Actress Christina Applegate was misdiagnosed with multiple sclerosis. How often does that happen?

Actress Christina Applegate was diagnosed with the neurological condition multiple sclerosis more than five years ago.

“It was my answer to everything that was going on,” she said.

Applegate embraced the MS community. She began speaking about her experience on her podcast MeSsy with actress Jamie-Lynn Sigler, who has MS, and became a prominent voice in the multiple sclerosis community.

So when Applegate’s doctor recently came to her and said, “Congratulations, you don’t have MS,” she recounted, speaking through tears: “I was like not happy at all.”

She described feeling lost after learning that she’d been misdiagnosed.

“I’m back at square one,” Applegate said, despite having what she described as “every single symptom” of MS including tingling, pain, tremors, incontinence, fatigue, intolerance to heat and cold, knee buckling and leg weakness and losing her ability to walk.

“I’m still dealing with all of those symptoms,” Applegate said in an Oct. 20 podcast episode. “And now here I am without a name.”

Misdiagnosis isn’t particularly rare when it comes to multiple sclerosis. Here’s what research tells us about the prevalence of erroneous MS diagnoses and how it can happen.

What is multiple sclerosis? 

Multiple sclerosis, sometimes shortened to MS, is a central nervous system disease that disrupts the brain and the rest of the body’s information exchange. It occurs when the immune system attacks and destroys myelin, the protective protein and fatty substance that surrounds and protects nerve fibers. This forms scar tissue called sclerosis, plaques or lesions.

MS looks different for each person. Symptoms can include numbness, pain, tingling, shaking, paralysis, partial or complete vision loss, mobility issues, coordination and balance issues, fatigue, weakness, memory trouble, mood changes and bladder and bowel problems.

The disease has no known cure. The National Multiple Sclerosis Society said about 1 million people in the U.S. live with MS.

How is MS diagnosed?

Doctors don’t perform one single test to diagnose multiple sclerosis. In isolation, no symptoms, or specific test results can prove the condition is MS.

Instead, doctors work to rule out other conditions that might explain a patient’s symptoms while looking for evidence that supports a multiple sclerosis diagnosis. Doctors typically look for evidence of damage in the brain, spinal cord or optic nerve. If damage is found in multiple places, doctors might also try to confirm that the damage happened at different times or search for lesions with MS-specific features or certain proteins in the spinal fluid, the National Multiple Sclerosis Society said.

“It’s a list of criteria,” Dr. Marwa Kaisey, a neurologist who treats and researches MS, told Applegate on MeSsy. “There’s room for error there,” because assessing criteria can be subjective and because the list can change over time, so doctors have to stay on top of developments.

“The symptoms of MS — like tingling in your feet or numbness in your feet, for example, fatigue, brain fog — are very common in other things that are not MS,” Kaisey said. Distinguishing “MS from its mimics can be challenging.”

Even doctors with good intentions who have closely examined someone’s case can get the diagnosis wrong, she said.

Dr. Michael Kornberg, an associate professor of neurology at Johns Hopkins University, told NPR that an MS diagnosis is reached after analyzing a patient’s various symptoms.

How often is multiple sclerosis misdiagnosed? 

MS researchers are very familiar with misdiagnoses.

Some studies have found about 5% of patients were misdiagnosed, while others have placed that number as high as 36%. A 2024 analysis pooled six studies and found that among 1,621 patients diagnosed with multiple sclerosis, 15% did not actually have it.

In a 2019 study, Kaisey and her coauthors found that in one year, roughly 18% of 241 people with established MS diagnoses who were referred to academic multiple sclerosis centers in Los Angeles had been misdiagnosed with the disease.

“When you really look at why they’d been misdiagnosed or what they had in common, most of them had some form of white matter spots on their MRI, some sort of lesions,” Kaisey said. The issue was that those lesions were caused by something other than MS. In that study, most of the people who were misdiagnosed actually had migraine, a neurological disease that causes intense headaches and other symptoms.

Misdiagnosis concerns drove MS researchers to seek signs that distinguish MRI white spots caused by MS from white spots with other causes.

One emerging method involves looking for something called the central vein sign in individual lesions, because that can help distinguish MS from other conditions that mimic it. The approach was incorporated into diagnostic criteria released in 2025, but not all hospitals are able to check for this sign, Kaisey said.

It looks for “little blood vessels sitting in the middle of these white spots or lesions” — their presence signals multiple sclerosis more clearly than white spots alone because that’s how MS creates its lesions, Kaisey said.

People can also be misdiagnosed with some other condition before they are diagnosed with MS. One 2017 survey found that approximately 42% of people had initially been misdiagnosed with conditions such as depression, migraine and fibromyalgia.

What happened in Applegate’s case?

Applegate recalled some of the test results that seemed to support the initial, now inaccurate multiple sclerosis diagnosis, including a brain MRI that showed white lesions and a lumbar puncture test that came back positive for oligoclonal bands, or antibodies found in the cerebrospinal fluid.

Kaisey said from what she had learned about Applegate’s case, it sounded possible her lesions didn’t meet the criteria for the central vein sign.

As for the lumbar puncture, normal results would return one or no oligoclonal bands in a patient’s cerebrospinal fluid.

Applegate said her test showed “three bands,” which is considered a positive test that signals inflammation in the central nervous system.

“Over 90% of people with MS are positive for this test,” Kaisey said. “But other things can cause it, it’s not just positive for MS. Anything that’s causing inflammation in the central nervous system would give you a positive result.”

What comes next for someone who was misdiagnosed with MS? 

Once the misdiagnosis has been identified, the next step is beginning the search for a new clinical explanation, Kaisey said.

Such errors can also bring harm. The diagnosis often becomes part of someone’s identity and community, and something their support network relies on, she said. Years of multiple sclerosis treatment can be extremely expensive. If someone’s disability paperwork is tied to the diagnosis, there can be financial consequences.

“You’ve been told you have this thing for many years,” Kaisey said. “To suddenly take that away, I think it is earth shattering. It’s life changing in a huge way.”

Often, doctors also don’t readily have another explanation, which can leave patients at a loss.

“We’re just starting from scratch, basically,” Applegate said, explaining that her doctor was beginning with blood tests to check for rheumatoid arthritis.

Testing for other rarer “cousins” of multiple sclerosis might also be in order, and blood tests exist for some of those, Kaisey said.

Cheryl Herbert, a National Organization for Rare Disorders spokesperson, said Applegate’s experience reflects the challenges many people with rare diseases face.

Getting an accurate diagnosis can take on average five or more years, Herbert said, “often involving multiple specialists, uncertainty and missed opportunities for earlier intervention.”

PolitiFact Staff Researcher Caryn Baird and PolitiFact Digital Research Analyst Erin Jones contributed to this report.