American actress Christina Applegate says she does not have multiple sclerosis five years after she announced her diagnosis. She shared the news on the Oct. 20 return episodes of MeSsy, the podcast she co-hosts with Jamie-Lynn Sigler, as first reported by People.

“She came into my room and said, ‘Congratulations, you don’t have MS,'” Applegate, 54, said of her doctor, according to People. “I was, like, not happy at all.” She said her symptoms have not improved: “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 added that she still uses a wheelchair at doctor’s appointments.

Applegate did not say what her doctors now think is causing her symptoms, only that they will now investigate. Variety, ABC News and Page Six also covered the episode. She first disclosed the MS diagnosis on Twitter in August 2021, CBS Los Angeles reported at the time.

Nothing she has said explains how doctors made or reversed her diagnosis. But MS misdiagnosis is a problem neurologists have studied for more than a decade.

Nearly 1 million US adults live with MS, according to Cleveland Clinic. For anyone wrongly given the label, the cost can be years of drugs they don’t need, while the real cause of their symptoms goes untreated.

No single test can confirm MS

No single test can confirm MS, the National Institute of Neurological Disorders and Stroke says. The diagnosis is a judgment built from several kinds of evidence.

Doctors start with a medical history and a neurological exam. They add an MRI of the brain and spinal cord, which looks for the scar-like lesions MS leaves on the central nervous system. Often they also order a lumbar puncture, or spinal tap, to check spinal fluid for immune proteins called oligoclonal bands or kappa free light chains. Blood tests rule out conditions that cause similar symptoms, such as vitamin B12 deficiency. Eye tests such as optical coherence tomography (OCT) or visual evoked potentials can reveal optic nerve damage.

Doctors then apply the McDonald criteria, the international rules for an MS diagnosis. As the National MS Society explains, the doctor must find evidence of damage in different areas of the brain, spinal cord or optic nerve. In some cases they must show that the damage happened at different times. The doctor must also rule out every other possible diagnosis.

The spinal fluid test cannot settle the question on its own. The Society notes that 5% to 10% of people with confirmed MS have normal spinal fluid. The same immune changes also show up in other diseases.

The 2024 revision targets look-alike conditions

Experts last revised the criteria in 2024, and The Lancet Neurology published them in October 2025. The update made the optic nerve a fifth place in the nervous system where MS damage can count. It also added newer markers on MRI, including the “central vein sign” and “paramagnetic rim lesions”. Its authors say these can add specificity when doctors suspect MS.

Applegate’s 2021 diagnosis came before this revision. Specificity, telling MS apart from conditions that look like it, is exactly where the research below finds doctors going wrong.

At specialist centers, roughly 1 in 8 to 1 in 5 referrals don’t have MS

In a 2019 study in Multiple Sclerosis and Related Disorders, Dr. Marwa Kaisey, Dr. Andrew Solomon and colleagues reviewed 241 new patients. All had arrived at Cedars-Sinai and UCLA with an established MS diagnosis over 12 months.

Doctors had misdiagnosed 17% of them at Cedars-Sinai and 19% at UCLA. The authors wrote that “almost 1 in 5” did not meet the McDonald criteria and had a more likely alternative diagnosis.

A 2023 study looked at 338 patients who came to the Johns Hopkins MS Center with an MS diagnosis. It found that 41 of them (12%) did not have MS. A 2024 systematic review and meta-analysis in Multiple Sclerosis Journal found misdiagnosis rates from 5% to 41% across studies. Its pooled estimate, from six studies covering 1,621 people, was 15%.

Correcting a misdiagnosis took anywhere from a few months to 15.9 years. Women were about twice as likely as men to get the wrong diagnosis. These divs come from referral centers, where patients with doubtful diagnoses tend to end up. So they are not a rate for everyone with MS.

A third of misdiagnosed patients carried the label 10 years or more

A 2016 multicenter study in Neurology measured what the errors cost patients. Solomon, of the University of Vermont, led the study, which analyzed 110 misdiagnosed patients from four academic centers.

One-third had carried the wrong diagnosis for 10 years or longer. Seventy percent had received MS disease-modifying drugs. About 31% suffered what the authors called “unnecessary morbidity” from the error.

The real diagnoses in that study most often turned out to be:

• Migraine, alone or with other conditions: 22%
• Fibromyalgia: 15%
• Nonspecific neurological symptoms with an abnormal MRI: 12%
• Conversion or psychogenic disorders (now often called functional neurological disorder): 11%
• Neuromyelitis optica spectrum disorder (NMOSD), a separate autoimmune disease of the optic nerve and spinal cord: 6%

The Cedars-Sinai and UCLA study found a similar pattern. Migraine led at 16%, followed by spine disease and nerve damage (neuropathy), each at 7%. At Johns Hopkins the most common alternative was cerebrovascular disease, meaning damage from small blood vessel problems in the brain.

Stray MRI spots drive many of the errors

What ties most of these cases together is the brain scan. Small white-matter spots appear on brain scans for many reasons, including migraine, aging and vascular risk factors. Solomon’s 2016 study named “overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms” as a leading cause of misdiagnosis.

The Johns Hopkins team reached the same place by a different route. In its data, nonspecific brain lesions were the strongest predictor of misdiagnosis, raising the odds about 7.7-fold.

The 2016 study also found that doctors had treated symptoms that don’t fit demyelinating disease as MS relapses. Sometimes they did so without objective evidence of a lesion behind them. The McDonald criteria themselves target patients with typical MS symptoms, which leaves room for misapplying them. In a 2019 Neurology article, Solomon and colleagues addressed atypical presentations. In those cases, they wrote, “further evaluation or monitoring rather than immediate diagnosis of MS is prudent.”

For patients, the most telling number may be this one. In 72% of misdiagnosed cases in the 2016 study, reviewers found an earlier opportunity to get the diagnosis right. Taken with the rest of the research, that suggests most of these errors were catchable. Doctors made them early, often on the strength of an MRI that showed something, and then carried them forward.

The same pattern shows up well beyond MS. A British woman lost part of a lung after pneumonia was mistaken for cancer. In another case, a six-year-old’s rare brain condition was first treated as the flu.

A second opinion is the check the research points to

None of this is a reason for someone with an MS diagnosis to stop treatment on their own. Questions belong in a conversation with a neurologist, and the research suggests a few to bring:

• Which McDonald criteria did my case meet, and what evidence was used?
• Were my MRI lesions in locations and shapes typical of MS?
• Did I have a lumbar puncture, and what did it show?
• Were conditions like NMOSD, B12 deficiency or vascular disease tested for?
• Has an MS specialist reviewed my scans?

That last question matters because specialty centers caught the misdiagnoses in these studies. Neurologist Dr. Jason Silversteen of ChristianaCare in Delaware spoke to the National MS Society’s Momentum magazine. He said that “everyone should, at least at the time of initial diagnosis, consider a second opinion, especially if they’ve been seen initially by a non-MS specialist.” In the same March 2026 article, he called an MS diagnosis made without any MRI or lab tests “a red flag.”

Applegate said her doctors are now working to find out what has caused her symptoms since 2021 and why the MS diagnosis happened. She has not named a new diagnosis.

With MeSsy back on the air since Oct. 20, any further update is likely to come from her there.