Years of Treatment and a Misdiagnosis
- Actress Christina Applegate, 54, revealed on her podcast “MeSsy” that she was misdiagnosed with multiple sclerosis (MS) in 2021.
- Applegate spent years on infusion therapy, and when her doctor later took her off treatment to watch her B cells, which didn’t change, that kicked off a review of her diagnosis.
- There is no single test for MS. Doctors rely on symptoms, MRI scans of the brain and spinal cord, and sometimes a spinal tap, while ruling out conditions that can look like MS.
- Dr. Nancy Sicotte says new MRI biomarkers — including the central vein sign and paramagnetic rim lesions — are giving neurologists far greater confidence in diagnosing MS, and SurvivorNet’s dedicated MS resource page helps patients understand these emerging tools so they can ask more informed questions and get to a clearer diagnosis sooner.
- Some patients can take days to reach a diagnosis, while others take months or even years; that difference often comes down to how and when symptoms first appear and are recognized.
- Young people with optic neuritis, an inflammation of the optic nerve that transmits signals from the eye to the brain, are usually diagnosed fastest. For others, symptoms can be easy to dismiss because they come and go.
The actress returned to “MeSsy,” the podcast she co-hosts with fellow MS advocate Jamie-Lynn Sigler, after a months-long break with news she says left her more unsettled than relieved.
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“Given how well our scanners work and how sensitive the sequences are, you really cannot diagnose someone with MS unless they have something abnormal on their MRI,” Dr. Nancy Sicotte, Chair of Neurology and Director of Multiple Sclerosis and Neuroimmunology at Cedars-Sinai in Los Angeles, tells SurvivorNet.
“If more than 50% of the lesions have a central vein sign, then it’s very likely we’re dealing with MS,” Dr. Sicotte adds.
Another emerging tool is the paramagnetic rim lesion, sometimes called a “PRL,” and these lesions are less common than central vein signs.
“About 40 to 50% of patients will have PRLs overall,” Dr. Sicotte notes, “and we’ve been seeing a lot more of them in newly diagnosed patients.”
The reason she wasn’t celebrating is simple: she still feels sick.
“You don’t get misdiagnosed and then all of a sudden I’m better, right? I haven’t gotten better,” she said.
Applegate is no stranger to frightening diagnoses. She was diagnosed with breast cancer in 2008 at age 36 and underwent a double mastectomy. She went public with her MS diagnosis in 2021 and stepped away from acting after the final season of Netflix’s “Dead to Me,” which she filmed while managing her symptoms.
How the MS Diagnosis Came About
On the podcast, Applegate walked listeners through the testing that led to her original diagnosis in 2021.
“This is 2021, and that’s when my doctor at the time started doing tests for MS, and he did brain MRIs, spinal MRIs, and this is really important, the spinal tap,” she explained.
A spinal tap, or lumbar puncture, collects cerebrospinal fluid, the fluid that surrounds the brain and spinal cord. Doctors look for proteins called oligoclonal bands, which are a sign of inflammation in the central nervous system and are found in most people with MS.
“I have three bands. At that time, I had three bands,” Applegate said, adding that she understood this to mean she didn’t have progressive MS.
Her symptoms worsened over time, she said, until her doctor delivered the news and showed her brain scans.
“As we saw in my life, I progressively got worse. And then finally came that day of the diagnosis when he said, ‘I’m so sorry,’ and showed me the lesions on my brain that were like almost 40.”
Years of Infusions — Then a Test That Didn’t Add Up
After her diagnosis, Applegate began infusion therapy, the treatment she has discussed openly on “MeSsy” for years.
“I’m doing all the infusions, which, as we know, play havoc on your body, right? Did that for years,” she said.
Then, about two years ago, her doctor tried something different.
“My doctor … said, ‘I want to see something. I want to take you off of the infusion, and I want to watch your B cells.’ And my B cells didn’t change. So, I guess that began kind of a study into my diagnosis.”
B cells are immune cells that play a central role in MS. Many of today’s most widely used MS drugs, including Ocrevus (ocrelizumab) and Kesimpta (ofatumumab), work by depleting them.
Applegate did not name the specific infusion she received.
That review ultimately concluded she does not have MS. Applegate said one of the hardest parts is that the answer raises more questions than it settles.
‘I have Every Symptom of Someone With MS’
Losing her diagnosis hasn’t taken away her pain, fatigue, or mobility issues. Applegate said her doctors now plan to dig into what has been driving her symptoms since 2021.
“I’m back at square one; I don’t know what’s going on with me. And that’s going to be an [ongoing] investigation my doctors are going to get into, just to find out what has been happening since 2021,” she said.
“I have every symptom of someone with MS. Every single one. Now, we both know that there are many things that mirror MS. Many different things.”
She also pointed to the broader problem of MS misdiagnosis.
“There’s a pretty damn high number of misdiagnoses with MS, and that’s after people have been going through the process of it with the infusions for many years,” Applegate said.
“So, it’s clear now that they’re finding something different, that something else is going on … from like the totally benign to … something else that’s kind of intense that you need to get treated for.”
Applegate also told Sigler she feels like she let people down after the two became public faces of the MS community, and that losing an explanation for her daily struggles has been deeply confusing.
Why MS Can Be Hard to Diagnose
MS is an autoimmune condition in which the immune system attacks myelin, the protective coating on nerves in the brain and spinal cord.
Some patients can take days to reach a diagnosis, while others take months or even years, according to Dr. Sicotte.
She says the difference often comes down to how and when symptoms first appear and are recognized.
“One of the things that we’ve worked really hard on in the MS community is to try and get an early diagnosis, because once people are diagnosed, we now have effective therapies, and the sooner people get on effective therapies, the better their outcomes are,” Dr. Sicotte tells SurvivorNet.
WATCH: Newly Diagnosed With Multiple Sclerosis? Understanding Your Treatment Options
“We definitely know that to be the case.”
Young people with optic neuritis, an inflammation of the optic nerve that transmits signals from the eye to the brain, are usually diagnosed fastest. Those patients often have a better outlook, Dr. Sicotte notes, likely because they are diagnosed quickly and reach the right specialists sooner.
For others, symptoms can be easy to dismiss because they come and go, appearing suddenly, lasting days or weeks, then fading.
“So someone might think, ‘Oh, I just had some weird, you know, pinched nerve and now it’s gone.’ And so those kinds of symptoms can sometimes be ignored,” Dr. Sicotte says.
Other symptoms that may be overlooked because they’re so common include fatigue, depression, brain fog, and sensory issues.
No Single Test
There is no single symptom or test that definitively confirms MS, Dr. Lauren Krupp, a neurologist at NYU Langone in New York City, tells SurvivorNet. MRI scans play a critical role, and blood tests may be used to rule out other conditions.
“Usually we see people who have had some neurological symptoms, and they often get worked up with an MRI of the brain … the brain MRI is a really important tool,” Dr. Krupp says.
In MS, MRI scans show small white spots, called lesions, that shouldn’t be there. A spinal cord MRI can help doctors confirm specific diagnostic criteria.
“If you want to get more technical, these are probably plaques,” Dr. Krupp explains. “That is a term that really refers back to the old days before we had MRI … so once you make the diagnosis and the lesions have to be in a specific location, then you want to get treatment.”
WATCH: Multiple Sclerosis: Dealing With Fatigue
That location matters because white spots on a brain MRI aren’t unique to MS.
Migraines, small blood vessel disease, infections, and other inflammatory conditions can cause similar-looking spots — one reason MS mimics can be mistaken for the real thing.
Cedars-Sinai neurologist Dr. Marwa Kaisey, who appeared on the episode, told Applegate and Sigler that misdiagnosis is fairly common precisely because no single test settles the question.
MS Symptoms and How It’s Treated
Dr. Krupp describes MS as an “immune-mediated condition,” in which the immune system works against itself.
“We’re not exactly sure why that happens, but it probably has to do with an exposure to a virus at some point in time. And in the effort to fight off that virus, the immune system turns against itself and specifically, a coating of the nerves called myelin,” Dr. Krupp explains.
“The myelin that it affects involves the central nervous system, and that’s the brain and the spinal cord.”
Since MS can involve different areas of the brain or spinal cord, “the symptoms can vary in location,” she says. They might include:
- Numbness and tingling in the face
- Numbness or weakness in the arms and legs
- A sensation of vertigo or the room spinning
- Vision loss or blurred vision
- Lack of coordination
Symptoms may affect one side of the body or, when the spinal cord is involved, both sides. Numbness can spread and may come with muscle weakness.
MS Treatment Options
Once MS is confirmed, patients have more choices than ever.
“There’s more than 25 different treatments available now for MS. They fall into a much smaller number of classes of medication, but I do think the big game changer was this class called B-cell depletion therapy (BCDT), and that includes Ocrevus (ocrelizumab) and Kesimpta (ofatumumab),” Dr. Sicotte tells SurvivorNet.
“Some people think of those as being like a heavy hitter, but we pretty much like to use that if all things being equal early on, because we do think that treating people with the most highly effective therapy at the get-go gives the best long-term outcomes,” she adds.
Other options include oral therapies that reduce inflammation, new lesions and relapses, as well as older injectable medications such as Copaxone and the interferons.
“We do offer all of those options to people,” Dr. Sicotte says.
“We do tend to steer people toward the higher efficacy if there are risk factors that we think make it more likely that they have a higher risk of developing more severe disease.”
Applegate’s experience is a reminder that these powerful therapies work best when the diagnosis is right, and that it’s worth revisiting the diagnosis if treatment isn’t producing the expected results.
Questions to Ask Your Doctor
If you’ve been diagnosed with MS, or are being evaluated for it, these questions can help guide the conversation:
- What findings support my MS diagnosis, and do they meet current diagnostic criteria?
- Which other conditions did you rule out, and how?
- Would a spinal tap or additional imaging add useful information in my case?
- How will we know whether my treatment is working?
- If my symptoms don’t improve on treatment, should we revisit the diagnosis?
- Would a second opinion at a specialized MS center be helpful?
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