Alicia Ault

June 02, 2016

NATIONAL HARBOR, Maryland — Neurologists, even those with a practice focus or fellowship in multiple sclerosis (MS), were not able in some cases to differentiate between MS and other common disorders, such as migraine and fibromyalgia, a new study suggests.

Andrew Solomon, MD, and colleagues from the University of Vermont, Burlington, solicited and collected data from four academic centers, asking for detailed reports on patients determined to have been misdiagnosed with MS.

Dr Solomon, assistant professor at the University of Vermont College of Medicine, presented an early look at the data at the Consortium of Multiple Sclerosis Centers (CMSC) 2016 Annual Meeting.

Fifty percent of the voluntary reports — in which patients were prospectively identified during a 13-month period — came from the Mayo Clinic, Rochester, New Minnesota; a quarter from the University of Vermont; 11% from Washington University, St. Louis, Missouri; and 9% from Oregon Health and Science University, Portland. They were asked to include patients who had received an MS diagnosis from a previous physician and those who were suspected of having another diagnosis. The misdiagnoses were identified after clinical and laboratory testing and imaging studies.

The centers submitted data on 110 patients who had been misdiagnosed with MS. The data did not include a denominator because the study was not designed to gauge what percentage of patients were misdiagnosed, Dr Solomon told Medscape Medical News.

Two thirds were misdiagnosed with five conditions: migraine alone or in combination with other diagnoses (23%), fibromyalgia (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI findings (12%), conversion or psychogenic disorder (11%), and neuromyelitis optic spectrum disorder (6%).

That data echo findings from a survey of MS specialists (Neurology. 2012;78:1986-1991) that Dr Solomon and colleagues conducted in 2012, he said.

"A lot of us perceive the differential diagnosis of MS to be quite broad," Dr Solomon said, noting that clinicians often are looking to rule out rare disorders first. But, he said, his data show that "disorders that we're mistaking frequently for MS are not rare — they are common disorders."

John Corboy, MD, professor of neurology at the University of Colorado School of Medicine, Denver, said he was not surprised at the findings. "Our own studies have shown that the possibility of MS is raised quite frequently in the migraine population due to similar demographic — young women — and the potential confusion in lesions seen on MRI scans," Dr Corboy told Medscape Medical News.

Although an MS diagnosis is challenging, the fact that such common disorders are being overlooked suggests a bigger problem, said Dr Solomon. "Perhaps people are not thinking about our diagnostic criteria in a rigorous way," he said. "And there's an overreliance on imaging" at the expense of looking at the patients' clinical presentation, he said.

Dr Corboy agreed. "There are reasonably formal and accepted MRI criteria for separating MS from non-MS," he said. Lesions in at least two typical locations are required, but "by far, the most common mistakes are to not see at least two locations and to misidentify one of the locations," Dr Corboy said.

He also said a three-step diagnostic checklist should be used. Symptoms should be typical of MS, not atypical; the neurologic exam findings should be consistent with the symptoms and reflect central nervous system problems seen with MS; and studies such as MRI should be consistent with MS.

Exposure to Harmful Therapies

In Dr Solomon's study, it wasn't just that MS was being misdiagnosed —patients were also taking disease-modifying therapies, sometimes for years, and some had even entered clinical studies for MS drugs, Dr Solomon found.

Thirty-two of the 110 patients (29%) had a misdiagnosis for 3 to 9 years. A little more than a third — 36 patients, or 33% — had carried their misdiagnosis for a decade or more. Dr Solomon called that finding "surprising."

Meanwhile, 70% of misdiagnosed patients had received disease-modifying therapy (DMT). Half were taking interferon β-1a or 1b, 40% were taking glatiramer acetate, and 13% were taking natalizumab. Thirty-six percent of patients received more than one DMT, and a quarter were taking a DMT with a known risk for progressive multifocal leukoencephalopathy. "The amount of disease-modifying therapy people were exposed to is troublesome," Dr Solomon told Medscape Medical News.

The amount of disease-modifying therapy people were exposed to is troublesome. Dr Andrew Solomon

The misdiagnosed patients were taking on excess risk: financial, in terms of the cost of the DMTs, clinical care, and imaging studies; emotional; and healthwise. Thirty-one percent of the 24 clinicians agreed that patients were exposed to an unnecessary risk for morbidity, said Dr Solomon.

Four percent (n = 4) of the misdiagnosed patients participated in clinical trials for an MS therapy. "That's really troubling," said Dr Solomon.

Red Flags Were There

Twenty-six patients were misdiagnosed by a neurologist with an MS fellowship training or practice focus and 35 by a neurologist without specialized training.

That shows that the misdiagnosis problem is "not confined to nonspecialists," Dr Solomon said. He said one of the more surprising findings to him was the fact that MS specialists had also made mistakes.

The 24 neurologists overall who participated said that in 72% of the misdiagnosed cases, there was clear evidence that the patients did not have MS.

So what were some of the reasons for misdiagnosis? Clinicians said that in 65% of the cases, there was inappropriate application of MS diagnostic criteria of neurologic symptoms atypical for a demyelinating attack. The diagnostic criteria were inappropriately applied to a historical episode of neurologic dysfunction without corroborating objective evidence of a lesion in 53 cases. In two thirds of cases, MRI was heavily leaned on despite the presence of nonspecific neurologic symptoms.

"I think we can conclude that over-reliance on MRI abnormalities in these patients in the setting of atypical syndromes and unverified prior symptoms may be a big cause of misdiagnosis," Dr Solomon told attendees.

How to Undiagnose

Walking back an MS diagnosis may present many hurdles, he said. In the survey conducted in 2012, 66% of the 122 MS specialists said they viewed disclosing a misdiagnosis as more challenging than delivering the original MS diagnosis.

Fourteen percent said they sometimes chose not to disclose when the patient had been diagnosed by a different physician.

"The problem is, if we permit that misdiagnosis to persist, then we're diminishing that patient's autonomy," said Dr Solomon.

Clinicians said in the 2012 survey that they were concerned that patients could lose disability benefits or emotional support if their MS diagnosis was removed. Potential harms do not justify withholding the information, however, said Dr Solomon.

The benefits of disclosure outweigh the risks, he said, noting that clinicians could potentially alleviate suffering with a correct diagnosis and that disability benefits are calculated on the basis of impairment, not condition.

Timing of discussion about a misdiagnosis is key, said Dr Solomon. Clinicians should likely wait until a second visit postdiscovery. Talking with the patient about the diagnosis and their fears is also important, he said.

Revealing a misdiagnosis often instills confusion, said Dr Corboy. Some patients "are simply relieved to hear their diagnosis was wrong." Others may still have a long list of symptoms that is not explained by MS, but the diagnosis still gave them something to wrap around, he said. In some cases, there is a psychiatric diagnosis at the heart of the situation, but for many, that's unacceptable, "perhaps due to some type of stigma," said Dr Corboy.

A common issue in the 2016 study was that patients frequently had been misdiagnosed by a previous physician. Overall, 107 of the 110 patients had their misdiagnosis disclosed to them, said Dr Solomon.

It's important not to jump to conclusions — no one is privy to the thinking of that doctor, and perhaps diagnostic criteria or technology has changed in the interim. A discussion with that physician "can be pretty challenging," said Dr Solomon.

The discussion should not assess blame or fault — it's really to aim to prevent misdiagnosis in the future, he said.

"It is important not to judge prior practitioners," agreed Dr Corboy.

It is not so surprising to see errors in diagnosis, said Dr Solomon. Clinicians are "under the gun to diagnose as quickly as possible," because of a growing body of "compelling data that suggests we should be treating early," he said. But, he added, "there may be cases where we need to wait," by perhaps obtaining imaging studies and following patients for a while.

"Do not use MS as a default diagnosis," said Dr Corboy. "Sometimes the answer is, 'I am not sure, let's follow along and see how you do.'"

The study was funded by the National Multiple Sclerosis Society. Dr Solomon is a consultant for the Haymarket Media Group for continuing medical education presentations. Dr Corboy has disclosed no relevant financial relationships.

Consortium of Multiple Sclerosis Centers (CMSC) 2016 Annual Meeting. Presented June 1, 2016.

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