An attempt to define and understand better patients who had overlap features between multiple sclerosis (MS), neuromyelitis-optica spectrum disorders (NMOSD), MOG-IgG associated diseases (MOGAD) and atypical inflammatory disorders of the central nervous system (AID-CNS) which may mimic either one.

Although that diagnostic criteria for MS and NMOSD exist and recently has been proposed for MOGAD, the principal diagnostic criterion in their differential is the serology (antibody-status). However, a significant number of cases show overlap features between MS and the antibody-associated diseases or AID-CNS disorders resulting in diagnostic and therapeutic challenges.

We have studied patients from our MS and NMO/MOGSD cohorts who had overlap features defined as sharing at least two of the clinical, imaging and/or serologic phenotypes of either diagnostic category and patients with AID-CNS who were suggestive of either MS or NMO/MOGSD, but were seronegative and didn’t fulfill any diagnostic criteria (N:31).

Based on the imaging (MRI), clinical, serologic and immunologic (CSF) phenotypes there were 31 overlap cases who were subclassified in four patterns:

Pattern 1: Clinical and imaging phenotypes consistent with MS who were seropositive for AQP4-IgG & MOG-IgG on repeated testing (N:2).

Pattern 2: Clinical and/or imaging phenotypes suggestive of NMOSD, who were seronegative for AQP4-IgG & MOG-IgG on repeated testing and/or with CSF consistent with MS (N:8).

Pattern 3: Clinical and/or imaging phenotypes who shared features suggestive of both MS and NMOSD with either serology (N:17).

The results of our observational study are suggestive that a significant number of cases share clinical, imaging and serologic features of both MS and NMOSD/MOG-Ab-AD that may be subclassified as overlap cases. Another subgroup with atypical features that may be associated with yet unidentified auto-antibodies also emerged with each having its diagnostic and therapeutic consequences.