Applegate, 54, who publicly announced her MS diagnosis in the summer of 2021, shared the shocking news during a new episode of her MeSsy podcast, which she co-hosts with Jamie-Lynn Sigler. The two actresses, both prominent figures who have spoken openly about living with chronic illnesses, were discussing their respective health journeys when Applegate shared the unexpected medical update.
Recounting the moment her physician delivered the news following a recent hospitalization, a tearful Applegate explained that the reaction in the room did not match her own internal reality. She recalled her doctor walking into her hospital room and saying, "Congratulations, you don’t have MS."
"I was, like, not happy at all. Everybody else was so happy," Applegate shared on the podcast. "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. So I’m back at square one where I don’t know what’s going on with me."
The actress added that her medical team is now launching an extensive review to determine what has actually been happening to her body since 2021. The misdiagnosis has left her feeling deeply unsettled and searching for answers about the true nature of her condition.
Multiple sclerosis is a chronic, lifelong, and currently incurable condition in which the body’s immune system mistakenly attacks the central nervous system, damaging the protective myelin sheath around nerve fibers in the brain and spinal cord. Symptoms vary widely from person to person depending on the location of the nerve damage, ranging from mild numbness and tingling to extreme fatigue, vision problems, muscle stiffness, coordination issues, cognitive difficulties, and severe mobility impairment.
Over the past several years, Applegate has been exceptionally transparent about the toll her symptoms have taken. She has relied on canes and wheelchairs for mobility, stepped away from her celebrated acting career, and spoken candidly about the profound grief and depression accompanying her loss of independence.
Reflecting on the psychological impact of the new diagnosis, Applegate expressed feelings of confusion and isolation. "I’ve gone through a great depression because of it," she said. "But I lost everything. I lost my job… What do you say to someone who’s been living with this for six years—God, I’m so sorry—because it stopped my life."
She continued, noting that she still requires a wheelchair during medical visits and struggles to walk even short distances from a car to an examination room. "Nothing magical happened when she said, ‘You don’t have MS.’ Nothing magical happened. It’s weird because I feel like I let everybody down. 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. I had a f***ing 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."
Calling the sudden shift a "mindf**k," Applegate admitted she remains in a state of shock as she grapples with the reality that her symptoms—which mirror MS precisely—might stem from an entirely different medical issue.
"I have every symptom of someone with MS. Every single one. Now, we both know that there are many things that mirror MS. Many different things," she noted. She acknowledged the mental hurdle of worrying about how others might perceive the revelation, adding, "I’m sure people are saying like, ‘Crybaby, you don’t have MS.’ You know, that’s a good thing. But no, no, no. I’m sitting here having slept all day yesterday feeling like absolute crap because of the heat. My legs aren’t working. You know, all the same stuff is happening to me."
The complexity of diagnosing conditions that mimic MS was further addressed during the podcast by Dr. Marwa Kaisey, an associate professor in the department of neurology at Cedars-Sinai Medical Center. Dr. Kaisey explained the diagnostic hurdles inherent in the disease, noting that there is no single, definitive test—such as a pregnancy test—to confirm MS definitively. Instead, neurologists rely on a complex set of clinical criteria. According to Dr. Kaisey, studies show that nearly one in five patients told they had MS—some for decades—did not actually have the disease, and a majority of them were actively taking medication to treat it.
Applegate’s revelation comes following a challenging period that included a prolonged hospital stay in Los Angeles. Sources close to the actress reported that she was discharged and returned home after spending months under medical care starting in late March. While specific details regarding the hospitalization were initially kept private, Applegate offered reassurance to her supporters in April via social media, posting a photo of her memoir, You With The Sad Eyes, and thanking fans for their well wishes.
"Health issues are a constant for me, but I’m a strong chick and I’m getting stronger and better every day," she wrote at the time. "I’m taking a moment to focus on my health, but I’ll be back with more to say soon enough."
Earlier in the year, Applegate opened up about being largely confined to her bed due to the excruciating pain and exhaustion associated with her condition. She explained that while the symptoms often keep her restricted to her bedroom, she pushes through the physical toll whenever possible to take her 15-year-old daughter, Sadie, to school, calling it her favorite time of day.
In her memoir, which was released in March, Applegate detailed the overwhelming fatigue that defines her daily existence, comparing it to being on a continuous three-day sleepless bender despite getting a full night of rest. She wrote that the relentless nature of her health battles has shifted her perspective entirely, leaving her with little patience for superficial matters or societal expectations.
Applegate first shared her diagnosis publicly in August 2021, later introducing her custom canes to the public in 2022 as she embraced mobility aids as her "new normal." Over the years, she has also spoken about the sheer frequency of her medical interventions, revealing on a previous episode of the MeSsy podcast that she had been hospitalized upwards of 30 times in the three years following her initial diagnosis, undergoing extensive testing and imaging procedures.
As Applegate and her medical team embark on a fresh investigation to uncover the root cause of her ongoing symptoms, the actress continues to navigate the emotional and physical complexities of her health journey with the raw, uncompromising honesty that has characterized her public advocacy. Representatives for Applegate have not issued additional comments regarding her ongoing medical evaluations.
