← MS Living Well: Key Info from Multiple Sclerosis Experts
MS Living Well: Key Info from Multiple Sclerosis Experts
MS & The Spinal Cord
00:39:50
The spinal cord serves as the main communication highway between the brain and body. Did you know that 80% of people with multiple sclerosis have spinal cord lesions on MRI? These lesions can disrupt specific neural pathways, leading to common MS...
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Foreign.
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Welcome Back to the Ms. Living well podcast. I'm Dr. Barry Singer, director of the Ms. Center for Innovations in Care at Missouri Baptist Medical center in St. Louis. This episode is Ms. And the Spinal Cord. This episode is sponsored by TG Therapeutics, a biopharmaceutical company focused on treatments for B cell diseases such as Brienvy for multiple scleros. When multiple sclerosis impacts the spinal cord, it disrupts crucial signals between the brain and the body, leading to symptoms like numbness, weakness, balance problems, and bladder issues. Recent advances in imaging technology and pathology studies are shedding new light on how Ms. Affects the spinal cord, offering better monitoring and renewed hope for treatment options, especially for those with progressive disease. I'm delighted to be speaking with two spinal cord experts on the podcast today. Later on, we'll be discussing imaging and treatment with Dr. Bruce Cree, but first, my conversation with Professor Gabriel DeLuca. Gabriel DeLuca is a professor of clinical neurology and experimental neuropathology and honorary Consultant neurologist at the University of Oxford in the United Kingdom. Professor DeLuca's research group explores the neuropathology of multiple sclerosis using postmortem brain and spinal cord tissue to identify new targets for treatment. He also leads an international neural rehabilitation partnership with the goal of revolutionizing restorative neuroscience. Welcome to the Ms. Living World podcast. Professor DeLuca hi.
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C
Thank you for having me, Barry.
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B
Absolutely. So first of all, can you tell us what is the spinal cord and what does it do?
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C
Well, the spinal cord is a long, thin tube like structure that measures around 17 to 18 inches in length. That's about 40 to 45 centimeters for those of us who use metric. And it has a diameter ranging between about a quarter of an inch to half an inch. Despite its diameter being so small. It's the main information highway for messages to be sent from the brain to our peripheral nervous system.
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B
So what kind of information is the spinal cord sending to and from the rest of our body?
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C
So the spinal cord has many different pathways. So it sends nerve fibers from the part of the brain responsible for movement, our motor control, to the body to allow us to move our arms, our legs and our trunk. But it's also important in that it sends signals from our nerves in our skin that sense pain, sensitive temperature, light, touch, vibration, so that those can go to our brain to enable us to feel what actually has touched us. But the spinal cord also coordinates reflexes when doctors tap your tendons with a reflex hammer. But it also houses circuits that are really important for us to coordinate Our movements, such as walking. But importantly, the spinal cord also allows us to control our bladder, our bowel and sexual function, and other involuntary functions that are key to our fight or flight and arrest and digest responses.
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B
Excellent. So, Gabe, how often is the spinal cord affected in someone with ms?
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C
The spinal cord is commonly affected in people with ms, but how often and to what extent depends on the stage of the condition. Several MRI studies have shown that areas of demyelination in the cord can be found in about 80% of people with Ms. And most people have more than one lesion when they do have one in the spinal cord. In early relapsing, remitting MS, we know up to 83% will have demyelination in their spinal cord. So it's pretty frequent. But we do know that spinal cord lesions can be detected on MRI scans in people who don't even have any symptoms. For example, there are some people who may get an MRI scan because they have a headache, and they're found to have lesions that look like Ms. In their brain, even though they don't have a diagnosis of Ms. We call this the radiographically isolated syndrome. And in those people, about 35% of them will have silent spinal cord lesions.
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B
Wow.
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C
And in people who've had their first episode of demyelination that affect a part of the central nervous system outside of their spinal cord, like, let's say, for example, losing vision in an eye, like optic neuritis, we call that a clinically isolated syndrome. About 27 to 53% will have a lesion in their spinal cord. And what's really fascinating, Barry, is that the presence of a spinal cord lesion not only increases the risk of later getting ms, but if someone has ms, having spinal cord lesions increases the risk of building up disability over time. So, really, spinal cord lesions are important.
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B
What kind of lesions do you see in the spinal cord of people living with ms?
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C
So, when I think of lesion type, I think of two different classifications of lesions. So how inflammatory the lesions are and where the lesions themselves are located. So to understand this better, I often compare the formation of lesions with cracking an egg at the beginning. When one cracks an egg, the egg yolk and white are concentrated in one place. Let's call it the center. And over time, the egg white gradually spreads outwards until it stops. This is similar to how inflammation marches. At first, there's a heap of inflammation that's concentrated around a center point that's typically surrounding blood vessels. And that's where we see the myelin Initially being broken down and where nerve fibers are damaged, time that inflammation spreads outwards like that egg white, and it causes further damage along the way. So when we look under the microscope, we call lesions with plenty of inflammation at the center an active lesion. Lesion where inflammation has marched outwards and is mostly concentrated along the outer border, we call those mixed active. And where inflammation has dissipated or gone away, we call those inactive lesions. So we have found at postmortem that almost 90% of Ms. Cases have spinal cord lesions that show signs of active inflammation at the time of autopsy.
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B
Wow, that's fascinating, because a lot of times we think, oh, the disease is kind of burnt out when someone might be in their 70s or 80s when they pass with Ms. So that's interesting that they do have active inflammation. I guess that gives us hope that we might be able to intervene with treatment.
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C
No, I agree. And these are people who've had the condition often for decades and who are not really closely monitored by neurologists. So I think there's a lot of things that we have to study and a lot of people we need to help.
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B
Let's turn to a little anatomy. So there's different parts to the spinal cord, cervical, thoracic, and lumbar spine. Where does Ms. Affect and how is this all structured? Sure.
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C
So the spinal cord is divided into segments, as you mentioned, and this is where you've got pairings of spinal nerves that are important for movement and sensation, that are formed to supply both sides of the body. So the uppermost part of the spinal cord, we call the cervical segment, the middle part, the thoracic segment. And the lowest parts, we call the lumbar and sacral segments. So there are two parts of the spinal cord that are larger than other parts. That is the uppermost part, the cervical segment, which corresponds to where all the nerves are responsible for movement and sensation in the arms. And the lowest part, the lumbar sacral elements, which correspond to where all the nerve for movement and sensation to the legs go. Now in ms, well, it's actually that uppermost part, the cervical cord, that seems to be most affected. And because that's an important part of that highway that brings nerve fibers from the brain down to the arms, trunk, and legs for movement, and from the skin all the way up the core to the brain to sense things like temperature, pain, and vibration, it being affected can lead to a whole host of symptoms.
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B
Yeah, you know, over on this side of the Atlantic, we call it cervical. Not cervical, but, hey, just potato, potato. But, you know, I think one thing that's kind of interesting that people don't realize is the lumbar spine in that segment of the spine is just spinal fluid. So there's no spinal cord down there. So when you get a lumbar puncture and they put a needle in your low back, you're not going to actually hit the spinal cord. It's just some nerve roots bathing in spinal fluid down there.
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C
That's right.
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B
So Ms. Lesions can interrupt specific tracks in the spinal cord. Can you explain what these tracks are in a little more detail? Sure.
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C
So we have one tract called the corticospinal tract, and that originates in the part of the brain called the motor cortex. And it sends fibers from the brain down into the spinal cord that controls our ability to move our arms, our legs, our trunk. And other tracks, for example, are those that go from the skin where we feel stuff. And it sends signals, for example, like pain, temperature, vibration, up the spinal cord in different tracks. One called the spinal thalamic tract, which is important for pain and temperature. Another called the dorsal column, important for things like sensing where our joints are in space, but also vibration, for example. So those are examples of a couple tracts, but there are several others that we know are important in function and. And can be affected in ms, too.
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B
So, Gabe, when we perform neuro exams in the office using vibration pinprick testing, we're looking to see if specific tracks have been affected. So vibration should be detected by those dorsal columns, and pimprix should be picked up by the spinothalamic tract, right?
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C
Absolutely. And that's why we have to be patient with our neurologists, who are taking out those various tools and poking and prodding and putting tuning forks on us, because they tell us important information about different ways the spinal cord is working. Working.
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B
So if you have a lesion in the back of the spinal cord, what tracts does that disrupt?
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C
So the back of the spinal cord would be disrupting what we call the dorsal columnar tract. And that's important for being able to sense vibration and joint position sense.
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B
So people that have an elision there frequently have numbness in their hands and their legs.
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C
Yeah, exactly. And that's a part of the spinal cord that is commonly affected. And so it is a good explanation as to why so many people with Ms. Have those symptoms of numbness and tingling that you describe.
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B
Now, what about weakness?
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C
So the spinal cord has an area on the sides called the corticospinal tract. And we call, where the fibers are mostly concentrated, the lateral cortical spinal tract. And this houses the motor fibers that are important to supply your ability to move your arms and your legs. And so the sides of the spinal cord. They are also quite commonly affected in Ms. And when they are, that can result in people having a sensation that a limb may feel heavy or may be weak, or they can't use it as easily as before. Like, for example, losing dexterity when they write or being able to pick up fine objects.
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B
For example, what about the Ms. Hug, which is a painful squeezing around the torso? Where do you see lesions with that symptom?
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C
So it depends where that hug is located. But often people talk about this hug around the trunk, and they sometimes describe a vice like grip sensation that can be almost suffocating. That is often due to pathology that's affected in the thoracic spinal cord, that middle segment that I described before.
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B
Excellent. You mentioned bladder problems or bladder urgency, constipation, sexual function. Where are the lesions in the spinal cord for people that are having these symptoms?
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C
Well, we do know that, for example, in the lower part of the spinal cord, that if you have pathology there, you can often get rather significant bowel and bladder symptoms as well as problems with sexual function. But it doesn't have to be restricted to that part of the spinal cord, because, remember, these signals go up and down the spinal cord. And so if we interrupt those, that can lead to a constellation of symptoms related to problems of bladder, bowel, and sexual function.
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B
Yeah, but at the tip of the spinal cord, we call the conus, at the very end of the thoracic spinal cord, a big lesion there can definitely cause some bowel, bladder, and sexual dysfunction. So I want to go back to, like, a really important question. For a lot of our patients that are older and unfortunately have some progressive disease, they get an mri. No change in their mri. The brain, no change in the mri, their spinal cord, but their legs are getting weaker. So what's going on in the spinal cord that leads to this kind of damage?
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C
The question more broadly is, what are the reasons why people have progressive Ms. Later in life? And we don't really know exactly why that is, but we do know that most people who enter the progressive phase of multiple sclerosis develop symptoms that relate to pathology of the spinal cord. So one end of the spectrum, there are people known to have a single lesion in the spinal cord and no lesion anywhere else in the brain or spinal cord. And they have a syndrome that we call solitary sclerosis. And they can develop progressive symptoms specifically related to that one Spinal cord lesion, so they can develop worsening function of immobility or weakness and sensory change. And people refer to that one lesion as a critical lesion. And depending on what part of the spinal cord is affected, that can certainly lead to specific symptoms that the person experiences. But when we talk about progressive decline and we can't find a critical lesion, work from our group and others basically show that the number of spinal cord lesions that you've got in the spinal cord doesn't really tell the full story. We know that there can be considerable amounts of inflammation in the spinal cord, even in the absence of of lesions. So it's likely that the nerve related injury and death that happens can occur not only because of lesions, but also because of inflammation. And that can lead to irreversible disability.
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B
So Gabe, let's dive into that inflammation. Are there specific cells that are playing a role in that inflammation in the spinal cord?
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C
So when we look under the microscope, we see a variety of different immune cells that are important. And one type are called microglia and macrophages. These are important immune cells that act as surveillance cells and they wake up when they see that there's damage, and they can cause damage by gobbling up different proteins and things around them. We know that this type of cell is significantly increased in people with Ms. In their spinal cord, and we think that it's an important contributor to, to damage that we see within the cord. But we do know that other types of immune system cells are important too, like T cells and B cells. These are refined cells that essentially attack specific proteins that they recognize. And we see a good number of them around the lining of the spinal cord called the meninges. And so the meninges and can get inflamed. And we think that inflammation can secrete different factors that can be toxic to nerve cells and that can contribute to their death. So in short, there's quite a bit of inflammation, both within the spinal cord, but also surrounding it, that causes trouble.
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B
So Gabe, are you optimistic that we'll be able to get this inflammation under control and help those people living with progressive Ms. Slow down the disease and prevent progression in younger patients?
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C
Well, I'm definitely optimistic. I think we need to step back and try to understand better what is the nature of that inflammation and how is it that we can detect it better during life, and how do we monitor how it responds to therapy over time? We also have to have an understanding better of the specific molecules and proteins that may be driving this inflammation, so that we could also treat the progressive parts of the disease that so far have been difficult to halt with our conventional therapies.
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B
Well, Professor DeLuca, we're going to be dependent on you and your research as well as our colleagues around the world to go after that information so we can try to change the course of the disease for those living with Ms.
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C
Well, it's definitely our mission to do that until no one suffers from brain diseases. And Barry, I think this podcast is really important, important at disseminating information so that people can be equipped and we can work together to pave a pathway to a cure. So thank you so much.
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B
Next up is Dr. Bruce Kray, a professor of neurology at the University of California, San Francisco school of medicine, UCSF. He obtained his doctorate in biochemistry medical degree at UCSF. Dr. Kuri completed his neurology residency at Columbia university and an Ms. Fellowship and master's degree in clinical research at UCSF. Dr. Cree's research focuses on the genetic epidemiology of MS, developing novel therapies for Ms. Through clinical trials. Welcome to the podcast, Dr. Kree.
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Thank you. Nice to be here.
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B
Great. So, Professor Toluca, shed light on spinal cord anatomy and inflammation. I like to start our conversation by digging a little deeper and Ms. Some people can develop transverse myelitis even as the first attack. Can you explain to our audience what that is?
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A
Great question. So transverse myelitis is one of those phrases that is often used to simply describe spinal cord inflammation that's not technically quite accurate. When one refers to transverse myelitis is referring to as inflammation of the spinal cord that affects both the front half of the spinal cord as well as the back half of the spinal cord. And the way the spinal cord is organized is you have discrete bundles of fibers that either are controlling motor movements or other bundles of fibers that are controlling sensory perception. Bowel and bladder is often affected as well.
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B
So when people with Ms. Get myelitis, what kind of symptoms would they tell you about?
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A
One of the most common presenting manifestations of relapsing Ms. Is spinal cord inflammation that results in tingling, paresthesias, abnormal sensation in a limb or perhaps both limbs. Sometimes both legs are affected, for example. This can be associated with a gradual degree of loss of sensation that often begins in the lower limbs and ascends up to a certain level on the body. But when you examine the patient, you can find normal motor function. Of course, you can have weakness and multiple sclerosis as well, but you don't have to have weakness. So that's a typical manifestation of Spinal cord inflammation or myelitis. And when you have both sensory problems as well as motor weakness and bowel and bladder involvement, then that's when we refer to the process as transverse myelitis.
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B
And so when you start out with you mentioned numbness starts in the feet and ascends up to the torso. So if it gets into your pelvis and stops there, it might be in the thoracic spinal cord, the inflammation. But if it keeps creeping up, then your hands get involved or your arms get involved, then it's more likely in the neck or the cervical spine, Right?
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A
That's exactly right. And that's just because of the way the nerves are organized. They come in through the legs and enter the spinal cord lower, and then the nerves that are coming in through the arms enter the spinal cord higher.
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B
So, Bruce, what about the bladder symptoms with spinal cord disease?
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A
Sure. Well, you can get both bowel and bladder involvement. It's not uncommon for patients to experience urinary urgency and frequency and excessive nocturia, which is urination at nighttime. But you can also develop urinary retention, where you're unable to void the bladder. And for the bowels, often the presenting manifestation when the spinal cord is involved is constipation. So these things together all create a lot of difficulty for an individual. And if you are retaining urine and unable to void, that's one of the things that will definitely bring you on into the emergency department.
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B
Yeah. And also sexual function could be affected, too, through the spinal cord.
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A
Oh, absolutely. Sexual function, too.
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B
Yeah. One tip off that a lot of people have is electric shock sensations down their spine when they flex their neck. And we call that lhermit sign. It's frequently a sign of cervical spinal cord myelitis.
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A
That's right. So the lhermit phenomena is exactly what you described. It doesn't mean that that's due to ms, though, because you can have a compressive lesion, or, for example, from a herniated disc that can make contact with the spinal cord, and then with neck flexion, that can trigger the same type of phenomena. So it doesn't tell you for sure that it's ms, but it is very commonly associated with multiple sclerosis.
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B
I've seen many patients with Ms. Who have gotten progressive weakness in their legs, and they blamed it all on the Ms. And you look in the MRI of the cord, and they actually have a big herniated disc or a narrowed spinal canal that we call cervical stenosis. And it kind of compresses on the spinal cord, and you have Surgery and boom, you're much better.
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A
Absolutely. And neuroimaging by MRI or even CT scan can be extremely helpful to understand the nature of the process, whether you're looking at a compressive problem, which is squeezing the spinal cord, or an intrinsic inflammatory process involving the spinal cord itself.
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B
So, Bruce, are there any other conditions that commonly mimic Ms. By affecting the spinal cord?
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A
Well, there are several conditions that are related to Ms. They're not Ms. Per se, they're distinct diseases. For example, neuromyelitis optica, also referred to as neuromyelitis optica spectrum disorder, often is associated with spinal cord inflammation. And a more recently defined condition, myelin oligodendrocyte glycoprotein associated disease, or mogad, is another condition that can affect the spinal cord. And these are both autoimmune conditions that can cause spinal cord inflammation. And it's important to understand whether one is dealing with multiple sclerosis or neuromyelitis optica or mogad, because each therapy may be beneficial for one condition and potentially not helpful or even detrimental for the others. But that's not where it ends. There's a very long list of infectious agents that can cause spinal cord problems, which includes things like varicella, zoster and other types of viruses. But also bacteria and even parasitic conditions can cause spinal cord inflammation as well.
- [24:38]
B
And sometimes we see sarcoidosis, which can sometimes mimic ms, but looks sometimes different on the mri.
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A
That's right. So neurosarco is another quite rare condition when it's isolated, but can cause inflammation of the spinal cord as well.
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B
So, Bruce, what's your guidance to patients if they want to know, does having spinal cord lesions affect my prognosis living with ms?
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A
The data there is quite mixed. I think when you look at the initial presentation with somebody, if they come in with a very severe spinal cord inflammatory process, and there's considerable motor involvement and sensory loss and loss of bowel and bladder control that actually does carry a negative prognosis for patients, and they may not recover fully from that event or may be left with deficits afterwards. It's an important, but fortunately, often rare phenomena for the initial presentation of Ms. Now, most patients with Ms. Are going to develop at some point over the course of their lives, lesions in the spinal cord. So simply having the presence of lesions in the spinal cord that either are asymptomatic or perhaps associated with mild symptoms themselves doesn't really influence the overall prognosis of multiple sclerosis. That's especially true today. Where we have the capacity to make diagnosis early in the course of the disease and initiate highly effective therapies for ms, especially the relapsing form of Ms. Early on. And often we can prevent further new lesions from forming. But there are circumstances where an old lesion can create problems for patients years and years down the road, and so we want to try and prevent that as much as possible.
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B
So let's say you have a patient and you do an mri, cervical and thoracic spinal cord, and you see lesions, maybe multiple lesions. Does that change how you're going to treat that patient in terms of which medication you choose?
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A
Not necessarily. In general, our field has moved toward use of more effective therapies earlier on in the course of the disease. We're still waiting for clinical trials to prove that that is optimal patient management. But many neurologists are going to see and perceive extensive spinal cord involvement as a negative prognostic factor for their patients. We tend to think of those patients as either having perhaps a more aggressive form of multiple sclerosis that's more inflammatory, or perhaps having had the disease for a longer period of time than realized. And generally speaking, the more disease you have, you have an increased risk of having more problems down the road. So we tend to act more aggressively in that setting.
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B
Yeah, it's sometimes hard to know exactly what you said. Like people in their 50s, the disease may have been very active in their 20s and 30s and they didn't know about it, and then they come in and they may be not as high risk for having new disease activity.
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A
That's exactly right. But those patients are at increased risk for development of progressive disease. And I think one of the big goals roles of treatment in Ms. In general is the prevention of progressive forms of multiple sclerosis. If Ms. Were just due to relapses and all you needed to do was treat the relapses with steroids, we'd have been done years and years ago and we wouldn't need all these disease modifying therapies. But really we're using the disease modifying therapies to prevent disability, especially the disability associated with progressive forms of multiple sclerosis. And so that is, in my mind, the leading reason for treatment in Ms.
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B
Yeah, and I think that's important. So if you see those lesions in someone that's relatively young and they may look great today, I'm always thinking about how are they going to be 20 years from now?
- [28:19]
A
I think that's an extremely important point. When we're speaking with our patients, often our patients are in their late 20s or maybe early 30s, they may have had, for example, an acute myelitis event from which they've largely recovered, and now they feel fine. And so they just want to continue with their life. And instead really, they need to go on treatment. And part of what we have to do as Ms. Specialists is convey the importance of these disease modifying therapies to prevent new lesions from forming, to prevent secondary progressive disease from occurring, and to give our patients an opportunity to have a full, productive life. And I think today we are in a very different position to be able to aspire to do that than we were 20 years ago.
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B
Excellent. So what's the best imaging technique to detect spinal cord and lesions?
- [29:09]
A
We tend to favor use of three tesla MRI scanners that are closed scanners for imaging the spinal cord. It's been my personal experience that open MRI scanners do not provide adequate imaging. The spinal cord is a very small structure. It's about the, the caliber of your pinky finger. And so trying to detect tiny lesions within that, when the structure is surrounded by so much bone and other tissues around the neck, one really needs a high field magnet with a good surface coil.
- [29:40]
B
Yeah, I think it's night and day on a 3 Tesla magnet. And we have two of them at our medical center. I think it's really critical because the older scans or open MRIs, we miss lesions, and sometimes we're guessing if they're really lesions there or they're not.
- [29:54]
A
That's right. You want the best possible imaging for your patients at all times.
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B
Bruce, when you get that MRI scan, what are you looking for?
- [30:01]
A
First off, you want to confirm that there aren't any compressive features that are involving the bones or other structures around the spinal cord. And then you want to get a good look at the spinal cord itself. And there when we speak about lesions, what we're really referring to are Ms. Plaques. Right. So these are areas where there has been inflammation, and sometimes we can see acute inflammation on a contrast enhanced sequence. But a lot of the time we see is the residua of that inflammation, which is basically an increased water content in that lesion. And that can show up as bright signal on a type of imaging called T2 weighted imaging. So that's basically what we're looking for, is evidence of Ms. Having affected the spinal cord. But we're also very keen on more advanced techniques that can quantify and measure the spinal cord in, in particular the spinal cord area. And we have very good techniques for looking at both the gray matter structures which Are where the neurons within the spinal cord exist. Those neurons are critical for conducting information from the brain and relaying that information to the muscles to activate those muscles. Every time we move a muscle anywhere below our neck, we're utilizing those neurons within the spinal cord cord. And so we can visualize those gray matter structures. We can visualize the tracts where sensory information is coming back up. We can visualize those white matter structures as well, and quantify the relative areas of gray matter and white matter, as well as total cord area. And this winds up being very important when we are trying to understand Ms. Related disability. One of the things that we look for in our patients is a kind of global measure of their disability, Something that we term the expanded disability status scale. And when we see a loss of that gray matter in the spinal cord, that has a strong correlation with physical disability and multiple sclerosis, as measured by the EDSS scale.
- [32:04]
B
With ms, some people have some shrinkage of the spinal cord, Is that correct?
- [32:08]
A
Exactly. So when you have damage to the spinal cord over time, you get loss of spinal cord tissue, and the spinal cord shrinks over time. That process, often referred to as atrophy, can be quantified and measured using these advanced imaging techniques.
- [32:25]
B
The brain is shrinking in everybody, but a little more accelerated in people with Ms. What about the spinal cord? Does the spinal cord shrink with normal aging?
- [32:33]
A
That is probably true, too. And so when we try to quantify any individual patients loss of spinal cord tissue, we want to understand that and contextualize it in terms of what might be expected for a patient of roughly the same age and same sex who doesn't live with Ms.
- [32:51]
B
Some patients, I noticed on their mri, they'll have a big lesion, and then they have vocal narrowing. So just at that one level, the spinal cord seems kind of narrowed. Is that a typical finding?
- [33:02]
A
Yes. And that's something called myelomalacia. And when people look this up, they often get very worried because it's irreversible damage to the spinal cord. And that is one of the features that we're trying to prevent happening in Ms. By use of our disease modifying therapies.
- [33:18]
B
Now, sometimes on mri, you'll see discrete plaques. They kind of look like round plaques, almost like in the brain. But then other people have more patchy change in their spinal cord on mri or more diffuse changes where it's bright and hazy in the spinal cord, as opposed to seeing, like, really well defined lesions. What's going on there?
- [33:37]
A
Well, I think it's important to understand that there are technical limitations to what the MRI can do. So, as good as the MRI is, its capacity to image things is down to about a millimeter. And of course, what's happening in multiple sclerosis is happening at the cellular level. When cells of the immune system infiltrate the brain and spinal cord and are causing tissue injury at amy microscopic level. And sometimes when enough injury has occurred in one particular location, we can see it clearly on the MRI as a well demarcated lesion. But a lot of the time, the lesions are too small to clearly visualize. And so when enough of that disease activity has aggregated at a particular spot, you can see these sort of hazy changes. It's all still inflammation, it's all still damage being caused by the immune system. It's just just below the level of resolution of the MRI scan. And of course, this process is going on both in the brain and spinal cord. And so often we see these sort of hazy changes. It's all the same type of inflammatory change.
- [34:42]
B
Yeah, thanks for explaining that. So do you routinely monitor Ms. Patients for new cord lesions?
- [34:48]
A
So I think it all depends on the nature of the therapy that one is using today. When we look at some of the treatments that we have, they're so effective at preventing new lesion formation that in my opinion, routine surveillance monitoring with MRI every year is no longer really necessary. So, for example, with the anti CT20 monoclonal antibodies, we have three of these approved for treatment in Ms. Today. They prevent 98, 99% of new lesion formation. And so you'd be really running an awful lot of scans in order to. To detect that occasional new lesion. So in my practice, it really depends on what treatment a patient is on. If a patient is on no treatment. Yeah, I'm going to monitor those patients periodically.
- [35:33]
B
So, Bruce, do you monitor patients with brain only, or are you monitoring for new spinal cord lesions?
- [35:38]
A
Both. So in an untreated patient or a patient who is on a far less effective therapy, then I will monitor for new lesion formation both in brain and spinal cord.
- [35:49]
B
Yeah, I do too. It's interesting because the guidelines don't really say that currently unless you're having new symptoms. And I find it very, very important.
- [35:57]
A
Yeah, I think the guidelines are based largely on the era when spinal cord imaging was still not very good. In ms, we have an area of medicine which is evolving rapidly, and so we do have to update our guidelines much more frequently.
- [36:15]
B
Yeah. Protecting the spinal cord for my patients is paramount.
- [36:18]
A
Absolutely.
- [36:20]
B
So MRI imaging has not routinely been performed in clinical trials. Generally, the clinical Trials all use brain imaging. That's changing to some degree, but what's the rationale for that?
- [36:31]
A
The imaging of the spinal cord has really improved and we now have sophisticated techniques that can quantify tissue injury to the spinal cord. And that's extremely important because that's where the disability is occurring. And so that we're not doing that and haven't done it tells me that we have missed an opportunity for many years now in Ms. Now, the reason for that was technical limitation. And so today we're in a much better position to image and monitor the spinal cord in clinical trials than we ever were before. And in fact, I think we can even use spinal cord imaging as a phase two endpoint for randomized controlled trials in progressive forms of multiple sclerosis, where we're looking for the proof of concept of a medication's potential to have an impact on long term disability. So I think there's a sweet spot for spinal cord imaging to help us de risk products that are intended for development of progressive forms of Ms. Do.
- [37:30]
B
You see imaging advances still coming?
- [37:33]
A
Yeah, I think we're going to continue to explore higher field imaging in multiple sclerosis. We have projects that are ongoing now looking at seven Tesla MRI scans, extremely powerful magnets that can resolve details of the anatomy and the central nervous system with greater and greater degrees of resolution. And I think one of our goals is to try and learn something from these high field magnets at 7t and develop approaches that can be then translated to the three Tesla MRI scanners that we use in clinical practice. And I think we're going to get there.
- [38:10]
B
Well, Bruce, thank you so much for being on the podcast and really providing tremendous amount of insights and think everyone out there listening learns a lot more about the spinal cord and where we're going with new research.
- [38:23]
A
Thanks, Barry. It's been a pleasure.
- [38:26]
B
Thanks to our listeners for downloading this episode of the Ms. Living well podcast on Ms. And the spinal cord cord. As you heard from Professors DeLuca and Cree, protecting the spinal cord is key to functioning better with Ms. And trying to prevent progressive disease. Advances in spinal cord imaging and treatment for chronic inflammation are definitely making the future much more optimistic. Thanks again to TG Therapeutics for sponsoring this episode. Keep in mind the top topics we discuss on the show are strictly informational and not medical advice. Any change in your treatment should be discussed directly with your healthcare providers first. Our show is Hosted by me, Dr. Barry Singer, produced by Karate Harmon with audio editing by Frank Garza. Our theme music is the Gold Lining by broke for free. If you like the show, please share it with others Living with Ms. I'd really appreciate a positive review on Apple Podcasts. It helps more people find out about the show. You can follow me on X at. Dr. Barry Singer More information about our guests and their websites can be found in the show Notes for this episode in the blog section of mslivingwell.org thanks so much for listening. This has been an Ms. Living well podcast.