The Causes and Consequences of Misdiagnosing Multiple Sclerosis

Despite improvements in radiographic diagnostic techniques, including magnetic resonance imaging (MRI), the misdiagnosis of multiple sclerosis (MS) is a common problem that can lead to treatment-related and psychosocial morbidity.

“Today, MRI is the best biomarker we have, but the specificity is not 100%. Even in the hands of experts who develop these criteria, you can only distinguish MS from other criteria 87% of the time among experienced researchers using formal criteria—and that’s actually high,” said John R. Corboy, MD, FAAN, Co-Director, Rocky Mountain Multiple Sclerosis Center, University of Colorado, Aurora, at the 2016 American Academy of Neurology meeting.

“In real-world practice, however, this formal MRI criteria is not in general use,” he added.

Common Conditions Misdiag­nosed as Multiple Sclerosis

A number of conditions can be misdiagnosed as MS, including migraine alone or in combination with other diagnoses, fibromyalgia, nonspecific or nonlocalizing neurologic symptoms with abnormal MRI results, conversion or psychogenic disorder, and neuromyelitis optica spectrum disorder.

The diagnostic potential of MRI has advantages and pitfalls, Dr Corboy explained. “We’re living in the era of effective therapy,” he said. “We can start highly effective therapy that we think has a significant opportunity to limit the likelihood of developing disability over time.”

“On the flip side, however, there’s fear that if you miss a diagnosis—or don’t diagnose fast enough—you’ll be contacted by a lawyer,” he added.

There can also be inducement on the part of physicians in the form of money for in-office infusions. “Ultimately, regardless of the motivations, if there’s misdiagnosis and there’s treatment, there is mistreatment,” said Dr Corboy.

How Diagnostic Mistakes Are Made

According to Dr Corboy, misdiagnosing MS can be attributed to several factors, including:

• Lack of correlation of symptoms and signs
• Desire and/or demand to “make a diagnosis”
• Unwillingness to say, “I don’t know,” and reassess over time
• Overreliance on MRI, because:
  • Many are read by general radiologists
  • Many are not read by a treating neurologist
  • Calling subcortical lesions “periventricular.”

Given the dramatic, “almost logarithmic” rise in prices of MS medications in the past 10 to 12 years, misdiagnosis can also be a costly mistake.

Furthermore, significant harm can befall patients who are mistreated. For example, one patient with relapsing-remitting MS died from progressive multifocal leukoencephalopathy after receiving natalizumab (Tysabri) and interferon beta-1a as part of a clinical trial, Dr Corboy reported.

“You’re not only treating the wrong disease, but you’re exposing those patients to potentially expensive and/or potentially deadly medications,” Dr Corboy emphasized.

One study of patients misdiagnosed with MS showed that 70% of them had received disease-modifying therapies, and >30% had suffered a significant level of morbidity. Furthermore, >50% of the patients had been misdiagnosed for a “prolonged period of time,” suggesting that “once someone gets misdiagnosed with MS, it becomes very difficult to ‘un-ring that bell,’” said Dr Corboy.

Improving Multiple Sclerosis Diagnosis

According to Dr Corboy, improving the diagnostic accuracy of MS starts with the following measures:

• Adhering to diagnostic criteria
• Keeping an open mind for alternative diagnoses
• Knowing the MRI features that give the greatest specificity
• Assessing the brain and spine
• Personally reading the MRIs
• Obtaining help if needed
• Enhancing education of neurologists, primary care physicians, and radiologists
• Making MS an affirmative diagnosis, not a default diagnosis
• Developing better biomarkers in blood, cerebral spinal fluid, or MRI.

“The development of better biomarkers will have a substantial impact on clinicians’ ability to make the diagnosis more accurate. For example, the detection of the central vessel sign using FLAIR [fluid attenuated inversion recovery] on 3T MRI may be helpful for the differentiation of MS from migraine,” Dr Corboy concluded.