When I was a child I became very sick. I remember the doctor looking at me and telling me there was nothing wrong with me.
We left the doctor’s room in confusion. I went home to lie on my bed, feeling absolutely terrible and disillusioned by the doctor’s words.
The next day my mother took me for a second opinion. I was told that I had tick bite fever.
When I read about Christina Applegate’s misdiagnosis with Multiple sclerosis (MS) I could hear the actress’ disillusionment and overwhelm in her words. I am not sure the public can fully comprehend how devastating and disorienting this news must have been for her. She must’ve felt tremendously confused by the doctor’s announcement.
While not having MS is good news for Christina, she has spent the past few years mentally coming to terms with a diagnosis which no longer fits, even though her symptoms persist.
When she was diagnosed in 2021, she had to readjust to a new identity which was forged through pain and tears, now she was left at square one, trying to understand the cause of her debilitating symptoms.
There are so many emotions tied to a diagnosis and when this is incorrect, it is often, as in the case of Christina, difficult to just shake off. So I take my hat off to her for handling a diagnosis and subsequent misdiagnosis of MS with such courage and determination to make meaning of both situations.
I have subsequently read that MS can be notoriously difficult to diagnose.
Speaking on her podcast, MeSsy, which she co-hosts with fellow actress Jamie-Lynn Sigler, she described the emotional shock of being told she did not have MS. Rather than feeling relieved, she was left facing another difficult question. This is, if MS was not responsible for her symptoms, what was?
Her experience illustrates an important issue in modern neurology. This is that MS is not always straightforward to identify, and several other diseases and conditions can produce remarkably similar symptoms. It also highlights why a diagnosis should never rest on one symptom, one scan or an assumption.
Why multiple sclerosis is so difficult to diagnose?
MS is an autoimmune disease affecting the central nervous system, which consists of the brain, spinal cord and optic nerves. In people with MS, the immune system mistakenly attacks myelin, the protective covering around nerve fibres. This damages the communication pathways between the brain and the rest of the body.
Depending on where the damage occurs, patients can experience numbness, tingling, muscle weakness, problems with balance and coordination, visual disturbances, bladder dysfunction, pain and severe fatigue. Some experience cognitive difficulties, including problems with concentration and memory.
The difficulty is that none of these symptoms is exclusive to MS. They can occur in a wide range of neurological, inflammatory, autoimmune and metabolic conditions.
There is also no single definitive test which can establish an MS diagnosis. Neurologists use a combination of medical history, neurological examinations, magnetic resonance imaging (MRI), blood tests and, in some cases, a lumbar puncture to examine cerebrospinal fluid.
MRI scans are particularly important because they can identify lesions, or areas of damage, in the brain and spinal cord. However, the presence of white matter abnormalities does not automatically mean someone has MS.
Migraine, ageing, vascular disease and other neurological conditions can also produce white matter changes on an MRI. When these findings are interpreted without sufficient supporting clinical evidence, the risk of misdiagnosis increases.
According to a 2023 review published in The Lancet Neurology, accurate diagnosis requires doctors to consider alternative explanations carefully, including conditions that can produce similar symptoms and imaging abnormalities.
The problem is not necessarily that the technology is inadequate. It is that the evidence must be interpreted in the context of the individual patient.
How often is MS misdiagnosed?
Although there is no universally agreed global figure, research suggests that MS misdiagnosis is more common than many people realise. A 2024 systematic review and meta-analysis published in the journal Multiple Sclerosis examined 62 studies, with 24 included in the statistical analyses. Researchers found that reported MS misdiagnosis rates ranged from 5% to 41%.
The pooled analysis of six studies, involving 1 621 people, estimated that approximately 15% of patients diagnosed with MS had been incorrectly diagnosed.
In other words, the findings suggest that roughly one in seven people in the populations studied may have received an incorrect MS diagnosis.
The researchers also identified a significant problem in the opposite direction: MS can be missed or diagnosed late. Their analysis estimated a pooled underdiagnosis rate of 36% across four studies, although this figure came from a separate group of studies and should not be confused with the rate of incorrect diagnoses.
The findings demonstrate the complexity of identifying the disease accurately. Some patients are incorrectly told they have MS, while others experience prolonged delays before their symptoms are correctly identified.
An earlier 2019 study by researchers at Cedars-Sinai Medical Center and the University of California, Los Angeles, provides another striking example. Of 241 patients referred to the two specialist centres with an established MS diagnosis, 17% at Cedars-Sinai and 19% at UCLA were found to have been misdiagnosed.
That is almost one in five.
The study, published in Multiple Sclerosis and Related Disorders, identified migraine, radiologically isolated syndrome, spinal conditions and peripheral neuropathy among the alternative explanations.
Importantly, the researchers found that patients who had been misdiagnosed had collectively received approximately 110 patient-years of unnecessary disease-modifying MS treatment.
These findings are particularly concerning because MS medications can have significant side effects and may suppress or alter immune system activity. Treating someone for a disease they do not have can expose them to unnecessary risks while delaying the investigation of the actual problem.
The 2024 meta-analysis is available through PubMed .
Which diseases and conditions can mimic MS?
One of the biggest challenges for neurologists is that several unrelated conditions can affect the same neurological pathways as MS.
Migraine is among the most frequently reported alternatives. People with migraine can experience visual disturbances, tingling, numbness, dizziness and neurological symptoms. Some also have white matter lesions visible on MRI, which can be mistaken for MS-related damage.
Fibromyalgia is another potential source of confusion. It is associated with widespread pain, fatigue, sleep disturbances and cognitive difficulties, sometimes described as brain fog. Although fibromyalgia does not cause the characteristic demyelinating lesions of MS, overlapping symptoms can complicate an initial assessment.
Neuromyelitis optica spectrum disorder (NMOSD) is a particularly important condition to distinguish from MS. It is an autoimmune inflammatory disorder that primarily affects the optic nerves and spinal cord. Patients can experience severe visual impairment, muscle weakness, sensory changes and bladder problems. The conditions require different treatment approaches, making accurate identification essential.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is another inflammatory neurological disorder that can resemble MS. It can cause optic neuritis, inflammation of the spinal cord and other neurological symptoms. Specific antibody testing can help distinguish it from MS.
Vitamin B12 deficiency is an important metabolic mimic. Vitamin B12 is essential for healthy nerve function, and a deficiency can cause numbness, tingling, weakness, balance problems and difficulties walking. If left untreated, neurological damage can become permanent. Copper deficiency can produce similar spinal cord and nerve problems.
Autoimmune diseases, including systemic lupus erythematosus and Sjögren’s syndrome, can also affect the nervous system. These conditions may cause neurological symptoms and, in some cases, MRI abnormalities that complicate the diagnostic process.
Other possibilities include Lyme disease, sarcoidosis, spinal cord compression, cervical spondylosis, peripheral neuropathy and certain vascular conditions affecting the brain.
The importance of getting the diagnosis right
MS diagnosis has evolved considerably over the years. Neurologists use internationally recognised McDonald criteria to establish whether a patient’s symptoms and test results are consistent with the disease.
The criteria were substantially revised in 2024, with the updated recommendations published in 2025. They incorporate advances in MRI technology and biomarkers, including the central vein sign, which can help distinguish MS lesions from abnormalities associated with other conditions.
The updated criteria also recognise the optic nerve as an additional anatomical location for evidence of MS and allow certain laboratory findings, including kappa free light chains in cerebrospinal fluid, to provide additional diagnostic support.
These developments are intended to improve diagnostic accuracy and reduce unnecessary delays. However, they do not eliminate the need for clinical judgement or careful consideration of alternative diagnoses.
For patients, one important lesson is that a diagnosis of MS should be supported by a consistent pattern of clinical and investigative findings. If symptoms do not fit the expected pattern, MRI results are inconclusive or treatment is not producing the anticipated response, further assessment may be warranted.
For Christina, the news of a misdiagnosis has not made her physical difficulties disappear. She has continued to describe problems with mobility and the need to use a wheelchair when attending medical appointments. Her doctors are now investigating other possible explanations.
It is important to emphasise that no alternative diagnosis has been publicly established. Her experience should not be interpreted as evidence that her symptoms were imagined or that the original medical investigations were necessarily unreasonable.
Rather, it demonstrates why medicine must remain open to reconsidering an initial conclusion when new evidence emerges.
The consequences of an incorrect diagnosis extend beyond treatment. Patients may spend years taking medication they do not need, experience avoidable side effects and miss opportunities to receive appropriate treatment for their actual condition.
Christina’s story is a reminder that a diagnosis is not simply a label. It influences treatment decisions, personal identity, emotional wellbeing and the way patients understand their future.
(Photo: abc13.com)