other people who are also living with NMO can be really helpful. One of the things you want to do is be proactive with this disease and it is scary. But you know what? You’re not alone. And there are lots of people that can help you, even if they’re not close by. Because I know Riverside, there’s probably not that many folks out there to be supportive. But it is really important that you take care of yourself and not stick your head in the sand. Because a relapse prevented is so much better than trying to catch up. And you don’t want to be back in the hospital again with another relapse. Right?

Dr. Nancy Sicotte:

And so, the treatments don’t have to be done in the hospital. You can do it in an infusion center that’s not in the hospital setting so that you’re not maybe triggered by being in that center. So-

Dr. Michael Levy:

Or even home infusions now.

Dr. Nancy Sicotte:

Mm-hmm (affirmative).

Dr. Michael Levy:

For Rituximab, yeah.

Dr. Nancy Sicotte:

Yeah. I’m happy to talk to you afterwards, because we’re not too far away at Cedars. I don’t know if other people had home infusions.

Dr. May Han:

Mm-hmm (affirmative). Especially if Rituximab is working.

Dr. Nancy Sicotte:

Yeah. Sounds like it.

Audience:

I apologize if this has been asked before, but Dr. Levy, during the stuff in the main auditorium, you had mentioned a wonderful thing about finding cures, two cures for mice. Do you mind elaborating on that a little bit?

Dr. Michael Levy:

I don’t mind at all. That’s my favorite topic.

Audience:

Thank you.

Dr. Michael Levy:

In mice, the way we created the model for NMO is we generate T-cells against aquaporin-4. And that’s all that they attack. And, when you put them into mice, they get optic neuritis and then transverse myelitis, very similar to the human. And so, what we’re trying to do is to reeducate those T cells. Before they attack, there’s two ways you could do it. You could either try to just kill off those T cells that are going to cause all the damage. And that works really well in mice. We’ve cured about a third of the mice that way. If we time it just right, we can do that. But it’s toxic because you need to use a lot of this medication, which like I said, kills about three out of 20 mice, which is not bad in mice at all. People would applaud me for that. But, in humans, that takes on a different… yeah, it’s different in human.

Dr. Michael Levy:

But another approach is to try to reeducate the immune system so that, when those T cells try to attack, the whole immune system can mobilize and try to keep that attack from occurring. And that’s a process that we’re using called desensitization. It’s very similar to allergy shots. When you’re really allergic to allergy shots or a bee sting, you get desensitized by starting with very low doses of the very thing that you just reacted to. But it’s in a very highly soluble form in very small doses. And then, it’s increased over time. And that basically teaches your immune system not to overreact to that next time it encounters it. And the idea there is you create a regulatory response that the next time the immune system decides it wants to attack aquaporin-4, it says to itself, no, no, no. I already know what aquaporin-4 is. I know it’s not harmful. I’ve been desensitized to it. I’m not going to attack. And so, that approach actually worked really well in mice too. And that’s what we’re hoping to translate to human study. Thank you for asking.

Audience:

So, the mom two rows in front of me said skin rash. And my son about five months ago started having a red and swollen nose. And he has seen ENTs and dermatologists who don’t think it’s rosacea. And he had-

Audience:

And dermatologists who don’t think it’s rosacea. And he has been tested for lupus and we’re waiting the results right now. It’s not a butterfly rash. It’s just his nose. It’s fairly symmetrical, not exactly, but fairly. And he has a couple bumps on under his skin on his face. He’s on CellCept and rituximab. Any thoughts?

Dr. May Han:

Could be a variety of reasons. NMO does co-exist with a lot of autoimmune conditions. So it may not be a lupus per se, but it could be immune mediated skin problem. He’s also on two immunosuppressive therapies. So common things being common; common skin dermatological problems and infection should be looked into it, as well. But I think sounds like you’re doing all the appropriate things by seeing a rheumatologist and a dermatologist.

Andrea:

Yes. Hi, my last two relapses have been hearing loss. And I’m just wondering if you guys have heard more about other cases of people having episodes of hearing loss? My vision’s gone. So now I’m worried that it’s attacking my hearing, which of course, wouldn’t want to lose that. But I’m just wondering if you’ve had any other cases in relation to MOG, that you’ve heard of, with hearing loss?

Dr. Bennett:

Yes. And our first question, I would ask you is are you aquaporin-4 and MOG positive? Because in about 10% of MOG patients can have acute episodes of hearing loss. And it’s one of the reasons that led me to diagnose a patient two weeks ago, who was coming in for multiple sclerosis therapy. And by all means, had everything that looked like MS, in terms of the lesions in his brain. But he told me about an episode of acute hearing loss several months ago that got better with steroids. And I said, “Hold on for a second. Let’s check one thing.” So it is not so… still not obviously a common area, because it takes a very discrete lesion to cause such a thing, because hearing, once it gets to the brain, is distributed very broadly, so. But for some reason, it is something that’s much more common in MOG than it is in MS or neuromyelitis optica aquaporin-4 positive.

Dr. May Han:

Yeah. So I can probably add into it a little bit. So, I know Andrea really well. So, after she has presented to me with two episodes of very severe hearing loss that responded really well to steroids therapy, and also that was documented by audiometry. So I went and talked to some of my colleagues in ENT and some of them who also look into auto immune issues. So aquaporin-4 is highly expressed in the inner ear canals. So that’s why it’s very commonly associated with NMO if you’re aquaporin-4 positive. But just like Dr. Bennett mentioned, a small sub-population of MOG patients can also present with the acute immune mediated hearing loss, because MOG also seems to be involved. We don’t know… we know less about anti-MOG disease in hearing loss, as opposed to aquaporin-4 positivity, but it’s also been documented.

Dr. Nancy Sicotte:

So I’ll just add that I had a case of a gentleman who had a multifocal relapse, but that included hearing loss, that recovered with steroids and plasma exchange. And I bet Dr. Levy’s had a few.

Dr. Michael Levy:

And actually your case came to my attention, because I’m not sure if it’s someone at UCF or Stanford, looked for new autoantibodies and found something in your serum. Do you recall what that?

Audience:

Ari Green?

Dr. Michael Levy:

I can’t-

Maureen Mealy, R.N.:

Ari Green.

Dr. Michael Levy:

Ari Green.

Audience:

Yeah.

Dr. Michael Levy:

Maybe.

Dr. Michael Levy:

Maybe it was him, asked if we’d ever seen that antibody, which is present in a lot of healthy people, as well… asked if we’d seen it in other MOG and aquaporin-4 cases and we haven’t. So I don’t know if it’s a separate condition, or if it’s an overlap, or if it’s actually MOG or aquaporin-4.

Audience:

Mediated, yeah.

Dr. Michael Levy:

It’s pretty sporadic. The other cases I’ve seen were involved with lupus, for example. But again, I don’t know if it’s the lupus or the aquaporin-4.

Dr. Jeff Bennett:

[inaudible 01:04:49] 70.

Dr. Michael Levy:

Just don’t know.

Dr. Nancy Sicotte:

We should put our cases together.

Dr. Michael Levy:

Yeah, we should.

Dr. May Han:

Absolutely.

Audience:

Hi. I’ve heard a lot about stem-cell therapy. And I just want to know what are your guys’ thoughts on that?

Dr. Michael Levy:

With stem-cell therapy there’s several different kinds, but I think the kind that you’re asking about is the restorative kind. So you take stem-cells, transplant it into damaged tissue and you hope to restore some sort of function. And we don’t have any trials going on in the US for stem-cell trials like that at the moment. Except for one private clinic in New York, most of those trials are going on in other parts of the world. There’s like 10 in China, for example. And one specifically in NMO, where they take stem-cells from your hip, process them in the laboratory, and then inject them back into your bloodstream. And they’ve published their interim numbers so far and they look pretty promising.

Dr. Michael Levy:

And this is something that other countries have a head start on compared to the US. But we’re going to learn from them. And as these trials and MS, and NMO, and other, traumatic spinal cord injury, for example, as they get published, we’ll see if there’s anything to it and how we can tweak it and improve upon it. Because that is… a lot of cases, we’re pretty good now at preventing relapses, where with rituximab and all these trials that have launched. But when you’re still stuck in a wheelchair, or you’re blind, or blind in one eye, you still kind of have the remanence of the disease. We need some treatments to improve those functions. So that’s something that’s kind of been ignored up to now. But stem-cells have that promise.

Audience:

There was a research talking about Zyrtec and NMO. Have you read, have you saw, or no?

Dr. Michael Levy:

Yeah. Do you guys know about [inaudible 01:06:59] study?

Dr. Jeff Bennett:

The results of the New York study?

Dr. Michael Levy:

Of the Zyrtec study for the… A group in California, they were screening different drugs to see which ones may have some benefit. This was in a tissue culture system. And they screened like 30,000 drugs. And the one they hit on was Zyrtec, that Zyrtec appear to be helpful. And we already had it on the market. So a group in New York said, “Okay, let’s just add Zyrtec to 20 patients who are already on whatever they’re taking, just add Zyrtec every day.” And they thought, “Let’s see if it improves the outcome.” And there was a small but modest, but real benefit that these patients experienced fewer attacks. So it was a two-year study, observational only, but the people who were taking Zyrtec seem to have fewer relapses than the natural history of the disease. So maybe there’s something there. Plus, they had fewer allergies. And then, three weeks in the sedation wears off. So it was almost like a harmless, no-risk, with potentially some benefit. Now, I wouldn’t say most patients are on it though, because it wasn’t like spectacular. It was just kind of modest.

Audience:

It was [inaudible 01:08:16]. There was a lot [inaudible 01:08:18], specifically when they checked the improvement in the patient.

Dr. Michael Levy:

Oh, oh, oh. You’re talking about-

Dr. Michael Levy:

Okay, that’s a different study.

Dr. Nancy Sicotte:

Yeah. Yeah.

Dr. May Han:

Yes, yes, yes.

Dr. Jeff Bennett:

No, that’s-

Dr. Jeff Bennett:

That’s Zyrtec.

Dr. Nancy Sicotte:

Yeah, the allergy medication for MS-related optic neuritis. There’s some evidence that, I don’t know if I’m saying it right, clemastine?

Dr. May Han:

Clemastine, yeah.

Dr. Nancy Sicotte:

Clemastine, which is already on the market for… it’s a-

Dr. Jeff Bennett:

It’s a-

Dr. Nancy Sicotte:

Yeah. An anti-histamine.

Audience:

It’s very similar.

Dr. Jeff Bennett:

It’s antimuscarinic.

Dr. Michael Levy:

No, it’s different. Different mechanism. Yeah.

Dr. Jeff Bennett:

Yeah.

Dr. Nancy Sicotte:

So there’s some promise for, potentially, remylination. That’s what they’re looking at. And there was a little bit of data and human trial that I think needs to be replicated in the larger numbers, but it’s promising. And it was found by this method, as you described, or as Dr. Levy described, where they’re just screening compounds to see if something looks promising. So that’s actually a nice way to do things, because you’ve got a model, presumably, that works well. And then you can do this rapid screen of all sorts of compounds. And the best is when you have something that’s already on the market, that’s been tested as safe, it’s FDA approved. So that will really quickly bring things to be tested. So a lot of times the phase two studies are really exciting and promising, but then when it gets out into the bigger studies, maybe doesn’t hold water. But I think there’s some promising results from that. We’ll have to wait and see.

Dr. Jeff Bennett:

So they took patients who had had optic neuritis-

Dr. Nancy Sicotte:

Oh yeah, this is your…

Dr. Jeff Bennett:

… who then had a normal OCT. So they didn’t appear to have lost much fibers from their eye, but still had a visual dysfunction. And so there’s an electrical test, called a visual evoked potential, that can show a delay after optic neuritis, that never really comes back to normal. So the thought was the cables are still there, but the myelin had not regrown from the injury. So this would be an opportune subgroup to give this drug to, which in all of this laboratory testing, had shown the ability to stimulate myelin producing cells called oligodendrocytes, to remake myelin. And when they gave it to patients for a little while and they had those on a placebo, and then they crossed the groups, they found that there was a improvement that was statistically significant in that visual evoked response tests, not their vision.

Audience:

Oh, okay.

Dr. Jeff Bennett:

Okay? That would be interpreted as suggesting that there was repair to the myelin. Now, of the significant delay, there was… the number of improvement was very, very small, but it was statistically significant. So now it’s tantalizing evidence to bring it forward into different formats, to look at whether it might have a more beneficial effect if it’s given at a different time in the injury or a different situation or a different subgroup of patients.

Dr. Nancy Sicotte:

But Zyrtec is also good.

Dr. Jeff Bennett:

For allergies. Yeah, sure.

Audience:

What are your thoughts on a patient whose recurrences are controlled on rituximab, but are still having a lot of symptoms, a lot of pain, discomfort, and it seems to respond well to low dose steroids, but nobody wants to be on chronic steroids. What are the pluses, minuses? Again, the recurrences are okay. It’s just the symptoms. And that’s what seems to be working for those symptoms?

Maureen Mealy, R.N.:

Well, I would say it depends on what the symptoms are. I think that it gets… the symptoms, the damage that’s already been done gets ignored often, because if a patient isn’t relapsing, then oftentimes you go to see the doctor and they say, “Great, I’ve done my job. Everything’s great.” But you’re not feeling great. And so that’s the problem. Again, it depends on the symptoms, but also, symptoms are very intertwined. So we know that sleep affects pain and pain affects sleep, and both of those affect cognition and mood and everything else. And so, it’s tough to answer, because it’s symptom dependent and there are so many symptoms you might have as a result of NMO. But I would say really, if you’re doing well from a neurologic standpoint, in terms of you’re not having any new relapses, then you should ask your neurologist at your next visit, to concentrate on something specific. And if it’s fatigue that’s bothering you, or pain that’s bothering you, you should lead the visit so that the neurologist knows what you want to focus on and knows better what’s affecting your quality of life. If you go in there with a list of 20 things, then it gives the neurologist the opportunity to cherry-pick what’s what he or she wants to address. But if you have very specific two or three, tops, agenda items, then they’ll be better focused on whatever it is that you want to address.

Audience:

And your thoughts on if 10, 20 milligrams of Prednisone takes care of those symptoms and every time you go out and they come back and it’s mostly pain, banding, sensory discomfort, I guess the question is how bad you think it is to be on low dose steroids as someone who’s relapsed controlled?

Maureen Mealy, R.N.:

We’re not fans of it, but I guess you’ve heard that before. My question to you would be, have you tried some of the more traditional things for those symptoms?

Audience:

And you’re talking medication, or techniques, or both?

Maureen Mealy, R.N.:

Both.

Audience:

Well, it’s not me, it’s my daughter. So I’d have to ask her.

Maureen Mealy, R.N.:

Oh, all right.

Audience:

But she doesn’t want to be on… hasn’t done well, I guess, on Lyrica, and Gabapentin, and some of the things like that. And she’s got herself off the steroids, because she doesn’t want to be on them, but is complaining of the symptoms constantly.

Maureen Mealy, R.N.:

Right.

Audience:

And when she’s back on the steroids, the symptoms go away and she’s doing so much better. So again, just trying to get a sense of what everybody thinks the negatives of low dose steroids in that situation.

Maureen Mealy, R.N.:

I would say that the negatives outweigh the positives, particularly in somebody… So managing pain is its own art, separate from everything else that neurologists and other healthcare providers do. And it can be very tedious, because it’s very individualized. So one patient who responds so well to amitriptyline might not respond to it at all, and another patient is on carbamazepine and it’s a home run for him or her. And so, there’s a lot of trial and error. And so, it takes a lot of patience. And I’ve said in every session so far, I’m an advocate of combining medical and nonmedical approaches to try and better attack pain. And so, I would say, I would not particularly be fond of the idea of being on steroids as a pain treatment. I don’t think… I think that there are so many side effects that come with that; diabetes, hypertension, bone loss, bone density loss, that it’s not worth taking for the subacute period, because, chronically, it’s going to be more detrimental to her.

Dr. Michael Levy:

You can also try to use other effects of the drug as a sort of incentive. So for example, topirimate, which we use for pain, is also good for weight loss. Or amytriptolene, which we use for pain, is also good for bladder dysfunction. So if she has some incontinence every once in a while, and that’s embarrassing to her, you could say, “Well, this drug does both and it’s sort of like a two for one.” And that may address some of the pain issues, as well.

Moderator:

Time for one last question.

Audience:

Pain management issue. So I’ve tried acupuncture, I’ve tried basically everything. My physiatrist is now recommending that I try prolotherapy.

Dr. Michael Levy:

Can you tell us what that is?

Audience:

Water injection?

Audience:

Yeah, it’s a… I don’t even know what… it’s a cocktail of a variety of different things that are in… So I have the severe banding stuff. And so her plan, as far as I understand it, because she just like, “I’m just going to inject you in all these spots and see if we can get the…” I don’t know if it’s trigger points. I mean, I don’t know. She went to medical school at Northwestern. So I figured she knows something, but.

Dr. Michael Levy:

I’ve never heard of it.

Dr. Nancy Sicotte:

Is it prolo, P-R-O-L-O?

Audience:

Yeah.

Dr. Nancy Sicotte:

Prolo?

Audience:

I kind of talked about it with my wife [inaudible 01:17:49]. Prolotherapy was, at one point, [inaudible 01:17:51], was one of the earlier stages of the [inaudible 01:17:53] pain management. All was just a dextrose injection into the site of the pain to stimulate sort of a, I guess, regenerative response, previous to trying PRP. Again, more of that [inaudible 01:18:07] sort of pain management procedure to kind of instigate the healing process.

Dr. Nancy Sicotte:

Okay.

Audience:

But if I’m not mistaken, and John, maybe I misconsidered, but was just a benign solution to kind of promote a response and

Dr. Jeff Bennett:

Of dextrose?

Dr. May Han:

Dextrose solution.

Dr. Jeff Bennett:

To feed the cells?

Dr. May Han:

Yeah.

Dr. Nancy Sicotte:

Dr. Google has something. And it starts with, “Los Angeles Prolotherapy.” So maybe it’s a West coast phenomenon.

Dr. Jeff Bennett:

Yeah, I’m surprised you don’t know about it.

Dr. Nancy Sicotte:

I don’t. It’s proliferative therapy.

Dr. Jeff Bennett:

Oh, there you get the “pro” part.

Dr. Nancy Sicotte:

It’s nonsurgical ligament and tendon reconstruction and regenerative joint injection. Okay. Well so, I’ve heard of that for people who have joint issues. It’s to regenerate the synovial lining.

Audience:

But it’s not plasma rich… it’s not PRP.

Dr. Nancy Sicotte:

Okay.

Audience:

It’s something different than that.

Audience:

It’s dextrose water.

Audience:

It’s dextrose, yeah.

Dr. Jeff Bennett:

Okay.

Audience:

I don’t know. Yeah.

Dr. Jeff Bennett:

Too bad you can’t drink it.

Dr. May Han:

Did it work?

Audience:

I haven’t tried it yet.

Dr. Nancy Sicotte:

So, as always, we learned . I’ll have to read up about it. I don’t know.

Audience:

Ever since I saw my first MRI I’ve stopped looking stuff up, because that grossed me out, so.

Dr. Nancy Sicotte:

This sounds like a slightly different… this prolotherapy that’s online at least, is more for joint disorders it looks like, rather than neuropathic pain, what you’re describing. So maybe it’s a… somebody who’s decided to try it in that setting, as well. I don’t know. Obviously, we’re clueless.

Dr. Jeff Bennett:

Yeah.

Dr. Michael Levy:

Yeah.

Moderator:

So your next step is the International Ballroom, back downstairs where you were. Thanks.

Audience:

Thanks.

Moderator:

Thank you.

Dr. Jeff Bennett:

Thank you.

Dr. Michael Levy:

Thank you.

 

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Welcome & NMO State of the Union – 2018 NMO Patient Day

2018 NMO Patient DayThe Guthy-Jackson Charitable Foundation Hilton LAX Los Angeles

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Next Steps to Cures – 2018 NMO Patient Day

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Ask the Experts – 2018 NMO Patient Day

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Update: NMO Clinical Trials – 2018 NMO Patient Day

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