In a new study, almost 1 in 5 patients with an established diagnosis of multiple sclerosis (MS) were found most likely to not have the condition.
For this analysis, all new patients referred with an established diagnosis of MS to two academic MS referral centers over a 12-month period were reexamined to establish whether the diagnosis was correct. Results showed that of the 241 patients, 17% at hospital 1 and 19% at hospital 2 were identified as having been misdiagnosed, did not fulfill contemporary McDonald’s Criteria, and more likely had an alternate diagnosis.
“These results may not come as a surprise to most MS specialists, but these figures will probably be shockingly high for most neurologists and patients,” said the lead author of hospital 1.
Misdiagnosis of MS in this study was associated with considerable patient risk and immense healthcare costs. The patients in our study suffered the consequences of misdiagnosis for an average of 4 years. One patient lived with her misdiagnosis for 20 years. In addition, 72% of those misdiagnosed were prescribed unnecessary disease-modifying treatments, with 28% exposed to a risk of progressive multifocal leukoencephalopathy (PML), an often-fatal infection.
Five patients additionally received off-label rituximab, cyclophosphamide, and mycophenolate.
The misdiagnosed group received approximately 110 patient-years of unnecessary MS disease-modifying therapy in total, which would have had an estimated cost of $10 million.
The most common alternative diagnoses for the misdiagnosed patients in this study were migraine (16%), radiologically isolated syndrome (9%), spondylopathy (7%), and neuropathy (7%).
The results suggest that doctors diagnosing MS are not following the diagnostic criteria thoroughly enough. “It is difficult because the diagnostic criteria can be cumbersome and sometimes are not definitive. For example, sometimes it can be difficult to distinguish whether white spots on the MRI are due to MS or another neurological condition,” the lead author said. “The most common condition misdiagnosed as MS in this study was migraine, which can also cause white spots on the MRI in some cases.”
Asked what advice she would give to neurologists when diagnosing MS or seeing a new patient who already has the diagnosis, the lead author replied: “I would say as a first step, they should always confirm the diagnosis—do not take it at face value if a patient is referred with MS.” This can be very time-consuming as it means completely reevaluating the patient, but it is worth it. And I would also advise that neurologists should examine the brain MRI themselves and not just rely on the radiologist’s report. “
He hopes that this data will start to change things. “First, it will raise awareness of the problem and it shows that the diagnostic criteria are not being applied appropriately in the real world. And secondly, it highlights the need for more accurate biomarkers for the diagnosis of MS,” he said. “These could include more specific MRI sequences now being developed that can distinguish MS lesions from those caused by other neurological conditions.”
Commenting on the study, Dr. Jeffrey said he was not surprised by the findings. “The potential for MS misdiagnosis has been noted for many years. Previous studies have reported similar rates,” he stated.
Dr. Jeffrey suggested that there were several contributing factors, including the wide range of manifestations that MS can cause variability from patient to patient, the lack of a single diagnostic test, and the impetus to make the diagnosis early to allow treatment to be started.
As discussed in the 2017 McDonald Criteria paper, the main way to avoid misdiagnosis is for clinicians to apply rigor to evaluating the data and applying the criteria, he added.
In the current study, clinical syndromes and radiographic findings atypical for MS were both associated with misdiagnosis. The comorbid autoimmune disease was also associated with misdiagnosis; the authors note that this suggests that such a history may pose a challenge for clinicians or unduly raise concern for MS.
The researchers point out that “an especially concerning finding was that 6 (14%) of the misdiagnosed patients had normal brain and spinal cord imaging and a different group of 6 (14%) had a normal neurologic examination; both characteristics should rouse caution when making a diagnosis of MS.”
A different physician misdiagnosed each patient, suggesting that the issue of misdiagnosis is not limited to a small number of physicians.