Reevaluation reveals MS misdiagnosis in 1 of 5 patients


Nearly one in five patients with a diagnosis of multiple sclerosis (MS) was found to be misdiagnosed upon further evaluation at specialized academic centers, according to a retrospective study published in Multiple Sclerosis and Related Disorders. Among patients with established MS diagnoses referred to the two academic MS centers, 18% were subsequently diagnosed with migraine, spondylopathy, neuropathy, or radiologically isolated syndrome, according to investigator Marwa Kaisey, MD, and colleagues in the department of neurology at Cedars-Sinai Medical Center, Los Angeles.

Dr. Marwa Kaisey

This frequency of MS misdiagnosis is concerning and has important implications for the presumed 2.3 million people living with MS worldwide.

“This frequency of MS misdiagnosis is concerning and has important implications for the presumed 2.3 million people living with MS worldwide,” said Dr. Kaisey and colleagues.

Those misdiagnosed patients needlessly received about 110 patient-years’ worth of unnecessary MS therapy, including exposure to some agents with known risk of potentially life-threatening infections, the authors said.

The study was based on a review of medical records for new patients evaluated at MS clinics at Cedars-Sinai and the University of California, Los Angeles, over the course of 1 year. As part of the new patient evaluations, specialists verified the MS diagnosis by evaluating whether the McDonald 2010 criteria. If those criteria were not met, investigators classified the case as a misdiagnosis.

At Cedars-Sinai, 19 of 112 patients (17%) included in the final analysis were misdiagnosed, while at UCLA, 24 of 124 (19%) were misdiagnosed, the investigators reported. The most common correct diagnosis was migraine, seen in 16% of cases.

Of those 43 misdiagnosed patients, 34 had received an MS diagnosis from 34 different neurologists, while 6 were diagnosed by different non-neurologists; in 3 cases, patients couldn’t recall the specialty of the diagnosing physician.

“A different physician misdiagnosed each patient, suggesting that the issue of misdiagnosis is not limited to a small number of physicians,” Dr. Kaisey and coauthors wrote.

More than half of the misdiagnosed patients (26, or 60%) received a disease-modifying therapy approved for MS, while another three patients were seeking a second opinion before starting such therapy, investigators found. Twelve of the patients were exposed to treatments with an established risk of progressive multifocal leukoencephalopathy, an “often fatal infection,” Dr. Kaisey and coinvestigators said.

“Misdiagnosis of MS in this study was associated with considerable patient risk and immense health care cost,” the investigators said. Patients experienced the consequences of misdiagnosis for an average of 4 years, while one patient lived with an MS misdiagnosis for 20 years, they found. The cost over time related to unnecessary MS treatment exposure was about $10 million, according to their report.

Knowing the incidence of MS misdiagnosis and its causes may lead to improved diagnostic approaches for the disease, according to Dr. Kaisey and colleagues. In this particular study, misdiagnosis was linked to overreliance on radiographic findings, or misinterpretation of those findings, in patients who had syndromes that were atypical for MS, they said.

“Many syndromes mimic MS, and application of the McDonald criteria relies on numerous clinical assessments,” they said. “Accurate diagnosis can be challenging.” Education on properly applying the McDonald diagnostic criteria might help ameliorate the MS misdiagnosis problem, investigators said.

From another perspective, the study results underscore real-world issues with applying currently available diagnostic criteria. Especially concerning, the investigators said, was the finding that 14% of misdiagnosed patients had a normal neurologic exam, and 14% had normal imaging results for the brain and spinal cord.

“Highly specific and objective biomarkers for MS are an important unmet need in ensuring accurate diagnosis,” Dr. Kaisey and coauthors concluded.

Image credit: Medical Body Scans/Science Source

Dr. Kaisey reported consulting fees from Celgene and Biogen, not related to the subject of this study. Dr. Solomon received consulting fees and research funding from Biogen, not related to the subject of this study. The remaining coauthors had no disclosures.