What's Next for Christina Applegate After MS Misdiagnosis
Because right now, the actress is still processing that she was misdiagnosed with multiple sclerosis (MS).
Sharing the news through tears, "I’m sure people are saying, ‘Crybaby, you don’t have MS. You know, that’s a good thing,’” Applegate said on the Oct. 20 episode of her and Jamie Lynn Sigler’s podcast MeSsy. "I’m just in the state of shock right now."
After all, it’s been five years since she was diagnosed with MS, an immune-mediated disease that affects the central nervous system.
First experiencing symptoms in January 2021, "I had numbness in my toes and that numbness grew to all of my legs," Applegate recalled. "And all that time, I was being tested for everything under the sun and not tested for MS right away because my doctor at that time said, ‘This isn’t really showing itself as MS.'"
But after a progression of symptoms and additional testing—including brain MRIs and spinal taps—the Don’t Tell Mom the Babysitter’s Dead alum received an MS diagnosis.
"Then finally came that day of the diagnosis when he said 'I’m so sorry,' and showed me the lesions on my brain—that were many, almost 40," she added. “That was it, right? That was my answer. It was my answer to everything that was going on.”
As a result, Applegate began treatment in hopes of preventing new symptoms from developing. "I’m doing all the infusions, which as we know, plays havoc on your body," she noted on the podcast. "Did that for years."
But a few years ago, Applegate continued, her doctor decided to stop the infusions and monitor her B cells. When her levels didn’t change, she explained, her medical team re-examined her diagnosis.
Remembering how her doctor “came into my room and she said, 'Congratulations, you don’t have MS,'" Applegate said she didn't feel the same relief those around her did.
"I was not happy at all," the Dead to Me star shared. "Everybody else was so happy."
Mainly because her symptoms—which she's shared have included excruciating chronic pain, effects to her mobility, incontinence, fatigue and others that have led to several hospitalizations over the years—haven’t gone away.
"You don’t get misdiagnosed and then all of a sudden I’m better," she told Sigler, who was diagnosed with MS about 25 years ago. "I haven’t gotten better, Jamie. If anything, I’ve gotten worse in some ways. So, I’m back at square one that I don’t know what’s going on with me."
Photo by Matt Winkelmeyer/Getty Images for Critics Choice Association
After openly detailing her health battle and feeling like one of the "poster children for MS," Applegate admitted she feared that she let people down.
"Everything that I was doing, it’s like I had a reason," the Married…With Children actress shared. "I had a f--king reason as to 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."
Still, Applegate isn’t giving up on her search for answers. The Anchorman alum noted she’s still doing physical therapy three times a week and that she and her medical team are going to "start the investigation" into what could be causing her symptoms.
But the toll has been more than physical as Applegate has been honest about how the diagnosis has affected her mentally and emotionally.
"Of course, I’ve gone through great depression because of it," the 54-year-old shared. "But I lost everything. I lost my job."
Fighting back tears, she added, "I get really emotional because it stopped my life. I still have to use wheelchairs when I go to the doctor’s offices. 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.'"
And Applegate knows that, in many ways, her journey is just beginning, noting her and her neurologist are now "starting from scratch basically to figure out what’s going on."
As she navigates this new path, read what Applegate has shared about her health over the years.
David Fisher/Shutterstock
Health Journey
Christina Applegate shared she was diagnosed with multiple sclerosis in 2021.
"Hi friends. A few months ago I was diagnosed with MS," she shared on her social media channels that August. "It's been a strange journey. But I have been so supported by people that I know who also have this condition. It's been a tough road. But as we all know, the road keeps going. Unless some a--hole blocks it."
Stewart Cook/Shutterstock
First Public Appearance
"Oh, by the way, I have a disease," she joked during her November 2022 Hollywood Walk of Fame induction ceremony, her first public appearance since her MS diagnosis. "Did you not notice? I'm not even wearing shoes."
Daniele Venturelli/WireImage
Early Symptoms
Applegate believes her MS journey actually began "six or seven years" before her 2021 diagnosis.
"I noticed, especially the first season [of Dead to Me], we'd be shooting and my leg would buckle," Applegate explained during a March 2024 interview on Good Morning America. "I really just put it off as being tired, or I'm dehydrated, or it's the weather. Then nothing would happen for months, and I didn't pay attention."
By the time she was shooting the Netflix series' third and final season, the actress said she was "being brought to set in a wheelchair."
"I couldn't move that far," she recalled, "so I had to tell everybody because I needed help."
X/Christina Applegate
Making Moves
The Dead to Me star captioned this photo of her cane collection amid her battle with MS: "Walking sticks are now part of my new normal."
Matt Baron/BEI/Shutterstock
Strong Statement
Joined by her daughter Sadie Grace LeNoble, Applegate had a simple message for multiple sclerosis while attending the 2023 SAG Awards: "F U MS."
And she's not the only one experiencing strong feelings towards the illness. "In my situation, Sadie only knew me as healthy and a runner and a Pelotoner and a dancer—and she only knew that," Applegate explained to friend Jamie-Lynn Sigler on an August 2025 episode of their MeSsy podcast. "So then when this came about in 2021, she was, like, stoic about it."
Yet, "I see her look at me when I’m in bed," Applegate continued, "and can't quite move or, I want to go say goodnight to her in her room but I can’t quite get down the hallway for whatever reason my legs aren’t working that day."
The whole experience has "broken" her teen, Applegate noted. "It was like losing the mom she had to this f--king thing. And the more she’s gotten older now, I think the more it’s hurting her."
Kevin Winter/Getty Images
Just Jokes
After a receiving standing ovation at the 2023 Emmys, the Married...With Children alum quipped, "You're totally shaming me with disability by standing up."
Matt Winkelmeyer/Getty Images for Critics Choice Association
Healing Through Humor
"I make these jokes because if I don't, I'll suffocate," Applegate shared on a March 2024 episode on Armchair Expert, explaining why she often pokes fun at her condition. "I'll be done."
So, yes, she's going to talk about the fact that she's already purchased burial plots.
"My friend and I are going to go take a picnic there," Applegate revealed on a March 2026 episode of NPR's Wild Card. "It's really pretty where it is." She just has to pick out a tree "'cause it's really sunny," she continued. "And I want my visitors to not be sweating."
Kevin Mazur/Getty Images for Critics Choice Association
MS On Her Mind
"I have 30 lesions on my brain," she noted on Armchair Expert. "My biggest one is behind my right eye, so my right eye hurts a lot."
Legions are caused by the immune system attacking the myelin sheath around nerves, according to the Multiple Sclerosis Trust.
Randy Holmes/Disney via Getty Images
Getting Candid
Applegate hasn’t held back when it comes to sharing her journey.
"It sucks," the Anchorman actress told late night talk show host Jimmy Kimmel of her daily struggles with MS. "I'm not going to lie. I think anyone who has MS isn't going to be like, 'This is the best thing that ever happened to me!'"
Besides, she'd taken that tack when discussing her breast cancer battle back in 2008. "I went out, and I was the good girl talking about 'Oh, I love my new boobs' that are all scarred and f--ked up. What was I thinking?" she said on Armchair Expert. "Everything I was saying was a freaking lie. It was me trying to convince myself of something, and I think that did no service to anyone."
While she started a foundation and "raised millions of dollars for women to get MRIs who were at high risk," she noted, "at the back of it, I was taking off my bra and crying every night. And I wish that I had said that."
Monica Schipper/WireImage
In Her Bubble
When talking about her day-to-day life with the disease, Applegate told Good Morning America in March 2024, "I live kind of in hell."
"But I might get to a place where I function a little bit better," she added. "Right now, I'm isolating, and that's kind of how I'm dealing with it—by not going anywhere because I don't want to do it. It's hard."
KMazur/WireImage
The Sweetest Support
Christina credited her Sweetest Thing costar Selma Blair—who was diagnosed with MS in 2018—for urging her to get tested for the disease.
"She said, 'You need to get checked for MS,'" Christina recalled during her GMA interview. "If not for her, it could've been way worse."
Phillip Faraone/Getty Images
Friendship Never Dies
Applegate confirmed that Dead to Me will likely be her last onscreen credit, telling Vanity Fair in May 2023, "I can’t even imagine going to set right now."
"I’m probably not going to work on-camera again, but I'm so glad that I went out with someone who is by far the greatest actress I’ve ever worked with in my entire life," she said of costar Linda Cardellini, "if not the greatest human I’ve ever known.
Charles Sykes/Bravo; Emma McIntyre/Getty Images for Netflix
The Dirty Truth
For Applegate, contracting sapovirus—a virus commonly transmitted through fecal-oral contact—meant having to rely on adult diapers.
"I woke up at three o'clock in the morning in a pool of s--t," she explained on an April 2024 episode of her MeSsy podcast. "I didn't know what happened, and having MS at three o'clock in the morning and trying to change your sheets, it's not fun. But this brings me to my next point, which we can talk about: I'm wearing diapers."
Their discussion was "so liberating," her co-host Sigler noted. "This is something you do by yourself and it feels terrible when you're doing it. I've done that hundreds of times in my MS journey through the years when I've experienced a flair or when I was sick."
Christina Applegate/Instagram
Dark Matter
"I am in a depression right now, which I don't think I've felt for years," Applegate confessed to Sigler on another 2024 episode of their MeSsy podcast. "Like a real, f--k it all, like real depression where it's kind of scaring me too a little bit because it feels really fatalistic."
Three years into her diagnosis, she continued, "And I'm still sitting here like ‘Boohoo, woe is me.' I'm still mad about it." But the truth was, added, "I don't enjoy living—I don't enjoy things anymore."
Tibrina Hobson/WireImage
Screaming Pain
Applegate acknowledged the reality of living with MS can be grim. “Everybody has different ways of it showing up,” she noted on a November 2024 episode of her podcast. "I lay in bed screaming. Like, the sharp pains, the ache, the squeezing."
At times, the discomfort even makes it hard for her to enjoy her one source of comfort, the reality TV that at times is "on 24/7 in my room," she noted. But, "I can’t even pick up my phone sometimes," Applegate added, "because now it’s traveled into my hands. So I’ll try to go get my phone or get my remote to turn on the TV or whatever, and sometimes I can’t even hold them."
Kevin Winter/Getty Images
Checking In
Since her 2021 diagnosis, Applegate has gotten used to the feel of an open-front gown. "I've been in the hospital upwards of 30 times from throwing up and diarrhea and pain," she relayed on her pocast in March 2025. "That is unimaginable, OK? They’ve done every test known to man on me, put so much radiation into my body from CT scans to everything else."
In the plus column, she noted, she has connected some of her gastro issues to her larger illness. "I have noticed that—and I’m going to be really honest—if I have to poop, I puke," she detailed. "And when I puke, I get all the pain and then all the things happen."
Mere months after her hospital confession, Applegate was checking back in. Returning from a family trip to Europe, "I'm like, 'I wanna be admitted. I'm staying here because I want answers,'" she recounted that August of what she told staff. "'I want every test that you can possibly think of or ones that you haven't even thought of, and I want them done.'"
Following a middle-of-the-night CT, she learned, "I had kidney infections."
Emma McIntyre/Getty Images for SiriusXM
Back to Square One
More than five years after sharing her battle with multiple sclerosis, she learned that she was misdiagnosed.
"She came into my room and said, 'Congratulations, you don't have MS,'" she recalled of her doctor's visit in the October 2026 podcast MeSsy. "I was, like, not happy at all. Everybody else was so happy."
Applegate emphasized that the confirmation of the misdiagnosis hadn't changed how she's continued to struggle physically.
"I haven't gotten better," she said. "If anything, I've gotten worse. So I'm back at square one where I don't know what's going on with me. That's going to be an online investigation that my doctors are going to be getting into just to find out what has been going on since 2021."
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