Christina Applegate, the actress who has been one of the most visible faces of multiple sclerosis since her diagnosis in 2021, made a stunning revelation this week: She doesn’t have MS after all. And his doctors still don’t know what’s causing his debilitating symptoms.
“I’m back to square one,” Applegate told fellow actor Jamie Lynn Sigler, who has MS, on Sigler’s podcast. Messy. “I wasn’t happy at all. Everyone was so happy.”
This is a difficult situation for Applegate, and I hope her medical team can get her the diagnosis and treatment she needs. But the fact is that his experience is not unique. Even as more and more Americans are diagnosed with multiple sclerosis, misdiagnosis remains all too common. According to a meta-analysis, about 15% of MS diagnoses may actually be false positives.
How can such a common disease — about 1 million Americans live with the disease, or about one in 350 people — remain such a mystery? After Applegate’s announcement, I called some leading MS experts to ask them why diagnosing the disease is such a challenge and what they want people to know. Here’s what I learned.
Why MS can be difficult to diagnose
Multiple sclerosis is an autoimmune disease: the body mistakenly attacks the 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 roller coaster of relapses and remissions; others see the disease progress steadily, eventually leading to serious disabilities.
The reality is that scientists still don’t really know what causes MS to develop, said Dr. Andrew Solomon, an MS neurologist at the University of Vermont. Smoking is a known risk factor. Obesity and metabolic problems play a role, but more research is needed. Even the precise role of genetics remains a mystery. “We don’t really know what causes or triggers the autoimmune response in any given individual,” Solomon said.
And this is where the diagnostic challenge begins.
First, the tests can be imprecise; There is no single test that can reliably diagnose MS. If a doctor suspects their patient has MS, they typically undergo an MRI, which their doctors then scan for lesions commonly associated with the disease. But these tests are still subject to interpretation: other rare diseases sometimes resemble MS in imaging, as do diseases of the blood vessels of the brain. You may also receive a spinal fluid test 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 at first: brain fog, fatigue, or general unhappiness. Tingling or vision problems may be similar to symptoms of other conditions that are not MS, and they are easily dismissed if they go into temporary remission, as often happens during the initial stages of the disease.
“Neurological symptoms can sometimes be vague — numbness, tingling — and they are usually short-lived,” Dr. Saud Sadiq, chief investigator and director of the Tisch Multiple Sclerosis Research Center in New York, told me. “Unless they are taken seriously initially, they may be ignored, because by the time the patient goes through the health system and is actually referred to a neurologist, the symptoms have subsided.”
If your doctor diagnoses you with MS, ask them directly: what is the evidence?
A 2025 study by Solomon and colleagues found that 40% of people later diagnosed with multiple sclerosis were initially misdiagnosed with a different disease.
“Because it’s very heterogeneous, it doesn’t present the same way in everyone and can have varying severity, it can sometimes be difficult to diagnose,” Solomon said.
Finally, when people experience debilitating symptoms, there is pressure to give birth. a few diagnosis — and that might push some doctors to turn to MS even if they’re not sure, Solomon said. The recent advent of effective treatments that help manage the symptoms of the disease, particularly when detected early, may add to this pressure, although the best solution would be to continue monitoring the person before starting medication.
“It may be that many clinicians, if they can’t find an explanation better than MS, are inclined to diagnose MS, even if they don’t really meet our diagnostic criteria, because they fear missing an opportunity to treat someone,” Solomon said.
There is reason to hope that the problem of MS misdiagnosis can improve. The National Multiple Sclerosis Society released new diagnostic criteria in 2024 that Solomon said more doctors should know about to better distinguish MS from problems like migraines or vascular disease. And as imaging is involved in diagnosis, there is optimism that AI could be a powerful new tool to provide more accurate results.
What Everyone Should Know About MS Symptoms and Diagnosis
The good news is that MS, when correctly diagnosed, is now a treatable disease. “The prognosis of new drugs is extremely good for long-term care,” Sadiq told me. “If patients stick to treatment at a good MS center, you can expect a disability-free life in 2026.”
So it’s worth being vigilant and speaking to your doctor if you experience any worrying symptoms. You should seek help if you have numbness or tingling that persists for more than 24 to 48 hours, Sadiq said, or if you have motor problems, such as a hand that doesn’t work when you try to play the piano. Dr. Annette Langer-Gould, who develops and evaluates MS care programs at Kaiser Permanente, said numbness in the abdomen, chest or back, as opposed to the extremities, is of particular concern. If one eye has normal vision and the other is blurry, that’s another good reason to get checked.
If you get tested, make sure your actual MRI images are reviewed by an MS expert. “The most common reasons the disease is still misdiagnosed are related to providers’ lack of expertise, usually in reading MRI scans,” Langer-Gould said. Lumbar punctures can seem scary, and doctors sometimes don’t recommend them because their insurance reimbursement is low — but they add to the confidence of the diagnosis. They’re worth it, she says.
“American patients are very afraid of lumbar puncture,” Langer-Gould said. “My message to patients is: Listen, just get the spine back. That way we’ll be sure.”
And don’t be afraid to seek a second opinion for such a serious diagnosis, Sadiq added. Each state has a recognized MS center. If your doctor diagnoses you with MS, ask them directly: what is the evidence? If your doctor recommends that you begin treatment, it may 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 wonder if their own diagnosis is wrong. Solomon said people should have a frank conversation with their doctor about how exactly their case met the diagnostic criteria. With proper imaging and spinal fluid testing, you can make a reliable diagnosis for the vast majority of people. But be your own advocate to make sure you’re happy.
“For many people, the diagnosis can be very simple,” Solomon said. “We really have no doubt what it is.”
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