Dr Marwa KaiseyMarwa Kaisey, MD
Results from a recent study of patients with a multiple sclerosis (MS) diagnosis suggests that up to 20% of patients carrying this established diagnosis do not meet the full McDonald criteria and therefore may have an alternate diagnosis.1

All told, 241 patients were referred to clinicis at Cedars-Sinai and the University of California Los Angeles (UCLA) with a diagnosis of MS, though 17% and 19%, respectively, were identified as misdiagnosed. The most common alternative diagnoses were migraine (16%), radiologically isolated syndrome (9%), spondylopathy (7%), and neuropathy (7%).

“This frequency of MS misdiagnosis is concerning and has important implications for the presumed 2.3 million people living with MS worldwide” the investigators, led by Marwa Kaisey, MD, of Cedars-Sinai, wrote. “Misdiagnosis appeared to be associated with misapplication of MS diagnostic criteria, specifically overreliance on—or misinterpretation of—radiographic findings in patients with syndromes atypical for MS.”

Kaisey and colleagues noted that one of the difficulties in diagnosing MS is that a number of syndromes present as mimics, thus the proper application of the 2017 McDonald criteria relies on utilizing a number of clinical assessments. Of course, some additional education on the criteria’s proper use could alleviate some challenges, but the criteria have some limitations in real-world application, as the study points out.

“Highly specific and objective biomarkers for MS are an important unmet need in ensuring accurate diagnosis,” the investigators detailed.

The study’s cohort consisted of 115 new patients at Cedars-Sinai and 126 at UCLA, all with an established prior diagnosis of MS upon referral. Upon confirming a diagnosis with the McDonald criteria and independent chart review, 3 and 2 patients, respectively, were excluded with a proper diagnosis of clinically isolated syndrome (CIS), while 93 and 100 patients, respectively, were deemed as properly diagnosed with MS.

Of the remaining 43 patients who were designated as misdiagnosed, 19 were from Cedars-Sinai and 24 were from UCLA. Notably, there were no discrepancies in which cases the MS specialists identified as misdiagnosed.

Daniel Ontaneda, MD, of Cleveland Clinic Mellen Center for MS, who was not part of the study, recently told NeurologyLive® at the Americas Committee for Treatment and Research in MS (ACTRIMS) forum that the field is facing a “bit of a problem” with misdiagnosis. In addition to the actual implications of improperly diagnosing the patient, the cost implications are significant.

“It's about $48.4 billion in costs to our health care system to take care of MS patients, and about anywhere between 30% or 40% of that cost is actually associated with the cost of therapies themselves,” Ontaneda said. “If you think that 20% of patients who have a misdiagnosis, that's a considerable amount of people that are one, causing expenses to the healthcare system and two, being exposed to risks associated with our disease-modifying treatments that they shouldn't be exposed to.”

Misdiagnosis of MS in the current study was also related to immense health care costs and patient risks. On average, Kaisey and colleagues noted that their patients lived with their misdiagnosis for an average of 4 years, with 1 patient going as long as 20 years without being properly diagnosed. With regard to costs, the estimated costs of the total of 110 patient-years equated to $10 million. As for treatment, 72% of patients were prescribed unnecessary disease-modifying treatments, with 28% exposed to the risk of progressive multifocal leukoencephalopathy (PML).

“By comparison, in a 2016 study of 110 misdiagnosed patients, a third carried a misdiagnosis for ten years or more; 70% received therapy with 48% of those patients exposed to PML risk,” they wrote.

Ultimately, the group identified a pair of limitations to the study: one, that the analysis was based in retrospective chart review methodology, and that the findings may not be completely representative of practices outside of the Los Angeles and the academic setting, due to the location and type of the 2 centers included.
REFERENCE
1. Kaisey M, Solomon AJ, Luu M, Giesser BS, Sicotte NL. Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Dis. 2019;30:51-56. doi: 10.1016/j.msard.2019.01.048.