Christina Applegate reveals she was misdiagnosed with MS after five years of treatment

Christina Applegate spent five years building a life around a diagnosis — the MS community, the podcast, the advocacy, the hard-won understanding of why her body had turned against her. On Tuesday, a doctor walked into her room and took it all away with a single word: 'Congratulations.'

Applegate, 54, revealed on the October 20 episode of her podcast 'MeSsy' that she had been misdiagnosed with multiple sclerosis, the neurological and autoimmune disorder she publicly announced in 2021 and had been treated for ever since. The news, she said through tears, brought no relief — only confusion, depression, and the same debilitating symptoms she has always had.

This may come as great news, but to me, it comes as like, very like I'm back at square one. But it's hard to say … [my doctor] came into my room and she said, 'Congratulations, you don't have MS. Congratulations.'— Christina Applegate, actress and podcast host

I was, like, not happy at all. Everybody else was so happy … You don't get misdiagnosed and then all of a sudden I'm better. I haven't gotten better, Jamie. If anything, I've gotten worse in some ways.— Christina Applegate

Applegate co-hosts 'MeSsy' with actress Jamie-Lynn Sigler, who was diagnosed with relapsing MS roughly 25 years ago and has been public about her condition. Applegate had taken a seven-month break from the podcast before returning Tuesday with the two-part episode. She said she needed that time to process what she called 'a great depression' triggered by the misdiagnosis.

Her physical condition has not changed. She still uses a wheelchair to travel from her car to the doctor's office. She still cannot walk that distance. She still has, in her own words, 'every symptom of someone with MS — every single one.' What she no longer has is an explanation.

I still have to use wheelchairs when I go to the doctor's office. I can't walk from the car to the room. I'm still in this. Nothing magical happened when she said, 'You don't have MS.' Nothing magical happened.— Christina Applegate

On the podcast, Applegate described how the misdiagnosis unraveled. A few years ago, her doctor paused her infusion treatment to observe how her B cells responded. The cell count neither increased nor decreased — an unexpected result that, according to CBS News, triggered a deeper review of her diagnosis. Eventually, doctors concluded she had never had MS at all.

Part of what led to the revised conclusion, according to Business Insider, was a newer diagnostic tool called the central vein sign (CVS) — an MRI biomarker that can help distinguish MS brain lesions from those caused by other disorders. Applegate said her brain lesions were missing the 'strings' associated with MS. CVS was only incorporated into recommended MS diagnostic criteria in 2025, four years after her original diagnosis.

At the time of her initial diagnosis, Applegate had undergone a spinal tap, MRIs, and other tests. Scans showed nearly 40 lesions on her brain, and her spinal fluid showed a low level of immune proteins that can support an MS diagnosis. Those findings, combined with her symptoms, led doctors to diagnose her with MS — a process that, experts say, is inherently imprecise.

We don't have one single test for MS. It's not like we have something like a pregnancy test that says, 'Yes. You have it.' 'No. You don't.' It's a list of criteria. Almost one in five of these people who'd been told they had MS, some for decades, didn't actually have it. And a majority of them were on medication to treat their MS.— Dr. Marwa Kaisey, associate professor of neurology, Cedars-Sinai Medical Center

Kaisey, who appeared in the follow-up episode of the podcast, attributed the high misdiagnosis rate to both the absence of a single definitive test and the fact that many MS symptoms — fatigue, numbness, balance problems, pain — are common to a wide range of other conditions. A 2024 meta-analysis published in the Multiple Sclerosis Journal found a 15 percent misdiagnosis rate in the cases it examined, according to The Guardian.

Dr. Andrew J. Solomon, a professor of neurological sciences at the University of Vermont who co-authored that meta-analysis, told Business Insider that doctors sometimes over-rely on a single diagnostic finding — such as an MRI result — without completing the full battery of tests needed to confirm MS. He said a 2019 study he co-authored found that patients initially diagnosed with MS were later found to have conditions including migraine, neuropathy, and spondylopathy, all of which can produce overlapping symptoms and similar brain scan results.

Kaisey told Business Insider that the double risk of misdiagnosis cuts both ways: patients may be exposed to the side effects of MS medications they don't need, while the condition actually causing their symptoms goes untreated.

For Applegate, the emotional weight of the misdiagnosis is inseparable from the identity she had built around it. She had written a memoir, become a public face of MS, and found community among others living with the disease. Losing the diagnosis meant losing the framework that made her suffering legible — to herself and to others.

It's weird because I feel like I let everybody down. It's this weird feeling because I became this — [Sigler] and I, the poster children for MS. And everything I was doing. I had a reason ... And now I don't have a reason and it's very unnerving and it's very confusing for me.— Christina Applegate

I've gone through a great depression because of it. But you know, I lost everything. I lost my job. I lost — sorry. What do you say to someone who's been living with this for six years? God, I'm so sorry, I get really emotional because it stopped my life.— Christina Applegate

Sigler pushed back on Applegate's sense of guilt. 'Everything you did, and shared, and were, and are to so many people doesn't go anywhere,' Sigler told her, according to The Guardian. 'You didn't mislead anyone. In no way should you feel bad or uneasy about your continuing to share your journey with people.'

Applegate said her medical team will now begin investigating what has actually been causing her symptoms since 2021. She said that investigation was set to begin the week of the podcast's release. She has physical therapy three times a week and continues to manage severe mobility limitations. Her last major acting role was on Netflix's 'Dead to Me,' which concluded in 2022, the year after her MS diagnosis.

That's going to be an online investigation that, you know, my doctors are going to get into, and just to find out what has been happening since 2021. Why did this happen?— Christina Applegate

Solomon told Business Insider that Applegate's experience, while painful, is valuable precisely because it is not rare. 'It's kind of wonderful that she's sharing this,' he said, adding that patients who receive a corrected diagnosis often still face an uncertain road — potentially losing access to specialists and worrying about insurance coverage for treatments that had been providing some relief.

Why it matters — Applegate's case puts a human face on a documented medical problem — MS misdiagnosis affects roughly one in five patients — and highlights how a corrected diagnosis can strip away not just a treatment plan but a person's sense of community, identity, and explanation for their own suffering.

Reported by variety.com, pbs.org, foxnews.com, thehill.com, cbsnews.com, abcnews.com, nbcnews.com, businessinsider.com, theguardian.com, people.com