‘Back at square one’: Christina Applegate says her MS was misdiagnosed

Actor Christina Applegate, who received a multiple sclerosis diagnosis in 2021, said Tuesday that she had been unexpectedly plunged back into uncertainty after a doctor told her she didn’t have multiple sclerosis after all.

“This may come as great news, but to me it comes as like I’m back at square one,” Applegate said on “MeSsy,” a podcast she hosts with actor Jamie-Lynn Sigler. She broke into tears as she described the doctor’s words: “She came into my room and she said, ‘Congratulations, you don’t have MS.’”

“Well, I was not happy at all,” she said, explaining that her symptoms did not go away when the diagnosis did. “Everybody else was so happy.”

“You don’t get misdiagnosed and then all of a sudden I’m better,” she added.

The about-face, Applegate said, doesn’t mean she’s not sick anymore. It means she’s still sick but doesn’t know why — a common experience for people with complex chronic illnesses, and one Applegate already went through for years before receiving her MS diagnosis.

Women are especially prone to these sorts of diagnostic odysseys, both because doctors are more likely to minimize their symptoms than men’s, and because many hard-to-diagnose immune conditions — including multiple sclerosis — are more common in women.

Applegate has been open for years about her illness, which she said on her podcast began with numbness in her toes that spread up her legs and advanced into pain. She developed balance, mobility and gastrointestinal problems as well.

In multiple sclerosis, the immune system attacks the myelin sheath that surrounds nerves, causing progressive damage. The symptoms — which often wax and wane, with flares and periods of remission — can include numbness and tingling, weakness, difficulty walking, fatigue and vision changes, among others.

Treatment can reduce symptoms and slow the disease’s progression, but there is no cure.

As with many autoimmune diseases, diagnosing MS is difficult because no single test can conclusively identify it, and many conditions can cause similar symptoms, said Bruce Bebo, the chief research and medical affairs officer at the National Multiple Sclerosis Society.

There are no definitive numbers on how often multiple sclerosis is misdiagnosed. But Bebo said it was a significant problem, and it goes both ways: Some people who don’t have MS are wrongly told they have it, and many people who do have it are initially told they don’t.

A study published in 2019 found that, of patients who were referred to two academic centers in California with an MS diagnosis, 18% did not have the disease. But because of the study’s small sample size, it is hard to say how representative that result is.

Applegate was diagnosed after imaging showed lesions in her brain and a spinal tap revealed markers called oligoclonal bands, which signal inflammation in the central nervous system. Those findings are characteristic of MS, but Dr. Marwa Kaisey, an associate professor of neurology at Cedars-Sinai in Los Angeles, told The New York Times that they could also be found in other conditions.

“Most people with MS will have bands, but not everybody with bands has MS,” said Kaisey, who also appeared in the podcast episode.

Bebo noted that the standard diagnostic guidelines for multiple sclerosis were updated in 2024. One of the changes reflects new technology that can more accurately distinguish between lesions caused by MS and those caused by other diseases.

It is unclear what tests led Applegate’s doctor to reverse her diagnosis. However, Applegate — whose publicist said she wasn’t available to speak Tuesday beyond what she had already shared — said on the podcast that she recalled her doctor talking about looking for “string” around the lesions in her brain. The details were fuzzy, she said, because she had been in shock while her doctor was talking to her.

Kaisey said that, while she could not be sure, Applegate’s description sounded as if it could be referring to the “central vein sign,” one of the markers newly mentioned in the 2024 diagnostic guidelines.

Multiple sclerosis lesions show up as white spots on MRI scans, but other diseases can also cause those spots. One thing that distinguishes MS lesions is that they tend to form around blood vessels, Kaisey said, and the new test allows doctors to see those vessels as dark spots in the middle of the white lesions. The presence of those vessels makes it likelier, though not definite, that the lesions are caused by MS; their absence makes it likelier that the lesions are caused by something else.

Applegate’s announcement came as a shock to some people with multiple sclerosis who understand how painful it is to suffer without answers.

Suni Conway, who has multiple sclerosis and does MS advocacy in addition to her work in financial services, said Applegate’s experience was “terrifying.” For six years, she said, she was repeatedly hospitalized for loss of vision, vertigo, fainting and numbness. She was told that she was dehydrated, or grieving her father’s death, or overly stressed. One doctor even told her that breast reduction surgery would fix the numbness. She had the surgery.

“I thought that everybody knew my body more than I did, and that this would solve things, and I was desperate for an answer,” Conway, now 35, said. When actor Selma Blair spoke about her own MS symptoms in 2018, they were so familiar that Conway lied to a neurologist, saying she had received an MS diagnosis and wanted a second opinion. The neurologist did an MRI and agreed she had it.

With a diagnosis, “at least we now can know, as far as science will allow, what can we do about it going forward,” Conway said. “The fear of what could be is something that every person living with an autoimmune disease wakes up with every day.”