SCIScienceExplainer NO. ---

MS misdiagnosis: roughly one in five referrals don't have MS

Peer-reviewed studies suggest roughly one in five people referred to specialist clinics with multiple sclerosis do not have the disease. Here is how MS is diagnosed, which conditions mimic it, and what patients can ask.

By Rowan Ashby Published 21.10.26 13:32 UTC 9 min read

Axial brain MRI scan using a double inversion recovery sequence, with white circles marking cortical and juxtacortical lesions — Alice Favaretto, Davide Poggiali, Andrea Lazzarotto, Giuseppe Rolma, Francesco Causin, Paolo Gallo / Wikimedia Commons / CC BY 4.0 · Source

Key takeaways

Peer-reviewed studies from US academic centres suggest that roughly one in five people referred to specialist clinics with a multiple sclerosis (MS) diagnosis turn out not to have the disease.
A 2019 study of 241 referrals to Cedars-Sinai and UCLA found misdiagnosis rates of 17% and 19%; migraine was the most common correct diagnosis.
Misdiagnosis is costly: in that study, 72% of misdiagnosed patients had been prescribed MS drugs, adding up to about 110 patient-years of unnecessary therapy.
There is no single test for MS. Doctors use the McDonald criteria, which combine symptoms, MRI, spinal fluid tests and, crucially, the exclusion of other conditions.
The newest revision of the criteria, published in The Lancet Neurology in September 2025, adds MRI markers intended to make diagnosis more specific and reduce errors.

Why MS misdiagnosis is in the news

How common is MS misdiagnosis? Peer-reviewed studies suggest roughly one in five people referred to specialist clinics with multiple sclerosis do not have the disease. A 2019 study of 241 referrals to Cedars-Sinai and UCLA found misdiagnosis rates of 17% and 19%.

This explainer does not discuss any individual's medical history. Instead, it looks at what the research says about how common MS misdiagnosis is, why it happens, how the diagnosis is supposed to be made, and what patients can reasonably ask their doctors.

What is multiple sclerosis?

MS is a chronic disease in which the immune system attacks myelin, the protective coating around nerve fibres in the brain, spinal cord and optic nerves. The damage leaves areas of scarring, or lesions, that can disrupt nerve signals. Symptoms vary widely and may include numbness, vision problems, fatigue, weakness, balance difficulties and bladder problems. Many of these symptoms are not unique to MS, which is one reason the disease is hard to pin down.

According to the Atlas of MS, an international effort led by the Multiple Sclerosis International Federation, about 2.8 million people worldwide were living with MS as of the 2020 update. The National MS Society said at the time that nearly 1 million of them live in the United States. Because the disease is common enough to be on doctors' radar, but its symptoms overlap with many other conditions, both missed diagnoses and false diagnoses occur.

How common is MS misdiagnosis?

The most frequently cited figure comes from a study led by neurologist Marwa Kaisey of Cedars-Sinai Medical Center, published in 2019 in the journal Multiple Sclerosis and Related Disorders. The researchers reviewed the records of 241 new patients who arrived at the MS clinics of Cedars-Sinai and UCLA over twelve months already carrying an MS diagnosis. Specialists concluded that 17% of those referred to Cedars-Sinai and 19% of those referred to UCLA did not have MS, or about 18% overall.

An earlier multicentre study, led by Andrew Solomon of the University of Vermont and published in Neurology in 2016, took a different approach. MS specialists at four US academic centres identified 110 patients they judged to have been misdiagnosed with MS, 51 "definitely" and 59 "probably". That study was not designed to measure how often misdiagnosis occurs, but it documented the harm: about a third of those patients had carried the wrong diagnosis for a decade or longer.

Speaking to CBS News this week, Robert Bermel, director of the Cleveland Clinic's Mellen Center for MS, said the largest studies on the question suggest that 15% to 20% of people diagnosed with MS do not actually have it. Kaisey told the same outlet that misdiagnosis is "fairly common".

An important caveat applies. These studies looked at patients referred to specialist academic centres, where people with unusual or doubtful cases tend to end up. The authors of the 2019 study noted that their findings, based on a retrospective review of records, may not represent practice outside Los Angeles or outside academic settings. The true rate across all MS diagnoses is therefore uncertain, and it may be lower in the general population of patients.

Key findings from two peer-reviewed studies of MS misdiagnosis
Measure	Kaisey et al., 2019 (Cedars-Sinai and UCLA)	Solomon et al., 2016 (four US MS centres)
Patients studied	241 referrals with an existing MS diagnosis	110 patients identified as misdiagnosed
Share misdiagnosed	17% (Cedars-Sinai), 19% (UCLA)	Not measured (case series)
Most common correct diagnosis	Migraine (16%)	Migraine (22%)
Other frequent diagnoses	Radiologically isolated syndrome (9%), spondylopathy (7%), neuropathy (7%)	Fibromyalgia (15%), nonspecific symptoms with abnormal MRI (12%), functional/psychogenic disorders (11%), neuromyelitis optica spectrum disorder (6%)
Received MS drugs	72% of misdiagnosed patients	70% (77 patients)
Other harms reported	About 110 patient-years of unnecessary therapy; estimated cost almost US$10 million	33% misdiagnosed for 10+ years; 31% had unnecessary morbidity

Sources: Cedars-Sinai newsroom and AHRQ PSNet summary of Kaisey et al. (2019); PubMed abstract of Solomon et al. (2016); RACGP newsGP.

Why does misdiagnosis happen?

Researchers point to a few recurring problems. The first is over-reliance on MRI. Small white spots on brain scans, known as white matter hyperintensities, are common and can be caused by migraine, high blood pressure, smoking, ageing and other conditions. When such spots are read as MS lesions in a person with vague symptoms, a wrong diagnosis can follow. In the 2016 study, the specialists cited heavy reliance on MRI abnormalities in patients with nonspecific neurological symptoms as a leading contributor.

The second is misapplying the diagnostic rules. The McDonald criteria were designed for people who already have symptoms typical of MS, such as an episode of optic neuritis or spinal cord inflammation. Applying them to people with atypical complaints, such as general fatigue or widespread pain, increases the risk of error. The 2019 study found that misdiagnosis was associated with clinical syndromes and scan findings that were atypical for MS.

The third is the absence of a definitive biomarker. Unlike some diseases, MS cannot be confirmed by one blood test. Most of its common mimics, including migraine and fibromyalgia, also lack a single diagnostic test, which makes careful clinical judgement essential.

How MS is diagnosed: the McDonald criteria

Doctors use the McDonald criteria, an internationally agreed set of rules first published in 2001 and revised several times since. The central idea is to find evidence that damage to the central nervous system is spread out in two ways:

Dissemination in space: lesions in more than one part of the central nervous system.
Dissemination in time: evidence that damage has occurred at different points in time, shown by new attacks, new lesions on follow-up MRI, or certain findings in the spinal fluid.

Just as important is the rule that there must be "no better explanation" for the findings. In other words, the criteria are meant to be used only after other conditions have been reasonably ruled out.

The tools typically involved include:

Clinical history and neurological examination, looking for symptoms and signs typical of demyelinating disease.
MRI of the brain and spinal cord, often with contrast dye to show active inflammation.
Lumbar puncture to test cerebrospinal fluid for oligoclonal bands, proteins that indicate immune activity in the central nervous system.
Evoked potentials or optical coherence tomography to assess the optic nerve.
Blood tests to exclude conditions that can look like MS, such as vitamin deficiencies, infections and other autoimmune diseases.

What changed in the 2024 revision

The latest update, known as the 2024 revisions, was presented at the ECTRIMS congress in 2024 and published in The Lancet Neurology in September 2025 by an international panel convened by ECTRIMS and the US National MS Society. Its stated aims include reducing misdiagnosis and speeding up treatment. Key changes reported by the Multiple Sclerosis International Federation and Practical Neurology include:

The optic nerve is now counted as a fifth anatomical region for showing dissemination in space.
Two MRI markers, the central vein sign and paramagnetic rim lesions, can serve as supportive evidence. The central vein sign, a small vein running through the middle of a lesion, is considered more typical of MS than of many mimics.
The kappa free light chain index in spinal fluid can be used as an alternative to oligoclonal bands.
Dissemination in time is no longer required in some cases where other supportive evidence is present.
Specific guidance was added for people over 50 and for those with other health conditions, groups in whom MS is harder to distinguish from other causes of brain changes.

Some reviewers have noted that detecting the new MRI markers depends on specific scan sequences and may take extra time, so access may vary between hospitals.

Conditions that commonly mimic MS

Based on the studies above and comments from specialists quoted by CBS News, the conditions most often mistaken for MS include:

Migraine, which can cause neurological symptoms and is associated with small white matter spots on MRI.
Fibromyalgia and other chronic pain or fatigue syndromes.
Radiologically isolated syndrome, in which MRI shows MS-like lesions in a person without typical symptoms.
Spine disease and peripheral neuropathy, which can cause numbness, weakness or tingling.
Functional neurological disorders, in which symptoms are real but are not caused by structural nerve damage.
Neuromyelitis optica spectrum disorder, a separate autoimmune condition with its own blood test and treatments.
Small vessel disease linked to high blood pressure, smoking or ageing; thyroid and sleep disorders; and rheumatological conditions.

Questions patients can ask

None of this means that people with an MS diagnosis should stop treatment on their own; doing so can be risky if the diagnosis is correct. Specialists quoted by CBS News suggested that patients whose symptoms are not improving, or who have doubts, consider a second opinion from an MS specialist. Questions that can help include:

Which version of the McDonald criteria was used, and how do my findings meet it?
Were my symptoms typical of MS, and what objective evidence of nerve damage was found on examination?
Were my MRI scans reviewed by a neuroradiologist or MS specialist, and was the spinal cord imaged?
Was a spinal fluid test done, and what did it show?
Which other conditions were considered and ruled out, and how?
Could newer MRI markers such as the central vein sign help clarify my case?

The National MS Society maintains a directory of MS care centres and specialists that patients can use to find a second opinion.

Unusual diagnoses can also come from outside neurology. In France, doctors identified the first documented human infection with Shamonda virus, a livestock virus spread by midges, in a severely immunocompromised patient in Lyon; see our report on the first human Shamonda case.

What it means

The evidence suggests that MS misdiagnosis is not rare, at least among patients who reach specialist centres, and that its consequences can be serious: years of unnecessary and sometimes risky medication, high costs, and delayed treatment for the condition a person actually has. At the same time, the figures come from a limited number of studies at academic centres, and the overall rate across all patients remains uncertain.

The 2024 McDonald revisions reflect an effort by the field to tighten diagnosis, especially in how brain lesions are interpreted. Whether they reduce misdiagnosis in everyday practice will depend on how widely the new imaging techniques become available and how consistently doctors, including those who are not MS specialists, apply the rule that there must be no better explanation. For patients, the practical lesson is that an MS diagnosis rests on a combination of evidence, and it is reasonable to ask how that evidence fits together.

Frequently asked questions

How often is multiple sclerosis misdiagnosed?

A 2019 study of 241 patients referred to Cedars-Sinai and UCLA with an MS diagnosis found that 17% and 19% respectively did not have MS. Specialists say the largest studies suggest 15% to 20%, although these figures come from academic referral centres and may not reflect all patients.

What conditions are most often mistaken for MS?

Migraine is the most common, followed by fibromyalgia, radiologically isolated syndrome, spine disease, peripheral neuropathy, functional neurological disorders and neuromyelitis optica spectrum disorder.

Is there a single test for MS?

No. Doctors apply the McDonald criteria, which combine symptoms, neurological examination, MRI of the brain and spinal cord, and sometimes spinal fluid tests, after ruling out other explanations.

What changed in the 2024 McDonald criteria?

The revision, published in The Lancet Neurology in September 2025, adds the optic nerve as a fifth region, allows the central vein sign and paramagnetic rim lesions as supportive MRI evidence, and accepts the kappa free light chain index as an alternative to oligoclonal bands.

Should I stop MS treatment if I doubt my diagnosis?

Specialists advise against stopping treatment on your own. A second opinion from an MS specialist is the recommended step if symptoms do not improve or the diagnosis is in doubt.