The “grey zone” between neuromyelitis optica spectrum disorders (NMOSD) and MS remains a diagnostic challenge for clinicians.
According to a study of almost 300 cases of suspected demyelinating disease from 23 adult and paediatric CNS clinics in Australia and New Zealand, a relatively high proportion were found to be suspected NMOSD but negative for aquaporin-4 autoantibodies.
There were 75 eventual diagnoses of NMOSD (AQP4 antibody positive and/or meeting 2015 IPND criteria), 89 suspected NMOSD (either antibody negative or not meeting the IPND criteria) and 101 cases of MS (AQP4 antibody negative and meeting 2010 McDonald criteria).
A comparison of clinical features found a significantly older age of onset in NMOSD than suspected NMOSD or MS (40 yrs v 34 and 32 yrs respectively) and a corresponding shorter duration of disease (3.8yrs v 6.5 and 11.5yrs).
The annualised relapse rate was higher in NMOSD than suspected NMOSD and MS (0.77 v 0.41 and 0.33) and NMOSD patients also had higher EDSS scores (4 v 3.5 and 2).
Initial MR imaging of the brain was more likely to be normal in NMOSD compared to MS (17% v 3%) but highest in suspected NMOSD (34%).
Longitudinally extensive spinal cord lesions were seen in 68% of NMOSD cases, 47% of suspected NMOSD and only 1% of MS cases.
“The profile of symptoms and relapse locations, with optic neuritis being more common in NMOSD and brainstem, cerebellar and cerebral lesions being more common in MS, is not surprising and is consistent with prior studies,” the Journal of Neurology study said.
NMOSD patients had higher CSF white cell counts and protein levels, lower frequency of oligoclonal bands in CSF, less delayed P100 latency on VEP and a higher frequency of co-occurring autoimmune diseases than MS patients.
There were no significant differences in clinical features observed between seropositive and seronegative NMOSD cases.
“Distinctly different profiles of clinical features between NMOSD and MS are of considerable assistance in identifying potential cases, but a significant number of cases with NMOSD-like features are antibody negative and do not meet current clinical criteria for a diagnosis of NMOSD, indicating that there is a persistent grey-zone between NMOSD and MS,” the study concluded.
Senior investigator Professor Simon Broadley, from the Gold Coast University Hospital and Griffith University’s Menzies Health Institute Queensland, told the limbic there was more work to be done to further define what those cases were.
“People are thinking there could be more antibodies that we just haven’t found yet, or they could be some people with MS with unusual features and there is just an overlap between the two,” he said.
“And then there is a remote possibility that some patients may actually have both conditions but that is probably very, very rare.”
Professor Broadley said the most commonly used treatment for NMOSD was currently rituximab.
“And it turns out another B-cell therapy ocrelizumab has been shown to be of benefit and is one of the more effective therapies we have for MS as well – even though we didn’t think it should work, it does.”