Christina Applegate ‘Not Happy at All’ After Learning She Was Misdiagnosed With MS

Christina Applegate arrives for the 29th Screen Actors Guild Awards at the Fairmont Century Plaza in Century City, CA, on February 26, 2023. Valerie Macon/AFP via Getty Images

• Christina Applegate revealed that she was misdiagnosed with multiple sclerosis (MS) after sharing her diagnosis publicly in 2021.
• While her doctor now says she doesn’t have MS, her symptoms have worsened, and the underlying cause remains under investigation.
• Research suggests that around 15% of people diagnosed with MS may have another condition, with females twice as likely to be misdiagnosed.
• Conditions often mistaken for MS include migraine, peripheral neuropathy, fibromyalgia, and radiologically isolated syndrome.
• MS can be challenging to diagnose because no single test confirms it in every case. Diagnosis relies on a combination of symptoms, neurological examination, and MRI findings.

Christina Applegate shared an unexpected health update on her return to the MeSsy podcast with co-host Jamie-Lynn Sigler. 

The two actors have detailed their experiences with multiple sclerosis (MS), a neurological disorder that can lead to debilitating symptoms affecting daily functioning and quality of life. 

Applegate, 54, has been raising awareness about the condition since her initial diagnosis in 2021.

In two podcast episodes released October 20, Applegate revealed that doctors had told her she was misdiagnosed with MS.

“She came into my room and said, ‘Congratulations, you don’t have MS,’ ” Applegate said as she fought back tears. “I was, like, not happy at all. Everybody else was so happy.”

The “Anchorman” and “Dead to Me” actor explained that her symptoms have continued to worsen, leaving her without an explanation for what she’s experiencing as doctors investigate the cause.

Being misdiagnosed with MS is relatively common. Applegate’s revelation highlights a difficult reality for people living with unexplained symptoms resembling MS. Her experience raises questions about how MS is diagnosed, why misdiagnoses may occur,  and what people can do when their symptoms don’t match their diagnosis.

While MS can be difficult to diagnose, an accurate diagnosis can help people with the condition gain access to appropriate treatment. A misdiagnosis, on the other hand, may lead to unnecessary interventions and medication, and take an emotional toll over time.

“MS can be challenging to diagnose because there is no single test that confirms it in every case,” said Steve Allder, MD, consultant neurologist at Re:Cognition Health. 

“An incorrect diagnosis can have significant consequences. Someone incorrectly diagnosed with MS may experience considerable anxiety, undergo unnecessary investigations, or receive treatments with potential risks and side effects. Equally, if MS is missed, treatment may be delayed, potentially allowing further neurological damage,” Allder told Healthline.

How common is MS misdiagnosis?

A 2024 systematic review and meta-analysis underscores that MS misdiagnoses remain a concern. 

Research suggests that around 15% of people diagnosed with MS may actually have another condition.

However, estimates vary across studies, with some reporting rates ranging from 5–41%.

While an accurate diagnosis can guide patients toward appropriate treatment, a mistaken one may lead to unnecessary medication, emotional distress, and years of uncertainty.

New diagnostic guidelines offer hope for greater accuracy, but they also raise important questions about how doctors can adequately distinguish MS from other conditions. 

“Research has shown that MS can be both overdiagnosed and underdiagnosed,” Allder said.

“Diagnosis relies on a combination of symptoms, neurological examination, MRI findings, and sometimes, additional tests. It is also important to recognize that diagnoses can evolve as new evidence emerges. As neurologists, we must remain open to revisiting a diagnosis when symptoms or test results do not fit, ensuring patients receive appropriate treatment and support.”

What health conditions are mistaken for MS?

MS symptoms may vary widely and overlap with several other conditions. These may include: 

• Migraine — may cause sensory disturbances, visual symptoms, and MRI abnormalities.
• Radiologically isolated syndrome (RIS) — MS-like lesions appear on brain or spinal imaging, but the person has no symptoms typical of MS.
• Peripheral neuropathy — nerve damage outside the brain and spinal cord can cause numbness and tingling as well as weakness.
• Fibromyalgia — may cause widespread pain, fatigue, and cognitive difficulties that overlap with symptoms reported by people with MS.

Because these conditions share certain features with MS, healthcare professionals should consider a patient’s full clinical profile rather than relying on a single symptom or scan.

“MS can cause numbness, tingling, muscle weakness, visual disturbances, balance problems, and fatigue. However, these symptoms are not unique to the condition,” Allder said.

“For example, numbness and tingling may indicate peripheral neuropathy, sometimes associated with diabetes or vitamin B12 deficiency. Weakness or altered sensation may result from a trapped nerve or spinal cord compression. Migraines can cause visual disturbances and sensory symptoms, while inner-ear disorders may affect balance,” he continued.

Allder noted that fatigue is particularly nonspecific and may be associated with:

• anemia
• thyroid disorders
• sleep problems
• other medical conditions

He explained that, as a neurologist, he considers the pattern, duration, and progression of symptoms alongside examination findings. 

“No single symptom automatically indicates MS. A thorough assessment is essential to identify the underlying cause and ensure the patient receives appropriate treatment,” he said.

Why does MS misdiagnosis occur?

There is no single test that definitively confirms every case of MS. 

Diagnosis typically involves reviewing symptoms, conducting neurological examinations, and evaluating MRI scans and laboratory results.

MRI findings may be tricky to interpret. Some white-matter spots resemble MS lesions but may result from migraine, aging, or other conditions. Misapplying diagnostic criteria or overlooking alternative explanations can also lead to mistakes.

“MRI abnormalities alone do not confirm MS,” Allder said. “The diagnosis must be based on the overall clinical picture, with alternative explanations carefully considered.”

Research also suggests that MS misdiagnosis rates may differ by sex.

Research shows females are 2.1 times more likely to be misdiagnosed with MS than males, highlighting the potential for diagnostic bias and differences in how symptoms are evaluated.

What changes have been made in diagnostic criteria?

The updated MS diagnostic criteria published in 2025 offer a framework for improving diagnosis. 

The updated guidelines introduce several important changes.

For instance, the optic nerve (the nerve connecting the eye to the brain) is now included as a fifth anatomical location for assessing evidence of MS.

The revised criteria also include new MRI biomarkers, such as the central vein sign and paramagnetic rim lesions. These features can help doctors distinguish MS-related abnormalities from other conditions.

These changes may help doctors diagnose MS earlier and more accurately. 

If you experience persistent or recurring neurological symptoms, seek medical advice. Your doctor can assess your symptoms and, if applicable, refer you to a neurologist. 

Sudden weakness, vision loss, or difficulty speaking requires urgent medical assessment, Allder said.

“Depending on the findings, investigations may include MRI scans of the brain and spinal cord, blood tests, and, in some cases, a lumbar puncture,” Allder noted. 

“It is important that results are interpreted alongside symptoms and examination findings, as no single test should determine the diagnosis in isolation.”

Allder said that if you’re unsure about a diagnosis, you can ask your neurologist what evidence supports it and whether alternative health conditions have been considered. 

“A second opinion or follow-up assessment may be appropriate. The priority is an accurate diagnosis that leads to the right treatment and support,” Allder said.