Christina Applegate says she was misdiagnosed with MS. It's more common than you might think.

Five years after being told she had multiple sclerosis, Christina Applegate now says she was "misdiagnosed."

In a new episode of her podcast, MeSsy , Applegate told cohost Jamie-Lynn Sigler, who has the condition, about receiving the news during an appointment earlier this year. "Congratulations, you don't have MS," she said her doctor told her. "I was not happy at all. Everybody else was so happy," she said. The Emmy winner said she was in a "state of shock" and that her months-long hiatus was in part a time to "process" the new information while also dealing with other health issues amid a book tour.

Shocking though the news is, perhaps what's more surprising is how often multiple sclerosis — often referred to as MS — is misdiagnosed. Research suggests that as many as 19% of patients who are told they have the neurodegenerative autoimmune disease actually do not.

For one, there is no single test to diagnose MS. It's a complicated chronic autoimmune disease in which the cells meant to fight infection and repair damage instead attack the protective sheath (called myelin ) around nerves. That causes a wide range of symptoms, which can be debilitating.

Determining whether someone has the condition is more like putting together puzzle pieces to see what fits. Someone has to have enough signs of MS in multiple parts of their body, often over time, to be diagnosed.

"That's where the 'multiple' in MS comes from: multiple locations and multiple times," Dr. Robert Bermel , director of the Mellen Center for Multiple Sclerosis at Cleveland Clinic, tells Yahoo.

If a patient has some of the most common signs — including painful vision loss in one eye , numbness, tingling or weakness on one side of the body or in both legs — that "increases the statistical likelihood of MS," he adds.

But the symptoms themselves may appear, to the untrained eye, unrelated. Issues such as vision problems, extreme fatigue, numbness or tingling, balance and mobility problems, vertigo, bladder issues and pain can all be caused by MS — or by other health conditions.

So, doctors also perform a brain MRI to look for white spots or lesions , and might sometimes do an MRI of the spine or a spinal fluid analysis . Patients who may have MS are often also tested for other conditions to rule them out, Bermel explains.

Taken together, all of this information can provide a good idea of whether someone has MS.

But the white lesions — one of the hallmarks of the disease — can be misleading, Bermel explains. Other health conditions can cause these lesions, and they can even be found in the brains of some healthy people. That's why, in 2024, the guidelines for diagnosing MS were updated (and officially published in full in 2025). Now, it's not just white spots but those with a vein going through the center of them or a "rim" around their edges that are considered indicative of MS.

"Using those other modalities on the MRI gives us more certainty" about a diagnosis, Dr. Josef Gutman , a neurologist at NYU Langone Health's multiple sclerosis center, tells Yahoo.

But detecting these differences requires special equipment that not all health care facilities have, and a well-trained eye, he adds. The whole process "really has to be in expert hands to make this diagnosis, because there is no thumbs-up, thumbs-down single test that can make the diagnosis alone," Bermel says.

Meanwhile, many patients are first diagnosed by what Bermel refers to as "comprehensive neurologists," who treat a variety of issues, including epilepsy, spinal problems, stroke and MS — but they aren't MS specialists. To care for their patients, doctors have to keep up with all of the latest science that might apply to their conditions. That means comprehensive neurologists are juggling a lot of different kinds of new information and patients, whereas MS subspecialists are highly experienced and informed about one condition.

Importantly, most MS patients are correctly diagnosed the first time. In fact, the 15% to 20% misdiagnosis rate is among people who have already been diagnosed with MS and came to specialist MS centers for second (or third, or fourth) opinions, Bermel notes.

Patients may seek out another expert's opinion because they don't seem to be responding to treatment or simply "if things aren't going well," Bermel explains. That's actually a meaningful clue, adds Gutman. "Our [latest] medications tend to be very effective for MS , so if someone is not responding to those medications, it makes us wonder if this is really MS or not."

Applegate said that despite receiving B-cell infusion treatments , which have been shown to slow the disease's progression, her symptoms didn't improve . That led her doctors to reassess her diagnosis and eventually reverse it. The actress said that the process of reevaluating her condition began "a couple years ago" when her doctor took her off the treatment. But her levels of the immune cells didn't change without the infusions. The doctor "had never seen that before," Applegate said. "So I guess that began kind of a study into my diagnosis."

An MS diagnosis is never welcome news but, perhaps counterintuitively, finding out it's a mis diagnosis can be difficult to hear too. "MS is often an appealing cause [for symptoms], as strange as that sounds," says Bermel. "When someone has multiple symptoms, it seems more approachable to have a single diagnosis as the root cause of all of that, like a single enemy to face."

In the absence of that clarity, Applegate said she feels like she's "back at square one."

"You don't get misdiagnosed and then all of a sudden I'm better," Applegate told Sigler. "I haven't gotten better, Jamie! If anything, I've gotten worse."

There are many possible explanations for Applegate's symptoms, which have often left her relying on a cane or wheelchair. Once MS has been ruled out, doctors often look for other possible causes — including conditions like fibromyalgia , lupus or chronic fatigue syndrome — and explore whether multiple issues may be at play. (For example, Bermel says, migraines may explain someone's headaches and certain brain lesions, while diabetes may cause numbness and tingling in their limbs, and a sleep disorder may lead to fatigue. A thyroid disorder could contribute to many symptoms that overlap with MS, he adds.)

Finding out about a misdiagnosis "isn't the end of the story — it's the beginning of another story," says Gutman.

And starting that new story can be fraught.

"The emotion is often a shift from a patient thinking that they've had answers until all of a sudden — they have nothing but questions, and that's extremely distressing for anyone," says Bermel. "A patient is often feeling that if they did have a support structure around MS, including their medical team, that whole support structure might be crumbling under them, and we need to reassure them."

After learning that she did not have MS, Applegate said she was "depressed" and worried that her relationship with the MS community would change. "It's weird because I feel like I let everybody down," she said. "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."

Finding out what's behind those debilitating symptoms might mean that Applegate has to keep seeing a neurologist, in addition to other specialists. And it can take time.

"It does seem daunting to sort of reopen these questions. But I think the pursuit of the right answer and the right treatment is worth it," says Bermel, adding that the process might involve managing symptoms while also searching for a cause. "That hopefully gives people a light at the end of the tunnel that is not just a name or a diagnosis, but also that striving for functional improvement is possible."