More than five years ago, actress Christina Applegate received a diagnosis of multiple sclerosis, a neurological disorder that she felt explained everything she was experiencing.
“It was my answer to everything that was going on,” she noted.
Applegate quickly integrated herself into the MS community. Alongside actress Jamie-Lynn Sigler—who also lives with the condition—Applegate began co-hosting the podcast MeSsy, establishing herself as a prominent and vocal advocate.
However, during a recent medical consultation, her doctor delivered an unexpected update. As Applegate recalled tearfully, the physician told her, “Congratulations, you don’t have MS.” She added, “I was like not happy at all.”
Learning she had been misdiagnosed left her feeling adrift and uncertain.
“I’m back at square one,” Applegate stated, noting that she still experiences what she characterized as “every single symptom” of the disease. These include pain, tingling, tremors, fatigue, incontinence, muscle weakness, trouble walking, knee buckling, and sensitivity to both heat and cold.
“I’m still dealing with all of those symptoms,” Applegate shared during an October 20 podcast episode. “And now here I am without a name.”
While an incorrect diagnosis of multiple sclerosis is not entirely unprecedented, experts note that such errors happen more frequently than many realize.
Understanding Multiple Sclerosis
Multiple sclerosis (MS) is a disorder of the central nervous system that disrupts communication between the brain and the rest of the body. The condition develops when the immune system mistakenly attacks myelin, the protective fatty tissue that surrounds nerve fibers. This damage results in scar tissue, often referred to as plaques, lesions, or sclerosis.
Because the disease affects individuals differently, symptoms vary widely. They can include numbness, tingling, pain, tremors, muscle weakness, severe fatigue, mobility challenges, balance and coordination difficulties, vision loss, cognitive fog, mood fluctuations, and bladder or bowel dysfunction.
There is currently no cure for MS. According to the National Multiple Sclerosis Society, an estimated 1 million individuals in the United States live with the condition.
The Diagnostic Process for MS
Diagnosing multiple sclerosis relies on a comprehensive evaluation rather than a single definitive test. No individual symptom or lab result can independently confirm the condition.
Instead, physicians must systematically rule out alternative explanations for a patient’s symptoms while gathering evidence that points toward MS. Clinicians typically look for signs of neural damage in the brain, spinal cord, or optic nerves. If damage appears in multiple locations, specialists check whether the lesions occurred at different times, exhibit MS-specific characteristics, or involve specific proteins within the spinal fluid.
“It’s a list of criteria,” Dr. Marwa Kaisey, a neurologist and MS researcher, explained during her conversation with Applegate on MeSsy. Because interpreting these standards involves a degree of clinical judgment and the criteria themselves evolve over time, she noted that “there’s room for error there.”
“The symptoms of MS—like tingling in your feet or numbness in your feet, for example, fatigue, brain fog—are very common in other things that are not MS,” Kaisey pointed out, adding that separating the condition from its mimics can prove exceptionally difficult.
Even highly experienced physicians who review a case thoroughly can occasionally arrive at an incorrect conclusion, she noted.
Dr. Michael Kornberg, an associate professor of neurology at Johns Hopkins University, explained to NPR that reaching an MS diagnosis requires a careful synthesis of a patient’s collective clinical picture.
Prevalence of Misdiagnosis
Medical literature indicates that misdiagnoses involving multiple sclerosis are not uncommon.
While some studies estimate an error rate of around 5%, others place the figure as high as 36%. A 2024 review combining six separate studies found that 15% of 1,621 patients evaluated did not actually have the disease.
Similarly, a 2019 study led by Kaisey found that approximately 18% of 241 patients referred to specialized MS centers in Los Angeles with established diagnoses had actually been misdiagnosed.
“When you really look at why they’d been misdiagnosed or what they had in common, most of them had some form of white matter spots on their MRI, some sort of lesions,” Kaisey explained. The core issue was that these spots stemmed from alternative medical conditions rather than MS. In that particular study, the most frequent alternative diagnosis among incorrectly labeled patients was migraine.
Such findings have pushed researchers to identify imaging markers that can differentiate MS-related white matter lesions from those caused by other issues.
One emerging technique looks for the “central vein sign” within individual lesions, which aids in distinguishing MS from mimicking disorders. Although this approach was incorporated into diagnostic guidelines released in 2025, Kaisey noted that not all medical facilities currently possess the capability to perform this specific check.
The sign involves identifying tiny blood vessels located directly in the center of these lesions, providing a clearer indication of multiple sclerosis than the appearance of white spots alone, she noted.
Patients are also frequently misdiagnosed with other conditions before receiving an eventual MS evaluation. A 2017 survey reported that about 42% of respondents were initially told they had conditions such as fibromyalgia, migraines, or depression.
The Specifics of Applegate’s Case
Applegate pointed to several diagnostic tests that initially pointed toward MS, including a brain MRI revealing white lesions and a lumbar puncture that detected oligoclonal bands—specific antibodies found in cerebrospinal fluid.
Reflecting on Applegate’s medical history, Kaisey mentioned it was plausible that her lesions lacked the central vein sign characteristics.
Regarding lumbar punctures, typical findings usually show one or zero oligoclonal bands in the cerebrospinal fluid.
Applegate noted that her results indicated “three bands,” a count generally categorized as a positive result pointing to inflammation within the central nervous system.
“Over 90% of people with MS are positive for this test,” Kaisey explained. “But other things can cause it, it’s not just positive for MS. Anything that’s causing inflammation in the central nervous system would give you a positive result.”
Navigating Life After a Misdiagnosis
Once a medical error is uncovered, the primary objective shifts to determining the correct underlying cause, Kaisey noted.
Incorrect diagnoses can carry significant personal and financial tolls. Patients often build parts of their identity, support networks, and community around the condition, while undergoing years of costly medical treatments. Furthermore, financial and disability accommodations tied to the initial diagnosis can be upended.
“You’ve been told you have this thing for many years,” Kaisey stated. “To suddenly take that away, I think it is earth shattering. It’s life changing in a huge way.”
Because alternative explanations are not always immediately apparent, patients can be left feeling unmoored.
“We’re just starting from scratch, basically,” Applegate remarked, sharing that her physician has initiated blood work to screen for conditions like rheumatoid arthritis.
Physicians may also investigate rarer conditions related to multiple sclerosis, for which specific blood markers exist, according to Kaisey.
Cheryl Herbert, a spokesperson for the National Organization for Rare Disorders, observed that Applegate’s experience mirrors the broader hurdles faced by individuals with uncommon health conditions.
Securing a precise diagnosis frequently requires five or more years, Herbert noted, “often involving multiple specialists, uncertainty and missed opportunities for earlier intervention.”
PolitiFact Staff Researcher Caryn Baird and PolitiFact Digital Research Analyst Erin Jones contributed to this report.