Christina Applegate says she was misdiagnosed with MS—how could that happen?

Actress Christina Applegate’s announcement on Tuesday that she was misdiagnosed with multiple sclerosis (MS) in 2021 immediately made headlines. Her experience, while not the norm, is far from unusual, experts say.

Applegate disclosed the revelation on an episode of her podcast with Jamie Lynn Sigler, MeSsy, which centers on their lives with MS. (Sigler disclosed that she has relapsing-remitting multiple sclerosis, or RRMS, in 2016.) “In January of 2021, I had numbness in my toes, and that numbness grew to all of my legs,” Applegate recalled on the podcast. “And then the pain started.”

After rounds of tests for a variety of conditions, her doctor found “almost 40” lesions on her brain and diagnosed her with MS, she said.

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MS can be devastating. The neurological condition causes the body’s immune system to attack the nervous system, including parts of the brain. Symptoms can include fatigue, mood changes, dizziness, vision issues and numbness in the arms and legs.

Now, five years later, Applegate said that, after analyzing brain scans with a “new technology,” her doctor told her she doesn’t have MS. “I’m back at square one,” she said.

Her experience is more common than you might think.

“Diagnosing MS is a little bit like putting a puzzle together,” says Bruce Bebo, chief research and medical affairs officer at the National Multiple Sclerosis Society. “There’s not a single diagnostic test that tells you, ‘You have MS.’” The disease’s symptoms overlap with other conditions, such as neuromyelitis optica, which have to be ruled out before a diagnosis can be made.

Estimates vary, but a recent meta-analysis found that around 15 percent of MS cases across studies were misdiagnoses. The absolute odds of a misdiagnosis can vary by patient population and clinical setting, however, Bebo says. For instance, a study performed at a patient referral center where MS patients have been sent for additional analysis may inherently show higher rates of misdiagnosis in that patient population, says Thomas Flagiello, a neurologist at NYU Langone.

Overall, “although misdiagnosis happens, the majority of cases are correctly diagnosed,” Flagiello says.

Diagnostic tools are getting better. In 2025 the International Advisory Committee on Clinical Trials in Multiple Sclerosis updated its guidelines on how to diagnose MS to reflect recent advancements, including the ability to look in brain scans for specific clues, such as the central vein sign, a small vein running through brain lesions, or a specific kind of brain feature called a paramagnetic rim lesion, Bebo says.

Identifying these markers in patients’ brains could help reduce misdiagnoses, Bebo says. But as of now, it’s impossible to totally rule out a misdiagnosis.

As Applegate’s story illustrates, the consequences of a misdiagnosis can be substantial. It could mean someone receives treatment they don’t need—or misses out on treatment that they do, Bebo says.

That’s why getting a diagnosis right “really matters,” Bebo says. “Whether you have MS or you ultimately have some other condition, people experiencing significant neurologic symptoms deserve to have a careful evaluation.”