HILTON HEAD, SC—Given the lack of a definitive diagnostic test for multiple sclerosis (MS), diagnosing the disease can prove difficult. When considering symptoms, signs, and MRI findings that are suggestive of MS, clinicians must rely on their clinical judgment and experience, skillful interpretation of tests, and knowledge of and willingness to consider alternative diagnoses. Because of the subjective judgments involved and the many conditions that may mimic MS, it is not surprising that physicians sometimes misdiagnose MS, said Harold Moses, MD, at Vanderbilt University’s 41st Annual Contemporary Clinical Neurology Symposium.
A study by Solomon et al suggests ways to reduce the likelihood of misdiagnosis, said Dr. Moses, Associate Professor of Neurology at Vanderbilt University in Nashville. “Neurologists should … avoid overreliance on MRI changes as the principal support for an MS diagnosis,” he said. “Nonspecific or atypical MRI findings should be interpreted cautiously. A diagnosis of MS should not be made or reinforced in patients with psychiatric conditions without evidence for MS.”
For patients with emotional distress and psychologically based functional disability who do not meet diagnostic criteria for MS, a diagnosis of MS should be avoided. When MS remains a possibility, the patient should be informed of that fact and followed with clinical assessment and, if appropriate, MRI, Dr. Moses added. “Neurologists should be open in admitting and discussing uncertainty with patients,” he said. “It’s important to be honest in … indicating the need for further testing or observation over time. When emotional factors are thought to contribute [to a patient’s symptoms], treatments should be directed at these issues concurrently.”
First, Do No Harm
Psychiatrists and other therapists may be able to help patients when the diagnosis remains an open question. “MS disease-modifying drugs should be prescribed only for patients who have definitive evidence for MS or for those who present with classical clinically isolated syndromes—optic neuritis, transverse myelitis, and brainstem events—accompanied by appropriate changes on MRI,” Dr. Moses said.
Challenging cases include asymptomatic patients with MRI findings; patients with a first occurrence of symptoms, especially when the presentation is atypical; and patients with mimics of MS, such as vasculitis. Neurologists should be vigilant to identify mimics, particularly because these conditions may be treatable. The presence of psychiatric illness also may create challenging clinical scenarios.
“Psychologic and psychiatric factors may be present, but that patient may still have MS…. The question is, how do you tease out why that person is not doing well—that discordance, if you will, between how their MRI and exam are versus how they feel and how they are functioning.”
A Survey of Specialists
Solomon et al conducted a cross-sectional, internet-based survey of 242 MS specialists. Of the 50.4% of physicians who responded, 95% reported evaluating within the past year at least one patient who had been diagnosed with MS but who they felt strongly did not have the disease. More than 90% of respondents reported the use of disease-modifying therapy (DMT) in a proportion of these patients, and 94% found clinical encounters with these patients to be of an equal or greater challenge than making a new diagnosis of MS. A smaller proportion of respondents (14%) reported that, in some cases, they withheld telling a patient their opinion that the patient did not have MS.
As the study’s authors observed, evidence of therapeutic benefit from early initiation of DMT in patients with MS generates a sense of urgency to diagnose the disease early and begin therapy, Dr. Moses said. However, misdiagnosis in many cases may have resulted from—in place of prudent clinical and laboratory monitoring—an overreliance on MRI findings in patients with syndromes for which established MS diagnostic imaging criteria have not been validated. “Ultimately, MS remains a clinical diagnosis,” said Dr. Moses. “You use an MRI as an adjunct to help you confirm a diagnosis.”
Misdiagnosis of MS can cause serious harm. For example, conditions such as neuromyelitis optica and cervical spondylosis can lead to irreversible disability if unrecognized and inappropriately treated. Use of DMT in patients without MS exposes them to unnecessary health risks and financial costs. Dr. Moses cited the case of a 45-year-old woman who probably did not have MS but whose treatment with interferon beta-1a likely resulted in her going on dialysis. “These drugs are not benign,” he said. “[Such an outcome] is a very rare thing, but keep in mind that if a patient does not have MS, he or she should not be on MS therapy.”
Invested in the Diagnosis
As discussed by Boissy and Ford, neurologists may be inclined to use a medically inaccurate label, such as “a touch of MS,” “mild MS,” “benign MS,” or “MS by history,” when talking with patients who have received a misdiagnosis of MS, Dr. Moses said. Patients who have attributed psychogenic symptoms to misdiagnosed MS often resist a psychogenic explanation. In addition, they may be invested physically, emotionally, and financially in the diagnosis of MS—making treatment challenging for clinicians, Dr. Moses said.
Therapeutic mislabeling raises ethical issues, however. Mislabeling may expose patients to risky therapies, lead to an inappropriate use of resources, compromise the credibility of the clinician, and cause psychologic harm to the patient.
Neurologists would do better to consider scheduling multiple visits to explore psychogenic factors, as well as the patient’s fears and emotions, with the aim of developing a rapport and encouraging appropriate evaluations, Dr. Moses said. “If physicians endorse an inaccurate diagnosis, this undoubtedly conflicts with their professional obligations for truth telling, avoiding harming patients, … acting in the patient’s best interest, and stewardship of medical resources,” he said.
Boissy AR, Ford PJ. A touch of MS: therapeutic mislabeling. Neurology. 2012;78(24):1981-1985.
Solomon AJ, Bourdette DN, Cross AH, et al. The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study. Neurology. 2016;87(13):1393-1399.
Solomon AJ, Klein EP, Bourdette D. “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS. Neurology. 2012;78(24):1986-1991.