Structural Myelopathies with Dr. Ligia Onofrei

Compressive myelopathy caused by degenerative spine disease is common, but the pathophysiology is surprisingly complex and there are potential surprises in the evaluation of these patients. In this episode, Katie Grouse, MD, FAAN, speaks with Ligia Onofrei, MD, author of the article “Structural Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Onofrei is an associate professor of neurology and neuromuscular medicine at the University of Utah in Salt Lake City, Utah. Additional Resources Read the article: Structural Myelopathies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud American Academy of Neurology website: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Guest: @Ligia_OnofreiMD Transcript  Full transcript available on Libsyn Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Dr. Ligia Onofrei about our article on structural myelopathies in the February 2024 Continuum issue on spinal cord disorders. Dr Onofrei is an Associate Professor of Neurology in neuromuscular medicine at the University of Utah, in Salt Lake City, Utah. Welcome to the podcast. Just to kind of get started, I wanted to ask you, the topic of your Continuum article is cervical and thoracic structural myelopathies - what are these and how common are they? Dr Onofrei: So actually, structural myelopathies are the most common myelopathies that we encounter clinically. I know in neurology we tend to focus on things like MS or NMO or transverse myelitis as the myelopathies that we talk about most commonly, but we actually see them a fair bit. As you will see in my article, it's really hard to actually give you a precise number as to how common they are. We know they're common because we encounter them a lot, but there are also a lot of patients out there who have them who are undiagnosed. Structural myelopathies really refer to both the symptoms of myelopathy but also having compression of the spinal cord. That's what you have to have in order to have a structural myelopathy. Dr Grouse: How did you become interested in this area of neurology? Dr. Onofrei: It’s a bit of a different kind of story in neurology than the usual career trajectory. Actually, when I was a resident, there was a patient at the VA who had Parkinson's disease and myelopathy, and he went undiagnosed for months because people kept blaming his dexterity issues and day changes on his Parkinson's. But, in fact, he really had a cervical myopathy that was actually quite severe. When we got him diagnosed. I remember thinking to myself, “I really want to learn more about it.” And I was asking around and what I saw, even though my attendance at the time were super smart and very well versed in neurological issues, they just weren't comfortable with degenerative disorders of the spine. I wanted to learn more. I read what was available and I actually went to the AAN Spine Course, which at the time was a full day. I met Dr JD Bartleson, who was my mentor - who became my mentor, I should say. He gave me some really terrific advice about how to learn more. When I finished my residency at the University of Utah, I went on to do a neuromuscular fellowship, also at the University of Utah. But during that fellowship, I actually had two months to spend as additional training time outside of neurology, and I chose to spend it with the spine and musculoskeletal physical medicine and rehabilitation specialists at the University of Utah. They taught me a lot about degenerative spine issues, musculoskeletal issues, and I felt I really, for the first time, had a really good grasp of the diagnosis, and also the interplay between degenerative spine issues and neurological disorders. And then after that, I did something even less typical for neurologists. After I graduated fellowship, I actually went on to have a clinic embedded within the neurosurgery department at our institution. I evaluated patients – like, a day a week - patients who had spine issues and were referred for surgical evaluation. I would evaluate the patients in conjunction with one of the neurosurgeons, and then we would decide together if they needed surgery. It was a really great education to understand the interplay between degenerative spine issues and neurological disorders. Dr Grouse: That sounds like a circuitous but very interesting path, and very fruitful in the end. You mentioned that even very adept clinicians can miss this important and actually common diagnosis. What are some early signs that are easily missed? Dr. Onofrei: I think, with myelopathy, the most important part is actually just thinking about it as a diagnostic possibility. If you think about it, then you will essentially ask the questions that are really important diagnosis. I think it can be especially difficult if it's a patient who has a preexisting neurological disorder because we get stuck in asking the kind of things we usually ask our patients with MS or Parkinson's, or whatever else they may have. But it's really important to understand the trajectory of symptoms always. If they're having dexterity changes, “Did that happen all of a sudden? Was there something else happening?” Asking about dexterity changes to start with is a super helpful, important part of the diagnosis. And then also asking about gait changes. Again, if they have a preexisting neurological diagnosis, asking them if they've had a big change, a rapid progression, if something else happened in their disease - that's the beginning step. It's actually very, very basic information, but asking about these changes is super important. Then, once people have identified those changes, then you can delve into the more specific questions that are really unique to myelopathy, like manipulating small objects, manipulating utensils - for example, zippers or buttons. That's a really sensitive way to ask for dexterity changes for myelopathy. For gait abnormalities, it’s a little bit less unique to myelopathy. A lot of the symptoms overlap phenotypically with, like, peripheral neuropathies. For example, having difficulty on uneven ground or getting your toes caught on something. But identifying a shift in your gait is usually that key initial diagnostic clue. Dr Grouse: Really, really helpful. And, I think, always a great reminder with almost anything - you don't think of it, you won't diagnose it. Sounds like for myelopathies - structural myopathies – this could be especially true. Thinking about this article, what do you think would come as the biggest surprise to our listeners who read the article? Dr. Onofrei: It’s a really great question. I think there can be a lot of different surprises in each little section. But, to me, the thing that stands out is how complex the pathophysiology of myelopathy actually really is. There's so much more than just direct compression of the spinal cord. When you have compression of the spinal cord, you are stretching the spinal cord; you are inducing changes to the gray matter, the white matter. But you're also changing the actual biology of the cells. When you're causing compression of the spinal cord, you're inducing hypoxic or ischemic injury, and that triggers a neuroinflammatory cascade and it causes apoptosis of the neurons and the oligodendroglia. I think what was really interesting to learn is that, when you're decompressing the spinal cord with surgery, that reduces that cascade of neuroinflammation but it doesn't eliminate it. You will still have some residual apoptosis of the cells even after decompression. This actually is probably one of the pieces of information that supports the idea that we really should be intervening at an earlier stage for these patients. Dr Grouse: Does this mean that, even after decompression, patients can continue to deteriorate or do worse as a result of that apoptosis and those changes? Dr Onofrei: I think that the way I would interpret that, more in practice, is that those patients might not improve. They might not have any improvement post surgery. In fact, any surgeon who is an ethical surgeon will tell you that they cannot promise improvement with decompressive surgery, but we do notice improvement in a significant proportion of patients. While you can never promise that there's actual hope for these patients, it's just that some patients may not improve and we don't have a great way to predict who will improve and who will not improve. Dr Grouse: I was also curious, when you mentioned about what chronic compression looks like, why does chronic compression look so different from acute compression of the cord, both how it presents and how the patients can look? Dr Onofrei: That's a really fantastic question. I think part of it is that, just like with other degenerative disorders of the spine – like, for example, lumbar stenosis with neurogenic claudication and cauda equina, there's an element of time and adaptation. When you have acute compression, you do not have those adaptive mechanisms in place, and you will have to deal with just acute loss of function. That's how I would think about it. The time component allows for some adaptive changes, and also for specifically degenerative myelopathies. When you have chronic compression, you usually have less compression than with an acute traumatic myelopathy. Dr Grouse: I want to ask, as well, what do you think is the biggest debate or controversy in this particular area - whether it comes to the underlying pathophysiology of what's going on, or else the management or treatment of it? Dr Onofrei: I would say, without a doubt, the biggest controversy is when to intervene. Obviously, that is a hugely important question for patients and physicians alike. There's a lot of debate because there are patients who remain stable with mild myelopathy for many years, and then there are people who decline. There is a yearly rate of decline for these patients. But right now, we don't have good ways to predict who will decline and who will remain stable. I think there's a huge potential for more research, especially in the field of imaging - and especially with diffusion tensor imaging - to see if that can be used as a way to predict who will be declining or who might respond better to treatment. Dr Grouse: That makes a lot of sense, and certainly, I think, something that a lot of our listeners grapple with as they try to counsel patients with these types of conditions. I was struck by another point you made in your article - which I thought was really interesting - which was that a common misconception is that pain is a significant manifestation of spinal cord dysfunction. And this made me think that this could definitely fall in the category of an easy mistake that you could make in this diagnosis. Tell us more about that. Dr Onofrei: Yeah, so we are very used to using pain as an alarm signal. I think it's important, again, at a provider level, to remind ourselves that, actually, function is a better proxy for dysfunction than pain for a lot of patients. But pain, again, continues to be a really important reason why patients come to us. From one perspective, even though pain is something that we worry about and patients think potentially has really bad consequences, pain can actually be reassuring in some ways. But for myelopathy, pain is usually an incidental finding, in the sense that, usually, pain with myelopathy will happen because you have axial pain – you know, pain because your posture is poor, or you might have a superimposed radiculopathy. Pain will be sometimes the symptom that will bring the patient to attention, but it's very unlikely to be a symptom of how bad the problem is or to actually tell you if there is underlying myelopathy. Dr Grouse: Thank you - that's a really important review, I think for all of us. Often we’ll ask that as almost one of the first questions, when we're thinking about it. Tell us a little bit more. I was reviewing some of the common signs of cervical myelopathy and - it's funny - a lot of them, especially the early signs, may not even be the ones you first think of. I think you've mentioned it before - the gait dysfunction and slight loss of dexterity. I also was interested in (and this maybe may not be quite as an early one) myelopathic hand - if you wouldn't mind telling us a little bit more about that as well. Dr. Onofrei: Of course. Assessing function is very important, just by asking the patient what they do that requires dexterity. So, starting there and then moving on to trying to understand if there’s any particular issues that would confound the patient's ability to perform these activities. Like, if they have arthritis of their hands or a painful finger (like a trigger finger, or something like that), that will change the way they can handle the types of activities that require them to be dexterous. That's the initial phase. Once they have had progression of their myelopathy, they will usually have more frank weakness. I think a lot of people will say they drop more objects, but that's probably the least helpful, from a clinical perspective, just because it happens with so many different pathologies. But really paying attention to loss of actual strength and then visually examining the hand – so, looking for loss of muscle for the hand and looking for loss of strength on exam. So, finger abduction is your most sensitive exam maneuver that you can do to assess for that. And even very subtle weakness can be a really good indication of myelopathy. And then, in patients who have more advanced pathologies, you'll see more significant atrophy of the hand - actual frank, like, muscle wasting and potentially fasciculations in the hand. I talk about the myelopathic hand from a pathophysiology perspective. I thought it was really interesting that you can see this myelopathic hand with compression at any level in the spinal cord. So, even if it's high cervical compression, you can still see the hand atrophy and weakness. So, it is important to visually inspect the hand, do the strength examination, and like I said, really ask the patient about their function. Dr Grouse: Thank you. That was really helpful. Being a neurologist, of course, I think, like many of our listeners, I'm a big fan of checking reflexes, and in your article, you mention some really interesting, different ones that we don't check every day. Do you have favorite or a few favorites that you'd like to call out for us to pay attention to? Dr. Onofrei: As I mentioned my article, hyperreflexia is a really common manifestation of myelopathy. While it's not always present, if you can elicit hyperreflexia, it's really helpful. I think you can do whatever reflexes are your favorites, as long as they're a measure of hyperreflexia. I do like the finger flexor reflex, and I included that in the paper. It's just one that people use less often, but it's super easy to do. And if it's asymmetric, in particular, it's a really helpful tool. But, again, I don't think it matters which ones you do as long as you do a complete exam and then you look at the presence of hyperreflexia. Dr Grouse: That's great, and I encourage everyone to check out the article and take a look at some of those reflexes that she referenced are very interesting. What role does DTI play for imaging of degenerative myelopathies, and what promise do they hold going forward? Dr Onofrei: Diffusion tensor imaging is a really interesting imaging modality for the spine. It's not as commonly used for the spine as it is for things like stroke, right? We all are super familiar with its amazing role in stroke and early diagnosis of stroke. In the spine, it's much more complicated. The spine is a much more difficult structure to image, in general. So, while it's not being used right now on a clinical basis routinely, there's a lot of active research in that arena to try to understand what the best protocol might be, and how to use it to either predict which patients might deteriorate or which patients might need to have earlier surgical intervention. I think the promise of it is really tremendous, but to date, there hasn't been a unified protocol. But I think that, as we have more sensitive imaging modalities, better software algorithms to analyze the images, we might actually be really able to have excellent sensitivity. Dr Grouse: Well, very interested to see how that develops over time. Just to finish up, is there any last sort of important key points you hope that our listeners will take away as they go forward into the world and look for patients with structural myelopathies? Dr. Onofrei: I think the most important things that I want people to remember from this article, number one, is that diagnosing myelopathy starts by thinking about myelopathy, first of all. If you're thinking about myelopathy, you're more likely to ask the questions to elicit myelopathies. And then, I do want people to think about the phenotypic overlap between myelopathies and other neurological disorders. Third, I think people just need to remember that they are already doing the work of discovering myelopathy, which is asking the questions, doing a really good history and a really good exam. Really, the key for the diagnosis is having a really good history, is understanding the function of the patient, and is doing a really good neurologic exam, especially in patients who have a preexisting neurological diagnosis. Having those serial neurologic exams is really, really important to understand if the patient has a new myelopathy or to give the patient a better understanding of how they might respond to surgery, or what proportion of their symptoms is really attributed to a neurological disorder versus a myelopathy. Dr Grouse: Thank you so much for coming to talk with us about this really important topic. Again, I can't encourage everyone enough to read this article. I think it was so helpful, so interesting, and just gets back to all the things I think we all love about neurology. Dr. Onofrei: Thank you for having me. Dr. Grouse: Again, today I've been interviewing Dr. Ligia Onofrei, whose article on structural myelopathies appears in the most recent issue of Continuum, on spinal cord disorders. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.