After Five Years of Treatment, Christina Applegate Learns She Does Not Have MS — Raising Questions About Misdiagnosis

Actress Christina Applegate's recent revelation — that she was misdiagnosed with multiple sclerosis (MS) — is raising questions about how a disease can be confused with other conditions, even after years of treatment.

The 54-year-old actress shared the news during an October 20 episode of her podcast 'MeSsy,' alongside co-host Jamie-Lynn Sigler, saying she was in a complete 'state of shock.'

Applegate was first diagnosed with MS in 2021 after experiencing debilitating symptoms and undergoing extensive testing, including brain and spinal MRIs and a spinal tap. She said doctors found dozens of lesions on her brain.

After years of treatment, her doctor decided to stop her regular infusions and monitor her B cells. 'And my B cells didn't change. They didn't go higher, they didn't go lower, they didn't change, and she had never seen that. So I guess that began kind of a study into my diagnosis,' Applegate shared.

After additional brain scans, the doctor came into Applegate's room and said, 'Congratulations, you don't have MS.' The actress did not consider this to be good news, however.

'Because you don't get misdiagnosed and then all of a sudden [you're] better,' she said. 'I haven't gotten better … If anything, I've gotten worse in some ways.' She noted that she has 'every symptom' of someone with MS, adding that there are many conditions that mirror the disease.

She recalled that her MRIs clearly showed around 30 lesions, but said her neurologist identified a different feature — which she described as a 'string' — that led to the conclusion that she did not have MS. 'So I'm back at square one [and] don't know what's going on with me.'

Dr. Marwa Kaisey, an associate professor of neurology at Cedars-Sinai in Los Angeles, said during a follow-up 'MeSsy' podcast episode that misdiagnosis of MS is 'fairly common.' Kaisey — who has not treated Applegate — said that in a study of patients referred to MS clinics at UCLA and Cedars-Sinai, she found that nearly one in five who arrived with an MS diagnosis ultimately did not have the disease.

'Some [had been diagnosed] for decades,' she said. 'And a majority of them were on medication to treat their MS.' The primary challenge, according to the doctor, is that there is no single test for MS. 'It's not like we have something like a pregnancy test that says, yes, you have it, no, you don't.' Instead, she said, 'It's a list of criteria, some of which remain a little bit subjective.'

Doctors say most misdiagnosed patients did have some type of white matter spots, or lesions, on their MRI scans, but they had a different cause that was not MS. Newer imaging techniques may help doctors distinguish them, including the 'central vein sign,' an MRI finding that looks for small blood vessels running through the centre of lesions, a characteristic associated with MS. The sign was incorporated into updated MS diagnostic criteria.

Richard Ransohoff, MD, a Boston-based neurologist who sits on the Board of Directors for the American Brain Foundation, called the central vein sign 'a real step forward.' Ransohoff, who also has not treated the actress, said there is no single element that tells with 100% certainty that it is MS, and that even after a diagnosis doctors should keep an open mind and reconsider when symptoms do not fit or treatment does not work.

According to both neurologists, many symptoms of MS — such as tingling or numbness in the feet, fatigue and brain fog — are very common in other conditions as well. Conditions that can mimic MS include certain strokes in younger people, neuromyelitis optica spectrum disease, MOG antibody disease, lupus and migraine, with migraine one of the most common alternative diagnoses.

Kaisey said being 'undiagnosed' with MS can be even harder than receiving the initial diagnosis, particularly when the disease has become intertwined with someone's identity, family and community, and she advised patients not to be afraid to ask questions and get a second opinion. Ransohoff recommends that everyone diagnosed with MS be seen by a specialist at a specialty MS centre, where treatment has grown to more than 20 medications today. In Applegate's case, however, no concrete alternative diagnosis has yet emerged, so her search begins again from the start.