Christina Applegate’s MS Misdiagnosis Reveals Why Answers Can Be Elusive

Applegate returns to uncertainty

Applegate, an actor who became a prominent public figure for multiple sclerosis after her 2021 diagnosis, said this week that she does not have MS. Her medical team still does not know what is causing her debilitating symptoms. Speaking to fellow actor Jamie Lynn Sigler, who has MS, on Sigler’s podcast MeSsy, Applegate said, “I’m back at square one.” She added that others were happy, but she was not.

Why MS can be difficult

Multiple sclerosis is an autoimmune condition in which the body attacks cells that protect the brain and spinal cord. The resulting damage can disrupt nerve signals, causing motor problems, tingling, or vision difficulties. Some people experience relapses and remissions, while others have a steady progression that can lead to serious disability.

Scientists do not fully understand what causes MS, said Dr. Andrew Solomon, a University of Vermont neurologist who specializes in the disease. Smoking is a known risk factor; obesity and metabolic problems may also play a role, but more research is needed. The contribution of genetics remains uncertain, Solomon said.

Tests and symptoms complicate diagnosis

No single test can reliably diagnose MS. Doctors commonly use MRI scans to look for lesions associated with the disease, but other rare conditions and diseases of brain blood vessels can look similar in imaging. Spinal fluid analysis can reveal immune-system abnormalities found in the vast majority of MS patients.

Misdiagnosis remains a concern

A meta-analysis estimated that roughly 15 percent of MS diagnoses may be false positives. In a 2025 study, Solomon and colleagues found that 40 percent of people later diagnosed with MS had first been given a different diagnosis.

Solomon said the disease’s varied symptoms and severity can make it hard to identify. He also said pressure to find an explanation for debilitating symptoms may lead some doctors to diagnose MS before they are certain. The availability of effective treatments, particularly when the disease is caught early, may add to that pressure.

For patients told they have MS, the article recommends asking directly what evidence supports the diagnosis. About 1 million Americans live with the disease, or roughly one in every 350 people.