Applegate's case is not totally unique, although MS diagnosis has improved over the years. Studies offer different estimates of how frequently MS is misdiagnosed, with rates ranging from 5% to over 40%, depending on the patient population and clinical setting. There is also some degree of underdiagnosis — cases in which people with MS aren't flagged as having the disease.
"It's also really important that doctors and patients be aware that it's not inappropriate to revisit a diagnosis — to make sure it's right," Dr. Ari Green, chief of the Division of Neuroimmunology and Glial Biology at the University of California, San Francisco, told Live Science.
This damage leads to distinctive scarring in nerve tissue and causes a range of symptoms, including vision problems, muscle weakness, tingling sensations, dizziness and bladder control issues. Patients with untreated and advanced MS can lose the ability to walk and stand or, in some cases, develop partial or complete paralysis.
Dr. Yohance Allette, a neuroimmunologist and researcher at Penn State Health
"It's moved from people ending up with severe, profound disability at 10 or 20 years of disease, and now it's at like 30 or 40 years of disease, they have modest disability," Green told Live Science. The disease most often emerges between age 20 and 40, although it can occur in any age group. Importantly, Green said, "the earlier people initiate treatment who have MS, the better they do over the long term."
"A diagnosis of exclusion"
However, there is no single, surefire test that can reliably show that a person has MS. "With MS, it comes down to the keyword 'criteria," Allette said.
So, what does diagnosis look like for a patient today? The first step is to recognize symptoms that might point to MS.
Once concerning symptoms are flagged, MRIs of the brain and spinal cord are taken. The scans may reveal evidence of myelin damage, and neurologists note the shape, size and location of those lesions. Damage often appears near blood vessels, since that's where immune cells access the brain, Green noted.
Myelin (yellow) helps neurons send messages efficiently. In MS, the immune system attacks myelin, causing it to break down. (Image credit: koto_feja via Getty Images)
MRIs of the optic nerves can also show MS-related damage, and these scans are emphasized in the latest diagnostic criteria, Allette noted. Electrophysiologic tests, which assess the function of nerves, are also "super important because they tell you something totally different than just seeing a lesion on MRI," Green said. Further signs of MS can be found via spinal taps, which sample the fluid around the brain and spinal cord that may carry proteins and inflammatory cells related to MS.
Other conditions — such as the inflammatory disease lupus and neuromuscular disease myasthenia gravis — can sometimes look like MS at first glance, as well. Some of these "MS mimics" can be ruled out with data from spinal taps or antibody tests, while others require a more laborious battery of assessments.
Conditions like MOGAD and neurosarcoidosis, an inflammatory condition sometimes mistaken for MS, can actually be worsened by MS medications, Green noted. So if a patient's MS flare-ups worsen after they start a treatment, that could hint that something else is the culprit, he said. But because there may be long gaps between flare-ups, doctors may need to track a patient for some time before their worsening becomes apparent.
Gaps to fill?
The updated diagnostic criteria for MS include new guidelines for how to examine brain MRIs. These criteria could likely be improved even more in future, Green noted. (Image credit: Douglas Sacha via Getty Images)"In general, there's a fair amount of diagnostic confidence that comes with MS diagnosis today," he said. However, that confidence is highest when the tools are in the hands of a specialist who is following the most up-to-date criteria, he noted. The test results require interpretation, and that's one place where uncertainty can creep in.
Without knowing the details of Applegate's case, Allette and Green said it would be difficult to speculate on what resulted in her misdiagnosis. (Applegate mentioned that her brain scans had been reassessed with a "new technology," but didn't go into specifics.)
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No proteomics-based diagnostic tests for MS have been approved yet, Green clarified. And even with those upcoming advances, Green doubts there will ever be a simple, one-time test that can determine a patient has MS. "I think that's probably unlikely, that it would ever be that straightforward," he said.
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