Samuel Pleasure, MD, Neurology, 07:27PM Jun 28, 2013
Neuromyelitis optica (NMO) is an interesting autoimmune disorder most commonly presenting with a clinical spectrum of optic neuritis and myelitis associated with long segments of signal abnormality on MRI of the cervical or thoracic spine. Over the last few years there has been much attention paid to the association of NMO as a clinical syndrome with anti-Aquaporin4 antibodies and the pathophysiologic role of these antibodies in the syndrome. One of the conundrums has been how to think about patients who have NMO clinically but who don't have anti-Aquaporin4 antibodies on testing - these range anywhere from 30%-70% depending on the experience of individual centers. Two recent studies in Neurology shed interesting light on this in two different directions.
First, Marignier and colleagues presented an interesting group of patients. This group has a large cohort of NMO patients (87) diagnosed by clinical and imaging criteria and they examined the anti-AQ4 antibody positive and negative groups. First they tested a new more sensitive assay to identify the most truly negative group of patients - in other words they wanted to exclude those whose antibodies were missed because of low sensitivity of the assay. Once these patients (ie the truly anti-AQ4 antibody negative NMO patients) were identified they compared these clinically to the expanded population of anti-AQ4+ patients. Interestingly, the negative patients were more likely to have presented with simultaneous optic neuritis and myelitis and were found to have a more aggressive disease course. This indicates that it is likely that there is an entirely different category of NMO patients, not associated with autoimmunity directed to AQ4 and who will prove to be an even more challenging group to treat effectively.
Second, Sato et al presented their data on a cohort of patients identified by their antibodies to AQ4. In this series the authors also devised a new sensitive assay and screened ALL patients with any evidence of neuroinflammation in their hospital regardless of meeting NMO criteria clinically. They found an entirely new set of patients who had less severe disease still associated with anti-AQ4 antibodies. Some of these patients had monophasic optic neuritis, brainstem disease or very limited spinal disease but still shared some of the other common features of NMO, including nausea/vomiting/persistent hiccups.
Taken together these studies indicate that the spectrum of disease associated with AQ4 antibodies needs to be looked at somewhat more generally and includes patients with less severe disease. What we don't know is whether these patients need or would benefit by aggressive anti-B cell therapy as is usually pursued in full fledged clinical NMO patients. And, what of the clinical NMO patients who truly don't have AQ4 antibodies? Are we waiting for another antibody to be found? In the interim should they still be treated with anti-B cell therapies (I'd say probably so)? Clearly the next couple of years will leave us with a lot more to say about this I'm sure.