Neuromyelitis Optica Spectrum Disorder

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: February 1, 2024

Expiration Date: February 1, 2025

Estimated Time of Completion: 28 minutes

Neuromyelitis Optica Spectrum Disorder

Justin Abbatemarco, MD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

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• American Medical Association (AMA)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• Certificate of Participation

A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

• American Board of Surgery (ABS)

Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

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Podcast Series Director

Imad Najm, MD

Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Justin Abbatemarco, MD

Mellen Center

Host 

Glen Stevens, DO, PhD

Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Neuromyelitis Optica Spectrum Disorder

Justin Abbatemarco, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Justin R Abbatemarco, MD	Genentech Advisor or review panel participant EMD Serono, Inc. Advisor or review panel participant Alexion Consulting Horizon Therapeutics Advisor or review panel participant  Research: Research Grant; Co- Principal Investigator TG Therapeutics, Inc Advisor or review panel participant
Imad Najm, MD	Eisai Advisor or review panel participant NIH Other activities from which remuneration is received or expected: Research Funding LivaNova, PLC  Advisor or review panel participant SK Life Science Inc Advisor or review panel participant  Teaching and Speaking
Glen Stevens, DO, PhD	DynaMed  Consulting

 The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

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Go to: Neuro Pathways Podcast Feb 1 2024 to log into myCME and begin the activity evaluation and print your certificate. If you need assistance, contact the CME office at myCME@ccf.org

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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: Neuromyelitis Optica spectrum disorder is a rare demyelinating autoimmune disease that affects the spinal cord and optic nerves. Several treatments are available, but recognizing the disorder can be challenging for clinicians due to its overlapping clinical presentation with multiple sclerosis. In this episode of Neuro Pathways, we're discussing the diagnosis and management of neuromyelitis Optica spectrum disorder.

I'm your host, Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. And joining me for today's conversation is Dr. Justin Abbatemarco. Dr. Abbatemarco is a neurologist in the Mellen Center for Multiple Sclerosis within Cleveland Clinic's Neurological Institute. Justin, welcome to Neuro Pathways.

Justin Abbatemarco, MD: Glen, thanks for having me.

Glen Stevens, DO, PhD: So, Justin, I know you, but our audience doesn't know you so well. So, tell us a little bit about yourself, where you came from, how you made your way to Cleveland and what you do in your daily practice.

Justin Abbatemarco, MD: Yeah, kind of meandered my way here, moved around a little bit when I was younger, lived in the West Coast, East Coast, Midwest, did training in Penn State and the University of South Florida and truly fell in love with the program when I was interviewing here, and met my wife. And so now Cleveland, Ohio is home. But in all honesty, the program here is tremendous. Our neuro immunology program, our colleagues to be able to collaborate, it's a place I call home now.

Glen Stevens, DO, PhD: Well, we're glad to have you and we're glad that you're interested in looking after this disorder. So, we're going to discuss specifically neuromyelitis Optica spectrum disorder. When I trained, this thing did not exist. We called it Devic's disease as it went through, but as I mentioned in the introduction, shares a lot of features with multiple sclerosis and in fact was really when I trained it was thought to be a variant of multiple sclerosis. Can you briefly give us some background on neuromyelitis optica spectrum disorder and maybe why they call them a spectrum disorder and how our understanding has evolved over time?

Justin Abbatemarco, MD: Yeah, no, it's incredible. It's one of my favorite things to talk about because I really think it gives us this past, present, future of neurology. It kind of encompasses it all in one disease. So yeah, the disease was previously known as Devic's disease. So, it was a French scientist who kind of described this association of optic nerve involvement and spinal cord involvement and was putting together the pathophysiology may be the same. It was in the 1800s, kind of incredible because those were kind of disparate systems and for him to link those two together is pretty incredible. But for many years this was thought to be maybe a variant of MS. It was also called lupus myelitis because many of these patients would have concomitant antibodies, Sjogren's myelitis. So it's gone by many, many names. It wasn't until 2004 when we discovered the aquaporin-4 antibody or AQP4 antibody just revolutionized the field. So now we have a biomarker for the disease that explains the pathogenesis. And since that discovery in 2004, we now have three, possibly four FDA approved treatment options coming for this available to patients to personalize our approach. Just like an incredible kind of bench to bedside and has a really interesting and rich history to kind of go through.

Glen Stevens, DO, PhD: So, is there a prototypical phenotype?

Justin Abbatemarco, MD: Definitely.

Glen Stevens, DO, PhD: With this patient population and what is it?

Justin Abbatemarco, MD: Yeah, so I think we think of three main kind of clinical syndromes. So, one optic neuritis and how do we differentiate that from the typical optic neuritis we see from MS patients? So usually seeing severe vision loss in one or both eyes, so 20/200 to even no light perception, so very severe. When we're looking at MRI sometimes, we can see optic chiasm involvement, which is very, very unusual in MS. So bilateral optic nerve involvement, chiasm involvement, severe kind of vision loss that doesn't respond well to steroids and leaves people with permanent vision loss, all kind of characteristics that are unusual in MS. So severe optic neuritis in one or both eyes. The next is transverse myelitis is what we commonly think of, and we usually characterize that as a longitudinally extensive transverse myelitis. So greater than three vertebral lengths usually involving the center of the cord causing severe disability. I think it's important to note though that 15, maybe even 20 percent of the spinal cord lesions in AQP4 positive NMOSD can be short segments. So, I don't think it has to always be longitudinally extensive, but something that definitely is characteristic and unusual again in MS or other demyelinating diseases. And in the third syndrome, which is very unique to AQP4 disease would be area postrema syndrome. So that's going to cause this intractable nausea, vomiting or hiccups. And I think when you're trying to tease that out in clinic, that's a hard thing to ask because experienced that. But when I talk to residents and fellows, we're talking about symptoms that are lasting hours to days, usually requiring some acute care kind of management, going to an urgent care center, hospital, things like that to require hydration or IV medication treatment. So those are the three main clinical syndromes that we see and it kind of helps to think about them when we contrast them in terms of MS attacks. There are other attacks that we can see, but they're much less common.

Glen Stevens, DO, PhD: And if we look at males versus females, just like MS, what do we see in this disorder? Who's affected more?

Justin Abbatemarco, MD: In MS, we typically see a three to one ratio, two and a half to three female to male predominance. Here, that relationship is exaggerated. It's almost a 10 to one. So, this disease is going to be seen in the vast majority of female patients. Another maybe characteristic it'll be non-white individuals, another kind of distinct feature from MS. So, we know that this disease is going to be much more common in patients who are non-white in areas of the world where MS is less common, Asia, Africa, the Caribbean areas.

Glen Stevens, DO, PhD: Warm places.

Justin Abbatemarco, MD: Towards the equator.

Glen Stevens, DO, PhD: Right towards the equator.

Justin Abbatemarco, MD: And we don't see that kind of same relationship where MS usually gets more common away from the equator.

Glen Stevens, DO, PhD: Right.

Justin Abbatemarco, MD: That same kind of relationship does not exist here.

Glen Stevens, DO, PhD: And what about age? Who's affected?

Justin Abbatemarco, MD: Anyone. We think of reproductive age females for autoimmune diseases. I think average age is around 39 to 40 years old, but truly can span the age spectrum. So, it can involve pediatrics less common, but it can also involve the elderly. So, we've had patients diagnosed in their 60s, 70s, so something we really have to keep on the differential at all age groups, which could be challenging.

Glen Stevens, DO, PhD: Yeah, I saw a patient when I was on the consult service several years ago that got referred into the neurosurgery service, and we were asked to see the patient. They were, I believe, in their 60s and they had long segment problem in the neck and there was just something that was very atypical about it. And we sent off the antibodies and they had the positive antibodies. The neurosurgery was going to do a surgical biopsy on this patient and fortunately we were able to abort that as it went forward. As you mentioned some of the features, it just seemed a bit atypical. The radar has to be up on these things, right? And especially when you get out of the typical age ranges, it's easy just to go, oh, it's not that.

Justin Abbatemarco, MD: 100 percent.

Glen Stevens, DO, PhD: But we always have to think about it. So, it's always good to review these things. When did they change? We called it NMO for a period of time and then they added the spectrum disorder. How long ago was that? I can't even tell you. But do you know?

Justin Abbatemarco, MD: It's come through a couple iterations and the field is evolving so fast now we have MOG.

Glen Stevens, DO, PhD: Yeah, I was going to ask you about MOG. So where does MOG fit into this? It's bewildering to me.

Justin Abbatemarco, MD: It feels like that, just throwing antibodies and we just love our acronyms, right? Patients are just like, what's going on? I tell them, we just have these MS cousin diseases. We're going to figure it out though. Now the field has gone through many iterations, and I think we'll be going through more. I think MOGAD, when the 2015 diagnostic criteria came out, and that's the one we're kind of quoting here. MOGAD was not as prominent. We didn't have commercial lab testing then. And so, I think we knew that AQP4 NMOSD, we had a good understanding of that, but we knew there were patients who were not positive that had similar symptoms. And so, we had diagnostic criteria available to help diagnose those patients. So, we can talk about that because a challenging group of patients, these antibody or seronegative patients, and I think we'll have further clarifications of how this diagnostic criteria look like in the future. We just had MOGAD diagnostic criteria. So, I think we're going to start being a little bit more biomarker specific when making these diagnoses because we now know the pathophysiology, the treatment's totally different, but that spectrum disorder just kind of encompasses that. They don't always have to have the antibody, especially when this criteria was being developed. And this can span multiple kind of parts of the nervous system.

Glen Stevens, DO, PhD: So, from a diagnostic criteria, obviously how the patient presents those types of things, you get your MRI, you looked at the features you suggest, you see stuff coming to the chiasm, is it bilateral, which is very atypical in multiple sclerosis. You look at the spine. Are there at least three segments? Do you need to look at the thoracic and lumbar spine or we don't see problems there or it should be done, you should do the whole axis?

Justin Abbatemarco, MD: Yeah, I think it depends on the clinical presentation, but we commonly get thoracic imaging. Those lesions can definitely span. These patients are usually symptomatic because the longitudinal extensive lesion is going to produce some type of symptoms. Lumbar imaging is really interesting. So, we don't see conus or nerve root involvement as often, but in MOGAD, we're starting to see that a little bit more often. Sarcoidosis, which those things are sometimes on a differential.

Glen Stevens, DO, PhD: So maybe we should be getting it.

Justin Abbatemarco, MD: And if that clinical suspicion, especially if you see this patient de novo, it's not easy to tell. And so those are times when we'll get whole neuro access, right? Brain to lumbar, trying to allow the clinical exam to help us. But there are times, and again, if you're seeing conus nerve root, we need to think of other diseases like MOGAD, neurosarcoid or other kind of neuroinflammatory diseases.

Glen Stevens, DO, PhD: So, waiting for an antibody to come back I understand is slightly longer than waiting for your coffee at Starbucks.

Justin Abbatemarco, MD: Just a tad.

Glen Stevens, DO, PhD: Just a tad. How long does it take? I mean, do you have time to wait, or do you have to have high clinical suspicion you should initiate treatment? I've always preached the same thing when we look at our encephalitis patients and we're worried if they had an autoimmune encephalitis. By the time antibodies come back, time is brain and antibodies are injuring brain. So, if your clinical suspicion is high, me, I'm a big fan of, if the risk is low of hurting them, let's initiate the treatment. It sounds like you're in the same camp.

Justin Abbatemarco, MD: 100 percent. And this is so much different than MS, that time is brain here. The MS patients are going to recover really even if you're delayed treatment. But we know that delay in treatment will absolutely cause worse outcomes for these patients. And we're talking about vision, right? Permanent blindness, inability to ambulate, significant disability, that makes a huge impact in people's lives. So, I think absolutely looking and making a clinical diagnosis based on your clinical history exam, MRI and CSF, usually that gives you enough of a gestalt to kind of start.

Glen Stevens, DO, PhD: You get CSF on most patients?

Justin Abbatemarco, MD: I think almost all patients because the differentials broaden that can look a little different than MS. So, MS, we almost never see patients with more than 50 cells. Usually it could be normal 10, 20 cells. In AQP4 NMOSD, it's not uncommon to see a highly inflammatory tap. I will say one caveat if you have optic neuritis is an isolated feature, sometimes it's less inflammatory. And then less than 20 percent of these patients will have oligoclonal bands or unique oligoclonal bands. So, some helpful kind of features before we even send that antibody off.

Glen Stevens, DO, PhD: And I guess as you've mentioned, if they have an underlying antibody disorder, they have lupus, they have myasthenia, they have one of these types of things and they develop one of these cardinal features, pretty cut and dry, right?

Justin Abbatemarco, MD: AQP4 disease should be at the top of our list and maybe we could talk about antibody testing. I think that's a challenge unlike how we approach that.

Glen Stevens, DO, PhD: All send out.

Justin Abbatemarco, MD: Needs to be, because this testing needs to be done in a specialized center that does it a lot. And we tend to harp on this with the residents and fellows. It has to be a cell-based assay.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: There's good evidence to show that an ELISA based assay is neither as sensitive nor specific, and a misdiagnosis in either direction has huge implications for these patients. So, sending it out before we treat, so before we give them steroids or plasma exchange is vital. And we commonly send out at this point the AQP4 antibody and the MOGAD antibody at the same time because they're hard to differentiate at that first visit.

Glen Stevens, DO, PhD: It's all in blood or CSF can be both or just should be blood?

Justin Abbatemarco, MD: Both of these tests are in blood. The residents hate, right? Each antibody has different sensitivity and specificity, but especially for AQP4 disease, we have good evidence that we only need to test blood. There's limited utility.

Glen Stevens, DO, PhD: You ever see both positive?

Justin Abbatemarco, MD: Yeah, because we think that the antibodies are produced peripherally and then they're going to enter into the CSF, but it adds no extra diagnostic value. So just serum, especially for the AQP4 test. We have good evidence for that on a cell-based assay before treatment is really, really important.

Glen Stevens, DO, PhD: And your turnover time, do you know?

Justin Abbatemarco, MD: It depends, but we're talking a week to 10 days, which is a long time.

Glen Stevens, DO, PhD: OK. And any other specific tests that you should do? Obviously. It's going to depend on the clinical presentation, but are there any standard tests you would do otherwise that need to be done or not really?

Justin Abbatemarco, MD: Especially in the acute setting, I think these are kind of standard tests. OCT, optical coherence imaging has been used more often. Sometimes that has some subtle clues to us, but again, that's hard to get in the inpatient setting when these patients come in really sick.

Glen Stevens, DO, PhD: And the other things in the differential diagnosis with these besides MS and you mentioned sarcoid and these types. Anything else?

Justin Abbatemarco, MD: If we have eye involvement that has its own differential and we're working with our ophthalmology colleagues to work through those pieces, but I mean we're dealing with mainly inflammatory diseases there. NMOSD, MOGAD and MS, rare infectious kind of complications that we can see in those regions. And genetic diseases can be a little challenging. I think the spinal cord involvement, like the differential for myelitis, is long. And I'll tell you, we've had patients, I have one right now with seronegative or antibody negative NMOSD that we're working up now for a potential spinal cord tumor. Keeping a differential broad and being thoughtful about some of these patients because it can be challenging, but neurosarcoidosis can definitely cause the longitudinally extensive myelitis.

Glen Stevens, DO, PhD: Do they get a big syrinx that goes down further or not typically?

Justin Abbatemarco, MD: In neurosarcoid?

Glen Stevens, DO, PhD: No. In NMO.

Justin Abbatemarco, MD: It definitely involves the central cord more than those peripheral short segment lesions that we think of MS. I don't as commonly see a syrinx associated with it, but that's not uncommon in the population.

Glen Stevens, DO, PhD: And you've mentioned a couple times if they're aquaporin positive or negative and I guess always a hard question to answer, but what percent are truly positive? What percent are truly negative as best as we can know?

Justin Abbatemarco, MD: This has definitely evolved over time and most of what we talked about here today is like AQP4 positive NMOSD because that antibody negative group, there are so many question marks still left there, right? In 2015, we didn't have MOGAD testing. Now we know about 20 to 30% of that population that was antibody negative, MOGAD.

Glen Stevens, DO, PhD: So, another couple of years we'll do another antibody.

Justin Abbatemarco, MD: We'll throw one more out there.

Glen Stevens, DO, PhD: One more.

Justin Abbatemarco, MD: I really do think that we have so far to go in that group of diseases, but I think there have been a few key themes that have emerged over the last couple of years in this group. With the FDA-approved medications in those clinical trials we consistently saw that if they were antibody negative, they didn't respond well to medications, which is a theme or a hint to me that that pathophysiology we don't have well described. I think it's a mixture of different ideas. And so, my piece of advice there, yes, I use that diagnosis, but that diagnosis keeps me up at night. I'm worried that I've missed something. When those patients come back, I'm trying to think through again. That patient I described, we went back, talked to our neurosurgery colleagues, said did we miss something? Are we doing an angiogram to look for a fistula? Some other rare disease that can affect that. So, I think really looking at that group and constantly reevaluating. I think in time we'll have other diagnostics to help us there. But I mean when I say truly it keeps me up at night when I make that diagnosis, I feel like I've missed something.

Glen Stevens, DO, PhD: Someone has sort of classic presentation. What's the likelihood they are antibodies positive?

Justin Abbatemarco, MD: The antibody is really good in a cell-based assay sensitive and specific. It's very hard to write this off. This is not like GAD65 or even MOGAD to some degree, which requires a little bit more pre kind of probability testing in my mind.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: This is a sensitive specific assay, it's very hard to write off.

Glen Stevens, DO, PhD: So, they come in classic syndrome, send off the antibodies, do the LP. What's your first treatment?

Justin Abbatemarco, MD: We here use a lot of IV methyl pred so a thousand milligrams.

Glen Stevens, DO, PhD: How many days?

Justin Abbatemarco, MD: Five days.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: And then we are going right to plex. So that combination approach. I think there's some.

Glen Stevens, DO, PhD: They like plex better than IVIG?

Justin Abbatemarco, MD: I think the combination, we really have to hit these guys hard, try to prevent that disability. And we know that time is brain here. So, the faster we get those therapies initiated, the better they'll do long term. And so, I try to tell the residents that the clinical suspicion's high, if it doesn't feel or look like MS, it's okay to add that plasma exchange while we're unsure.

Glen Stevens, DO, PhD: And how many exchanges do you do?

Justin Abbatemarco, MD: Typically, five. It's somewhat historical, right in what we've always done. Over about seven to 10 days. I also want to acknowledge that we're very lucky here. That's not difficult for us. So, do we have those resources and expertise?

Glen Stevens, DO, PhD: Yeah, I'll echo that. It's been my whole career here having ability to do plex has been amazing.

Justin Abbatemarco, MD: No, we have a tremendous team here, so that's not a difficult decision for us. But I think this is another reason if you're at a hospital where that's maybe not as doable. Calling and asking for help when this comes up, I think, is absolutely appropriate.

Glen Stevens, DO, PhD: How long will you delay to give them IVIG if they don't improve on plex?

Justin Abbatemarco, MD: There is good evidence that IVIG is not very effective here, so I don't use very much IVIG. IVIG now though has some evidence in MOGAD. And so now this world becomes much more complicated. And I think again over these coming years we're going to see there are clinical trials going on in MOGAD to help us manage that disease better. But it's confusing.

Glen Stevens, DO, PhD: So, you mentioned that there's some new drugs, maybe this is a good time to mention it. They have difficult names; I can't pronounce them. So, tell me about the drugs. Probably very exciting for you.

Justin Abbatemarco, MD: Truly to have FDA-approved options to talk to patients and personalize it. I mean to go from, again, we were calling this disease in 2003, MS, 2004, we have a biomarker and then by 2018-2019 we have three FDA-approved options. It's just an incredible success story and ones that target the underlying pathophysiology of the disease. Like I was talking about that past, present, future of neurology. I think it's how these medications have come about and how they target the exact pathophysiology. It's just incredible. We can talk about maybe the three meds in a little more detail.

Glen Stevens, DO, PhD: Yeah. But before that you guys over at the Mellen Center, you're probably giving the rituximab first.

Justin Abbatemarco, MD: I think our pattern has shifted a little bit, but we can talk about rituximab first because it's tried and true and I think we're comfortable with it in neuroimmunology. There is good retrospective data and there was actually a prospective study done.

Glen Stevens, DO, PhD: It's not an FDA-approved drug for this disorder, right? I think we need to.

Justin Abbatemarco, MD: It's not an FDA-approved option, but good retrospective evidence. And there was a randomized clinical trial in Japan. Small, I think a total of about 40 patients. Again, but showing good efficacy there. And so, it's one of the most common questions that we get is rituximab a reasonable option? And I do think it is, but they now have some other options to at least think about. And I tell this to the residents that these medications that we're talking about are being used in other diseases. So, we are going to have to become comfortable with them. They're going to be used in other disease states.

Glen Stevens, DO, PhD: So, let's go through these three drugs.

Justin Abbatemarco, MD: Yeah. So, we have three, possibly four. One is probably about to come on, but maybe the first one since we just talked about rituximab is inebilizumab. So, this is an anti-CD19 monoclonal and has many similarities to rituximab. So, the CD19 molecule hits a larger kind of plethora of B cells. So, we're hitting the plasma blast or the antibody producing cells. So, we think that may offer some additional benefit, maybe have a little bit faster onset too and helping these patients in the acute setting because we think those antibodies are pathogenic.

Glen Stevens, DO, PhD: And these are all administered the same way or is there a difference?

Justin Abbatemarco, MD: Inebilizumab is infused. So, it's an infusion-based therapy.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: Same kind of schedule as rituximab. So that first cycle requires the dose to be split and then it's once every six months, so really easy, convenient. And the side effect profile similar, right? It's infusion reactions, infections because we're dealing with these B cells. But those are the main kind of elements there. And I think people are comfortable with this idea of a B cell and this kind of infusion schedule. So yeah, that kind of caps off in inebilizumab I think in my mind. The next kind of medication, eculizumab and there's a medication that's likely related to ravulizumab. So, these are complement inhibitors. Eculizumab is FDA-approved. Ravulizumab is under investigation. They're actually in talks with the FDA right now. So, this is a complement inhibitor. We know that when the antibody enters into the brain, it stimulates the complement system. It's a complemented mediated disorder. And so, this is kind of stopping that right at that level and has been proven to also be very effective. The trouble with this, so the side effect profile is that when we mess with the complement system, we have this risk of infections with encapsulated bugs. So, Neisseria meningitidis is the big example, but strep pneumonia, other examples here. And so that is something that we have to monitor when you get these patients vaccinated with a meningitis vaccine before or you can start antibiotics. It's a frequent infusion. So eculizumab is every two-week infusion. So, we have to weigh that with patients. Ravulizumab is going to be an every two-month infusion, but a similar kind of mechanism and it's used in other disease states, but another way to kind of attack this disease in a pathophysiology kind of minded way.

Glen Stevens, DO, PhD: So, who's the guy out there combining these therapies because they have different mechanisms of action. So, if one's good, are two better?

Justin Abbatemarco, MD: I think I was just having this conversation. Our rheumatology colleagues, they like to hit patients with four medications all at once. I think in our neuroimmunology space, especially now that we have clinical evidence, we can usually go forward with monotherapy. We should be able to find one medication that works. And so, we're not usually doing that besides that bridge that we'll use with a little bit of prednisone initially. We have one more medication to talk about. Satralizumab is injectable. So, our first two were infusion based. Satralizumab is an IL6 inhibitor and it's really nice to offer a different mechanism for these patients. So self-injection for patients who.

Glen Stevens, DO, PhD: Subcu?

Justin Abbatemarco, MD: Mm-hmm. Really easy, convenient, it's once a month, so not terribly often. Side effect profile. Again infections, upper respiratory infections. And we see some changes in the CBC and LFTs that we have to monitor, but most patients tolerate these medications really well and all of them have been proven very effective. They're very hard to compare. If you were asking me which one's the better one, I think it needs to be a personalized choice that works with a patient and then their comorbidities, but all of them can be used in monotherapy and change the game.

Glen Stevens, DO, PhD: And you start these drugs or hope to start these drugs how soon after the plex?

Justin Abbatemarco, MD: Yesterday.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: Truly, you want to start them as soon as you can.

Glen Stevens, DO, PhD: Can you give them in-house?

Justin Abbatemarco, MD: We have started to do that.

Glen Stevens, DO, PhD: OK.

Justin Abbatemarco, MD: But I think when we're talking about it in a patient level, we're advocating for their best outcomes and there is emerging evidence that acute treatment, especially in a hospital, offers better long-term outcomes.

Glen Stevens, DO, PhD: Well, I'm personally always OK if you're advocating for a patient's health.

Justin Abbatemarco, MD: That's how I feel. So, I think, and we're going to start seeing more data I think on this.

Glen Stevens, DO, PhD: Okay, so bad disease, drugs available now, treat soon. Stabilization rates are what?

Justin Abbatemarco, MD: Really good. If you have patients on therapy, these patients can do well. I think they're left sometimes with significant disability related to even just the first attack. But I think supportive care, symptomatic care like this requires a team. Maybe one other nuance from MS, I think we're starting to see patients come off medications in multiple sclerosis. I don't think that we can do that for this disease.

Glen Stevens, DO, PhD: Yeah. That's what I was going to ask you. Is this a lifetime at this point?

Justin Abbatemarco, MD: Truly. And we really mean lifelong. I think MS, we're starting 55, 65, there's discussions to stopping. For this disease, we know that stability for five, even 10 years does not pretend to a better prognosis. They can still have disabling attacks. So, they really require lifelong treatment, which is why being thoughtful when that initial diagnosis, sending the right test off in the beginning, huge implications for these patients.

Glen Stevens, DO, PhD: Can we predict who's going to relapse?

Justin Abbatemarco, MD: Everyone. We know that this is a relapsing disease.

Glen Stevens, DO, PhD: So, do we change therapy at relapse? Do we have to?

Justin Abbatemarco, MD: Yeah. So, if we're on one of these treatments and it's been effectively given, yeah, I think we would definitely have to think about that.

Glen Stevens, DO, PhD: So, we just go to one of the other three, maybe four or rituximab. And then final takeaways for our audience or things we haven't discussed you think are important?

Justin Abbatemarco, MD: I think reaching out for help. There's always a friendly autoimmune neuroimmunologist. They don't have to do this alone. These are complicated. Which sample do we send? Which best antibody tests are we're using, right? This world is becoming more and more sub-specialized, but don't do it alone. We're here because it's complicated.

Glen Stevens, DO, PhD: Well Justin, I very much enjoyed our conversation today. As always, I learned new things and from having a mother that had MS, I know it's different than what we're talking about now, but just looking at the field that you guys do in neuroimmunology, the changes over my 30-year plus career. It's astounding. We could give patients steroids and that was it. And now it's sort of how do you make the decision of which of these dozen medications you give? It's a good problem to have. So, I'm very excited about what you guys are doing and the strides that you're making, and I appreciate your efforts and thanks for all you do, and thanks for joining us today.

Justin Abbatemarco, MD: Thanks for having me.

Conclusion: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's consultqd.clevelandclinic.org/neuro, or follow us on Twitter @CleClinicMD, all one word. And thank you for listening.