Even though inflammation of the optic nerve, called optic neuritis, is the first symptom of multiple sclerosis (MS) for an estimated 20% of patients, until recently, the optic nerve was not formally considered in the process of diagnosing MS. Last year, the International Advisory Committee on Clinical Trials in Multiple Sclerosis revised the McDonald Diagnostic Criteria to recommend that neurologists now incorporate optic nerve damage as part of the new diagnostic criteria.
The updated criteria, published in The Lancet Neurology this October, specifically adds the optic nerve as one of five lesion sites — meaning a location where central nervous system injury has occurred — when diagnosing MS. The hope is that by including the optic nerve in the diagnostic process, doctors will be able to identify MS sooner in patients, allowing them to start treatment earlier and help delay damage to the body’s central nervous system.
However, the change may lack specificity to ensure that misdiagnoses do not happen, warns Jeffrey Bennett, MD, PhD, a professor of neurology and ophthalmology at the University of Colorado Anschutz. As a physician-scientist involved in the Rocky Mountain MS Center, Bennett has spent years treating and researching MS. In response to the new criteria, Bennett and fellow neuro-ophthalmologist Steven L. Galetta, MD, chairman of neurology at the New York University Grossman School of Medicine, published a comment in The Lancet Neurology that notes the potential benefits and drawbacks of the change.
“The whole idea of the McDonald criteria, in general, is to recognize MS early so treatment can be instituted as soon as possible. Putting the optic nerve into the diagnostic criteria allows you to accomplish that objective,” Bennett says. “The issue is specificity. The updated criteria, as laid out with all the other criteria needed to make the diagnosis of MS, may reduce the specificity more than intended.”
The National Multiple Sclerosis Society estimates that nearly 1 million people in the United States have been diagnosed with MS, a chronic neurological autoimmune disorder where the immune system attacks healthy cells.
Symptoms can vary from mild to debilitating, with some people experiencing vision issues, muscle weakness, tingling in the arms and legs, tremors, and dizziness. It is estimated that up to 70% of all patients with MS will have optic neuritis at some point, Bennett explains.
Diagnosing MS can be difficult because there is no singular test for it. Instead, neurologists consider a variety of factors and tests to identify the disease. The McDonald Diagnostic Criteria, named after neurologist W. Ian McDonald, sets forth methods for clinicians and researchers across the globe to identify MS.
“There isn’t any specific test or assay that will confirm if a patient has MS, so we have to look at the clinical exam, patient history, and the results from labs, radiology, and MRI scans to make a diagnosis,” he says. “The question is: Can we diagnose people at the start of the disease’s development without sacrificing the specificity of testing to confirm a patient isn’t experiencing something else that mimics MS?”
One of the factors of diagnosing MS is assessing if lesions (damage to the tissues) have “disseminated in space,” meaning that different parts of the nervous system have been affected. Traditionally, when diagnosing MS, neurologists would check four different sites of the nervous system for damage — the spinal cord, infratentorial (back of brain), periventricular (near center of brain), and cortical (immediately beneath the cortex) regions.
“Those were the four domains of space, and the optic nerve didn’t count as a domain despite the prevalence of optic neuritis among many MS patients,” Bennett says. “That meant that if a new lesion emerged on the optic nerve, it wouldn’t necessarily count as proof of MS in the same way as a lesion in a different area of the brain would. Hence, someone who had optic neuritis as the first attack of MS would need extra injuries to happen in the future to get a diagnosis.”
The McDonald criteria initially resisted adding the optic nerve as a domain of space because there are many different disorders in addition to MS in which optic neuritis occurs. However, that changed under the updated criteria, which has officially added the optic nerve as a fifth domain.
“Hopefully, this change will help people get a diagnosis and begin treatment earlier,” he says. “The therapeutic drugs work more effectively when used earlier because they work against the inflammatory factors that drive MS. By preventing future damage to the nervous system, people will have less neurologic disability over time.”
Optic neuritis can be difficult for some practitioners to detect because it requires specialized skills to examine the back of the eye — skills that are typically more developed among neuro-ophthalmologists than neurologists.
“Many studies have shown that many patients with MS had subclinical evidence of injury to the optic nerves,” Bennett says. “The updated McDonald criteria introduced three different ways that involvement of one optic nerve — or asymmetric involvement of both optic nerves — could be detected and potentially contribute to diagnosing someone with MS.”
Although incorporating the optic nerve into the diagnostic criteria is an important step forward, Bennett cautions that the updated criteria may not be specific enough, particularly for practitioners who are less experienced with examining optic nerve injuries.
“For example, asymmetries that develop are not always due to an optic nerve injury,” he says. “If a clinician is not able to effectively examine the optic nerve, that could result in them inappropriately giving a patient a diagnosis of MS when something else is going on.”
Patients may also have evidence of an optic nerve injury, but it may not necessarily be optic neuritis — a key distinction that clinicians need to be able to make.
“Also, there are other disorders that cause optic neuritis, but the current criteria doesn’t require that the markers for these other disorders be absolutely excluded for adult patients,” he says.
Bennett notes that future research and analysis on the accuracy of the updated criteria will be important to evaluate how it performs and if there is a need for more specificity.
“While I see a great boon for including the optic nerve, these criteria will have to be assessed with these caveats to make sure that we aren’t sacrificing specificity,” he says. “Now that it’s one step easier to make the MS diagnosis, we want to make sure people are not getting misdiagnosed with this chronic disease.”