• Christina Applegate recently learned that she was misdiagnosed with multiple sclerosis (MS).
• Applegate was first diagnosed in 2021 after multiple tests and worsening symptoms.
• About 15% of MS patients are believed to be misdiagnosed, given how complex the disorder is.

After being diagnosed with multiple sclerosis (MS) in 2021, living with severe symptoms, and becoming one of the most famous celebrities with the disorder, Christina Applegate learned some shocking news: She doesn't actually have MS.

In an October 20, two-part episode of her podcast "MeSsy" with Jamie Lynn Sigler (another actor diagnosed with MS), Applegate shared that she took over half a year off from recording the podcast to process the news of her MS misdiagnosis.

According to Applegate, her doctor framed the revelation as a positive update. "She came into my room and said, 'Congratulations, you don't have MS,'" Applegate said in the podcast.

But to Applegate, no longer having an explanation for the pain, balance issues, tremors, incontinence, and fatigue she'd been living with for years felt more like being "back at square one."

"You don't get misdiagnosed and then all of a sudden, I'm better," she said. "If anything, I've gotten worse, in some ways."

Applegate's story is far from a medical anomaly. MS researchers estimate that about 15% of worldwide MS patients are actually misdiagnosed, based on a 2024 meta-analysis of multiple studies.

The risks to patients are two-fold, Dr. Marwa Kaisey, an associate professor of neurology at Cedars-Sinai, who also appeared on the podcast, told Business Insider. "One is thinking you have MS — a lot of the medications we use to treat MS have side effects and risks like infections," she said. "The other category is, if you don't know what you have, then you're not getting treated for your actual diagnosis."

Kaisey and another researcher shared why MS is so challenging to diagnose — and why more people might end up with Applegate's experience in the future.

The race to diagnose a hard-to-diagnose disorder

There is no single blood test that can diagnose MS.

Instead, doctors often piece together an MS diagnosis using a neurological exam (testing balance and reflexes), MRI scans, a lumbar puncture (or spinal tap), and possible blood tests to rule out other conditions such as Lyme disease.

Sometimes, doctors overrely on a single diagnostic, such as an MRI finding, without performing enough other tests, Dr. Andrew J. Solomon, a professor of neurological sciences at the University of Vermont who co-authored the meta-analysis, told Business Insider.

In 2019, Solomon co-authored an MS misdiagnosis study that found that patients who were initially diagnosed with MS were later told they actually had other conditions, such as migraine, radiologically isolated syndrome, spondylopathy, and neuropathy, which can share overlapping symptoms with MS and similar brain scan results.

In the podcast, Applegate revealed that she had a nerve test to rule out peripheral neuropathy, as well as MRIs and a lumbar puncture. While her spinal fluid test showed a low level of immune proteins that can support an MS diagnosis, she had nearly 40 brain lesions and worsening symptoms, leading doctors to diagnose her with MS.

Solomon said MS should be diagnosed by "confirming each element of our diagnostic criteria and ruling out other things," rather than assuming it must be MS if the MRIs and symptoms fit.

The problem is, both physicians and patients are eager to diagnose MS as early as possible, he said. Correctly spotting MS early can lead to better treatment results and a higher likelihood of disability prevention, according to research.

Plus, for patients dealing with a plethora of debilitating symptoms, "a period of diagnostic uncertainty is uncomfortable," he said, even though the best course of action is to wait and perform more tests.

A new testing protocol revealed Applegate's misdiagnosis

In the podcast, Applegate shared that her brain lesions were missing "strings" associated with MS.

It's a finding associated with a new, more accurate diagnostic tool for Kaisey, who also co-authored the 2019 study with Solomon, explained on the podcast.

The central vein sign (CVS), is an MRI biomarker that can help differentiate MS brain lesions from ones associated with other disorders. It refers to a small vein that appears as a dot or thin line through the center of a brain lesion.

CVS was only recently adopted as part of the recommended MS diagnostic criteria, in 2025 — four years after Applegate was first diagnosed with MS. Kaisey told Business Insider that part of her work is expanding education around newer diagnostic tools, noting that not all physicians are using CVS yet.

Solomon hopes more doctors will include CVS in their diagnostic protocols, especially for existing MS patients or those who switch providers without being evaluated by their current doctors. "If something doesn't fit, there's an opportunity there to reevaluate if the diagnosis is right," he said.

Many misdiagnosed MS patients feel exactly like Applegate does

When it comes to learning about an MS misdiagnosis, Solomon said experiences like Applegate's aren't that uncommon.

"I've heard many stories where some doctor was very enthusiastic about telling a patient they actually didn't have MS," he said. "But many of these patients are suffering, and they still have symptoms. So it's not always necessarily a happy thing."

For Applegate, her initial MS diagnosis provided clarity and direction. "That was my answer to everything that was going on," Applegate said. Some might relate to Applegate's "square one" feeling, particularly if their doctor was an MS specialist and won't see them anymore, Solomon said. Without a formal diagnosis, they might also worry about insurance coverage for treatments that have provided some relief.

There is also the emotional part of having an MS diagnosis. "I leaned into other friends, I leaned into the community," Applegate said. "I had a reason as to why my day sucked every day, and now I don't have a reason."

Knowing she doesn't have MS also made her feel like she "let everybody down" after becoming one of the "poster children for MS," she said. It made her wonder if she was somehow imagining symptoms or at fault for her pain.

Given how common MS misdiagnosis is, Solomon believes it's a good thing that Applegate is sharing her story.

"It's kind of wonderful that Ms. Applegate is public with this because if the number is really 15%, you can do the math," he said. "There are a lot of people out there who might ask their doctors about the accuracy of their diagnosis and find out that, in fact, they had something else."

A top Democratic super PAC is launching a $1.2 million ad campaign in the Mississippi Senate race, adding the deep-red state to its list of targets as the party seeks to flip the Senate in November. Senate Majority PAC (SMP) announced Tuesday that it will spend the money on television and digital ads through Election…

Republicans made their pitch to Michigan voters at a Fox News town hall Monday night, with GOP Senate nominee Mike Rogers arguing Democrat Abdul El-Sayed is vulnerable among Black and Jewish voters as one of the nation's most closely watched Senate races enters its final two weeks.

Fox News host Sean Hannity also spoke with Republican gubernatorial nominee Rep. John James and House GOP Conference Chair Lisa McClain, R-Mich., as the candidates sought to tie Michigan Democrats to government spending, socialism and the party's progressive wing ahead of Nov. 3.

Early on in the night, Rogers argued that his opponent, El-Sayed, could underperform among a handful of key demographics that traditionally support Democratic candidates, presenting political opportunities for Republicans.

Casting doubt on El-Sayed's grip on Black voters in Michigan

EL-SAYED GRILLED ON PIKER, ISRAEL AND SOCIALIST TIES AFTER MIKE ROGERS SKIPS SENATE DEBATE

Hannity pressed Rogers about El-Sayed's past criticism of former President Barack Obama, whom El-Sayed described as "not the right choice" to advance a progressive agenda following Obama's 2012 re-election.

"He is dismissive in Detroit. We have just dozens of black pastors that we have talked to, neighborhood leaders in the city of Detroit that we’ve talked to. They’re looking for a change," Rogers said.

Notably, Obama is scheduled to campaign with El-Sayed in Detroit on Oct. 24 and has released a video urging voters to support the Democratic nominee.

Unique opportunity for Republicans amid alienated Jewish voters

ROGERS WARNS MICHIGAN VOTERS AGAINST EL-SAYED’S ‘EXTREME’ AGENDA AHEAD OF ELECTION

Rogers argued the Jewish community could present a unique opportunity for Republicans amid El-Sayed's criticism of Israel.

Recently, El-Sayed declined to answer whether he viewed Iran or Israel as a greater threat.

"I think both of them have proven dangerous in their own way. One, at risk of attacking us. One, getting us into wars we have no business fighting," El-Sayed said in a recent debate.

Rogers noted that if only half of Jewish Democratic voters in Michigan felt alienated by El-Sayed’s remarks enough to support his campaign, it would provide a significant boost.

"There are about 70,000 Jewish Democrats. If we get half of them to vote for us, which we think — we had an event last night. Had over 1,000 people at it. We’re fired up and excited and scared for their children, by the way. They’re afraid for their children. They’re with us, and they’re going to vote, we think, 35,000 votes out of the Jewish Democrat — these are normally solid Democratic votes."

"That’s changing the dynamic," Rogers added.

Gubernatorial hopeful promises to target fraud, trim fat on Democrat-led spending

MINNESOTA FRAUD SCANDAL WILL HAUNT FLANAGAN IN HIGH-STAKES SENATE RACE, TOP HOUSE REPUBLICAN WARNS

Rep. John James, R-Mich., the state’s Republican candidate for governor, also appeared with Hannity, presenting his pitch to attendees on what he would do differently if elected.

Alongside promises to reshape education, James promised to create more scrutiny around government programs and expenses.

"Michigan is spending 50% more right now under Gretchen Whitmer than we spent under Rick Snyder’s administration, the last Republican, and $20 billion more per year than at the height of the pandemic."

"Michigan does not have a taxation problem. Michigan has a spending problem," James added.

Snyder left office in 2019.

James also raised concerns about potential fraud in Michigan, drawing comparisons to Minnesota's sprawling taxpayer-funded fraud investigations.

"If a 19-year-old journalist named Nick Shirley can find $9 billion of fraud in Minnesota, a state with 50% of our population and 60% of our budget, what do you think he can find here?" James said, referring to a videographer who had become famous for investigating Somali fraud rings.

Shirley drew national attention to suspected fraud involving Minnesota childcare providers, although he did not uncover $9 billion in fraud. That figure came from former federal prosecutor Joe Thompson, who estimated last year that fraud across 14 high-risk Medicaid programs could total $9 billion or more. Minnesota officials have disputed the estimate. Federal and state investigators in Minnesota have uncovered fraud involving taxpayer-funded childcare, food assistance and healthcare programs, including schemes in which defendants allegedly billed the government for services they never provided.

Top House Republican accuses Democrats of concealing 'Communist' agenda

OBAMA'S STAR POWER GETS A REALITY CHECK FROM BLACK VOTERS IN CRUCIAL SENATE RACE: 'IT'S A TURNOFF'

At the close of Hannity’s town hall, Rep. Lisa McClain, R-Mich., the House GOP conference chair, accused Democrats of hiding their true character.

"I don’t even call them Democrats anymore; it’s the Communist Party," McClain said.

"They want to pack the Supreme Court, they want to abolish the police, they want to let people out of prisons."

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With primaries in the rearview mirror, Michigan heads to the polls alongside the rest of the country on Nov. 3.