Christina Applegate, the actor who has been one of the most visible faces of multiple sclerosis since her 2021 diagnosis, made a stunning revelation this week: She does not have MS after all. And her doctors still don’t know what is causing her debilitating symptoms.
“I’m back at square one,” Applegate told fellow actor Jamie Lynn Sigler, who does have MS, on Sigler’s podcast MeSsy. “I was not happy at all. Everybody else was so happy.”
It is a harrowing predicament for Applegate, and hopefully her medical team is able to get her the diagnosis and treatment she needs. But the fact is, her experience is not unique. Even as more and more Americans get diagnosed with multiple sclerosis, misdiagnosis remains all too common. According to one meta-analysis, roughly 15 percent of MS diagnoses may actually be false positives.
How could such a common medical condition — roughly 1 million Americans are living with the disease, about one in every 350 people — remain such a mystery? After Applegate’s announcement, I called some leading experts on MS to ask why diagnosing the disease is such a challenge, and what they want people to know. Here’s what I learned.
Why MS can be challenging to diagnose
Multiple sclerosis is an autoimmune condition: The body mistakenly attacks cells meant to protect your brain and spinal cord, and the resulting damage interrupts nerve signals and causes the disease’s telltale symptoms of motor impairment, tingling sensations, and vision problems. Some people experience a rollercoaster of relapses and remissions; others see the disease steadily progress, eventually leading to serious disability.
The reality is, scientists still don’t really know what causes MS to develop, said Dr. Andrew Solomon, a neurologist at the University of Vermont who specializes in MS. Smoking is a known risk factor. Obesity and metabolic problems play a role, but we need more research. Even the precise role of genetics remains something of a mystery. “We don’t really know what causes or triggers the autoimmune response in any given individual,” Solomon said.
And that’s where the challenge in diagnosing it begins.
First, the testing can be imprecise; there is not a single test that reliably diagnoses MS. If a doctor suspects their patient may have MS, they usually undergo an MRI, which their physicians then scour for lesions that are typically associated with the disease. But those scans are still subject to interpretation: Other rare conditions sometimes resemble MS in imaging, as can diseases of blood vessels in the brain. You can also receive a spinal fluid analysis to check for abnormalities in your immune system, which the vast majority of MS patients have.
The nature of MS symptoms adds to the difficulty. They can often be vague early on: brain fog or fatigue or a general malaise. The tingling or vision problems can be similar to symptoms for other conditions that are not MS, and they are easily dismissed if they go into temporary remission, as often happens during the initial phases of the disease.
“Neurological symptoms sometimes can be vague — numbness, pins and needles — and it’s usually short-lived,” Dr. Saud Sadiq, chief research scientist and director of the Tisch Multiple Sclerosis Research Center of New York, told me. “Unless they’re taken seriously initially, they may be ignored because by the time the patient goes through the healthcare system and is actually referred to a neurologist, the symptoms have abated.”
If your doctor is diagnosing you with MS, ask directly: What’s the evidence?
One 2025 study by Solomon and his colleagues found that 40 percent of people who had later been diagnosed with multiple sclerosis were initially misdiagnosed with a different disease.
“Because it’s so heterogeneous, it doesn’t present in the same way in everybody and can have varying severity, it can be hard to diagnose sometimes,” Solomon said.
Lastly, when people are experiencing debilitating symptoms, there is pressure to deliver some diagnosis — and that may push some doctors to leap to MS even if they are not sure, Solomon said. The recent advent of effective treatments that help manage the disease’s symptoms, especially when it is caught early, may add to that pressure, even if the better course would be to continue monitoring the person before they start a medication.
“There may be a lot of clinicians who, if they can’t find a better explanation than MS, may be inclined to diagnose MS, even if they don’t really meet our diagnostic criteria, because they’re worried about missing a window of opportunity to treat somebody,” Solomon said.
There is reason to hope the MS misdiagnosis problem could get better. The National Multiple Sclerosis Society released new diagnostic criteria in 2024 that Solomon said more physicians should become familiar with to better distinguish MS from problems like migraines or vascular disease. And because imaging is involved in diagnosis, there is optimism that AI could be a powerful new tool in delivering more accurate results.
What everyone should know about MS symptoms and diagnosis
The good news is that MS, when diagnosed properly, is a treatable condition these days. “The prognosis with new drugs is extremely good for long-term care,” Sadiq told me. “If patients stick to treatment at a good MS center, you can look forward to a life without disability in 2026.”
So it is worth being vigilant and talking to your doctor if you experience any concerning symptoms. You should seek care if you have numbness or pins and needles that persists for more than 24 to 48 hours, Sadiq said, or have motor problems, like one hand won’t work as you try to play piano. Dr. Annette Langer-Gould, who develops and evaluates programs for MS care at Kaiser Permanente, said numbness in your abdomen, chest or back, as opposed to your extremities, is a particular cause for concern. If one eye has normal vision and the other is blurred, that’s another good reason to get checked out.
If you do get tested, make sure the actual images of your MRIs end up being reviewed by an expert in MS. “The most common reasons the disease is still misdiagnosed are related to the providers’ lack of expertise usually in reading MRI scans,” Langer-Gould said. The spinal tap may sound scary, and doctors sometimes don’t recommend them because their insurance reimbursement is low — but they add to the confidence of a diagnosis. They are worth it, she said.
“American patients are very afraid of the spinal tap,” Langer-Gould said. “My message to patients is: Listen, just get the spinal. This way we’ll be sure.”
And do not be afraid to seek a second opinion for such a serious diagnosis, Sadiq added. Every state has a recognized MS center. If your doctor is diagnosing you with MS, ask directly: What’s the evidence? If your doctor is recommending that you start treatment, it could also be worth checking whether they have a relationship with a pharmaceutical company that affects how you perceive their judgment, Langer-Gould said.
People who have already been diagnosed may also be shaken by the Applegate news and question whether their own diagnosis might be wrong. Solomon said that folks should have a frank conversation with their physician about how exactly their case met the diagnostic criteria. With proper imaging and the spinal fluid tests, you can get to a confident diagnosis for the vast majority of people. But be your own advocate to make sure you’re satisfied.
“For many people, the diagnosis actually can be very straightforward,” Solomon said. “We really have no question about what it is.”