Christina Applegate misdiagnosis: Why can MS be difficult to diagnose?

Christina Applegate recently announced that a reevaluation of her condition revealed she does not have multiple sclerosis (MS). However, this revelation has left her without a diagnosis, feeling "back at square one," unsure of what's wrong with her.

MS diagnosis can be challenging for several reasons. It's a complex autoimmune disorder where the immune system attacks the central nervous system, causing damage to neurons and the myelin sheath surrounding them. This leads to a variety of symptoms including vision problems, muscle weakness, tingling sensations, dizziness, and bladder issues. In severe cases, patients may lose the ability to walk or stand, or develop paralysis.

Despite advancements in diagnosis, studies suggest that MS is misdiagnosed 5% to over 40% of the time, depending on the patient population and clinical setting. There's also underdiagnosis, where people with MS are not recognized as having the disease.

Dr. Ari Green, a neuroimmunology expert, emphasizes that it's crucial for doctors and patients to be aware that revisiting a diagnosis is not inappropriate. Early diagnosis is vital as it allows patients to start critical treatment sooner, preventing further nerve damage and improving long-term outcomes.

However, there's no single definitive test for MS. Diagnosis relies on a combination of criteria, including lab tests, brain and spinal cord scans, and the patient's symptoms. The latest MS diagnostic criteria, published in 2025, emphasize the importance of detecting and interpreting specific patterns of myelin damage, particularly in the optic nerves. Electrophysiologic tests, which assess nerve function, are also crucial.

Doctors must also rule out other conditions that can mimic MS, such as neuromyelitis optica, MOGAD, lupus, and myasthenia gravis. These conditions can be ruled out using spinal taps or antibody tests.