Nearly 1 in 5 Patients Referred for MS Are Misdiagnosed

Damian McNamara

October 31, 2018

BERLIN — Almost 1 in 5 people with an established diagnosis of multiple sclerosis (MS) who were referred to one of two academic medical centers did not meet full diagnostic criteria for MS and more likely had a different condition at presentation, a new study shows.

An atypical clinical presentation and brain imaging findings featuring radiographic "red flags" for a different diagnosis were common, the researchers report. In this retrospective study, the factor most often associated with misdiagnosis was misapplication of McDonald diagnostic criteria.

"Never take the diagnosis of multiple sclerosis at face value," Marwa Kaisey, MD, a neurologist specializing in MS at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News.

"We saw that almost 1 in 5 patients who had a firm diagnosis of MS did not turn out to have MS," said Kaisey. "These were not people referred to us for possible multiple sclerosis. These patients had the diagnosis for an average of 4 years, and up to 20 years."

Kaisey presented the findings during a poster session here at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018.

A Diagnostic Challenge

With no biomarker to diagnose MS with high sensitivity and specificity, diagnosis often relies on clinical symptoms, diagnostic criteria, and imaging findings. However, "many conditions mimic MS, and accurate diagnosis can be challenging," the researchers write.

The current prevalence of MS misdiagnosis remains unknown, Kaisey and colleagues note.

To learn more, the investigators examined electronic medical records and MRI findings among 236 patients with established MS. Patients presented to either Cedars-Sinai Medical Center or the University of California, Los Angeles (UCLA) MS clinics between July 2016 and June 2017.

Participants who did not meet full 2010 and 2017 McDonald criteria and presented with a more likely, alternative condition were considered misdiagnosed as having MS.

The investigators excluded anyone who was referred for confirmation of a tentative MS diagnosis.

Other Diagnoses

A total of 43 patients were misdiagnosed with MS, representing 17% of the Cedars-Sinai cohort and 19% of the UCLA participants.

Six patients had migraine, the most common MS misdiagnosis in the study. Radiologically isolated syndrome, seen in four patients, was the next most common, followed by cervical spondylosis with stenosis, peripheral neuropathy, and optic neuropathy without optic neuritis (three patients each).

A majority of misdiagnosed patients presented with an atypical clinical syndrome for MS: 74% of the Cedars-Sinai group and 67% of the UCLA group.

The researchers also reported that 79% and 83% of these misdiagnosed groups, respectively, had atypical imaging findings.

In terms of treatment, 72% of the misdiagnosed patients in the study were prescribed an MS disease-modifying therapy (DMT). The investigators noted that nearly half of these medications, 48%, carried a risk for progressive multifocal leukoencephalopathy, a serious, often fatal complication of such treatment.

The researchers calculated that the 110 patient-years of unnecessary DMT translated to a cost of almost $10 million.

Kaisey and colleagues also identified factors associated with a greater likelihood for MS diagnosis, some of which were statistically significant.

Table. Significant Factors Linked to MS Misdiagnosis*

Factor Cedars-Sinai Cohort Odds Ratio P Value UCLA Cohort Odds Ratio P Value
Migraine history 1.488 .496 2.733 .042
Non-MS autoimmune comorbidity 3.795 .037 3.133 .098
Family history of autoimmune disease 1.262 .650 3.250 .013
Family history of neurologic disease 0.844 .745 4.008 .004
Atypical presentation 22.222 <.001 7.524 <.001
Radiographic "red flags" 21.061 <.001 36.667 <.001
*Based on univariate logistic regression analysis.

Patient age, sex, employment status, time since misdiagnosis, a history of seeing an MS specialist or neurologist, and an abnormal neurologic examination were not significantly associated with misdiagnosis.

"When people with MS come to see us, we always confirm the diagnosis first for all patients," Kaisey said.

"Our next step is to develop MRI biomarkers that are more specific to MS," she said. We need "something that can distinguish MS from migraine and other neurologic conditions."

A "Lot of Validity"

"I believe there is a lot of validity" to the findings, Cretan P. Gandhy, MD, assistant professor of neurology and associate program director of the Multiple Sclerosis Fellowship at the University of South Florida College of Medicine in Tampa, told Medscape Medical News.

"It seems that anyone with white spots on their MRI are told they have MS," added Gandhy, who was not affiliated with the study. "Interestingly, other providers miss the final criterion of McDonalds's criteria, that there can be no other explanation for the lesions on MRI, which means MS is a diagnosis of exclusion."

He has changed the diagnosis of some people referred to him with MS, he said.

Also asked to comment by Medscape Medical News, Kathy Costello, MS, CRNP, an adult nurse practitioner and research associate at the Johns Hopkins MS Centerin Baltimore, Maryland, said, "I think the study was not terribly surprising, and the reason I say that is that MS is difficult to diagnose.

"Even under the best circumstances with highly trained experts in MS, you can have a misdiagnosis," added Costello, who is also associate vice president for Healthcare Access for the National Multiple Sclerosis Society.

She recommended that clinicians question MS diagnoses over time, especially early on. A high level of clinical suspicion is warranted whenever a new, atypical symptom emerges.

"In this study, people came to these medical centers with a diagnosis of MS, and in a relatively large number, wound up not [having] MS," she added. "So it's not always clear."

Dr Kaisey, Dr Gandhy, and Kathy Costello have disclosed no relevant financial relationships.

34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018. Abstract P656, presented October 11, 2018.

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