Christina Applegate announces MS misdiagnosis

Applegate was diagnosed with MS in 2021 after imaging showed lesions in her brain and a spinal tap showed markers called oligoclonal bands, which signal inflammation in the central nervous system. Her illness began with numbness in her toes that spread up her legs and eventually progressed to pain, she said on her podcast. She later developed balance, mobility, and gastrointestinal issues as well.

Recently, however, Applegate shared on her podcast that she had learned she was misdiagnosed with MS. She said the news has made things more difficult, leaving her without an explanation for symptoms that affect her daily life and mobility.

"You don't get misdiagnosed and then all of the sudden I'm better," she said. "If anything, I've gotten worse. So I'm back at square one where I don't know what's going on with me. And that's going to be an online investigation that my doctors are going to be getting into just to find out what has been going on since 2021, why did this happen?"

According to Marwa Kaisey, an associate professor of neurology at Cedars-Sinai, the findings that led to Applegate's diagnosis are characteristic of MS but can also occur in other conditions.

It's unclear what tests led to the discovery of Applegate's misdiagnosis, but she mentioned on her podcast that she recalled her doctor talking about looking for a "string" around the lesions in her brain.

Kaisey said that, while she wasn't sure, Applegate's description sounded like it was referring to the "central vein sign," which is one of the new markers of MS mentioned in 2024 diagnostic guidelines.

How common is an MS misdiagnosis?

A 2024 systematic review and meta-analysis by researchers in the United States, Sweden, and Switzerland and published in Multiple Sclerosis found the frequency of MS misdiagnosis ranged between 5% and 41%, with a pooled proportion of 15% based on six studies.

Kaisey, who spoke on a follow-up episode of Applegate's podcast, said that around 20% of patients diagnosed with MS don't actually have the condition.

"Almost one in five of these people who'd been told they had MS, some for decades, didn't actually have it, and a majority of them were on medication to treat their MS," she said.

According to the review, women were 2.1 times more likely to be misdiagnosed with MS than men, with the time to fix a misdiagnosis ranging from 0.3 years to 15.9 years from the initial diagnosis.

However, underdiagnosis is also common, the review found, ranging from 3% to 58% with a pooled proportion of 36% based on four studies.

"In my experience, misdiagnosis most commonly occurs when the clinician has not considered a diagnostic 'red flag' carefully enough or has inappropriately applied the MS diagnostic criteria when a patient's history, exam, or MRI findings are not typical for MS," said Ilana Katz-Sand, associate director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in New York.

Why do MS misdiagnoses happen?

Doctors say there's not one sole test that can diagnose MS because a diagnosis depends on a variety of factors, including a patient's symptoms and test results, all of which can change over time.

"Unfortunately, there is no single diagnostic test for MS," Katz-Sand said. "Rather, an MS diagnosis is made by considering all available data and appropriately applying the diagnostic criteria."

Katz-Sand explained that clinicians look at a patient's health history, including a description of their symptoms, as well as neurological exam results and an MRI of the patient's brain and spinal cord.

For example, one common symptom of MS is optic neuritis, which is the inflammation of the optic nerve that can interrupt electrical signals that carry visual information from the eye to the brain. According to Katz-Sand, this symptom can also appear in other inflammatory conditions like neuromyelitis optica spectrum disorder, which is a rare autoimmune condition in which the immune system mistakenly attacks healthy cells and proteins, particularly optic nerves.

"Other symptoms that are common in MS, like fatigue and cognitive fogginess, are common in many other illnesses and are not specific to MS," Katz-Sand said. "The clinician will need to use clues from the way the symptoms present, the pattern of lesions on MRI, blood and spinal fluid testing, and sometimes additional diagnostics to help differentiate MS from other conditions when it is not initially clear."

When a misdiagnosis happens, typically the root cause is misinterpretation of abnormalities on brain scans, according to Robert Bermel, director of the Mellen Cancer Center for MS. While lesions on the brain are considered a hallmark of MS, they can also be caused by other health issues like high blood pressure, smoking, or migraines. Bermel added that more advanced MRI sequences can help differentiate between MS lesions and others.

When doctors are concerned about a potential misdiagnosis of MS, the next steps usually involve running specialized tests, which can include advanced MRI sequences, a spinal MRI, or a spinal fluid analysis that can identify specific abnormal immune proteins, Bermel said.

If a misdiagnosis is determined, then doctors will start looking at other potential causes for the patient's symptoms, which could be one single condition or several, Bermel said, noting that a misdiagnosis "really sidetracks things."

"MS can sometimes be a gratifying solution to a patient with many symptoms because it's thought of as kind of a single, solitary root cause of things," he said, adding that he's seen patients whose fatigue is caused by a sleep or thyroid disorder, while their pain and swelling were caused by rheumatoid conditions or fibromyalgia.

According to Bermel, anyone concerned about their MS diagnosis should be comfortable seeking a second opinion. Even if the original diagnosis is correct, a second opinion can also help patients find other resources about the condition.

"MS is a life-changing diagnosis, and anytime somebody is facing something like that, I always think a second opinion is potentially in order," Bermel said.