Christina Applegate’s MS Misdiagnosis: What Her Case Reveals About a Difficult Diagnosis

Christina Applegate said she learned she does not have multiple sclerosis after being diagnosed in 2021 and living for years with severe symptoms. On her podcast “MeSsy,” she described the news not as simple relief, but as feeling “back to square one” because her pain, balance issues, tremors, incontinence, and fatigue remain unexplained. Her case underscores a difficult reality for patients: losing a diagnosis can also mean losing clarity, treatment direction, and community support.

Business Insider reports that there is no single blood test that diagnoses MS. Doctors often combine neurological exams, MRI scans, lumbar punctures, and blood tests that help rule out other conditions, such as Lyme disease. Researchers cited in the article say misdiagnosis can happen when one test result, such as an MRI finding, is given too much weight without confirming every part of the diagnostic criteria.

Researchers estimate that about 15% of MS patients worldwide may actually be misdiagnosed, according to a 2024 meta-analysis cited by Business Insider. Dr. Marwa Kaisey told the outlet the risks are two-fold: patients may take MS medications that can carry side effects, and they may miss treatment for the condition they actually have. Applegate’s situation highlights why persistent or changing symptoms may warrant reevaluation, especially when something does not fit the diagnosis.

Applegate said her brain lesions were missing “strings” associated with MS, a finding tied to the central vein sign, or CVS. Business Insider describes CVS as an MRI biomarker that can help distinguish MS brain lesions from lesions linked to other disorders. The article says CVS became part of recommended MS diagnostic criteria in 2025, after Applegate’s original diagnosis, and experts hope more doctors will use it in diagnostic protocols.

Patients should not treat Applegate’s story as a reason to self-diagnose or stop treatment, but it can be a prompt for better conversations with clinicians. Useful questions include whether every part of the MS diagnostic criteria has been confirmed, what other conditions have been ruled out, and whether newer imaging markers such as CVS are relevant. As the original article notes, medical reporting is not a substitute for professional medical advice, diagnosis, or treatment.