While seen as an adult disease, multiple sclerosis presents before age 18 in up to 10% of patients. Fortunately, prompt identification combined with newer therapies can lessen damage and protect future well-being. In this talk, pediatric neurologist Mary Karalius, MD, guides providers through assessing MS, MOGAD and anti-NMDAR encephalitis, describing acute presentations, workup steps, and what's known about the likelihood of future attacks. Karalius shows what MS looks like on MRI, explains safe use of MS drugs, and shines a light on the cognitive and emotional health needs of children and teens with the disease. Describing improvements in the understanding of both MOGAD and autoimmune encephalitis, she also offers a resource for navigating the complexities of an anti-NMDAR diagnosis.
And thank you so much for inviting me to give this talk. I'm really excited, specifically because not only is March MS um, month, but this is actually MS week, um, within the month of March. So I'm really excited to hopefully share some information about pediatric MMS, um, as well as, uh, a couple other common neuroimmuno immunologic, uh, conditions. So again, thank you guys so much for inviting me and for your attention. Um, I have no disclosures. So, like I said, um, I will, uh, I will kind of give you guys an overview of three of the most common neuroimmunology, uh, conditions that we see in our clinic. And these conditions are probably gonna be the most likely things that you, that, that, that, uh, may, you, you may have some patients on your panel that have a history of, of these diagnoses. So hopefully by the end of the talk, you'll have a, a better understanding of kind of The biology behind these diseases, basic workup symptoms to look out for, some, some uh uh treatment recommendations, um, and then really kind of when to reach out to us and kind of how we can work as a team to, to, to manage uh some of these conditions. Um, so starting with, with MS, which is, uh, the most common out of these three, as you guys probably remember, it's a, it's a chronic autoimmune condition that affects the central nervous system, so the brain and the spinal cord, and it is our classic demyelinating disease. So, um, what we mean by that is the immune system attacks the myelin, which is kind of the protective layer around the neurons, um, And, and that damage uh disrupts the nerve uh signaling between, uh, between neurons, and that can lead to a variety of, of neurological symptoms. Um, MS is actually pretty common, so there's about 1 million individuals living with MS in the United States, uh, currently, which equates to a prevalence of about 80 to 300 per 1000 per 100,000. Um, there is a female predominance, like many other autoimmune conditions. We still don't know the exact cause of MS and um likely it's a combination of multiple factors. There is some genetic predisposition, um, but it's likely polygenic, meaning we, we have been unable to identify one specific gene that's inherited, for example, that That um causes MS, um, but certain, uh, certain, uh, abnormalities do put you at a higher risk of developing MS, but, but unlikely to be the sole cause. We also think that there's some environmental triggers as well, um, such as low vitamin D, cigarette exposure, obesity, and EBV infection. Um, but again, not one of these has really been linked to a cause. It's likely kind of a combination of, of genetic predisposition in addition to Um, in addition to an environmental trigger. Um, unfortunately, there is no cure though here at UCSF there's always, we're always working on clinical trials and such to to try to figure out if we can find a cure, but we do have really great, uh, treatment options. Um, and if that's one thing you guys can take away from the talk, MS no longer is, you know, uh, I mean, we don't love giving the diagnosis, but, but we do have much better treatments nowadays than Uh, were available 20-30 years ago. So I think historically, a lot of people think, um, when they think of MS, they envision people needing a wheelchair by the age of 30 or 40 and having pretty significant disability. Um, but we are, uh, that, uh, with, with the advent of much newer and more efficacious treatment that, uh, that disability, um, occurs much, much later in life. Um, the other thing is, is, in pediatrics, we, we actually do see, uh, multiple sclerosis quite often. So up to 10% of patients with MS present before the age of 18. So I think that's oftentimes surprising for people because again, I think people typically think of it as like onset in late 20s, early 30s, um, but, but we do see patients present much earlier. I think we even have, you know, 4 or 5 year olds in our clinic that, that have a diagnosis of MS. Um, in general, pediatric patients with MS, um, have pretty active disease early on, and oftentimes will have multiple disease relapses. Um, however, like, uh, in many conditions, children are very resilient and recover very well from these attacks. Um, but given they, um, just have the disease for a longer period of time. They do tend to accrue disability again later in life and sometimes more so than their adult counterparts, just given the length of time that they have a diagnosis of MS which is kind of shown on the right where time is on the X-axis and expected number of relapses is on the right, and you can see the dotted line is a pediatric patients, so definitely have more uh higher rates of relapse. I will say this is um a little bit outdated. Um, so this was published back in 2009. And since then, again, I'll, I'll talk a little bit about, more about treatments, but since, since the advent of newer treatments, this graph um looks actually much better and we're, we're doing a much better job of, of preventing relapses. Um, signs and symptoms of MS. So, so typically they're pretty significant neurological deficits. So unlike most of the kids end up presenting to an emergency room, um, because the symptoms can be so disabling. Um, the one of the most common first presenting signs is the transverse myelitis, which is inflammation of the spinal cord, and this can cause weakness or numbness. And we usually say rule of thumb that it, it has to last greater than 24 hours to, to really be concerning for a demyelinating event, which can be difficult. Lots of patients have random numbness, tingling sensations that come and go, but really, when patients have their first attack, it, it's usually persistent numbness followed by weakness. Um, This oftentimes can lead to difficulties with walking or balance. Um, again, usually it's in one leg or one arm, so patients or, or families will say, yeah, you know, he just started walking funny, um, and that's what prompted us to go to the emergency room. Um, optic neuritis is also pretty common, so that's inflammation of the optic nerve. Um, it can involve one eye or both eyes. Most commonly, it presents with blurry vision, pain with eye movements, though not always, and changes in color vision. So I think in Kids, mostly, it's like, it's, oh, like something funny. I'm feeling something funny with my eye, especially in the younger kids, it can be kind of a difficult history to get. But, but usually it kind of progresses to, to very blurry vision, pain, um, and then, and then difficulty with seeing colors. Um, AM or acute disseminated encephalomyelitis, um, Uh, is a less common first presentation of MS, um, and that's characterized by much more, uh, much bigger areas of inflammation in the brain in the brain, which I'll show you some images later. Um, and clinically, it presents with altered mental status and seizures. Keep this in mind for the next uh disease that I'll talk about. Um, I just put it here because in rare cases, MS can present like more of like this altered mental status type picture, but, but usually it's uh either a transverse myelitis or an optic neuritis. Oftentimes, um, if you dig a little bit deeper in the history, some patients may endorse that they've had more subtle symptoms that have popped up in the last couple of months prior to the first, you know, acute attack of demyelination. Patients will say, oh yeah, you know, I've been feeling more tired, or school's been a little bit more difficult, or I've been more moody, or I've, you know, uh, noticed that it's, you know, more difficult to, to pay attention in class. So, so there can be some more subtle symptoms, um, uh, and another less common is, is muscle spasms, but, but usually, again, the first attack is one of these more, more drastic presentations. Um, this is the current diagnostic criteria. So if you dig in on the left is 2010 and on the right is the 2017 1, so we'll focus on the 2017 1, but if you dig back to medical school, you probably learned about the dissemination in time and dissemination in space as being criteria for making a diagnosis of MS. Um, this is based on adult literature, but we apply it to our kids, um, as well, and really, uh, we, we kind of look at a couple of different things when we're concerned about, about MS. This, this is looking at, uh, the MR criteria for an MRI, um, so if you remember dissemination in space. is, is based on the location of the demyelinating lesions, and the lesions need to be present in 2 out of the 4 locations. So perioventricular, juxtacortical, aeratororial, which means um uh in the brain stem or in the spinal cord. So you really need to have two, the lesions in two of those, and I have some examples of that to show you um in a couple of slides. And then also you have to meet this criteria of dissemination in time. So this means there, there needs to be two distinct clinical episodes. Um, based on, on MRI you have to have an enhancing lesion, so meaning an acute, uh, more acute lesion and evidence of a non-enhancing lesion, so two different time periods of potential demyelination, or The presence of oligoclonal bands in the CSF. So most of these kids to make the diagnosis, we need an MRI. We like getting a CSF studies, um, to look for a little clonal bands. Um, and if a kid has aligoclonal bands present, that definitely uh raises our suspicion for, for MS in comparison to some of the other um inflammatory diseases. So definitely, I need to look at if you're seeing a patient that has a, has gotten an LP for concern for something inflammatory. If you see the folligoclonal bands being positive in the CSF, that should kind of raise your suspicion. This is sort of the classic MRI findings, so you can see here on the left that these are 2 T2 flare hyper intense T2 flare uh signals and you can see these white spots, so perioventricular again, is surrounding the ventricles, and then this is also a juxtacortical lesion, so really abutting the cortex. And then on the right, we have kind of the classic Dawson's-like fingers that, that uh we all learned about uh back in medical school. So this is pretty typical. If you're getting an MRI for some other reason, like headaches, maybe they had some concerning neurologic symptoms in the past, and you're getting an MRI and it's looking like this, then that, that would definitely raise suspicion for a diagnosis like MS. That's in comparison to something like this, which sometimes we get referrals for where there's, you know, abnormal white matter changes or spots on the MRI. And these, you can tell, uh, this is in a patient that has migraine headaches and so we sometimes see these abnormal white spots. Um, but again, They're not as classically located along the, the uh the ventricles. They're much smaller, can be much more punctate like this white spot up at the top. Again, it's much smaller than the types of lesions that we typically see in MS. So, I'm always happy to see these types of patients too. Um, but just trying to keep in mind, a lot of these punctate sort of smaller, uh, lesions can be caused by migraine headaches, can be caused by remote injury. In adults, we see this a lot with hypertension, diabetes, but obviously less pertinent in, uh, our pediatric patients. Thinking about treatment, so we, we kind of break it into acute treatment. So a patient comes in with the first demyelinating attack concerning for a new diagnosis of MS and then preventive treatment. So usually, and this will be a theme, the one thing in common with all kind of our neuroinflammatory neuroimmune disorders that acutely, we oftentimes treat patients with IV steroids to decrease the inflammation. And then we also uh administer IV immunoglobulin or IVIG. Um, if, if patients are unresponsive to steroids initially, or more invasive things like plasmaphoresis if they have a really severe presentation. We then move on to discuss disease prevention, and oftentimes this is a conversation that's had in the office cause it can be a little bit more nuanced, um. We know that MS, unlike the next two disorders I'll talk about, is, is truly a chronic lifelong condition, and so it is really important to put patients on disease modifying therapy to prevent further relapses and to prevent further episodes of demyelination. Um, Unfortunately, we only only one medication has been FDA approved for patients with MS that's called Fingolimmo. It's an oral, it's an oral medication. Nonetheless, we use a lot of different treatments um off-label that we pull from um the adult, our adult colleagues and adult literature. So, I won't get into too much detail about the different, the details of the different treatment options, um, but I will just point out a couple of things. So interferon beta one and glier acetate are kind of the oldest medications that were used for MS and these are IM or sub-Q injections. Which as you can imagine for kids can be pretty traumatic. Um, we also know that these medications, um, are, are less efficacious than some of the newer medications.ingolliad again was the one that's, uh, that is FDA approved, um, and it's a pill that needs to be taken once or twice a day. And then our newer medications, uh, well, rituximab has been on for, has been on the market for, it's a very old medication, but new for newer for treatment of MS. And this is a B cell depleting therapy, so it, uh, basically lowers your B cells. We think there's a big role for B cells in MS and so by lowering your B cells, we think that it, it, uh, decreases, we know that it decreases the chance of disease progression and, and, um, Uh, and demyelinating events. Uh, natallizumab is also, uh, uh, it doesn't deplete the B cells. Um, it just prevents the B cells from infiltrating the central nervous system. This is a monthly infusion. You may remember there is a, there is a big black box warning, um, for this medication, uh, where if you are JC virus positive, which is basically a common virus, many of us are exposed to it. Um, Then there is a risk of uh something called PML or progressive multifocal leukoencephalopathy, which, um, Which is very severe and can be fatal. So, uh, so, um, oftentimes, well we, we are required to test for JC virus before starting this medication. And then, um, every 3 to 6 months, we repeat, uh, the, the test, uh, to make sure that it doesn't turn positive. So, again, it's a great medication, but I think with this risk, a, a lot of families, uh, rightly so, are kind of nervous. It also it's a monthly infusion versus a 6-month infusion. Um, so, so oftentimes a six-month infusion is easier for family. Um, a little bit what I alluded to, but the choice of treatment really depends on a variety of factors, severity of the disease, the efficacy of the treatment, the delivery mechanism, and then the side effects. Um, so, so oftentimes, uh, we think of kind of the B cell depleting therapy, so the rituximab, should be most efficacious, um. But that also means that it has the most, um, it can, it can have the most uh serious side effects when it comes to recurrent risk of infection because we are lowering the immune system so much that these kids sometimes can have recurrent infections, so that's the main counseling we give, um. Uh, and then oftentimes, uh, the delivery mechanism is really important, especially in teenagers or kids that are gonna be going off to college, to remember a daily pill can be really challenging. Um, and so patients actually really don't mind, uh, the 6-month infusion option because it's actually quite easy to come into our infusion center, a local infusion center, get their infusion, and then don't have to worry about treatment for 6 months. So it actually, uh, uh, not only is it one of our best medications, but, um, it's, it's, uh, takes a burden off of the patients and families to, to have to remember to take a pill every day. So that's why I think a majority of our patients um are on ibup rituximab. You may hear Ocrelizumab or Ocrevus, um, as another, uh, another, uh, it's the newer brand name, um, that sometimes can be more difficult to get, but it basically, it's also B cell depleting and works in the same way as rituximab. In terms of disease monitoring, this is important to know. So if you have a patient with MS on your panel, um, we usually recommend getting safety labs every 6 months. Um, with that, we recommend a CBC with differential because rituximab can cause neutropenia, so we do worry about that if kids are having frequent infections. We also get lymphocyte subsets to trend D cells, um, and we check immunoglobulins as well, cause, uh, vertuximab can cause low IgG. And if, uh, patients start to have recurrent infections and they have a low IgG, we have to think about whether or not uh the benefits of staying on a basal depleting therapy outweighs the risks, and then there can be some liver dysfunction as well. In general, we, once patients are stable, we usually recommend uh surveillance MRIs about every year. And then if there's a history of eye involvement, we like to involve our neurophthalmology, or ophthalmology colleagues to do yearly vision exams, um, with some special testing, uh, that can kind of track um demyelination and uh uh can track visual acuity better than what we can do in the office. Um, patients with MS again, uh, outside of the acute attacks and relapses, we know that, uh, patients and, and teenagers with the MS do have uh higher rates of cognitive challenges. So almost a third of kids will have difficulty with school at the onset of their disease, and then we know later on their uh their IQ can also be impacted, um. And so just something to be aware of that kids may need a little bit of extra support uh in school. We also know that patients with MS, like many other chronic conditions, can increase the rates of depression and anxiety. So, so we do a lot of counseling around that. Um, one of the biggest, uh, symptoms, uh, or more chronic, I guess, symptoms of MS is also fatigue. Um, so patients will Complain of of always feeling tired. Um, that, that is a difficult, uh, symptom to, to, to manage, but we really try to focus on, you know, healthy lifestyle choices, getting good sleep, um, things like that. And then Uh, patients also may have a little bit of exercise intolerance, so, um, we know that, uh, in the warmer weathers, sometimes flares, uh, or old MS symptoms can kind of recur, and especially with exercise, if you get overheated, sometimes patients can, uh, not, it can't cause a relapse, but your old symptoms can kind of come out, so it can be difficult sometimes for patients to resume their regular exercise regimen um after their diagnosis. Um, so things that you can do in the office again, like with every kid, um, diet and exercise counseling is super, super important. So patients and families will also be like, well, what else can I do? Like, I feel like I want to do everything I can to, to prevent, you know, MS from taking over. Um, we know that daily exercise definitely reduces the risk of long-term disability, so even just 30 minutes of, of mild exercise a day can, can really go a long way. We also know that elevated BMI can increase risk of relapse. So there's no, we get a lot of questions about is there any sort of dietary recommendations, you know, things like should they be on an anti-inflammatory diet, gluten-free, all that kind of stuff. We don't have great evidence for that. We just know that eating healthy, general Mediterranean style diet, uh, uh, is, is probably the best, um, and it's more, you know, about, about a balanced diet as opposed to specifically a specific, you know, type of diet. Again, sleep hygiene is super important, encouraging seeking mental health support if there are concerns for anxiety or depression. Um, and then reminders uh for patients to schedule infusions, obtain safety labs, schedule their MRIs. We always do their best, but we, to remind them and, but sometimes things get lost or slipped through the cracks. So if you're seeing a patient that has MS in your office, really helpful to, to make sure that they have a plan to get their MRI. They know when their next infusion is, they are getting their labs. So, so things like that can be really important, um, just to make sure that things don't fall through the cracks. And then the National MS Society is an amazing resource, so if patients, um, are looking for more support. Um, this has uh tons of great information on the different treatment options, support groups, webinars, um, and so I encourage patients to explore this website if they, if they want to learn more, it's definitely like highly vetted, good quality evidence, um, so definitely a, a good source. Um, so when to reach out to us. Um, uh, obviously, if there's new signs or symptoms of an acute relapse or even a, you know, if you're thinking about this as a previously healthy teenager and you're developing these symptoms, um, I would definitely, if, if they haven't been diagnosed with the mass, encouraged going to the ER. But if they have a known history and they're developing numbness or tingling of one limb that's lasting greater than 24 hours, difficulty with balance or walking, difficulty with vision, we definitely wanna know. And then things to think about to help with triaging, um, thinking about if it's a new symptom or a prior symptom. So sometimes patients can have quote unquote pseudo relapses, which is basically worsening of prior symptoms when the body is under stress. So we see this a lot when kids get sick or they're having a stressful week at school, they'll say like, Oh, I, you know, when I first presented with MS, my left leg was weak. I got totally better, but I've been feeling really, you know, off this week. I've been, you know, school's been really stressful and I feel like my left leg now is feeling, uh, a little bit weak. So that usually, um, is a pseudo relapse, meaning there's no changes on the MRI. It's just an old, one of the old symptoms, uh, temporarily kind of recurring. Um, but obviously if it's a totally new symptom or if the, the, the old symptoms are lasting for, you know, longer periods of time, that would be, would be more concerning. I'm thinking about when their last treatment was, so sometimes we will see relapses and we'll realize, oh, they accidentally skipped their last rituximab infusion or stopped taking their their funolimad. um, so trying to figure out when the last treatment was, when the last MRI was can be really important. Um. I mentioned this before, the recurrent infections with all of our immunosuppressive medications, that's always a risk. Usually, it's, it's more mild respiratory infections that don't require antibiotics or hospitalizations, but if it's getting to the point where, you know, a patient needs to be hospitalized for a bad infection or they're unable to clear infection, uh, then sometimes we do discuss different treatment options. Um, with patients and then the laboratory abnormalities, um, excuse me. Um, laboratory abnormalities, like I mentioned, especially empty cell depleting therapy, so neutropenia. Definitely, we'd want to know about, um, and then low IgG if there's concern for recurrent infections. Um, so those are just important things that, that may come up, um, if you are caring for a patient with a mess. OK, so I think that covers and mass how am I doing on time. OK. I try to spend about 10 minutes, um, each on the last two. SoOG or myelooligodendrotrite glycoprotein antibody disease, it's a mouthful we now call it MOG, um. This is also an antibody mediated autoimmune disorder, which attacksligodendrite sites, which are the cells that uh produce myelin, and so it, it, it over time damages uh and impairs myelination, so this also is kind of considered a demyelinating disease, um. Before the discovery of antibody, many patients who were classified, many patients were actually classified as MS given they had very similar over clinical presentation, so transverse myelitis optic neuritis, um, but now it's really recognized as a distinct disease. This really is a pediatric disease. So we see it in adults, but the rates in kids are 3 times as high. Um, it is a little bit less common than, than MS though. So probably less likely to see it in your clinic, but, but as we're recognizing it more, definitely something we're seeing more commonly like in our clinic this morning we had. Like 4 cases of, of MOg. So it's definitely out there. Um, we don't know the exact cause, but many of our kids have a, uh, a viral, uh, a viral, um, have a viral prodrum and then start to develop kind of uh transverse myelitis or an optic neuritis. So we think probably it's something with the response to the, uh, the immune system's response to a, a viral infection. Um, but again, we don't have a great, uh, we don't have great biomarkers or genetic studies that really, uh, suggests an exact cause. This I won't get into detail, but basically illustrating thatOG antibodies um are created in response to some trigger, ultimately penetrate the central nervous system, attack the oligodendro oligoligodendrocytes causing demyelination. Signs and symptoms again, similar to MS which is why originally, um, many of these children were diagnosed with MS. Outside of the fact that ADMs, the acute disseminated encephalomyelitis, which presents more with kind of the seizures, altered mental status, is really the most common initial presentation. Optic neuritis is also pretty common. It can be more severe and it's more often involving the both eyes compared to, to MS and then transverse myelitis. Um, it's also usually much more extensive, so it's we call it longitudinally extensive. It goes last over uh lesion, they're typically longer than 3 vertebral segments, whereas in MS usually they're more like smaller, uh, smaller lesions, shorter lesions in the spinal cord. This is a comparison again of MS versus MOGA. Um, and on the right is a MRI of of what we classically think of ADM. So you can see here the lesions are, we kind of call them fluffier. Um, they're much uh less well-defined. They're often bigger. Um, and so this, this would be more consistent with the a sort of mog type presentation. Similarly, optic nerves here, usually more bilateral. And the spinal cord is usually more involved as opposed to some of this, this, the more smaller discrete lesions that we see in MS. Um, Diagnosis and treatment, so, so, uh, diagnosis again based, is based on clinical history and MRI findings. MOG antibody is actually detected better in the blood than the CSF. So we send for most kids that present with abnormal brain MRIs and neurologic symptoms similar to, uh, or, uh, brain MRIs similar to what I showed you. Um, we will send a serum mog test um that reports back as a tier, uh. Uh, and then, uh, CSF we also usually obtain and it can show signs of inflammation, but not always. Similar to acute attacks of MS we treat with steroids initially, and then in more refractory cases like MS we'll consider IVIG or plasmaphesis. The biggest difference is the one, probably the biggest takeaway between MS and MOGAD is that from what we from as much as we know right now about MOGAD, 70% of patients will only have one attack, meaning it's not a chronic disease. We think it's just a monophasic abnormal response to a virus, um, uh. If kids are gonna relapse, they usually relapse within the first year, typically within the 1st 3 years. We don't have a great sense, unfortunately, with with why some patients relapse, why some don't. There's many, many active areas of research looking into this. Um, and so when we talk about disease modifying therapy or long-term treatment, it's a very different conversation than with MS. In MS we say we know that this is a progressive disease, this is a chronic disease. We know these kids need to be get on treatment. Whereas for MGA, it's a little bit more nuanced. We usually reserve for very severe presentations, or if they have a relapse, we'll consider starting monthly IVIG or rituximab like we use in MS. But this, we're still learning a lot and the the practice kind of varies across different institutions and different providers. Um. And, and again, some families are like, we are so nervous for relapse. Like I would rather have my kid treated than not. And then it's a discussion again of the risks and the benefits of something like IVIG. It is a monthly infusion, which can be burdensome. But other families are like, my kid is totally back to normal. I'm OK. I don't want to do any extra treatment. Let's just wash them. So it kind of can go both ways, um, but, but definitely again big point, usually more likely to be monophasic than polyphasic like MS. So you're seeing a patient who was just diagnosed with MOGA or has a history of MOGAD. Again, I think the most important thing from, from the primary care standpoint is, is monitoring for symptoms and acute phase for, for recurrence. Most common relapses are optic neuritis, so really trying to pay special attention for visual symptoms again, which can be really hard in young kids, and MOCAD can present again pretty early, like 456 years old. Um, so really trying to take the vision symptoms seriously. Like I mentioned, the further out from the disease, the less likely for disease to recur. So that can be reassuring to families. Um, kids may also need additional support at school for the first month, especially if they present with AM. They may have some cognitive challenges initially. But in general, patients recover very, very well, um, and this is kind of a one-time thing that, that never comes back. We do recommend one follow-up. MRI usually and repeats your MOG testing. If the MOG antibody turns negative, sometimes you feel a little bit better, like maybe this won't come back, but the evidence is still uh uh pretty uh mixed. And then the MRI, unlike an MS where the lesions will stay, um, kind of as plaques or uh scars forever. The MRI's and MOGAD actually tend to improve over time. So oftentimes we like getting that follow-up MRI, making sure the inflammation has decreased. We can reassure families things are reassure families and patients that things are looking better, and then usually we don't recommend getting any more surveillance MRI's unless there's concerns for new symptoms. OK, so that's basics of MOGAD. I'm doing OK with time. The last uh disease I wanted to talk about was anti-NMDA receptor encephalitis. Um, so autoimmune encephalitis is a little bit of a different category compared to MS and MOGAD, which we think of more as a demyelination. Um, whereas autoimmune encephalitis, um, we think of more as an acute or subacute encephalopathy, um, that's caused by inflammation. It is autoimmune and etiology, um, uh, and, and, uh, again, there can be a variety of different antibodies, a variety of different causes. Um, I specifically will focus a little bit more on NMDA because that's the most common etiology in kids. It's about as common as MOGAD but still pretty rare, definitely less definitely less common than multiple sclerosis. There are pretty high rates of morbidity as well as mortality. Kids do, um, as, as the trend, kids oftentimes do better than adults, but it can depend on kind of the specific antibody and the specific cause. Um, uh, and then in terms of the, the demographics and kind of the trend for age, about 40% of patients, uh, with autoimmuno cephalitis present before the age of 18. So again, pretty, we do see this quite often in, in, in kids. Um, The these the autoimmun encephalitis. Can present pretty severely. It can, these kids can be, uh, they're more likely to be hospitalized for longer periods of time, um, and can have more challenges long term, which I'll get into a little bit. But just thinking kind of compared to MS and, and autoimmune encephalitis can definitely result in, in much more severe, severe courses that that can include sort of ICU, prolonged ICU uh stays. So, so definitely again, higher, higher rates of morbidity. Um, Historically, encephalitis was actually most commonly thought to be caused by infection. But over the last 10 to 15 years, there have been increasing number of autoimmune causes being identified, partly because of increasing recognition. So I don't know if anyone's read this book or is familiar with this Netflix series that kind of put it's called Buring on Fire, and it kind of put NMDA receptor encephalitis um on the map. We also are constantly developing new laboratory techniques that have identified new autoantibodies, um, up to the point where we now have about 10 or 15 antibodies that we know that can cause encephalitis. This is the point I wanted to make about NMDA being the most common etiology in kids. It's almost in a large, large cohort of almost 3000 kids with encephalitis. NMDA was, uh, by and large the most common. MOG, you can see also was there, so mog can cause kind of an encephalopathy Alike picture. And then got 22 other antibodies that I won't get into today, but again, NMDA most common. We don't, also, we don't have a great cause for autoimmune encephalitis, but we do know there are certain risk factors like other autoimmune conditions. Um, you may remember the buzzword of like NMDA and ovarian teratoma. So we know that there is a uh, a link to underlying malignancy and oftentimes, if we do find an ovarian, ovarian teratoma and remove it, patients actually do quite well. We also think that there probably is an environmental or viral trigger, given that many patients will present with progerinal fever or prodermal viral infection. And then we think that there is possibly some genetic predisposition, but again, like the other diseases, we haven't been able to identify like one specific gene that we think causes this. Signs and symptoms again, a little bit different than the demyelinating category. These kids definitely present with, with altered levels of consciousness, disturbed sleep, movement disorders. It's pretty common, specifically in NNDA receptor encephalitis, seizures, cognitive changes, so it's much more of a kind of mental status, mental status changes that is less common to be seen in sort of first MS uh attack. Behavioral changes are also really common. Um, and this is really difficult, um, and to detecting kids, um, and oftentimes this, this can unfortunately be missed where kids will come in and parents into the ER and the parent, the, you know, they'll be like, oh, you know, my kid has had some developmental regression, and, uh, the ED will, you know, say, oh well, you know, there's, they just started a new school or a new sibling came along, we're not worried, but so, so it can be definitely difficult to, to kind of detect uh truly. If it's sort of a normal period of regression or not, but, but, uh, but, uh, definitely, uh, can be a clue if, if things are progressing, getting worse, sometimes it can even progress to psychosis. Definitely should be raising red flags that that needs to be, that, that something needs to be worked up. Um, diagnosis. So I'm putting here a link to, I won't get there is kind of a complicated algorithm for diagnosis. Um, so I put a QR code for one of the best papers that I still use that goes over the differential diagnosis, things to think about for NMDA. Um, but again, it's mostly based on clinical history, neurologic exam, brain MRI, and then CSF studies. This paper also goes over in detail treatment guidelines. So you'll get the theme. If it's an acute treatment, acute attack, we usually treat with steroids and IVIG. Um, sometimes we continue treatment in the outpatient setting, um, uh, for a couple of, of, uh, months, up to 2 years, if, if it's a pretty severe presentation. Um, and then second line treatments can include rituximab or cyclophosphamide and in really rare cases where kids are in the ICU, we will even escalate to further immunomodulation. Um, And MDA kind of falls in betweenOA and and um MS and thinking about long-term treatment. Um, if it's a pretty severe um attack, sometimes, again, we'll, we'll treat patients for 6 months, sometimes up to 2 years, but in general, um, after the 2-year mark, we, we, we do think of this more as a monophasic uh the disease relapses can occur, but typically, these patients are not on lifelong immunosuppression. These are some of the symptoms that while admitted can occur, so this is what results in patients needing to be in the ICU, um, and then after discharge, things to be aware of. Many patients struggle with ongoing epilepsy and psychiatric symptoms, sleep disturbances, cognitive memory and language deficits. That being said, a lot of kids still do very well. So in a cohort, again, granted small cohort, about 3/4 of patients uh made a full recovery within 2 years. Some patients had lingering deficits, uh, uh, mostly behavioral or school issues, so about 20%, and then in a rare, in the rare, uh, 10% of patients, patients can be even more severely, severely impacted. Definitely younger age of onset does pretend to a slightly worse prognosis. Um, but I think in general, as this entity is becoming more recognized, we're catching it earlier, we're treating it earlier and so patients in general are doing a lot better. Um, so if you're seeing a patient with a history of NMDA, like I kind of alluded to, many children will have ongoing cognitive challenges, poor memory, language deficits, behavioral challenges. Some of these can persist lifelong depending on which area of the brain was, was more impacted. If there's a particularly long hospital course, I have a few patients that were hospitalized for 2 or 3 months. Um, you can imagine that reintegrating back into school can be challenging. So oftentimes we work a lot with schools, IEPs, 504 plans, um, to often times kids will start with a half day, a few days a week, and we slowly try to, try to reintegrate them, but it can definitely be tough at the beginning. Patients may have a new diagnosis of epilepsy, which can be challenging. Um, definitely still encourage clinical monitoring for relapses. Again, as the later on, the, the longer you get out from the disease onset, the less likely you are to relapse, but it still can occur. And then we usually recommend Um, several follow-up MRIs, um, to assess for inflammation. And then depending on the treatment regimen, if a kid is put on rituximab for, um, you know, 6 months or 12 months, we'll have, we have to do the appropriate rituximab screening labs. Um, But again, in general, think of this like severe onset, uh, kids can get pretty sick, uh, but by and large, kids do recover and do really well. They just may have a few lingering kind of cognitive, uh, cognitive concerns. Um, OK, great. So that's all I have multiple sclerosis, mog, and anti-NMDA receptor encephalitis. Uh, the other main category of demyelinating disease is NMO, but that's much more of an adult disease. And then, um, the other types, smaller types of, or the other less common types of, of encephalitis I mentioned. But again, this is probably gonna be the most common things that you're seeing or most common types. The patients that you're likely um to have on your panel. So hopefully, I was able to give you a little bit of background, some signs and symptoms to think about, uh, treatment regimens and, and how we can, uh, you guys can be helpful in terms of, of, of, you know, if you're seeing these patients in outpatient setting, things that we would be worried about, things to be on the lookout for, ways that you can help with counsel, counseling families.
