Distinguishing autoimmune demyelinating diseases from MS

The importance of an accurate diagnosis

While the most common central nervous system (CNS) demyelinating disease is multiple sclerosis (MS), other CNS demyelinating diseases are associated with antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG), which drive harmful autoimmune responses. Identifying the antibodies associated with autoimmune CNS demyelinating disease enables diagnostic certainty and implementation of an appropriate treatment regimen, which minimizes the risk of relapse and patient disability.

Neuromyelitis optica spectrum disorders

Neuromyelitis optica (NMO) is an inflammatory, CNS demyelinating disease, characterized by severe relapsing attacks of optic neuritis and transverse myelitis. Unlike attacks associated with MS, NMO attacks commonly spare the brain in the early stages.

The spectrum of NMO was traditionally restricted to the optic nerves and the spinal cord. In 2004, Mayo Clinic scientist Vanda Lennon, M.D., Ph.D., reported an antibody that targets aquaporin-4 (AQP4), the water channel on astrocytes, which is a sensitive and specific biomarker for NMO. Since that discovery, a much broader category called NMO spectrum disorders (NMOSD) has evolved.

Myelin oligodendrocyte glycoprotein (MOG)-opathy

Detection of MOG-IgG is diagnostic of MOG-IgG associated disease (MOGAD), which is a CNS inflammatory demyelinating disease where the clinical phenotype (NMO, optic neuritis, transverse myelitis, acute disseminated encephalomyelitis [ADEM]) may be similar, but the immunopathology (astrocytopathy vs. oligodendrogliopathy) and clinical outcome (worse vs. better) are different. Detection of MOG-IgG also predicts disease relapse.

More importantly, MOGAD is distinct from MS and treated differently, with many MS treatments reported to worsen MOGAD.

By the numbers


of patients with NMOSD are initially misdiagnosed with MS1


of AQP4-IgG-negative patients are positive for MOG-IgG2


probability of second optic neuritis episode within one year of initial attack in AQP4-positive patients3

Ensuring better patient outcomes

Due to significant overlap in the clinical phenotypes, we recommend testing for AQP4-IgG and MOG-IgG at the same time. This synchronized testing method allows for a faster diagnosis and treatment plan decision for your patient.

Elevating outcomes through early detection

Learn more about NMOSD and the critical importance of sensitive and specific AQP4-IgG laboratory testing for early diagnosis and treatment in this “Hot Topic” presentation given by Sean Pittock, M.D.

Similar characteristics, different treatment

  • While NMOSD and MOGAD are treated by immunosuppressant therapy, MS is treated by immunomodulatory therapy, which may worsen NMOSD.
  • For patients who are AQP4-IgG positive, optimal immunosuppressive therapy should be initiated as soon as possible (a negative result in a subject where NMOSD is suspected should receive follow-up testing in 3 to 6 months).
  • For patients who are MOG-IgG positive, disease identification gives crucial information on diagnosis prognosis and can help guide acute treatment, including decisions about when to initiate attack-prevention immunosuppressive therapy, which is usually reserved for those who have two or more attacks. Follow-up testing in 6 to 12 months is recommended, as persistence of MOG-IgG seropositivity predicts a relapsing course.

Early diagnosis
is critical

  • Initiating NMOSD therapy early in the course to eliminate recurrence of attacks will minimize patient disability.
  • If not treated appropriately, within five years, 50% of NMOSD patients lose functional vision in at least one eye or are unable to walk. Recent data suggests that patients with MOGAD may have less disability.

FACS: A superior method of testing

Mayo Clinic has developed the only fluorescence activated cell sorting (FACS) live cell-binding assay currently available in the U.S. for antibody detection of AQP4 and MOG. FACS is recommended by international leaders in neuroimmunology for its increased sensitivity and specificity.

  • Yields 76.7% sensitivity, compared to 60% sensitivity through ELISA
  • 100% specific for AQP4
  • Risk of false-positive result with ELISA methodology is at least 5x greater when compared with the Mayo Clinic FACS assay

Key testing

Learn more about how to order this evaluation at your institution.


Testing brochure

Additional resources


  1. Pittock SJ, Lennon VA, Bakshi N, et al: Seroprevalence of aquaporin-4-IgG in a Northern California population representative cohort of multiple sclerosis.  JAMA Neurol 2014;71(11):1433-1436.
  2. Hamid SHM, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017 Oct;264(10):2088-2094.
  3. Pittock SJ, Lennon VA, Bakshi N, et al: Seroprevalence of aquaporin-4-IgG in a Northern California population representative cohort of multiple sclerosis.  JAMA Neurol 2014;71(11):1433-1436.
  4. Water PJ, McKeon A, Leite MI, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays.  Neurology.2012;78(9):665-671