One in Five MS Patients Misdiagnosed

April 18, 2019

Almost 1 in 5 patients with an established diagnosis of multiple sclerosis (MS) were found most likely to not have the condition, in a new study.

For this analysis, all new patients referred with an established diagnosis of MS to two academic MS referral centers in Los Angeles over a 12-month period were reexamined to establish whether the diagnosis was correct. Results showed that of the 241 patients, 17% at Cedars-Sinai and 19% at University of California Los Angeles (UCLA) were identified as having been misdiagnosed, did not fulfil contemporary McDonald 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," lead author Marwa Kaisey, MD, Cedars-Sinai Medical Center, Los Angeles, commented to Medscape Medical News.

The study is published in the May issue of Multiple Sclerosis and Related Disorders; the results were also presented last fall at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018 Congress.

"Misdiagnosis of MS in this study was associated with considerable patient risk and immense healthcare cost," Kaisey and colleagues write.

"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," they noted. In addition, they report that 72% of those misdiagnosed were prescribed unnecessary disease-modifying treatments with 28% exposed to 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%).

"We knew misdiagnosis of MS was a phenomenon, as we often see it in the clinic," Kaisey explained. "But with this study we wanted to try and quantify it and see which patients in particular are being misdiagnosed."

She says 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," Kaisey 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, Kaisey replied: "I would say as a first step they should always confirm the diagnosis — do not take it as 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."

She 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," she 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 for Medscape Medical News, Jeffrey Cohen, MD, of the Cleveland Clinic's Mellen Center for Multiple Sclerosis in Ohio, 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.

Cohen suggested that there were several contributing factors, including the wide range of manifestations that MS can cause, variability from patient to patient, lack of a single diagnostic test, and impetus to make the diagnosis early so as 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.

Kaisey and colleagues say that, to their knowledge, this is the only contemporary study to evaluate a cohort of patients with an established diagnosis of MS for the frequency of MS misdiagnosis.

"Although several prior studies have considered the frequency of MS misdiagnosis, they were either conducted prior to routine clinical use of MRI, or included patients with a possible MS diagnosis in addition to those misdiagnosed," the authors write.

In the current study, clinical syndromes and radiographic findings atypical for MS were both associated with misdiagnosis. 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.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Kaisey has received consulting fees from Celgene and Biogen, not related to the subject of this study.

Multiple Sclerosis and Related Disorders. Published online February 1, 2019.  Abstract.

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