Introduction

The spinal cord is a fragile network containing hundreds of millions of neurons, all passing through a conduit about the size of a dime. A consistent, organized approach to the diagnosis of spinal cord disease is necessary to give patients the best possible care.

In this episode, Teshamae Monteith, MD, FAAN, speaks with Carlos Pardo, MD, author of the article "Clinical Approach to Myelopathy Diagnosis," in the Continuum February 2024 Spinal Cord Disorders issue.

Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida.

Dr. Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Myelitis and Myelopathy Center in Baltimore, Maryland.

Additional Resources

Read the article: Clinical Approach to Myelopathy Diagnosis

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Host: @headacheMD

Transcript

Full Transcript Available Here

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 Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing Dr Carlos Pardo about his article on an Integrative Clinical Approach to Myelopathy Diagnosis, which is found in the February 2024 Continuum issue on spinal cord disorders. Dr Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome to the podcast. Carlos, thank you so much for this wonderful article. I think it was great!

Dr Pardo: Thank you very much for the invitation and, particularly, to continue to write about myelitis and myelopathy - that is one of my passions in my activities as a clinical neurologist. And I think that this is basically one of the areas in which I thought, after finishing my residency training here, to focus, because there was absolutely no good understanding of the biology, clinical profile – particularly, understanding of the pathophysiology of myelitis and myelopathies, and what was called (at that time) transverse myelitis. So, that is what I have spent the past 25 years is try to understand that concept and apply what I was trained, as a neurologist and neuropathologist, to be translated in the clinical practice.

Dr Monteith: Great. Well, I definitely want to know - how did you get into this area?

Dr Pardo: That's a very nice question.

Dr Monteith: I'm going to give you an easy one.

Dr Pardo: I was trained as a clinical neurologist, but at the same time was trained as a clinical and experimental neuropathologist. When I finished my residency training, along with some of my co-residents and colleagues in my residency training, we took the challenge to take a neurological disorder that was called at that time transverse myelitis, to investigate diagnosis, clinical neurology of those patients, and investigate the etiological factors contributing to that. Very soon, we discovered that that group of patients that we call transverse myelitis was a very heterogeneous group of patients. And that basically put us in the situation to expand our approach to investigate what were those etiological factors contributing to those pathologies that we call, at that time, transverse myelitis. Since then, we have been focused on that. We have been focusing on characterizing patients with inflammatory myelopathies, with vascular myelopathies, with patients with infection disorders associated myelopathies. That is one of the main messages of the paper, and is - we need to think in a very etiological approach, because the variety of etiological factors that may contribute to spinal cord disorders is quite broad - it's very extensive. We need to be extremely careful when we approach those patients. There are very common myelopathies, there are very rare myelopathies. So, obviously, we always look for the commonalities and common pathologies, but we shouldn't basically forget about those myelopathies that may be rare but are present. I will say, frequently, we ignore the possibility of metabolic-associated myelopathies because we don't see those too much. But after we do an analysis of that equation - the clinical profile, temporal evolution, lesion topography, and biomarkers in imaging, blood, spinal fluid - and we don't find a clear explanation, we need to stop a little bit and think more about other things that we are missing. And frequently, metabolical disorders of the spinal cord are missed, or other type of pathology. That the reason the clinician need to have open mind and, occasionally, need to think out of the box, particularly when there is no clear answer to the search for etiological factors.

Dr Monteith: I mean, when we think about spinal cord lesions, they can obviously be devastating because they affect patient's ability to ambulate. Why don't you tell us the most important takeaways from your article?

Dr Pardo: Yeah, so this is a very important aspect of the article. The first thing is, if we are going to treat the patient, if we are going to focus in the management of a clinical problem, we need to understand first, what is the clinical diagnosis? What is the cause of the problem? Importantly, what is the etiology or the etiological factors contributing to that problem? The first thing that I always emphasize is, we are not able to treat a patient with a neurological condition if we don't have a very precise diagnosis, regardless what we are investigating in that patient. Specifically, for spinal cord disorders, there is a multitude of etiologies and pathogenic factors and other causes of the disease that may be involved. For that reason, the clinician, the health care provider, need to be aware about how to approach that question; is, we need to answer first the cause and the profile of the spinal cord disorder. And when we need to answer the cause, we need to focus first in evaluating clearly what has been the evolution of the symptoms, how is the neurological exam, how the evolution of the symptoms are going to help us to identify those etiological factors that we are looking for. For that reason, in the approach that I am suggesting to take in patient with the spinal cord disorder, the first critical element of that approach is to sit down and talk very well with the patient about what is going on - what are the main symptoms that are present, what has been the temporal evolution of those symptoms, and what has been basically the pattern of progression of those symptoms - because those are the clinical elements that will facilitate the clinician a much better understanding for the clinical diagnosis. Evaluating the clinical profile of symptoms and evaluating the temporal profile of symptoms is probably the first step for solving that critical equation about the diagnosis of spinal cord disorders. The main target is to establish a diagnosis.

Dr Monteith: And that's really the bread and butter of neurology, because we have a global audience and we have some neurologists that practice in areas with very limited resources. But you do speak of some very cool things that I want to also touch on, such as precision medicine, the advances in biomarker development and neuroimaging, as well as investigating different viral etiologies in the pathology of spinal cord disease. So, can you just speak to some of that? You've been in this field now - you said, 25 years - how that evolution has helped you better treat patients.

Dr Pardo: That's a very important question, because in 25 years we have learned tons about myelopathies, myelitis, and noninflammatory myelopathies - and it's quite amazing. I think that one of the most important aspects of spinal cord disorders is that, in the past 25 years, we have learned about mechanism of the disease in spinal cord disorders. Back in the 20th century we used the term transverse myelitis, and one of the main messages that I have for the clinicians who are reading the article is, please stop using that terminology. We have now capability to establish a more precise diagnosis, a more etiologically oriented diagnosis. If you can take a look at what happened in the past 25 years, understanding spinal cord disorders is quite amazing. We have a better understanding of the immunological factors that contribute to myelopathies. We are able to diagnose myelopathies associated with aquaporin 4 disorders, or MOG-associated disorders, or demyelinating diseases, or infectious disorders. So, in the past 25 years, with a combination of different tools in laboratory studies, studies of spinal fluid analysis, studies of the blood, we have basically able to identify biological markers that may guide us to treat more precisely those patients that are suffering from immune-related disorders. In the same way, imaging has contributed dramatically to improve our understanding of myelopathy. We are able to use neuroimaging studies to differentiate in better way, what are the myelopathies that are associated with vascular etiology, versus myelopathies that are associated with inflammatory etiology. In other words, the 25 years have provided all set of tools (assays, imaging techniques) that allow us to establish a better and precise diagnosis that facilitate etiological diagnosis. And in that way, we avoid the use of the term, transverse myelitis, that I frequently say is a basket diagnosis that is not taking us anywhere, because we are not using properly the etiological diagnostic approach.

Dr Monteith: In the setting of all of this evolution, what do you still find challenging, and as well, rewarding in treating these types of patients?

Dr Pardo: The best reward that we obtain when we establish this type of diagnosis is that we are able to facilitate better recovery, we are able to identify the factors associated with the problem, and eventually, to target, in a better way, those factors that are contributing to the problem and identify potential avenues for full recovery of the spinal cord. If we are dealing, for example, with patients with suspected inflammatory myelopathies, and we are able to identify an antibody that is contributing to that inflammatory myelopathy - like in the case of neuromyelitis optica - I think that the reward is that we are going to avoid a very long process that is going to decrease our ability to rescue that spinal cord and facilitate improvement of that patient. If we identify a vascular myelopathy and we are able to establish promptly a precise diagnosis of a stroke of the spinal cord, that will avoid that the patient goes in a very long road of treatments that even may be more harmful for that patient. And in that way, we are able to contribute the recovery and facilitate improvement of those patients with vascular spinal cord disorders. This is the reward: the reward is that we are able to facilitate a much better recovery of those patients and, in that way, to improve outcomes in those patients that are suffering myelopathies.

Dr Monteith: What's been some of the more surprising cases in your practice, in terms of patient presentations, surprise recoveries, or whatever?

Dr Pardo: One of the best rewards that we have seen in our research (clinical research) in the past several years is to be able to provide a much better framework for evaluating patients. The other aspect is to be able to identify patients that have very specific pathologies, like strokes of the spinal cord - ischemic pathology of the spinal cord that may be acute ischemic pathology or even chronic evolving pathology. In that way, actually, we have been able to establish much better protocol for assessment of those patients. That is actually one of the major aspects of our progression in terms of understanding the spinal cord disorders. And that is the reason - once again, I emphasize that when we use the term transverse myelitis and we erroneously diagnose patients with transverse myelitis when they are experiencing vascular pathologies of the spinal cord, we are basically not serving well those patients. That is one of the emphasis that I always include in the manuscript is, it is much better to spend time establishing a diagnosis (etiological diagnosis) rather than treating empirically diagnosis that probably are not going to be very well served by using treatments that probably are not going to benefit the patient. For example, when we deal with patients that have vascular myelopathies associated with chronic venous abnormalities, like happen in dural arteriovenous fistula, we are deserting those patients by treating them with IV methylprednisolone or treating them with IVIG, or treating them with immunosuppressive treatments. This is a critical element of the precision approach to establish a better diagnosis in patients with myelopathy.

Dr Monteith: And then, your article spoke a little bit about recent outbreaks of infectious etiologies - viral etiologies. Can you talk a little bit about that? Because sometimes we send off these tests and they come back nonspecific or negative, and we have a sense that this was an infectious process. Maybe there was a prodromal phase, or something like that. Can you speak about your excitement in the area of advances in these methodologies?

Dr Pardo: Yeah - this is an important aspect of the clinical conversation. Our patients may provide initial clues for identification of potential risk factors, such as infections, as etiological factors contributing to spinal cord disorder. When you are discussing with patients about specific symptoms that emerge after they have experienced either illnesses or systemic symptoms (like fever, chills, rash, or anything that look like an infection disorder) it's extremely important for the clinician to try to characterize that in much better way so we can use those elements of the investigation to determine if infection disorders may be involved as etiological factors in those myelopathies. We were trained to think about transverse myelitis as either an immunological-mediated disorder or an infection-mediated disorder. That's the reason I think that the clinician need to be open-minded when he's interviewing the patients to acquire, as much as possible, elements of the clinical history that may focus or avoid that the clinician pay too much attention to things that are not involved as etiological factor. Infection disorders frequently may produce neurological problems, and, obviously, spinal cord inflammation is one of those neurological problems. However, it's very important that the clinician be critical in the assessment of those potential risk factors. I frequently discuss with the students and residents in our ward that it's okay to think about West Nile myelitis when we are in the summer, but we are not able to discuss specifically about West Nile myelitis in middle of the winter, and particularly because those are etiological factors that are associated with seasonality and those are etiological factors that are associated with some risk factors that include, for example, mosquito transmission of a virus. When we talk about acute flaccid myelitis with our pediatric patient population, we need to think about circulation of viruses, and we need to think about if that is the right period of circulation of the virus that we are suspicious that is producing that spinal cord disorder. Again, the clinician need to be aware about the particularities of some infection disorder - seasonality, modes of transmission - to think about what is going on in terms of etiological factors, particularly infections, as part of causes of spinal cord inflammation.

Dr Monteith: Let's talk a little bit about some controversies - things that maybe lead to overdiagnosis or underdiagnosis.

Dr Pardo: It's a very good question, and I appreciate the controversy, always. One thing that is going back to the basis of the article is the precise diagnosis is strictly dependent of equation that involves different factors. We are not able to diagnose spinal cord disorders just using one factor of that equation. This is something that is extremely important for the clinician and health care provider. We are not able to establish a precise diagnosis just when we use only neuroimaging studies. We need to bring the clinical profile of that patient, the neurological examination, the neuroimaging studies, the spinal fluid analysis to the same equation. That is one of the controversies, because in the past, we relied heavily on neuroimaging studies for establishing a diagnosis of myelopathies. But I believe that has been a little bit of a mistake because we have been ignoring major elements of the clinical history and neurological examination. And probably the best example of that is the example of spinal cord strokes. When patients show up in the emergency department with acute onset of weakness and sensory problems, and an MRI show a lesion in the spinal cord, that is not automatically a myelitis. That is an acute spinal cord disorder in which the clinician has the responsibility to establish the precise diagnosis. This is one of the major messages that I want to give to our colleagues in the clinical setting is, we need to interview the patient; we need to characterize the clinical profile and make sure that what we see in the spinal cord MRI fits the clinical profile, the neurological examination, and even the spinal fluid analysis of that patient. One of the controversies that we have frequently is to diagnose patients with spinal cord strokes, because there is no gold standard for those diagnosis, unfortunately. It's a diagnosis that is comprised by several layers of assessment. In that way, we need to reach, basically, a consensus how to deal with those patients and how to manage those patients correctly.

Dr Monteith: So, of course, we have a broad, I guess, "background" of listeners - from residents, medical students, even lay audience, as well as, of course, from neurologists. But why should a resident go into spinal cord disease as a subspecialty?

Dr Pardo: It's a very important aspect of the central nervous system function. I always equate the spinal cord as the major avenue for the neurological function in the human body. If there is a very good connectivity in our brain and brain hemispheres, that connectivity is not going to be effective if there is not a healthy and very good function in the spinal cord. The spinal cord is the best avenue for execution of many of the function of the central nervous system. And in that way, a clinician who is working in neurology need to be aware about the spinal cord - need to be aware about the pathophysiology of the spinal cord. Because even if there is not any element of cognitive function in the spinal cord, we have all of the major avenues that facilitate the human function in the spinal cord - motor function, autonomical function, sensory function – so, most of the central nervous system function needs to go through the spinal cord. And the clinician (neurologists and residents) need to be aware - fully aware - about how to approach disorders of the spinal cord, how to identify correctly disorders of the spinal cord, and how to evaluate and treat those disorders.

Dr Monteith: Well, thank you - I really appreciate this talk. I really appreciate your article. It was very thorough, including "the bread and the butter," the approach to a patient clinically, but also all the new innovation in your field and all of the excitement. And of course, your story, too. So, thank you so much.

Dr Pardo: Thank you, Tesha, for inviting me to this interview, and I hope that at least the main message is very well taken. Remember, the main goal of my proposal in this article: number one, is to get rid of the diagnosis of transverse myelitis; number two, that the clinician and health care providers establish a better etiological diagnosis that facilitate better recovery of patients, better management, and better outcomes in patients with spinal cord disorders.

Dr Monteith: Thank you, Dr Pardo for joining me on Continuum Audio. Again, today we've been interviewing Dr Carlos Pardo, whose article on an integrative clinical approach to myelopathy diagnosis appears in the most recent issue of Continuum on Spinal Cord Disorders. 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 the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.