Christina Applegate Says Her Multiple Sclerosis Diagnosis Was Incorrect

Emmy-winning actor Christina Applegate revealed this week that her doctor said her diagnosis of multiple sclerosis (MS), which she first announced in 2021, was incorrect.

“I’m back at square one where I don’t know what’s going on with me,” Applegate said on her podcast “MeSsy,” which she co-hosts with “The Sopranos” actor Jamie-Lynn Sigler, who also has MS.

“I still have to use wheelchairs when I go to the doctor’s office. I can’t walk from the car to the room,” she said, adding that she still has “every symptom of someone with MS.”

This news puts her in an odd place as she and Sigler have become prominent advocates for people with MS, Applegate said. “It’s weird because I feel like I let everybody down,” she said. “It’s very unnerving, and it’s really confusing for me.”

Misdiagnosis occurs in MS but “there’s varying reports on the frequency,” observed Marisa McGinley, DO, a neurologist at the Cleveland Clinic. Some studies show it’s less than 10%, while others report close to 20%, she noted.

“Ideally, there would be zero misdiagnosis, but it is a reality in the MS field that this does happen,” McGinley told MedPage Today.

“A big crux of the issue is that there’s no single test that equals an MS diagnosis. It’s a very complex algorithm of things — and this is not necessarily unique to MS,” she pointed out. “A lot of other autoimmune or chronic disease conditions have complex algorithms where you have to work through differentials to get to them.”

Estimates about the extent of MS misdiagnosis hinge on several factors. “I would be a little cautious about attaching a particular percentage to it,” noted Bruce Bebo, PhD, chief research and medical affairs officer at the National Multiple Sclerosis Society. “A lot of those studies come from referrals to specialty centers. They’re getting the really hard cases to diagnose,” he told MedPage Today.

Diagnosing MS is “like putting a puzzle together,” Bebo said. “The symptoms of MS can occur in other conditions. And sometimes those abnormalities that show up on an MRI don’t automatically mean someone has MS. It’s about putting all those pieces together.”

MS diagnostic algorithms have changed in recent years, with the last update to the McDonald criteria in 2024. An abnormal MRI showing typical lesions is required to make a diagnosis of MS. In certain situations, this could include the central vein sign or paramagnetic rim lesions to help increase diagnostic specificity.

“Criteria evolve with the goal of ultimately trying to diagnose people sooner, but we also learn more about the disease and we come up with more specific markers to help with that diagnosis,” McGinley said. “Historically, MRI is our mainstay, and the quality of MRI has exponentially increased. We now have more advanced imaging biomarkers.”

MS affects women three times more often than men, Bebo noted. “It’s often diagnosed in early adulthood between ages 20 and 40. And there are now a plethora of disease-modifying therapies that can address the relapsing-remitting inflammatory form of MS,” he said.

“We want to diagnose MS as early as possible because we know the earlier we deploy disease-modifying therapies, the better the outcome’s going to be,” he added.

While early diagnosis means earlier access to treatment and care, “we can’t sacrifice speed for accuracy,” Bebo emphasized. “This is a constant tension we have in the diagnosis of MS — trying to diagnose it earlier but also more accurately at the same time.”

Reporting from the Associated Press contributed to this article.