Christina Applegate had been living with debilitating symptoms of multiple sclerosis (MS) for six years, but a devastating medical revelation has now left her searching for answers all over again.
The 54-year-old actress returned to her MeSsy podcast on Tuesday, October 20, after a seven-month hiatus, tearfully revealing that doctors had determined she does not have MS.
While the news might have initially sounded positive to listeners, Applegate said her physical condition has continued to worsen despite the misdiagnosis.
“I’m back at square one,” she admitted, revealing what comes next in her search for answers.
Christina Applegate tearfully revealed that she had been misdiagnosed with multiple sclerosis (MS)
Christina Applegate is now preparing to work with her medical team on an extensive investigation into her health history, reviewing records dating back to 2021 to understand what led to her original diagnosis.
Multiple sclerosis (MS) is a disease of the central nervous system in which the immune system attacks myelin, the protective covering surrounding nerve fibers.
Symptoms vary widely from person to person, but common signs include muscle weakness, vision changes, numbness, memory and concentration difficulties, and fatigue.
For some people with MS, symptoms can temporarily worsen when body temperature rises due to heat, exercise, or a fever.
Stress can also aggravate symptoms in some cases.
Speaking on MeSsy, which she co-hosts with actress Jamie-Lynn Sigler, Applegate said her doctors began an in-depth review to understand what had been happening with her health and why the diagnosis changed.
“What’s going to happen is we’re going to do an online investigation… to find out what has been going on since 2021. Why did this happen?” she said. “How many specialists am I going to have to find for something I don’t even know what I’m looking for?”
Christina’s doctors are now looking into other possible explanations for her symptoms, including potential inflammatory causes affecting her central nervous system.
Rheumatoid arthritis is among the conditions she mentioned as being explored.
The actress is now launching a medical investigation to find out what has been causing her symptoms
For now, however, she has no definitive explanation for the physical challenges she continues to experience.
Applegate first publicly revealed her MS diagnosis in 2021, after experiencing neurological symptoms that affected her mobility and daily life.
She previously described feeling tingling in her toes before the sensation spread through her lower body.
During filming for Netflix’s Dead to Me, she also experienced leg buckling and needed a wheelchair on set.
Over the years, the actress has spoken openly about numbness, pain, balance problems, and difficulties walking.
She has also discussed how her health affected her career, including her appearance at the 2024 Primetime Emmy Awards, where she used a cane.
However, learning that she did not have MS did not bring the physical relief she might have hoped for.
“You don’t get misdiagnosed and then all of a sudden I’m better,” she said on the podcast. “I haven’t gotten better, Jamie! If anything, I’ve gotten worse.”
Applegate also revealed that she still needs a wheelchair when attending medical appointments because she cannot manage the walk from her car into the doctor’s office.
During the second part of the podcast’s return, Christina and Sigler were joined by Dr. Marwa Kaisey, an associate professor of neurology at Cedars-Sinai Medical Center.
Christina said her symptoms have worsened despite learning she does not have MS
The neurologist explained that diagnosing MS can be complicated because “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,” she added.
Doctors typically consider a patient’s medical history, neurological symptoms, MRI findings, and other test results when assessing whether someone has MS.
Kaisey said that “almost one in five of these people who’ve 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.”
Christina’s case has therefore brought renewed attention to the difficulties patients can face when symptoms overlap with multiple neurological or inflammatory conditions.
Beyond the uncertainty surrounding her health, Applegate is also processing the emotional consequences of losing a diagnosis that had helped her make sense of what she was experiencing.
Since announcing her MS diagnosis in 2021, she has become a prominent voice for people living with the condition.
Her openness about her struggles helped bring attention to the realities of living with a chronic illness.
Now, she has admitted that the change has left her questioning her place in the community she spent years supporting.
The Dead to Me star admitted she feels she has “let everybody down” after years of advocacy
“It’s this weird feeling because I became this, you and I, the poster children for MS. And everything I was doing. I had a reason,” she said.
“I had a f**king reason as to why my day sucked every day. And now I don’t have a reason, and it’s very unnerving, and it’s very confusing for me.”
Christina also expressed guilt about the possibility that people who had followed her journey might feel disappointed by the revelation.
She described feeling as though she had “let everybody down.”
The actress also got emotional as she spoke about the depression and disruption her health struggles had brought into her life.
“I lost my job, I lost my, I’m sorry. What do you say to someone who’s been living this for six years? God, I’m so sorry, because it stopped my life,” she said.
Despite the emotional toll, Applegate intends to continue MeSsy with Sigler and document this next chapter of her health journey.
She described the situation as “the same game with a different name,” emphasizing that the diagnostic uncertainty hasn’t changed the reality of her daily struggles.
For now, the actress is continuing to seek answers while navigating her symptoms.
“Praying for you, Christina, in finding exactly what has caused all this pain and suffering,” wrote one netizen
