Christina Applegate was misdiagnosed with multiple sclerosis after years of believing she had the condition, highlighting the difficulties doctors face in identifying a disease with no single confirming test.
The actor disclosed the development on her podcast, MeSsy, where she discusses life with MS alongside actor Jamie-Lynn Sigler. Applegate said the incorrect diagnosis had left her still searching for an explanation for symptoms that affect her daily life and mobility.
Dr Marwa Kaisey, an associate professor in the neurology department at Cedars-Sinai Medical Center, said almost one in five people told they have multiple sclerosis do not actually have it.
Multiple sclerosis occurs when the immune system attacks the central nervous system. Symptoms vary widely and the disease can progress in different ways, making diagnosis complex.
Why multiple sclerosis can be misdiagnosed
Dr Robert Brumel, director of the Mellon Center for MS at Cleveland Clinic, said a misdiagnosis is often uncovered when a patient seeks a second opinion because their symptoms have not improved.
That does not necessarily mean the original diagnosis is wrong, he said, but it can prompt more detailed investigations. Tests may include advanced MRI scans, a spinal MRI or analysis of spinal fluid for abnormal immune proteins.
Lesions seen on brain scans are regarded as a hallmark of MS, but they can also be linked to conditions including high blood pressure, smoking and migraines. More specialised MRI sequences can help doctors distinguish between them.
Dr Josef Gutman, director of NYU Langone’s Long Island Comprehensive MS Care Center, said the diagnosis depends on a combination of a patient’s symptoms, MRI findings and other markers such as spinal fluid.
“It’s not like diabetes, where there’s one blood test and if it’s above this number, it’s diabetes, if it’s below this number, it isn’t,” he said. “There’s a lot of things going into the diagnosis.”
Studies examining the issue have found that between 15% and 20% of patients diagnosed with MS are later found not to have the disease, according to Dr Brumel.
Revised diagnostic criteria developed by an international panel of experts and published in 2025 aim to reduce the risk of misdiagnosis. The criteria are more specific than earlier guidance, particularly in how brain lesions are interpreted.
What happens after an MS misdiagnosis
Once multiple sclerosis has been ruled out, doctors begin investigating other possible causes of a patient’s symptoms. These may include autoimmune conditions, fibromyalgia, migraines, chronic pain or fatigue syndromes.
Dr Brumel said some people may have more than one condition. Fatigue, for example, can be linked to a sleep or thyroid disorder, while rheumatoid conditions or fibromyalgia may account for pain and swelling.
“MS can sometimes be a gratifying solution to a patient with many symptoms because it’s thought of as kind of a single, solitary root cause of things,” he said.
Applegate said that discovering she had been misdiagnosed had not brought relief because her debilitating symptoms remained unexplained.
“You don’t get misdiagnosed and then all of the sudden I’m 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.”
She said her doctors would investigate what had happened since 2021 and why her symptoms had developed.
When to seek a second opinion
Dr Brumel said patients who are worried about an MS diagnosis should feel able to seek a second opinion, even though only a minority are misdiagnosed.
“MS is a life-changing diagnosis, and anytime somebody is facing something like that, I always think a second opinion is potentially in order,” he said.
Patients can also consult an MS specialist, who is more likely to be familiar with conditions that mimic the disease, up to date with diagnostic criteria and able to access more specific tests.
