Why MS can be hard to diagnose, after Christina Applegate reveals misdiagnosis

Five years after revealing she was diagnosed with the autoimmune disorder multiple sclerosis (MS), actress Christina Applegate has announced that she was misdiagnosed.

Speaking on Tuesday's episode of her MeSsy podcast, which she co-hosts with actress Jamie Lynn Sigler, Applegate said she wasn't happy to learn of the misdiagnosis, revealing that she has "gotten worse in some ways" and is "back at square one that I don't know what's going on with me."

Doctors say there's no single test that can diagnose MS. That determination depends upon multiple factors, including a patient's symptoms and various test results, all of which can change over time. Additionally, improper application of diagnostic criteria, and that fact that MS symptoms can resemble those of other conditions, can sometimes lead to misdiagnosis.

How is MS diagnosed?

"Unfortunately, there is no single diagnostic test for MS," Dr. Ilana Katz-Sand, associate director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai in New York, told ABC News. "Rather, an MS diagnosis is made by considering all available data and appropriately applying the diagnostic criteria."

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

Doctors will look for damage in the form of lesions in different areas of the central nervous system, according to the National Multiple Sclerosis Society (NMSS).

Sometimes, if additional data is needed, a doctor will recommend a lumbar puncture to check for the presence of certain proteins in cerebrospinal fluid.

"Other testing, such as examining the optic nerves and blood tests to appropriately rule out other conditions, may also be performed," Katz-Sand said.

When MS diagnostic criteria were first introduced, the average time to get an MS diagnosis was four years, the NMSS said. Then in 2024, MS diagnostic criteria were updated to help patients receive a diagnosis in days or weeks as opposed to months or years. The updates include new and enhanced tests for diagnosis, as well as specialized criteria for diagnosing children, those aged 50 and older, and those who also have other medical conditions, according to NMSS.

How common is MS misdiagnosis?

A 2024 systematic review and meta-analysis from researchers in the U.S., Sweden and Switzerland, published in the Multiple Sclerosis Journal, found that the frequency of misdiagnosis ranged from 5% to 41%, with a pooled proportion of 15% based on six studies.

Dr. Marwa Kaisey, a board-certified neurologist and associate professor of neurology at Cedars-Sinai Medical Center, said during Tuesday's MeSsy podcast episode that about 20% of patients diagnosed with MS don't 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.

Women were 2.1 times more likely to be misdiagnosed with MS compared to men, according to the 2024 review, with the time to rectify an MS misdiagnosis ranging from 0.3 years to 15.9 years from the initial diagnosis.

However, underdiagnosis was also common, according to the review, ranging from 3% to 58%, with a pooled proportion of 36% based upon 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," Katz-Sand said.

Can MS symptoms resemble other conditions?

MS symptoms can sometimes "overlap" with those of other conditions, which can make diagnosis difficult or prolong it, according to Katz-Sand.

One example is optic neuritis, which is inflammation of the optic nerve that can interrupt electrical signals carrying visual information from the eye to the brain. Katz-Sand said this is a common MS symptom but it can also appear in other inflammatory conditions, such as neuromyelitis optica spectrum disorder, a rare autoimmune condition in which the immune system mistakenly attacks healthy cells and proteins, primarily targeting the 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."

If someone learns that they have been misdiagnosed with MS, Katz-Sand said they should speak with their doctor to understand "why the clinician has changed their impression."

Next steps for patients may differ depending upon whether symptoms have changed or a new lab test result became available, she said.