Christina Applegate has said her doctors now believe she was incorrectly diagnosed with multiple sclerosis, five years after she went public with the condition. The actress disclosed the development on a two-part episode of MeSsy, the podcast she co-hosts with Jamie-Lynn Sigler, released Tuesday, according to CBC.
Applegate said her physician delivered the news as though it were good news, but she did not experience it that way. She told Sigler she has not recovered and in some respects feels worse than before. No alternative diagnosis has been offered to explain the symptoms she continues to live with.
Why it matters
Applegate became one of the most visible advocates for people with MS after announcing her diagnosis in August 2021. She and Sigler built their podcast around candid conversations about living with the disease, and Applegate described the pair as having become "the poster children for MS." Her account now draws attention to how MS is identified and how often the process goes wrong.
Misdiagnosis is a recognized problem in MS care. A 2019 study from Cedars-Sinai researchers in the United States put the rate at close to one in five patients, CBC reports. A 2024 review of published research found reported rates spanning 5 to 41 per cent, and a pooled estimate of about 15 per cent across six studies.
The stakes are practical as well as emotional. Dr. Mark Freedman, who directs the multiple sclerosis research unit at The Ottawa Hospital, told CBC that treating MS in a patient who does not have it carries risks, because some of the stronger therapies work by dampening the immune system.
A diagnosis built over months of testing
Applegate said her symptoms began in early 2021, before her public announcement, with numbness in her feet that gradually climbed her legs, followed by pain. She was tested for a wide range of conditions, she said, undergoing spinal and brain MRIs and a spinal tap. Doctors initially suspected a milder form of the disease.
Her condition continued to deteriorate. When imaging revealed close to 40 lesions on her brain, she received a formal MS diagnosis. In the podcast episode, she recalled feeling relief at finally having an explanation.
The reassessment came in stages. A couple of years ago, her doctor paused her infusion treatments to observe how her B cells would respond, and their levels stayed the same. That prompted a closer look at the diagnosis, including the use of newer brain MRI technology, she said. In 2024, an expert committee updated the official diagnostic criteria after reviewing scientific advances, among them more precise imaging tools.
The conclusion was that Applegate does not have MS. What she does have remains unidentified.
"It's very unnerving"
Speaking through tears to Sigler, Applegate said she felt she had let people down. She described the strangeness of losing the explanation for her daily difficulties: previously, she said, she had a reason her days were hard, and now she does not.
MS is an autoimmune disease in which the immune system attacks myelin, the sheath that insulates nerves in the central nervous system. Freedman compared the damage to the rubber coating on a wire wearing away and leaving bare copper, which conducts poorly and is more vulnerable to inflammation that can sever the nerve entirely. Symptoms include numbness, fatigue, memory problems, difficulty moving and sometimes vision loss. The disease follows different courses in different patients, with some cycling through relapses and remissions and others declining steadily.
Diagnosis is complicated because other conditions produce similar signs. Migraines, for example, can leave white spots on a brain MRI, and nerve damage from unrelated causes can cause numbness.
Applegate stepped back from acting after her 2021 announcement. Her credits include Anchorman: The Legend of Ron Burgundy, Bad Moms and the Netflix series Dead to Me, for which she received an Emmy nomination. She had been absent from the podcast for several months, partly, she said, to absorb the news.
Roughly 3.1 million people worldwide live with MS, according to the MS International Federation. Canada has among the highest rates globally, with more than 90,000 people affected — about one in 400 — and around seven in ten cases occurring in women.
What to watch: whether Applegate receives a diagnosis that accounts for her ongoing symptoms, and whether her disclosure prompts wider scrutiny of how MS is confirmed.
