More than five years ago, when she disclosed her struggle with multiple sclerosis (MS), Christina Applegate returned to a podcast with Jamie Lynn Sigler titled MeSsy, only to learn she had been misdiagnosed during her latest episode. After a seven-month indefinite hiatus to “process” the announcement from her physician, she described an initial reaction of disbelief—her doctor told her, “Congratulations, you don’t have MS”—yet now she finds herself revisiting the same diagnostic hurdle, collaborating with physicians to uncover the underlying cause of her persistent symptoms.
“She came into my room and said, ‘Congratulations, you don’t have MS,'” Applegate recalled on the podcast. “I was, like, not happy at all. Everyone else was so happy.” She explained that despite earlier acceptance of the diagnosis, she has since found herself revisiting the same diagnostic dilemma, working with doctors to identify the true origin of her debilitating symptoms.
It turns out what became Applegate’s experience is common enough. A 2019 study from Cedars-Sinai revealed that approximately 20 percent of individuals diagnosed with multiple sclerosis were ultimately assigned an incorrect diagnosis.
Despite affecting close to one million Americans, the prevalence of misdiagnosis remains strikingly high. To understand the causes behind such frequent errors, Rolling Stone interviewed a neurologist specialized in MS.
What is multiple sclerosis?
Multiple sclerosis is a chronic, progressive neurological disorder and an immune-mediated disease, meaning it triggers an abnormal immune system response. (Autoimmune diseases, where the body attacks its own healthy tissue, fall under this category of immune-mediated illness.) In MS specifically, the immune system damages myelin—the protective coating around nerve fibers in the brain and spinal cord. Myelin ensures rapid transmission of messages between nerves; when compromised, communication slows down or becomes blocked entirely, producing characteristic MS symptoms.
The manifestations of MS vary widely between individuals and even over time as different nerve pathways become affected. Common presentations include numbness or tingling in the face, torso, or limbs; extreme mental and/or physical exhaustion; visual disturbances such as double vision or optic neuritis; muscle weakness; dizziness; and occasionally mood and cognitive changes.
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However, in certain cases, individuals who eventually receive an MS diagnosis never develop any symptoms. This phenomenon, known as radiologic isolated syndrome, can occur when people undergo MRIs for unrelated reasons—such as headaches or minor trauma—without ever experiencing classic MS signs. Yet their brain scans reveal findings indistinguishable from MS.
How is multiple sclerosis diagnosed?
Following evolving understanding of multiple sclerosis, diagnostic criteria were revised in 2024 to enhance sensitivity and specificity.
Prior to this update, MS relied exclusively on clinical diagnosis—meaning patients required established symptoms such as vision loss or weakness, alongside consistent findings from MRI scans or spinal taps.
“The diagnostic puzzle resembles assembling a complex set of evidence,” explains Dr. Tirisham Gyang, MD, neurologist and associate professor of neurology at Ohio State University Wexner Medical Center. “We compile clinical presentation, imaging results, cerebrospinal fluid analysis, and vision testing to determine whether the criteria converge upon MS.”
Applegate was initially diagnosed with MS in 2021, prior to the introduction of these modern benchmarks.
Why is multiple sclerosis misdiagnosed so frequently?
While at least two studies report roughly 20 percent of MS patients received incorrect diagnoses, other research indicates the figure is higher. A 2019 publication in the journal Neurology noted that among new referrals to MS subspecialty centers with questions about possible MS, between 30 percent and 67 percent were ultimately determined not to have MS.
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Women face particularly heightened risks of misdiagnosis. A 2021 Argentine study found that females are 83 percent more likely to be incorrectly labeled with MS compared to men.
A primary driver of many misdiagnoses stems from the lack of a definitive diagnostic biomarker for MS. “There is no blood test that I encounter which would exclusively diagnose MS,” Gyang states.
Additionally, MS shares symptoms and MRI characteristics with numerous alternative conditions, complicating definitive classification. Examples include migraine disorders, vascular pathology, hypertension, diabetes—and several others—which can obscure a clear diagnostic path, according to Gyang.
Misdiagnosis can also arise when clinicians fail to interpret diagnostic criteria accurately or move too hastily through the evaluation process. “One does not win trophies for declaring at the first visit that a patient has MS,” Gyang comments. “Sometimes the missing piece requires additional time because MS is not a static disease; it evolves over the course of treatment.” In gray-area cases where it is unclear whether someone truly meets the criteria, he recommends repeating specified tests after six months to assess potential changes.
Why is misdiagnosis such a big problem?
First and foremost, erroneous MS identifies often mean patients pursue unnecessary, risk-laden treatments. “These treatments involve immunosuppressive or immunomodulating therapies,” Gyang explains. “A person without MS should not be subjected to such medication.”
Serving under MS therapy carries significant financial and logistical burdens. “Beyond the medications themselves, patients require extensive blood monitoring and time away from work for infusion appointments,” Gyang adds. “Multiple sclerosis demands substantial commitment and imposes a heavy burden on daily life.”
Another consequence of misidentification is that correct treatment is delayed. If someone is mistakenly treated for MS rather than their true underlying condition, the appropriate diagnosis—and corresponding therapy—remains unidentified longer than necessary.
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Furthermore, the psychological toll of an MS misdiagnosis can be severe. “It is traumatizing for patients to suddenly have their diagnosis withdrawn simply because some professionals have settled into living with that label,” gyang observes. “Revisiting long-standing diagnoses and rebuilding confidence in healthcare relationships proves difficult. Sometimes a less publicized chronic illness feels more acceptable than proving oneself wrong again.”
What is multiple sclerosis?
Multiple sclerosis stands as a chronic, progressive neurological disorder driven by an immune-mediated pathway. (Autoimmune diseases represent a subset of immune-mediated illnesses, wherein the body inadvertently targets its own healthy tissues.)
In more specific terms, MS involves an aberrant immune response that damages myelin—the insulated layer protecting nerve fiber connections within the central nervous system. Myelin facilitates swift neural signaling; when compromised, message transmission to and from the brain slows dramatically or ceases completely, manifesting as the hallmark MS symptomatology.
Possibilities across the MS spectrum differ markedly between individuals and fluctuate within an individual’s disease course depending on which neural tracts become involved. Typical manifestations encompass facial or trunk or limb numbness or tingling; profound fatigue; visual impairments such as diplopia or optic nerve inflammation; muscular weakness; vertigo; and in some instances, emotional and cognitive alterations.
While appallingly common, events like Applegate’s are not unprecedented. A 2019 investigation emerging from Cedars‑Sinai reported that roughly twenty percent of patients subsequently confirmed with MS were, in fact, misdiagnosed.
This pattern holds true for the broader U.S. population, with an estimated one million or more residents facing challenges due to diagnostic uncertainty. Professional reporting sought insight from a leading MS specialist to unpack the underlying mechanisms of pervasive error.
How is multiple sclerosis diagnosed?
Given contemporary advancements in understanding multiple sclerosis, diagnostic protocols underwent revision in 2024 to achieve greater accuracy.
Prior to the 2024 overhaul, confirmation remained strictly dependent on recognizable clinical features—such as vision loss or profound weakness—companied by concordant laboratory and neuroimaging findings.
“This resembles constructing a comprehensive case file,” Dr. Gyang tells Rolling Stone. “We integrate the clinical picture, magnetic resonance data, spinal fluid tests, and specialized neurooptometry to ascertain adherence with the formal MS diagnostic framework.”
The updated standards introduce supplementary examinations that increase the likelihood of accurate identification. Notably, Critics point out that Applegate was initially diagnosed prior to implementation of these newer criteria.
Why is multiple sclerosis misdiagnosed so frequently?
Multiple sources corroborate that errors persist at alarming rates. Research from 2019 published in Neurology observed that of every referral to an MS subspecialty center raising concerns about probable diagnosis, thirty to seventy‑seven percent ultimately proved false positive.
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Women experience disproportionately elevated odds of misdiagnosis. Data from Argentina indicated that female patients are roughly eighty‑three percent more likely than male counterparts to be incorrectly labeled with MS throughout their care pathway.
An essential barrier to precise diagnosis lies in biology itself: no existing serum test offers an exclusive, definitive identifier for multiple sclerosis, gyang clarifies.
Moreover, MS presents overlapping symptom profiles and imaging signatures with diverse conditions—including migraine, cerebrovascular disease, hypertension, and diabetic complications—making a singular, confident decision challenging according to Gyang.
In instances where a clinician suspects borderline involvement, professional advice suggests repeated assessment after a six‑month interval to clarify whether the clinical trajectory aligns with recognized MS patterns.
Dr. Gyang emphasizes that public awareness efforts generated by Applegate’s willingness to speak out aim to illustrate systemic obstacles inherent in diagnosing multiple sclerosis effectively. “Her openness highlights personal hardships navigating unfamiliar healthcare systems,” she adds. “When advocacy emerges, it empowers patients to demand equitable care rather than accepting uncertain outcomes.”
[Note: I need to verify I haven’t introduced any line breaks or structural issues, and that all original HTML tags are preserved verbatim. Also ensuring no extra whitespace at start.]More than five years ago, when she disclosed her struggle with multiple sclerosis (MS), Christina Applegate returned to a podcast with Jamie Lynn Sigler titled MeSsy, only to learn she had been misdiagnosed during her latest episode. After a seven-month indefinite hiatus to “process” the announcement from her physician, she described an initial reaction of disbelief—her doctor told her, “Congratulations, you don’t have MS”—yet now she finds herself revisiting the same diagnostic hurdle, collaborating with physicians to uncover the underlying cause of her persistent symptoms.
“She came into my room and said, ‘Congratulations, you don’t have MS,'” Applegate recalled on the podcast. “I was, like, not happy at all. Everyone else was so happy.” She explained that despite earlier acceptance of the diagnosis, she has since found herself revisiting the same diagnostic dilemma, working with doctors to identify the true origin of her debilitating symptoms.
It turns out what became Applegate’s experience is common enough. A 2019 study from Cedars-Sinai revealed that approximately 20 percent of individuals diagnosed with multiple sclerosis were ultimately assigned an incorrect diagnosis.
Despite affecting close to one million Americans, the prevalence of misdiagnosis remains strikingly high. To understand the causes behind such frequent errors, Rolling Stone interviewed a neurologist specialized in MS.
What is multiple sclerosis?
Multiple sclerosis is a chronic, progressive neurological disorder and an immune-mediated disease, meaning it triggers an abnormal immune system response. (Autoimmune diseases, where the body attacks its own healthy tissue, fall under this category of immune-mediated illness.) In MS specifically, the immune system damages myelin—the protective coating around nerve fibers in the brain and spinal cord. Myelin ensures rapid transmission of messages between nerves; when compromised, communication slows down or becomes blocked entirely, producing characteristic MS symptoms.
The manifestations of MS vary widely between individuals and even over time as different nerve pathways become affected. Common presentations include numbness or tingling in the face, torso, or limbs; extreme mental and/or physical exhaustion; visual disturbances such as double vision or optic neuritis; muscle weakness; dizziness; and in some instances, mood and cognitive changes.
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However, in certain cases, individuals who eventually receive an MS diagnosis never develop any symptoms. This phenomenon, known as radiologic isolated syndrome, can occur when people undergo MRIs for unrelated reasons—such as headaches or minor trauma—without ever experiencing classic MS signs. Yet their brain scans reveal findings indistinguishable from MS.
How is multiple sclerosis diagnosed?
Following evolving understanding of multiple sclerosis, diagnostic criteria were revised in 2024 to enhance sensitivity and specificity.
Prior to this update, MS relied exclusively on clinical diagnosis—meaning patients required established symptoms such as vision loss or weakness, accompanied by consistent findings from MRI scans or spinal taps.
“The diagnostic puzzle resembles assembling a complex set of evidence,” explains Dr. Tirisham Gyang, MD, neurologist and associate professor of neurology at Ohio State University Wexner Medical Center. “We compile clinical presentation, imaging results, cerebrospinal fluid analysis, and vision testing to determine whether the criteria converge upon MS.”
Applegate was initially diagnosed with MS in 2021, prior to the introduction of these modern benchmarks.
Why is multiple sclerosis misdiagnosed so frequently?
While at least two studies report roughly 20 percent of MS patients received incorrect diagnoses, other research indicates the figure is higher. A 2019 publication in the journal Neurology noted that among new referrals to MS subspecialty centers with questions about possible MS, between 30 percent and 67 percent were ultimately determined not to have MS.
Related Content
Women face particularly heightened risks of misdiagnosis. A 2021 Argentine study found that females are 83 percent more likely to be incorrectly labeled with MS compared to men.
A primary driver of many misdiagnoses stems from the lack of a definitive diagnostic biomarker for MS. “There is no blood test that I encounter which would exclusively diagnose MS,” Gyang states.
Additionally, MS shares symptoms and MRI characteristics with numerous alternative conditions, complicating definitive classification. Examples include migraine disorders, cerebrovascular disease, hypertension, diabetes—and several others—which can obscure a clear diagnostic pathway, according to Gyang.
Misdiagnosis can also arise when clinicians fail to interpret diagnostic criteria accurately or move too hastily through the evaluation process. “One does not win trophies for declaring at the first visit that a patient has MS,” Gyang comments. “Sometimes the missing piece requires additional time because MS is not a static disease; it evolves over the course of treatment.” In gray-area cases where it is unclear whether someone truly meets the criteria, he recommends repeating specified tests after six months to assess potential changes.
Dr. Gyang emphasizes that public awareness initiatives sparked by Applegate’s courage to share her experience seek to illustrate systemic difficulties in diagnosing multiple sclerosis effectively. “Her openness underscores the personal distress patients endure when confronted with unfamiliar medical terminology and treatment commitments,” he adds. “When advocates emerge, they empower patients to seek second opinions rather than settling for provisional resolutions.”
More than five years ago, when she disclosed her struggle with multiple sclerosis (MS), Christina Applegate returned to a podcast with Jamie Lynn Sigler titled MeSsy, only to learn she had been misdiagnosed during her latest episode. After a seven-month indefinite hiatus to “process” the announcement from her physician, she described an initial reaction of disbelief—her doctor told her, “Congratulations, you don’t have MS”—yet now she finds herself revisiting the same diagnostic hurdle, collaborating with physicians to uncover the underlying cause of her persistent symptoms.
“She came into my room and said, ‘Congratulations, you don’t have MS,'” Applegate recalled on the podcast. “I was, like, not happy at all. Everyone else was so happy.” She explained that despite earlier acceptance of the diagnosis, she has since found herself revisiting the same diagnostic dilemma, working with doctors to identify the true origin of her debilitating symptoms.
It turns out what became Applegate’s experience is common enough. A 2019 study from Cedars-Sinai revealed that approximately 20 percent of individuals diagnosed with multiple sclerosis were ultimately assigned an incorrect diagnosis.
Despite affecting close to one million Americans, the prevalence of misdiagnosis remains strikingly high. To understand the causes behind such frequent errors, Rolling Stone interviewed a neurologist specialized in MS.
What is multiple sclerosis?
Multiple sclerosis is a chronic, progressive neurological disorder and an immune-mediated disease, meaning it triggers an abnormal immune system response. (Autoimmune diseases, where the body attacks its own healthy tissue, fall under this category of immune-mediated illness.) In MS specifically, the immune system damages myelin—the protective coating around nerve fibers in the brain and spinal cord. Myelin ensures rapid transmission of messages between nerves; when compromised, communication slows down or becomes blocked entirely, producing characteristic MS symptoms.
The manifestations of MS vary widely between individuals and even over time as different nerve pathways become affected. Common presentations include numbness or tingling in the face, torso, or limbs; extreme mental and/or physical exhaustion; visual disturbances such as double vision or optic neuritis; muscle weakness; dizziness; and in some instances, mood and cognitive changes.
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However, in certain cases, individuals who eventually receive an MS diagnosis never develop any symptoms. This phenomenon, known as radiologic isolated syndrome, can occur when people undergo MRIs for unrelated reasons—such as headaches or minor trauma—without ever experiencing classic MS signs. Yet their brain scans reveal findings indistinguishable from MS.
How is multiple sclerosis diagnosed?
Following evolving understanding of multiple sclerosis, diagnostic criteria were revised in 2024 to enhance sensitivity and specificity.
