However, she has now revealed that doctors have told her she does not appear to have the condition, leaving the cause of her ongoing symptoms uncertain.
Applegate shared the news during her return to the MeSsy podcast, which she co-hosts with fellow actress Jamie-Lynn Sigler, who also lives with MS. The latest episode, released on Tuesday, marked her return after several months away from the show.
Despite receiving the unexpected news, Applegate said her health has not improved. She continues to experience serious mobility problems, and her doctors are still working to understand what is causing her symptoms.
“I haven’t gotten better, Jamie! If anything, I’ve gotten worse. So I’m back at square one, where I don’t know what’s going on with me,” Applegate said during the episode.
Her experience also highlights a broader medical challenge: diagnosing MS can be complicated, and some people initially told they have the disease later discover that another condition better explains their symptoms.
Christina Applegate’s Unexpected MS Diagnosis Update
Applegate first publicly revealed her multiple sclerosis diagnosis in August 2021, while she was filming the final season of Netflix’s Dead to Me.
She had started experiencing symptoms earlier that year, including tingling in her limbs. Over time, her difficulties with movement became more severe, and she sometimes needed a wheelchair to get around.
Although she completed her work on the series, Applegate subsequently stepped away from on-screen acting as she focused on managing her health.
In March 2024, she launched the MeSsy podcast with Sigler, who is widely recognised for her role in The Sopranos. The show features conversations about living with MS, chronic illnesses and the personal challenges that can accompany long-term health conditions.
Earlier this year, the podcast took a short break while both hosts focused on their book projects. Applegate was also hospitalised in late March, although the reason for her hospital stay was not publicly disclosed in the original report.
When the podcast resumed in April, Sigler continued hosting episodes on her own. Applegate remained absent for several months before returning to explain that part of her time away had been spent processing the news that her original diagnosis might have been incorrect.
‘You Don’t Have MS,’ Her Doctor Told Her
During the podcast, Applegate described the moment her doctor informed her that she did not have multiple sclerosis.
“[My doctor] came into my room and said, ‘Congratulations, you don’t have MS,’” she recalled.
Rather than feeling relieved, Applegate said she struggled to process the announcement. While other people around her were happy to hear the news, she was left facing an uncomfortable reality: her symptoms remained, but the explanation she had relied on was no longer certain.
Her experience illustrates the emotional difficulty of receiving a revised diagnosis, particularly when a person has spent years adjusting to life with a serious illness.
Although ruling out MS may be reassuring in some circumstances, it does not automatically identify the real cause of a patient's symptoms or provide an immediate treatment plan.
For Applegate, the uncertainty surrounding her health remains a major challenge.
What Is Multiple Sclerosis?
Multiple sclerosis is a chronic disease that affects the central nervous system, which includes the brain and spinal cord.
The condition involves damage to myelin, the protective covering around nerve fibres. This damage can interfere with the transmission of signals between the brain and other parts of the body.
Symptoms vary from one person to another and may include:
- Numbness or tingling in the arms and legs
- Muscle weakness
- Pain and unusual sensations
- Problems with balance and coordination
- Difficulty walking
- Changes in vision
- Fatigue and other neurological difficulties
Some people experience symptoms in separate episodes, followed by periods of improvement. Others develop symptoms that gradually become more severe over time.
Researchers believe MS develops through a combination of genetic, environmental and immune-system factors. Studies have also found a strong association between Epstein-Barr virus infection and the development of MS, although the relationship is complex and infection alone does not mean someone will develop the disease.
Because its symptoms can overlap with those of other medical conditions, establishing the correct diagnosis is essential.
Why Can Multiple Sclerosis Be Misdiagnosed?
Diagnosing MS is not always straightforward. Doctors consider a patient's medical history, neurological symptoms, MRI scans and other test results when assessing whether the disease is present.
MRI scans can reveal lesions in the brain or spinal cord that may support an MS diagnosis. However, similar findings can sometimes occur in other conditions, and there is no single test that confirms every case of MS.
Doctors therefore need to assess the full clinical picture and determine whether the findings meet established diagnostic criteria. They must also consider other possible explanations for a patient's symptoms.
During the second part of the podcast's return, Applegate and Sigler spoke with Marwa Kaisey, an associate professor in the neurology department at Cedars-Sinai Medical Center, about the issue of MS misdiagnosis.
Kaisey discussed research published in 2019 that examined patients who had previously been diagnosed with MS. The study found that approximately 18% of patients referred to two specialist clinics had been misdiagnosed.
Some of those patients had already begun treatments intended to manage MS or slow its progression before doctors identified another explanation for their symptoms.
The findings demonstrate why careful assessment and specialist review can be important when a diagnosis is uncertain.
Which Conditions Can Be Mistaken for MS?
Several medical conditions can cause symptoms that resemble multiple sclerosis or produce findings that complicate the diagnostic process.
According to the research discussed on the podcast, some of the alternative diagnoses identified among patients included:
- Migraine: A neurological condition that can cause recurring headaches and other symptoms, sometimes including sensory disturbances.
- Radiologically isolated syndrome: A condition in which MRI scans show abnormalities associated with demyelination, even though a person has not experienced the typical symptoms required for an MS diagnosis.
- Spondylopathy: A term referring to disorders affecting the spine that may contribute to neurological symptoms.
- Neuropathy: Damage or dysfunction involving peripheral nerves, which can cause numbness, tingling, pain or weakness.
The study reported that migraine accounted for 16% of alternative diagnoses, followed by radiologically isolated syndrome at 9%, spondylopathy at 7% and neuropathy at 7%.
These figures relate to the patients examined in the study and should not be interpreted as rates for everyone diagnosed with MS.
The findings nevertheless underline the importance of considering other conditions before confirming a diagnosis.
Christina Applegate Says Her Daily Struggles Have Not Changed
Although learning that she does not have MS may have changed how doctors understand her condition, Applegate said it has not made her physical difficulties disappear.
She explained that she still needs a wheelchair when visiting her doctor's office and cannot easily walk from her car to the examination room.
“Nothing magical happened when she said, ‘You don’t have MS.’ Nothing magical happened,” she said.
Applegate described her situation as essentially unchanged, despite the possibility that the explanation for her symptoms may be different.
Her comments highlight an important distinction between receiving a diagnosis and finding an effective way to manage an illness. Even when doctors rule out one condition, patients may continue to experience debilitating symptoms while further investigations take place.
At present, the cause of Applegate's ongoing health problems remains unclear based on the information shared in the podcast.
How Many People Have Multiple Sclerosis?
Multiple sclerosis affects people around the world, with potentially significant effects on mobility, daily activities and quality of life.
The National Multiple Sclerosis Society has estimated that nearly one million people in the United States live with MS. Estimates cited in the original report place the worldwide total at approximately three million.
These figures are estimates rather than a precise count of every person affected by the disease.
Applegate's experience has also brought attention to the difficulties patients can face when symptoms persist despite changes in their diagnosis.
Her story serves as a reminder that medical diagnoses sometimes need to be reassessed as new information becomes available. When symptoms remain unexplained, continued medical evaluation can help doctors investigate other possible causes and determine the most appropriate care.
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