Christina Applegate returned to her podcast "MeSsy" on Tuesday, October 20 after a seven-month hiatus and tearfully told co-host Jamie-Lynn Sigler that a doctor had told her she does not have multiple sclerosis, a diagnosis she first revealed publicly in August 2021.

"It's hard to say that she came into my room and said, 'Congratulations, you don't have MS,'" she said, adding she was "not happy at all" while everyone else reacted with joy.

Applegate had recently taken a break from co-hosting to process the news, spending months in the hospital earlier this year before being discharged in August.

The announcement upends five years of public advocacy. Applegate received a standing ovation at the 2024 Emmy Awards, appearing on stage with a cane, and described living "kind of in hell" in an interview that year.

"I feel like I let everybody down," she told Sigler, saying the two had become "the poster children for MS." Crucially, the misdiagnosis does not mean she is well: "You don't get misdiagnosed and then all of a sudden I'm better," she said.

"If anything, I've gotten worse in some ways. I'm back at square one, that I don't know what's going on with me."

Her doctor's change of heart emerged after she was taken off an infusion treatment a few years ago and her B-cell counts neither rose nor fell, prompting a study into her original diagnosis.

Misdiagnosis may be more common than patients realize.

On the podcast's second episode, Dr. Marwa Kaisey, a neurologist and associate professor at Cedars-Sinai Medical Center, said nearly one in five people who have been told they have multiple sclerosis "didn't actually have it," and called misdiagnoses "fairly common."

Because there is no single test for MS — "It's not like we have something like a pregnancy test," she said — doctors rely on a list of criteria that changes roughly every seven years, leaving "room for error."

Common symptoms like tingling or numbness in the feet, fatigue and brain fog overlap with many other conditions, so distinguishing MS from its mimics can challenge even careful doctors. Applegate said her original workup included a spinal tap and MRIs that showed lesions on her brain.

Applegate, 54, continues to face debilitating symptoms that affect her mobility and daily life. She said she still uses a wheelchair to get to doctor's offices and cannot walk from the car to the exam room, and she does physical therapy three times a week.

She previously told The New York Times in 2022 she could not walk without a cane and used a wheelchair while filming Netflix's "Dead to Me." "Nothing magical happened when she said, 'You don't have MS,'" she said.

Sigler pushed back on any self-doubt: "What you're feeling is real and you can't take that away because you don't have the MS diagnosis around it." Applegate admitted that losing the label brought a strange grief — "I felt comfort in having a name, an answer and a community."

Applegate's story is a high-profile reminder of how much weight rides on a diagnosis. The reversal also highlights the subjective nature of MS criteria: as Kaisey explained, doctors must constantly stay current as the criteria evolve, and even the deepest look at a case can still get it wrong.

For patients who build identity and community around a label, having it "taken away" can be, in Kaisey's words, "earth-shattering."

Applegate said her medical team will begin a new investigation next week to determine the underlying cause of her symptoms, which she described as "an online investigation... to find out what has been happening since 2021. Why did this happen? I had every symptom of someone with MS. Every single one."

She noted there are "many things that mirror MS" and that "it's clear now that they're finding something different. Something else is going on."