Ep 92 Multiple Sclerosis: Scarred nerves & skating saints

is not has anything to do with MS. So she sent me for an MRI and I did the test and she called me the very same day. And the fact that she called me the very same day, I was like, Oh God, what's happening. Something really bad is going on. And she's like, you know, best case scenario, you might have migraines. She goes, worst case scenario, I think you might have multiple sclerosis. So now I'm really panicking because I'm twenty seven years old. I don't know

anything about multiple sclerosis. I know it exists, you know from the media and the famous people that you here have it. Now I'm thinking I'm going to die and I'm twenty seven I haven't lived the life that everybody gets to live. I am I going to get be able to get married?

It's hard to kind of grasp the concept that your lifespan is going to be shortened. We all know we're going to die, but we it's off in the far future. We don't think about it on the day to day. We don't grasp it. It's not something we worry about. But at that point, my death seemed to be right around the corner, and it was very scary, and feelings of depression and helplessness kind of took over, and I was just not in a good place in my head just thinking about how all of this was going to

play out. But I did end up finding a fabulous multiple sclerosa specialist, and he is the best thing that I could have ever hoped or and honestly I can say without him, I would not be here talking with you today. So over the next nine years, it took that long to find a medication that I would respond to.

We tried everything. My body will either reject or not respond to lots of different medications, So with the choral medications, I just went into complete allergic reactions on every single one and it was just not going to be able to happen to stay on it. So then there's the self injectable medications, but they would burn when they would go in, and I ended up creating a lot of scar tissue around my body from where I had to inject because there's only so much skin areas you can

put them into. But when we were doing MRIs, because each drug that you go through you have to wait about six to eight months to see if they actually work, the self injectable medications did not stop any of the progression of the disease. At this point, Like I said, it had been nine years and I was just still progressing and falling down this horrible hole, and my prognosis

was really grim. At that point, we didn't really know if I was going to respond to anything or if I was just needed to prepare myself and get my affairs in order type of thing. But God loved my specialists because you did not give up on me. And there are infused medications. So I've actually been on an infused medication now for five years and it is working, which is fabulous. It really has slowed the progression of the disease. The downside of my infusions one is the cost.

My infusion is about seventh dollars a month, and had I not had insurance, there would be no way for me to receive this medication that would save my life. I would have to just die because you can't afford seven thousand dollars a month. Also, with my medication, I get very tired, like the day before and the day of I'm tired, and sort of the day after I'm tired. So it's good like forty eight hours to seventy two hours where I'm kind of just have to be still

and relax. My body just doesn't function. And the last thing that's kind of scary about my infusions is it interacts negatively with something called the JC virus, which we all have, most of us have in our brains, but nothing really happens with it because it's never really activated.

But this drug will activate it. And when it is activated and you're on this medication, your risk for PML goes right up, which is a really long medical term, but basically it's a brain infection that can cause death. So that's kind of scary. Every time I sit in the chair once a month, going is this the day? I don't know. Since it took such a long time for me to find the medication that would help me, I had gone from the beginning stages of MS to the secondary stages of MS. What that means is I

don't have flare ups anymore. My conditions and my symptoms are with me every day, all the time. Nothing changes. So my motor nerves are what's mostly affected, and so my coordination's off, my balance is off. I trip and fall a lot, and a lot of people get.

the nerve endings at the end of my fingers. It just isn't there. I get tired a lot.

explain to you what's happening. But I would have to say the most humbling symptom that I have with my multiple sclerosis is the loss of bladder control. That is an incredibly embarrassing, sort of dejecting thing to experience because it makes you feel like you're incapable as an adult. You know, you've gone back to being a child and not being able to make it to the bathroom on time. Recently, my short term memory is evading me. I need sticky notes to get through my day. Otherwise I don't know

where I am. Sometimes I'll be in the car, I'll be driving and I have completely forgotten where I'm going. But even after all of that, I'm still one of the lucky ones who have multiple sclerosis because at this point, I don't need any assisted devices to move around. I don't need a cane yet or a walker. I do know, though, that in the future I will most likely be confined to a wheelchair. I'm not thrilled about that, obviously, but

I'm sort of resigned to it. My worry is that as my disease progresses, I'll become a burden on my loved ones that will have to take care of me because I won't be capable of doing that. And I'm scared as to how my final days will play out, because multiple sclerosis won't kill me, but the fact that I don't have an immune system will kill me. So I don't know if it'll be pneumonia or some sort of sepsis or at this point COVID. It's like a

grab bag. And so that sort of fear of the unknown really just overwhelms you at times, and you just want to sit on the couch and say, well, what's the point. But at the end of the day, you just have to do your best and get up and try to.

think that it really shows how inadequate. Are you know, diagnostic criteria are not even diagnostic criteria, but how inadequate our definitions of disease really are.

You can find everything, anything.

of the pathology at its core. What's happening in MS is that our neurons become demyelinated. We've talked about myelin I think before on this podcast, but I can't remember what episode, and I tried to look through my notes and I couldn't find it. But anyways, myolin is the sheath. It's the outer layer of our nerve axons. It's like an insulating layer that surrounds our nerve fibers. You can think of it as like the insulation around an electrical wire.

myelin sheath is going away. As this myelin sheath becomes destroyed, nerve impulses aren't traveling from our brain to whatever target organ they're supposed to. And then this can lead to any and all different kinds of neurologic symptoms because of this lack of signal transduction. And so that's what the kind of symptoms can look. What does that actually mean in terms of disease, Let's talk about it.

One relatively common presentation that happens in about twenty percent of people as the first sign of MS is something called optic neuritis. This is when the demylination and this inflammation happens to affect the optic nerve, which is our

second cranial nerve. Optic neuritis, when it's like this, presenting sign of MS usually happens as a pretty abrupt onset of blurry vision or loss of color vision, or complete loss of vision in one eye or sometimes the presence of like a black spot or a scotoma in the middle of your vision and pain with eye movement because of this inflammation that's happening in the nerve.

nerves are in our brain or our spinal cord. So some other common presentations of this clinically isolated syndrome or this first time presentation of what will then be MS. Could be weakness in one or more of your limbs. It could be spasticity on the flip side, which is where you know the muscles become very either flexed or they get stuck in an extended position and that can

be very painful. You can have abnormal sensation like numbness or tingling in the arms or legs, or even one that kind of comes up commonly is like a band like sensation of like a squeezing band feeling around the rib cage.

and then does resolve. And generally, especially with a clinically isolated syndrome or a first time presentation, people do tend to recover to about eighty to one hundred percent capacity. So in the case of something like optic neuritis, you have loss of vision or drastic change in your vision, it lasts for at least twenty four hours, and then it gradually improves back to pretty close to or at your baseline level of vision. And that happens with essentially remyelination of oh of your nerves.

whether or not there are associated MRI changes. So MRI magnetic resonance imaging is a type of imaging that's really good at looking at soft tissues and our nervous system. And there are a number of different MRI changes that you can see on different types of MRI imaging, which I'm not a radiologist, so I'm not about to get into, but there are a number of different findings on MRI

that can be relatively specific two MS. Right, So if you have these symptoms consistent with a cis a clinically isolated syndrome, and you have these typical findings on MRI, you are very likely to then go on to develop MS. Okay, and with new diagnostic criteria, if you find more than one of these MRI findings that are separate in time

and space. So either like two symptoms with two different lesions on MRI, or maybe you have lesions without symptoms, but you have lesions in different stages of healing in different places in your brain and spinal cord that together can lead to a diagnosis of MS even with a first time presentation. Does that make sense?

other things that you can do. You can do lumbar punctures to look for findings that are indicative of MS. So there's a lot of different, you know, kind of things that you can put together to try and make an earlier diagnosis of MS now than we ever used to before, which is a big deal, as we'll talk about later when it comes to like starting early treatment.

those neurologic presentations. One time it might be my hands are tingling, another time it might be I can't move my legs at all. Another time it might be I go blind in one eye. It could be any of those or any combination there. And over time, as these relapses recur, they result in progressive worsening of disability, progressive

loss of neuronal function. Because what happens is that every time this demyelination process occurs, not only do you have acute inflammation and a lot of immune reaction in that area, but then there is damage to the underlying nerves and that's difficult to repair. So our brains and spinal cord can repair the milin sheath. We have cells. That's their job is to make myelin, and they can do that, but as part of our body's natural repair process, they'res

scarring that happens in the brain. We call this gliosis, and this scarring then leads to progressive disability over time.

of our body's natural repair process. But that scarring then leads to neuronal damage.

So over time, especially without treatment, relapsing remitting MS can lead to what's called secondary progressive MS, which is where instead of seeing these discrete relapses of like new symptom onset and then recovery, you just now have like a progressive accumulation of neurologic dysfunction and disability.

your hands, right, it's not one specific nerve. And so I think, like I said, how you can have radiologic findings on MRI that maybe don't correspond to a specific symptom, but maybe lots of little demyelination events in various areas can then result in these more generalized symptoms like a fatigue or et cetera.

to be a little different. But there's also so much overlap between these two that there's also some question whether they truly represent two different, you know, phenotypes of this disease or not. So when it comes to MS, there's a lot of questions, but there are two big, kind of separate but very related questions that full disclosure, we don't fully have answers to, and that is what is the ultimate cause of MS and what is the underlying

mechanism of damage? So the underlying mechanism of this damage is still not entirely clear. There are a number of papers that I will point listeners to with a lot of like really immunology geek heavy details on like what specific immune mediators, inflammatory markers, et cetera. Are involved. We know that especially B cells and to a lesser extent, T cells and self reactive antibodies aka autoimmunity is heavily

involved in the in the mechanistic underpinnings of MS. And we know that it's a combination of this immune response and inflammation that results in the destruction and damage to the mielin sheath and then those cells that produce it, and then that's what makes it more and more difficult to recover, et cetera.

this is an immune regulated disease. And there is some good evidence that some of these regions overlap with other autoimmune diseases, which isn't that surprising.

good at hiding out in our immune system. Now. EBV is a virus that preferentially infects and replicates within a certain subset of our white blood cells. Are b lymphocytes. These are cells that, if we think all the way back to season two, are vaccines part one episode. If you remember that far back, barely b lymphocytes are responsible for producing antibodies. That's their number one drop. So EBV is a virus that preferentially replicates in our antibody producing cells,

and it is an incredibly ubiquitous virus. It infects ninety five percent of the human population. By the time we reach adulthood, all of us have it, and most of us will never ever even know that we were infected. Some of us might have been unlucky enough to have gotten mono infectious mononucleosis that's EBV. That's an acute EBV infect if you get it as like a teenager or young adult, but most of us get it as kids

and we never even knew that we had it. ABV has been known for a really long time to be implicated in the development of a whole bunch of different cancers Hodgkins lymphomas, B cell lymphoma's, nasopharyngial carcinoma, like the list goes on. So why am I talking about it?

contenders to be the virs potentially associated with MS. And there have been a lot of papers throughout the years that provide evidence of kind of epidemiological support for this, and a lot of them had pretty solid links showing that infection with EBV puts you at higher risk of MS, especially symptomatic infection. So infection that results in infectious mononucleiosis or MONO is a substantially greater risk factor than just

asymptomatic EBV infection. I think people are two or three times more likely to develop MS after infectious mononucleiosis compared to asymptomatic EBV. But back to this new paper. This new paper that just came off the press lends even more support to this idea. This paper, which was published in Science on January thirteenth, twenty twenty two, showed that infection with EBV increases year risk of MS by thirty

two times. Thirty two times. Some of the early studies of lung cancer and smoking showed like a twenty five times increase in risk of lung cancer from smoking. But the other thing is that so this paper, and I just encourage everyone to read it because I'm not going into as much detail because I would talk for too long.

But they used serum samples from over ten million active duty military personnel that spanned over a decade, and they looked at eight hundred and one people who were diagnosed with MS during their time in the military and compared them to like twice as many matched controls. And from this study they were able to establish a very causal association between first EBV sero conversion that came first, then

markers of axonal degradation, degradation of the axons. They were able to find markers of that in the serum, and then later diagnosis of MS, so a causal relationship first EBV, then symptoms of neurons starting to degenerate, then a diagnosis of MS.

associated with autoimmune demyelination. And that's a lot I know, But basically this second paper that came out provided at least one possible mechanistic link that basically says, hey, this anigen that ABV has looks a lot like one of our cell anigens, right, like something on our human cells, And in people with MS, they're making antibodies that are cross reacting.

cells are so involved in this dysregulated immune response. Or other components of our immune system inflammatory system that are directly targeting the mechanisms of DAMA image trying to prevent this damage, prolong the time between relapses in relapsing remitting MS, and prevent the development of disability. There unfortunately aren't as

many therapies for primary progressive MS. So in both primary progressive and in relapsing remitting MS, there's also a lot of other therapies that are more towards whatever the symptoms are rather than treating the underlying disease. So there's always like a multifaceted approach to treatment. Right, that was long winded, But that's MS.

I can't do that. I don't because we don't know, like you said, what exactly causes it still, the mechanism of disease, and I can't even really make a guess because we just lack that knowledge. If it is caused in part by EBV, then you know, it seems as though EBV, like most herpes viruses, has been co evolving with humans, so it's been infecting humans since before humans

were humans. If it's caused by EBV plus genetic predisposition or EBV plus genetic predisposition plus adolescent vitamin D exposure or other environmental exposures, then we still don't know, like I said, how all of those things interact and what that means from an evolutionary perspective. I did read, though, one paper that discussed typothetically, why humans spontaneously get MS whereas other primates don't seem to, although it can be

induced experimentally, which I think is really interesting. Yeah, And in this paper it was suggested that it might have something to do with the fact that humans have big brains with a lot of myelination, so it's just like a lot of myelination and that's a costly thing, and that the peak onset of MS typically occurs around the same time that myelination kind of like ends or starts to decline or something.

So is this an indication that people assigned female at birth are developing MS at higher rates today than they have historically or could it be partially an artifact from how difficult to diagnose diseases were viewed differently between men and women, especially in the days when hysteria was considered a valid diagnosis, Like this is all pre MRI, right, like before you could see a physical sign of MS as a physician.

that shift. Okay, So that's all like a very long winded way of saying, I don't know the evolutionary origins of this disease because we don't know enough about it. Yeah, okay, fair enough, Okay, so what do we know. Let's go back to what are commonly reported as the earliest recorded cases of MS. The first is Saint Ludwina of schidem

In Holland, who was born in thirteen eighty. Around the time she was fifteen, Ludwina went out to do some ice skating and while she was skating, she lost her balance, she fell down, and she broke a rib. She never fully recovered from this, and for the rest of her life she experienced difficulty moving around, paralysis, pain, and visual deficits, all of which would come and go, but time got progressively worse until she died at the age of fifty two.

Throughout her life, Ludwina felt that she was sent to accept this suffering for the sins of others, and this was taken to be a sign of a miracle. So after she died, she was canonized and is the patron saint of ice Skaters and the chronically ill.

of Saint Thorlax. So, sometime between twelve ninety three and thirteen twenty three CE, Halla suddenly lost her sight and speech. She prayed for them to recover and they did. MS could be something else, could be that, Yeah, but that was it. It was just that, just essentially. I mean, I think there was like a little bit more to it, but that was the gist.

Shortly after the funeral, I was obliged to have my letters read to me and their answers written for me, as my eyes were so attacked that when fixed upon minute objects, indistinctness of vision was the consequence. Soon after, I went to Ireland, and without anything having been done to my eyes, they completely recovered their strength and distinctness of vision. For most of his life, Dest kept a journal describing his symptoms, the way he felt about them,

and his experiences with the doctors he saw. And it's a really valuable and interesting insight into this disease and how it was perceived, and it kind of shows in some ways how far we've come, but also in other ways how some things haven't really changed very much at all. So I want to read another quote from Desk from eighteen forty three, about twenty one years after that other entry.

I read quote. What I complain of now is that sitting produces a numbness all down the back part of my thighs and legs, and gives me a curious numb sensation in the lower region of the belly. When standing or walking, I cannot keep my balance without a stick. I sleep well when I am not annoyed with little nervous twitching in my legs and feet. For the first time in my life, I was attacked by giddiness in the head, vertigo, sickness, and total abruption of strength in

my limbs. I was able to drive to my own house, but totally incapable of getting out of the phaeton. I was carried up to my bedroom, where I was sick as a dog and broke out in the most profuse perspiration. And so some of these descriptions, even though they were from the early eighteen hundreds, they may sound completely familiar to people living with MS today. But hopefully what will not sound familiar are the treatments that doctors prescribed for

dest here's the selection. Leeches, beef steaks with wine twice a day, back rubs with alcohol, opium and oils being slapped, extremely hot baths, strychnine, quinine, nitric acid, ammonium carbonate, mercury, cinnamon, rhubarb, horseback riding, and a little bit of light electrotherapy. It's like getting shocked. Yeah, extremely hot baths, Like we didn't talk about this in the bio, but that's that would have exacerbated the symptoms so much it would have felt horrible.

a disease. Throughout the first half of the eighteen hundreds, several different anatomus described lesions in the brain or along the spinal cord while doing an autopsy, which, if you remember from our pupil fever episode, had become quite popular around this time. Pathology had grown greatly as a field, and many people wanted to make a name for themselves

by identifying a new disease. One of these was Jean Martin Sharco, whose name may be familiar from our endometriosis episode, or because of a genetic disorder that bears his name Charkson Marie tooth disorder, or just because he's kind of a big figure in the early history of neurology. He played a role in the identification of many neurological disorders.

motor problems to be his housemaid. He thought she had neurosyphilis. He kept iran until her disease progressed to the point where he was like, you can't really clean anymore, so you're going to this hospital for poor Parisian women. And he shipped her off there, oh gosh, and that's where she lived until she died, at which point he performed an autopsy and he noticed some plaques scattered throughout her

nervous system. And within a few years he had seen several more of these plaques in several more of the autopsies, and so he was thinking, hmm, okay, I think I might have a new condition here, because a lot of the people that had these plaques had reported things like numbness, vision, parlbs,

movement difficulties, speech problems, et cetera. And he noticed too that these signs and symptoms tended to relapse and roomIt and so yeah, he was like, this has got to be a new disorder, and I'm gonna go describe it. So in eighteen sixty eight, Charco gave a series of lectures that named the disease, although they didn't he didn't use the name multiple sclerosis. That would really only be settled upon in like by the nineteen fifties or so, like,

there was disseminated sclerosis. There were a ton of different names for this, but he also drew like boundaries around it.

common in women than in men. Does this mean that Charcot was ahead of his time, because, like I said, that's something that really only in since the mid nineteen hundreds or so people recognized and kind of yes and no. If he was ahead of his time, it wasn't for the right reasons, because let's hear why he thought people, especially women, developed ms oh yeah quote long continued grief or vexation, such for instance, as might arise from illicit

pregnancy or the disagreeable annoyances and carking cares which a more or less false social position entails. This is often the case as regards certain female teachers. Having said so much with respect to women, the question of the male sufferer arises. These are, for the most part, persons who have lost caste and who thrown out of the general current and too impressionable, are ill provided with the means of maintaining what in Darwin's theory is called the struggle for life.

to even try to undo. But anyway, for decades, Charco's description of MS from these lectures basically remained unchanged, with just a little refinement here and there not because no one was studying the disease. Charko's lectures kicked off a huge amount of interest in MS. But just because the general outline of the disease remained the same, that doesn't mean that the way it was perceived also was unchanged.

So going back to dest and his journals, I think reading through them, as well as other people's accounts of their experiences with MS in the late eighteen hundreds and early nineteen hundreds, it helps us to better consider this

disease through the lens of history. Pick any point in the history of MS from the mid eighteen hundreds and ask what else was going on in biomedical science at the time, what new discoveries have been made or technologies developed, and you'll see how that historical context affected not only the diagnosis of this disease, but also how it was

treated and what was thought to be the cause. So improvements in microscopes and the autopsy trend that led to this disease being defined because it allowed people to see the connection between these lesions and the symptoms of MS, and since germ theory was in full swing around the time MS was first fully characterized, researchers proposed microbe after microbe responsible for the disease, and even produced some MS vaccines,

none of which was able to be repeated or panned out. Really, and this focus on a microbiological cause of MS so early on it was surprising to me initially, but it also makes sense in light of the ability of syphilis to cause neurological disease. Until a lot of people were like, oh, if syphilis can do this, then you know, we see

neurological disease. This could be caused by another pathogen. Yeah, And more recently, you know, one of the current trends is the gut microbiome in general, and what are microbiota, how that influences our health and other diseases, and so there has been attention more recently regarding what role that has to play in MS. So we don't, you know,

we don't know. Maybe we'll learn more, and I think, you know, we've now with this EBV super robust study, we've kind of come full circle, and maybe some EBV vaccines in the works. Yeah. A quote from the early nineteen hundreds by Pierre Marie, a student of Charcot, may

soon seem very prophetic. Quote. I have little doubt in fact, gentlemen, that in the employment of such a substance as the vaccine of pasture or the lymph of cook, the evolution of insular sclerosis will someday be rendered absolutely impossible.

relying more on signs than symptoms for many diseases. So like, signs are things that are observable detectable by someone who's not the person experiencing them, and symptoms are only able to be described by the person experiencing them, and so this switch from focusing more on signs rather than symptoms

that also applied for MS. In the days before MRIs, diagnosis was often described as being difficult, or maybe it was that a proper diagnosis required that a physician had to listen to and believe their patient difficult, difficult, and people with MS were often diagnosed with a variety of other conditions. In the seventeen hundreds and eighteen hundreds, that

was often paraplegia. This is what dest was diagnosed with, and paraplegia was this umbrella term under which a lot of diseases that included partial paralysis or movement disorders were thrown. And then when the spira keet that causes syphilis was identified in the late eighteen hundreds, it was common for a person living with MS to get a diagnosis of neuisiphilis, which is what another couple of people in the eighteen hundreds or early nineteen hundreds were diagnosed with formally or

just suggested to have the German poet Heinrich Heiney and WNP. Barbellian, pen name of Bruce Frederick Cummings, who wrote a book describing his life with MS titled The Journal of a Disappointed Man. So they were both thought to have neurosiphalis, but more likely MSMs, but doctors also suggested to Barbelian

that it was all in his head. And in that same vein, Margaret Gaddi, who was a Victorian novelist and naturalist who also had MS, was told by her physician that her illness was quote caused by her tendency to use excessive physical effort in gardening, using heavy tools in the manner of a man.

the disease. And I don't love this term because I think it can be misused to undermine or discredit the very real things that people with one of these diseases are experiencing. If I can't say you're sick, then you must not be sick, or those things you say you're feeling are just not real, like you're exaggerating them, right, And this is the kind of logic that led to hysteria being diagnosed for all manner of diseases, including MS.

As Maya Dusonberry puts it in her book Doing Harm quote, perhaps one of the clearest examples of an autoimmune disease carved out of the waste basket of hysteria is multiple sclerosis. That phrase is so excellent, the waste basket of hysteria, because it's like, how many things were misdiagnosed as hysteria? And this was even commented on in the early twentieth century.

Doctors were like, MS is not that difficult to diagnose, but there are a lot of misdiagnoses, with doctors most commonly confusing it with hysteria, and people living with MS were diagnosed with hysteria well into the nineteen fifties. It happened at such a high rate, in fact, that it drove the definition of hysteria to change in the early twentieth century to distinguish it from MS.

were simply more neurologists. By the nineteen tens the nineteen twenties or so, there had been a substantial rise in trained neurologists in the US, and not just restricted to cities but also to smaller towns and rural areas, and by the nineteen fifties, what had once been thought to be a rare disease was now considered one of the

most common illnesses of the central nervous system. And with this rise of neurologists there also grew to be more focused at ten, specifically on MS wider scale studies such as you know, the one that was able to be done with soldiers from World War One and World War Two, where we had a lot more medical information about thousands and thousands of people readily available. Which is kind of funny that this twenty twenty two paper is mirroring the same thing, but from the data from World War One

and World War Two. That's where it sort of paved the way for these large scale epidemiological studies looking at geographical trends where it seemed to be occurring at higher rates or more often diagnosed in people from more northern areas, northern regions that I want it like. I'm very excited to hear you talk more about that, because I know

it's like a more complicated story than that. But this pattern where MS seems to be more frequent in not as you go farther away from the equator, but just more northern climates and northern hemisphere has led some people to suggest that this disease has Viking roots, as in the frequent travels of Vikings in history essentially disseminated that

MS predisposition around certain places. Yeah. I don't know how much evidence there is to support this, but my guess is that as better and better genetic tools are being developed all the time, maybe we will be able to tease out some sort of historical story for why we

see what we see. By the mid nineteen fifties, there was much more awareness about multiple sclerosis among the medical community, and scientific advancements had helped to understand more about what was going on inside someone living with MS, which helped in the development of some treatments to manage the signs and symptoms of the disease. But this growth and awareness was not just limited to healthcare workers working directly on MS.

One of the biggest turning points in the history of MS happened on May first, nineteen forty five, when a woman named Sylvia Lowry, whose brother Bernard had MS, and Sylvia had gotten so frustrated by the lack of clear information and adequate treatment from her brother's physicians, and so she posted an ad in The New York Times with the following request quote multiple sclerosis, Will anyone recovered from it?

Please communicate with patient? And she got dozens of replies, like way more than she expected, and so she thought, Okay, I can't be the only person who could use this information. I'm going to bring all of these people together. And in nineteen forty seven she brought over twenty leaders in the field of neurology together to try to set objectives for an organization that was dedicated to understanding the disease

and finding a cure. Wow, and Sylvia, like I said, didn't stop at founding the Multiple Sclerosis Association, which was later changed to the National Multiple Sclerosis Society. She also helped found the Multiple Sclerosis International Federation, and for the rest of her life she campaigned incredibly hard to raise awareness of this disease and bring in more funds for research as well as supporting people living with the disease,

and her efforts were hugely successful. Her work and the work of these and other MS organizations show once again how incredibly important it is for people to share their story and how much of a positive impact patient advocacy groups can have on bringing awareness to a disease and providing support and resources to those who need it. Within ten years of the National MS Society being founded, there

were one hundred and twenty thousand members. She brought in celebrities and politicians, including Shirley Temple, which I'm now realie would have been a great quarantine. But that's okay, I would have been.

And this is also still a common theme today, which I think is wonderful, with celebrities like Jamie Lynn Siegler who plays Meadow on The Sopranos, which I'm finally watching right now, and former US Representative Donna Edwards and many

others raising funds and awareness for the disease. I would also just like to encourage anyone who is interested in learning more to check out the National MS Society website because it's an amazing resource for seeing the latest news, finding support, understand the signs and symptoms of the disease, and so much more.

nature of this disease. And finally, the development of the MRI in the late nineteen seventies meant that you could finally visualize this disease, which helped not only with understanding more about it, but it also lent edence to the people who had had their symptoms repeatedly dismissed. Kind of reminiscent of the way that laparoscopic surgery was used to

legitimize endometriosis, just parallels. But it's true that the MRI revolutionized diagnosis, especially early diagnosis for people with MS, which, like you said, has been tremendously helpful for coming up with a treatment and management plan for people living with a disease, as well as being able to evaluate which

medications might have an impact. There is so much more that I could have included in this history in terms of like the specific medical developments and who discovered what, and who wrote this paper and who found this sign or whatever. Over the past one hundred and sixty years and that information is out there if you're interested in

learning more. I recommend the book multiple Sclerosis, The History of a Disease, but I'm going to leave off with the history here where Since them, we have many medications that seem to be very helpful in managing symptoms, and we are now so much better than we used to be in our knowledge about multiple sclerosis. But at the same time, there are still so many unanswered questions why first and foremost, because without a why, it's going to be nearly impossible to find a cure right or it's

going to be very difficult. And I also think that we still have a long way to go in terms of understanding how much of the criteria that we use to define multiple sclerosis actually captures the experience of someone living with it. So, Aaron, can you tell me more about where we stand today with MS?

into that. In the Global Burden of Disease study, which looked at data from nineteen ninety to twenty sixteen, it was estimated that in twenty sixteen there were over two million, two hundred thousand prevalent cases of multiple sclerosis globally.

across the globe. You mentioned, Aaron, there is some kind of question where sometimes people say it's it's closer to the equator is less, or northern latitudes is greater. And there's even been some studies that have tried to look at even within countries, whether there are like north to south gradients in cases, and part of that is why the idea of sun exposure and vitamin D has some support as in more northern areas where you have less sun exposure is where you have higher rates of MS.

But it also doesn't hold true like one hundred percent, because there are specific indigenous populations and areas that actually have very low rates of MS, even though they live in very northern areas. So it's not the whole story, like a north to south gradient isn't the whole story, but there does seem to be at least some associations.

combined might explain some of this increase. So there's still a question as to whether an increase in prevalence means also that there is a true increase in MS, or if we're just diagnosing it better and people are living longer with it, which is always going to increase the prevalence.

adjusted life years. And we've talked about how that's not a perfect measure of the impact of a disease, but it is at least a measure that we have that this is something that is significantly impacting people's lives, right.

just so much that we don't know. And I think that what's especially exciting about research on MS is that the kinds of studies that are being done are incredibly important not just for MS, but also for our understanding of neurodegeneration and cell regeneration, right, and this can help in the treatment of so many different diseases and neurodegenerative disorders. This is also what has led to so many new treatments for MS and related disorders as we better understand

these kind of mechanistic underpinnings of this damage. Right, this kind of basic science is phenomenally important. And then there's also so many questions as to, you know, the genetics of why does one person develop MS after an infection with EBV and another person doesn't, Like, what is it about those immune responses? And and that is important not just for MS, but also for so many other immune disorders, right, Understanding what these triggers are, what these predispositions are, and

like what we can actually do about them. Yeah, And these new studies really showing that EBV is likely, in fact a necessary precursor to the development of MS, meaning that MS is like viral sequelae of infection with this virus. That means that we could prevent MS, right, Yeah, if we could prevent infection with EBV, And it also means we could prevent so many other things that EBV also causes, right, brickets, symphoma, mono, like so many other things, right, and moderna of COVID

vaccine fame just started. Like literally, this press release also came out within the last couple of weeks. They just started phase one trials of an mRNA vaccine targeting EBB.

very exciting, published January twenty twenty two. And like I also said, I do want to give a special shout out to the National MS Society website because I think that it is just such a helpful breakdown of so many different aspects of MS, but especially like different symptoms of MS, because I think that's something that most of the papers just don't do a good job of explaining.