Guidelines to aid diagnosis of NMOSD published
Disease can resemble other neuroautoimmune conditions, which can result in misdiagnosis
Experts in Germany have published recommendations to help clinicians diagnose neuromyelitis optica spectrum disorder (NMOSD) and distinguish it from other disorders with similar symptoms.
The guidelines were detailed in “Update on the diagnosis and treatment of [neuromyelitis] optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis,” published in the Journal of Neurology.
NMOSD is a neuroautoimmune disease marked mainly by inflammation of the spinal cord (myelitis) and optic nerve (optic neuritis). The optic nerve relays signs between the eye and brain.
This damaging inflammation, which can be detected on MRI scans, can lead to pain, movement problems, and vision loss. These imaging and clinical findings can be similar to those of other neuroautoimmune conditions — MOG antibody-associated disease (MOGAD) and multiple sclerosis (MS), resulting in misdiagnoses and delayed diagnoses, which can affect disease progression and patients’ quality of life.
The Neuromyelitis Optica Study Group (NEMOS), a network of specialty treatment centers in Germany focused on improving care for NMOSD, created new recommendations for a NMOSD diagnosis. NEMOS will be publishing companion guidelines about treating NMOSD.
The researchers emphasized the importance of diagnosing NMOSD using the most up-to-date criteria, which were revised in 2015. Using older criteria may result in inaccurate diagnoses, they said.
The 2015 criteria outline six core clinical characteristics of NMOSD. They are: myelitis, optic neuritis, or involvement in any of four particular brain regions — the diencephalon, cerebrum, brainstem, or area postrema of the dorsal medulla.
Since most NMOSD patients will have myelitis and/or optic neuritis, symptoms indicative of these characteristics may raise a clinical suspicion of NMOSD. The disease can result in a range of symptoms, however, so clinicians should consider it as a potential explanation, the experts noted.
Confirming a diagnosis of NMOSD
To confirm an NMOSD diagnosis, a patient must have at least one of the six core characteristics and test positive for antibodies against AQP4 (AQP4-IgG), the specific and most common type of self-reactive antibody driving NMOSD.
Antibody testing should be done as soon as possible if the disorder is suspected, experts emphasized, noting that cell-based assays are the gold standard and repeating testing is needed since false-positive results can occur.
If AQP4-IgG status is negative or unknown, a NMOSD diagnosis can still be made if the patient has two of the six main characteristics, other specific features seen on MRI, and all other potential explanations have been ruled out.
“The most important antibody-related differential diagnosis of NMOSD is MOG-EM/MOGAD,” the experts wrote.
While MOGAD was once considered a form of NMOSD, it’s now understood the diseases are distinct and require different types of clinical management.
MOGAD is associated with antibodies against a protein called MOG and testing for their absence is key to confirming NMOSD, especially in patients with NMOSD-like symptoms who are negative for AQP4-IgG.
Testing should also rule out MS as well as other diseases, from infections to brain cancers, in order to ensure the accuracy of the diagnosis.
The researchers said that there is an unmet need in NMOSD care to define better diagnostic guidelines for patients who are negative for AQP4-IgG, but otherwise meet the criteria for the disease. More studies to understand the cause of disease in these patients are needed, they said.
Clues that can lead to NMOSD diagnosis
Some demographic clues may help raise the clinical suspicion of NMOSD and rule out related conditions. The disease usually appears around age 40 and about one-quarter of cases are late-onset (after age 60). The median age at symptom onset in MS and adult MOGAD is about 30.
NMOSD affects many more women than men, while MOGAD affects both sexes at generally similar rates. MS shows a women-to-men ratio similar to that reported for NMOSD negative for AQP4-IgG.
Also, “female patients with NMOSD are significantly more likely to be AQP4-IgG-positive than male patients,” the researchers wrote.
Previous data suggested NMOSD may be more frequent “among nonwhites than among whites,” the experts wrote, adding “this is in contrast to MS, which is most common in Caucasians of northern European ancestry.”
Nonetheless, the experts emphasized NMOSD can occur in people from diverse backgrounds, making it important to consider a diagnosis when patients show neurological symptoms that suggest the disease.