Distinguishing autoimmune demyelinating diseases
from multiple sclerosis.
The importance of an
Identifying antibodies that are contributing factors in CNS demyelinating diseases allows physicians to provide a clear diagnosis for patients and implement an appropriate treatment regimen designed to reduce the risk of relapse.
Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. NMO is characterized by severe relapsing attacks of optic neuritis and transverse myelitis. Unlike the attacks associated with multiple sclerosis (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, and it 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 central nervous system (CNS) inflammatory demyelination, 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.1 Detection of MOG-IgG also predicts disease relapse.
More importantly, MOG-IgG seropositive inflammatory demyelinating diseases (IDDs) are distinct from MS and are treated differently, and these MS treatments have been reported to worsen MOG-IgG seropositive IDDs.
By the Numbers
Recurrent optic neuritis patients
who are positive for AQP4-IgG or MOG-IgG.
of AQP4-IgG (-) NMO patients
are positive for MOG-IgG.
frequency that MOG-IgG is
positive compared to AQP4-IgG.
Ensuring better patient outcomes
Due to significant overlap in the clinical phenotypes, we recommend testing AQP4
and MOG-IgGs at the same time. This synchronized testing method allows for a faster diagnosis and treatment plan decision for your patient.
Similar characteristics, different treatment
Although NMOSD and MOG-opathies can have very similar clinical and radiologic characteristics to MS, the appropriate treatments differ significantly:
- While NMOSD and MOG-opathies 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 in 3 to 6 months).
- For patients who are MOG-IgG positive, immunosuppressive therapy may be justified as soon as possible; follow-up in 6 to 12 months is recommended as persistence of MOG-IgG seropositivity predicts a relapsing course.
Unlike MS, the neurological disability caused by NMO spectrum disorders and MOG-opathies is based on the number of attacks rather than a progressive phase of the illness:
- Initiating therapy early in the course to eliminate recurrence of attacks will minimize patient disability.
- If not treated appropriately, within five years, 50% of NMO patients lose functional vision in at least one eye or are unable to walk. Recent data suggests that patients with MOG-opathy may have less disability.
Which test should I order?
When should I order the CNS Demyelinating Disease Evaluation?
The Meaning of a Positive Result
Optic neuritis in the era of biomarkers
Antibodies to aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) are recently described biomarkers seen in a subset of atypical optic neuritis which have revolutionized our understanding of the condition. In this “Hot Topic,” my colleague, Dr. John Chen, will review these advances and how they impact the clinical care of our patients with optic neuritis.
Webinar - Autoimmune gliopathies and CNS demyelinating disease
This "Specialty Testing" webinar, presented by Sean Pittock, M.D., will provide an overview of novel biomarker discoveries and advances being made in the study of autoimmune gliopathies.
Study shows drug reduces risk of relapse with neuromyelitis optica
The drug eculizumab, a synthetic antibody that inhibits the inflammatory response, significantly reduced the risk of relapse with neuromyelitis optica spectrum disorder (NMOSD). This rare but severe autoimmune inflammatory disorder can cause blindness, paralysis, and death.