Differential Diagnosis and Types of NMOSD


Flavia Nelson, MD, and Robert Shin, MD, FAAN, provide insight on the forms of neuromyelitis optica spectrum disorder and how its attacks differ from multiple sclerosis.

Brian Weinshenker, MD: Dr Nelson, Dr Miller has well-outlined for us some of the more common attacks, but I’d be interested in your perspective about other attacks that can occur in NMO/NMOSD (neuromyelitis optica spectrum disorder). And for you, what are the main distinguishing features from MS [multiple sclerosis] and other conditions that make you particularly suspect NMO?

Flavia Nelson, MD: Yes, as Dr Miller said, it can be similar to MS. I think in my impression, the destruction, the irreversible damage of these attacks tends to be higher, and the degree of severity also tends to be higher, especially when it comes to optic neuritis. As Dr Miller mentioned, it can be bilateral. When it comes to the brainstem syndromes, they can be very debilitating. And I think in terms of when we speak of transverse myelitis, it also tends to be more aggressive and more debilitating, and often with more irreversible disability as compared to MS.

Brian Weinshenker, MD: So, severity and poor recovery are certainly important clues that we should take into account.

Flavia Nelson, MD: Exactly.

Brian Weinshenker, MD: I’m going to turn to Dr Shin now. I think that we have more than one NMOSD that to a large extent are distinguished by antibody testing. Can you tell us about the different forms of NMOSD?

Robert Shin, MD, FAAN: Sure. Well, when we’ve been talking about neuromyelitis optica spectrum disorder that already implies there can be a broad number of manifestations. Now, which will be discussed more later, the discovery of antibodies to aquaporin-4 [AQP4] in the serum as a distinguishing feature between NMOSD and MS was really revolutionary in our understanding of the distinction between the diseases. We can still make a diagnosis of NMO spectrum disorder and someone without those antibodies using clinical criteria. So you can talk about a category of people who might be aquaporin-4 antibody negative NMOSD and, even more recently, another antibody’s been identified. There are some individuals who have antibodies to myelin oligodendrocyte glycoprotein, or MOG, who have what we might call a MOG-antibody associated disorder. Dr Miller’s already alluded to differences between MS and NMOSD, but there are also some clinical and radiologic differences between MS, NMOSD, and MOG-antibody associated disorder, or MOGAD. So really now a spectrum of different conditions.

Brian Weinshenker, MD: And what are the key clinical differences between patients with an aquaporin-4 antibody and foreign MOG disease?

Robert Shin, MD, FAAN: Well, they can be very similar, and they had overlapped, and I think we diagnosed many people with MS without knowing that they had NMOSD or MOG-antibody associated disorder. Dr Nelson mentioned if you have bilateral optic or simultaneous optic neuritis, that’s very suspicious for either NMO or MOG. Not something that we would really see typically in MS.

In my mind, MS often is an issue with hemicord presentations, so the left side or the right side may be affected. Whereas when I think of NMOSD and MOGAD sometimes really both sides can be affected because of the central inflammation within the cord. With MOG-antibody associated disorder specifically, sometimes we see an involvement of the conus or the lower part of the spinal cords. So that might be lower body weakness, bladder symptoms, and those are the clinical features. There can be other subtleties radiologically as well.

Brian Weinshenker, MD: I think sometimes the lesions we see in the spinal cord are less severe and lesions that occur in the brain with MOG tend to clear up much better and may disappear. So that can be a clue.

Transcript edited for clarity

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