Fred Lublin, MD: The other point that Patricia raised that has become a part of standard practice is looking at antibodies aquaporin-4 IgG [immunoglobulin G] and anti-MOG [myelin oligodendrocyte glycoprotein]. When the aquaporin-4 IgG assay came out, I think it was around 2006 or thereabouts, we did find people who had been carriers of MS [multiple sclerosis] who actually had NMO [neuromyelitis optica]. And it was the cusp of the NMO spectrum, so they weren’t the classical Devic disease that was pretty much a disastrous disorder. Well, we learned that the NMO spectrum could be considerably milder and had some overlap with MS. I don’t see that happening so much anymore. That syndrome is much more clearly recognizable now that we’ve expanded things, looking at the lower brainstem lesions, the longitudinally extensive spinal lesions.
The patients with MOG are a little more concerning because I’m not entirely clear which are a syndrome and which are resulting from having inflammation in the central nervous system. MOG sits right in between NMO and MS and overlaps with both, and this one is causing us some more concern.
Sven Meuth, MD, PhD: Based on the pathophysiology, one would assume that entire MOG disorders are directed against oligodendrocytes, so it should be more in the spectrum of multiple sclerosis, in my opinion, compared to aquaporin, which is obviously expressed on astrocytes.
Fred Lublin, MD: That’s a very good point. I never thought to distinguish them, and trying to figure out when it’s pathogenic and when it’s not.
Patricia K. Coyle, MD: The first thing we need to do is assign what populations are MOG positive, what syndromes are MOG positive. Some of them are transient, very common in post-infectious encephalomyelitis, ADEM [acute disseminated encephalomyelitis]. A good proportion of them fade away and disappear. But if the MOG antibodies persist, then that patient with ADEM is at increased risk for later optic neuritis.
Sven Meuth, MD, PhD: This might also be the reason why we have 20% of MOG-positive children where it’s, from the very beginning, not so easy to distinguish between relapsing inflammation, so MS, or monophasic disorder.
Wallace Brownlee, MBChB, PhD, FRACP: I do think, though, that the syndromes associated with MOG spectrum or MOG-IgG are becoming clearer, just like it took some time for the full spectrum of NMO SD [spectrum disorder] associated with aquaporin-4 antibodies to become clear. We are getting better at recognizing the sorts of patients who are likely to have MOG antibodies. For example, people with unilateral or bilateral optic neuritis in which there is prominent optic disc swelling or prominent pain, or the patient with transverse myelitis where there is a long lesion involving the conus. These are some clinical situations where the suspicion for MOG-IgG is high.