Christina Applegate has revealed that, despite an earlier diagnosis, she is not suffering from multiple sclerosis.

But rather than being a relief, the news has left the 54-year-old actor and MS campaigner bereft and still struggling with an unknown debilitating illness.

Speaking on the MeSsy podcast this week, Applegate said being informed of the misdiagnosis was “worse in some ways” and she is “back at square one that I don’t know what’s going on with me”.

So how common is an MS misdiagnosis and how does it happen?

Diagnosing difficulties

Part of the difficulty in diagnosing MS is that there no single test that can identify the condition.

A diagnosis depends on multiple factors, including the symptoms and various test results, all of which can change over time.

This is exacerbated by the fact that some MS symptoms can resemble those of other conditions.

Doctors look at a patient’s health history, including a description of their symptoms, neurological exam results and an MRI of the brain and spinal cord when making a determination.

They will also look for damage in the form of lesions in different areas of the central nervous system, according to the US’s National Multiple Sclerosis Society.

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

Symptoms of the autoimmune, neurodegenerative disease often include numbness or tingling, trouble walking, vision loss and slurred speech.

While the cause of MS is not known, factors including age, family history, race, vitamin D deficiency, obesity and smoking can increase the risk.

Misdiagnosis ‘common’

Dr Elena Grebenciucova, a neurologist who specialises in MS, said unfortunately misdiagnosis was quite common.

“Statistically speaking, about one in five people who carry a diagnosis of multiple sclerosis may actually have been misdiagnosed and have an alternative explanation for their symptoms,” Grebenciucova told US media Wednesday.

“In order to diagnose MS, the MRIs need to show very specific areas of abnormalities in the brain and spinal cord or optic nerve to explain those symptoms and correlate,” she said.

A 2024 systematic review and meta-analysis from researchers in the US, Sweden and Switzerland, published in the Multiple Sclerosis Journal, found that women were more than two times more likely to be misdiagnosed with MS compared to men

It also found that the time to rectify an MS misdiagnosis ranged from just months to almost 16 years from the initial diagnosis.

However, the review warned that under-diagnosis was also common, ranging from 3 per cent to 58 per cent, with a pooled proportion of 36 per cent based upon four studies.

What other conditions could it be?

Dr Ilana Katz-Sand, associate director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, told US ABC News that MS symptoms can sometimes “overlap” with those of other conditions.

Katz-Sand said one example was optic neuritis, which is inflammation of the optic nerve and can interrupt electrical signals carrying visual information from the eye to the brain.

She said while this was a common MS symptom, it could also appear in other inflammatory conditions, such as neuromyelitis optica spectrum disorder, a rare autoimmune condition.

“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.

Grebenciucova said B12 deficiency, which is not uncommon in general population, could also mimic symptoms of MS.

“And people can present with progressive tingling and cognitive changes, and their MRIs can actually have white matter abnormalities,” she said.

Applegate – a breast-cancer survivor – was first diagnosed with MS in 2021.

She later said she experienced early symptoms  – including tingling in her toes and balance issues – years earlier while filming the Netflix series Dead to Me.

In February, she told People magazine she spent much of each day on or in her bed because it was too painful to move around.