Diagnostic Challenges and Treatment Implications for Multiple Sclerosis: A Q&A With Patricia K. Coyle, MD

Evidence increasingly suggests that early treatment of MS is essential toward reducing disability in later stages of the disease. In this interview, Patricia K. Coyle, MD, Director of the Comprehensive MS Care Center and Professor of Neurology at Stony Brook University, examines this and other challenges associated with MS diagnosis and treatment.

AJMC®: What are the most significant unmet needs when it comes to understanding multiple sclerosis (MS) disease pathology?

Coyle: One of the major issues would be the heterogeneity of MS: What are the major pathologic damage mechanisms? Do they differ in subsets of individuals with MS or [are] they in a different time frame? Regarding the neurogenerative component of MS—the injury to axons, neurons, synapses that we believe underlie progressive MS—what are the damage mechanisms? What’s responsible for that neurodegenerative injury? And that may change over time. We really don’t know the answers. The problem is, we don’t get much pathology information in MS at all, [because] it’s not typically a fatal disease, and even when patients present, they have had the disease for a prolonged period of time. I think there are a lot of unknowns and mysteries about the MS disease pathology that would be very helpful to understand better.

AJMC®: Can you discuss the challenges of making a diagnosis of MS and the implication these challenges might have for selecting optimal treatments?

Coyle: We believe it is very important to make an early diagnosis of MS and institute appropriate treatment, because the data are increasingly supporting that early treatment is critical to minimize late disability. The benefits of early treatment compared to late treatment are being proven in study after study. But that makes it more urgent to make the diagnosis at the first attack. We know that, overall, there is a 5% to 10% misdiagnosis rate of MS. In one very recent series at 2 academic Los Angeles centers, 18% of their MS cohort was misdiagnosed. It really argues for a complete workup, although that is not always done, as we’re trying to make a diagnosis at the very earliest stage. It is important to be aware of the differential diagnosis and to rule out mimickers. For example, an entity called neuromyelitis optica spectrum disorder was for many years considered a variant of MS. It produces optic neuritis and transverse myelitis. We now recognize that it is not MS, but rather an independent neuroimmune disorder. [Moreover], a number of the MS disease-modifying therapies [DMTs] actually make this other disorder worse. So, it is key to make the diagnosis early. But the diagnosis has to be accurate so that we are treating patients who truly have MS and do not have another disease where they may even be harmed by MS treatments or inadequate treatment.

AJMC®: Could you discuss imaging techniques and the extent to which the evolving MRI technologies may impact the diagnosis of MS?

Coyle: We have very sophisticated neuroimaging on a research basis, but let’s talk about our practical, daily, clinical imaging with MRI [magnetic resonance imaging] scans. This is critical to help us make an early, accurate diagnosis, yet we haven’t even gotten our act together sufficiently to standardize protocols across the country on how we do brain or spinal cord imaging in suspected MS cases. That’s a big issue.

Suboptimal studies are being done. If you’re trying to look at MS, probably a 3-component scan is ideal (brain, cervical cord, thoracic cord). You want very thin slices; you want no gaps. We have had protocols put forward recommended for MS in imaging the brain and spinal cord, but they haven’t been universally adopted yet, and we’ve had some poor studies that have been done. When we do follow-up surveillance monitoring scans, they need to be comparable to previous studies. That means, ideally, going to the same place, making sure the patient is positioned in an equivalent manner, so you can make an accurate comparison. There are many exciting techniques on the horizon, such as the central vein sign. This appears to be a technique that would allow you to say lesions on a brain MRI are due to MS as opposed to other disorders. But that is still a research protocol and is probably several years away. Neuroimaging with MRI is critical, but there’s a lot that we could do to make it better.

AJMC®: How does the lack of diagnostic biomarkers influence the treatment process for MS?

Coyle: We don’t have a single diagnostic biomarker that says unequivocally if a patient has MS or does not have MS. That would be extremely helpful to remove a misdiagnosis. We would like diagnostic and predictive biomarkers as well as biomarkers that tell us that someone is responding to treatment quickly so that we don’t have to wait for a breakthrough relapse or the development of disability or macroscopic MRI lesions. Biomarkers are very important, but you need to go through a whole procedure to really standardize them and document their efficacy and reliability, and make sure that the biomarker is available and economically viable, so this is a big area in research. There is neurofilament light protein and optical coherence topography, both which look like very promising biomarkers. Segmental atrophy, atrophy of grey matter, also looks promising in MS. Atrophy of spinal cord is also a potential biomarker, but a lot of work still has to be done. We are seeking meaningful biomarkers to help us in diagnosing, evaluating, and following MS, and even picking the DMTs and then being able to tell quickly whether a patient is responding or not.

AJMC®: Could you discuss some of the most notable challenges and opportunities associated with the growing treatment landscape?

Coyle: Selecting the best disease-modifying therapy for each individual patient can be difficult, given that we have multiple options. Should we be using high-efficacy agents in everybody from the very beginning? Are they ultimately all going to do better if we follow that practice or are there people [who] have milder MS [who] don’t require high-efficacy agents and can take perhaps more convenient, safer, or more tolerable, lower-efficacy agents? We really don’t have the answer to that. Can we determine a suboptimal responder quickly? This comes back to the biomarker issue. We have difficulty in telling who is really not responding appropriately. Are we going to be able, with our disease-modifying therapies, to prevent relapsing MS from transitioning to secondary progressive MS? The challenges we face is that we don’t have very good treatments for progressive MS, and we don’t have any meaningful CNS [central nervous system] repair strategies at the current time.

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