Christina Applegate reveals she was misdiagnosed with MS

After five years of tireless advocacy for those who shared her diagnosis of multiple sclerosis (MS), Christina Applegate has revealed that doctors now believe she was misdiagnosed. 

“To me it comes as, like, I’m back at square one,” she said of the news.  

Applegate shared the story in a two-part Tuesday episode of the podcast MeSsy, which she co-hosts with Jamie-Lynn Sigler, who has MS. She had spent some months away from the show, which she explained was partially to process the revelation.

Audibly emotional at times, Applegate said that while her doctor had congratulated her when revealing she didn’t have MS, she didn’t feel happy — only lost. 

“You don’t get misdiagnosed and all of a sudden I’m better. I haven’t gotten better … if anything, I’ve gotten worse, in some ways,” she said. 

“My legs aren’t working, you know, all the same stuff is happening to me.”

Multiple sclerosis is a complex autoimmune disease of the central nervous system. With MS, the immune system mistakenly attacks the myelin, part of the central nervous system that serves as a protective coating for the nerves. This inhibits the brain and the body from sharing information, resulting in symptoms including numbness, pain, memory issues, fatigue and mobility issues. 

The disease takes many forms, with some patients experiencing periods of remission and relapse, and others dealing with more consistent progression causing increasing disability. 

Misdiagnosis is not uncommon globally — one study from 2019 by researchers at Cedars-Sinai found that the rate of misdiagnosis was nearly one in five patients. A 2024 review looked at studies reporting misdiagnosis rates ranging from five to 41 per cent, and found an estimate of 15 per cent misdiagnosis rate when they pooled six studies.

Applegate arrives for the 29th Screen Actors Guild Awards in Century City, Calif., in February 2023. (Valerine Macon/AFP via Getty Images)

‘It’s been a tough road’

Applegate first announced she had MS on social media in August 2021, saying at the time that “it’s been a tough road.”

In Tuesday’s podcast episode, she said that it all started in January 2021, when she began to experience numbness in her feet, which slowly moved up her legs. 

“And then the pain started,” she said. “All that time, I was being tested for everything under the sun.”

She said she underwent spinal MRIs, brain MRIs and a spinal tap, and that doctors thought she might have a low-grade version of the disease at first. But her symptoms kept getting progressively worse. When doctors found nearly 40 lesions on her brain, she was officially diagnosed with MS.

“I felt like, ‘OK, I have an answer,’” she said in the podcast episode.

But a few years in, her doctor paused her infusion treatments to see how her B cells would respond. When their levels didn’t change, doctors began to look closer at the diagnosis. Ultimately, it was concluded she didn’t have MS — but she wasn’t given another diagnosis to replace it, leaving her in the dark as to what was causing her ongoing symptoms. 

Applegate attends the 26th Annual Screen Actors Guild Awards in Los Angeles in January 2020. (Mike Coppola/Getty Images for Turner)

“I feel like I let everybody down, you know?” Applegate said tearfully to co-host Sigler, saying she felt like they’d become “the poster children for MS” together. The two started their podcast in 2024, featuring conversations about parenting and ordinary life struggles while dealing with the disease. 

“It’s like I had a reason … for why my day sucked every day, and now I don’t have a reason. It’s very unnerving and it’s really confusing for me.”

The actress, who announced she was stepping away from the screen in 2021 with her diagnosis, is known for roles in movies such as Anchorman: The Legend of Ron Burgundy, and Bad Moms, and for TV roles including her Emmy-nominated turn in Netflix’s Dead to Me. 

Global rates of MS

Globally, more than 3.1 million people are living with MS worldwide, according to MS International Federation. Canada has one of the highest rates of the disease in the world, with more than 90,000 Canadians, roughly one in 400, affected by it. Around seven out of 10 cases are among women.

In the podcast, Sigler reassured Applegate that her advocacy was still important even if she was misdiagnosed, and admitted that even if Applegate couldn’t feel happy, her first thought on hearing the news had been that one day, her friend might be able to dance again. 

“I’m going to continue holding in my heart that this is a blessing for you,” Sigler said.