Why Is Multiple Sclerosis So Commonly Misdiagnosed?

Christina Applegate announced that she was wrongly diagnosed with MS — but she's far from the only one

More than five years after revealing that she had multiple sclerosis (MS), Christina Applegate announced on Tuesday that she was misdiagnosed with the condition on the most recent episode of her and Jamie Lynn Sigler’s podcast, MeSsy. This was her first time back on the show, she said, after taking a seven-month break to “process” the news after receiving it from her doctor. 

“She came into my room and said, ‘Congratulations, you don’t have MS,’” Applegate recalled on the podcast. “I was, like, not happy at all. Everybody else was so happy.” Now, she says she’s “back at square one,” working with doctors to try to identify the actual cause of her debilitating symptoms. 

As it turns out, what happened to Applegate isn’t all that unusual. According to a 2019 study out of Cedars-Sinai, nearly 20 percent of patients once informed they were suffering from MS were actually given the wrong diagnosis. 

But why is a condition estimated to affect nearly one million people in the United States misdiagnosed so frequently? And why are these misdiagnoses so problematic? Rolling Stone spoke with a neurologist specializing in MS to find out.

What is multiple sclerosis?

Multiple sclerosis is a chronic, progressive neurological disorder as well as an immune-mediated disease, meaning it causes an abnormal immune system response. (Autoimmune diseases, when the body attacks its own healthy tissue, are a subset of immune-mediated disease.) More specifically, in MS, the immune system damages myelin, the protective coating around the nerve fibers in the brain and spinal cord. Myelin’s job is to help nerves send messages quickly, so when it’s compromised, messages between your brain and body slow down or get blocked altogether, causing MS symptoms.

The symptoms of MS can vary from person to person, as well as during the course of the disease, depending on which nerve fibers are affected. Common symptoms include numbness or tingling of the face, torso, or limbs; extreme mental and/or physical fatigue; vision problems (like double vision or inflammation of the optic nerve); muscle weakness; and dizziness. In some cases, MS can cause mood and/or cognitive changes.

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However, in some cases, people who go on to be diagnosed with MS don’t have any symptoms. “It’s called radiologic isolated syndrome,” says Tirisham Gyang, MD, a neurologist and associate professor of neurology at the Ohio State University Wexner Medical Center. “They get an MRI for a different reason, like headaches or an accident. Nobody is thinking they have MS. They’ve never had any symptoms of MS. Yet the brain MRI looks just like MS.”

How is multiple sclerosis diagnosed?

Because of the evolving understanding of multiple sclerosis, the diagnostic criteria were revised in 2024 to be more sensitive and specific.

Prior to that, MS was exclusively a clinical diagnosis — meaning the patient had to have specific symptoms, like vision loss or weakness, for example. In addition to this, they would need to have results consistent with MS from tests like an MRI or spinal tap, Gyang says.

“It’s like a puzzle we’re trying to build,” she tells Rolling Stone. “We’re putting pieces together — the clinical aspect, the MRI, the spinal fluid, the vision test — and we try to figure out if they fit the criteria for MS.”

The revised diagnostic criteria includes additional tests that are more likely to lead to an accurate diagnosis. Applegate was diagnosed with MS in 2021, before these new benchmarks were established. 

Why is multiple sclerosis misdiagnosed so frequently?

While at least two studies found that roughly 20 percent of MS patients were misdiagnosed, other research puts that number even higher. A 2019 study published in the journal Neurology indicated that “of all new referrals to MS subspecialty centers with a question of MS diagnosis, 30%–67% were ultimately determined not to have MS.”

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Women, like Applegate, are at an even greater disadvantage. A 2021 study out of Argentina found that women were 83 percent more likely to be misdiagnosed with MS than men.

A major reason for all the misdiagnoses is the lack of a definitive diagnostic biomarker of MS. “There’s no magic blood test that I’m aware of that is exclusively going to diagnose MS,” Gyang says.

Additionally, MS shares both symptoms and MRI findings with other diseases, complicating diagnoses. For example, MS can look a lot like migraine, vascular disease, high blood pressure, and diabetes, among other conditions, which can make definitive diagnoses more difficult, according to Gyang. 

Misdiagnosis also may occur when the clinicians don’t apply the diagnostic criteria correctly, or rush through the process. “You don’t get a trophy for saying on the first day you see a patient that they have MS,” Gyang says. “Sometimes the additional piece of the puzzle we need is time. MS is not a static disease; it evolves over time.” In cases when a patient falls into a diagnostic gray area — where it’s unclear whether or not they have MS — she typically suggests that they repeat the tests in six months to see what, if anything, has changed.

Why is misdiagnosis such a big problem? 

To start with, it often means that patients are taking risky and unnecessary drugs. “These are immune suppressive or immune modulating treatments,” Gyang explains. “A patient without MS should not be on medication like that.”

Being treated for MS is also extremely expensive. “And it’s not just the treatments,” Gyang says. “It’s the blood work you have to get to monitor you while you’re on the treatment, [and] the time off you have to take from work to go for infusions. MS is a huge commitment and a huge burden.”

Another factor is that if someone has been misdiagnosed with MS and actually has a different condition, it means that their real diagnosis — and proper treatment — has been delayed, Gyang explains.

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And then there’s the psychological impact of an MS misdiagnosis. “It’s traumatizing to patients to all of a sudden pull their diagnosis because some people have made peace with it, [or] have formed community,” Gyang says. “It’s very difficult having that discussion and saying ‘This is not MS. You have to start from square one.’ Sometimes that’s more frustrating to patients, and they would rather have a serious chronic disease because they have accepted that diagnosis.”

Ultimately, Gyang says that Applegate coming forward about her misdiagnosis will help bring awareness of the challenges of MS. “I know it’s intimidating and it’s scary, and it’s difficult to navigate the health system,” she says. “But we want patients to be empowered, and if there’s nobody that’s advocating for them, to find a voice to advocate for themselves.”