As many as 10% of patients diagnosed with multiple sclerosis actually don’t and are receiving treatment for the wrong condition. How do physicians manage patients in that situation, including the ethical concerns of an “undiagnosis.”
By Stephen Spotswood
BURLINGTON, VT — A patient presents with a combination of any number of symptoms, including tingling and numbness, impaired vision, balance problems, fatigue, dizziness, impaired cognitive function and others. A physician does an examination, takes a patient history and likely orders an MRI, which may or may not come back with abnormal readings.
When a diagnosis of multiple sclerosis (MS) is made, the physician and patient will discuss treatment options. The patient then will finally have an answer to the debilitating symptoms they have been struggling with for months, if not years.
Or that’s the way it’s supposed to work.
Studies have found, however, that as many as 10% of patients diagnosed with MS do not have the disease and are receiving treatment for the wrong condition. Even worse, they are not being treated for the condition they actually have.
Physicians managing MS patients now have to consider the possibility that their patients were misdiagnosed at an earlier stage of their treatment — sometimes many years earlier. In some cases, they even have to wrestle with the ethical question of what it means to “undiagnosed” their patient.
A Heterogeneous Disease
From 2009 to 2011, Andrew Solomon, MD, was doing his fellowship in MS and neuroimmunology at the Portland, OR, VAMC, the site of an MS Center of Excellence (MSCOE). That was where he first became aware of the frequency that patients would arrive having been misdiagnosed with MS.
Now an assistant professor at the University of Vermont’s Department of Neurological Sciences, Solomon has authored and co-authored a number of studies all looking at how these mistakes happen and what the fallout can be.
“During my fellowship, I’d see patients who carried a diagnosis of MS often for a number of years, and I wasn’t so sure they had MS,” Solomon explained.
In conversation with his mentor Dennis Burdette, MD, MSCOE co-director, Solomon began investigating what the best approach was when presented with a questionable MS diagnosis.
“It’s a unique challenge to undiagnose MS,” Solomon said. “With many diseases you have a specific test with a yes or no answer. If you’re having a seizure, you can take an EG and capture the electrical event. With MS there’s no highly specific or sensitive test.”
A diagnosis of MS is based on clinical decision-making. Patient histories are considered, as are their presentation of symptoms. The problem is that MS is a very heterogeneous disease; one patient’s experience with MS will not necessarily look like the next patient’s experience.
Clinicians also rely on MRIs. If an MRI comes back with an abnormal reading, that could help strengthen an initial suspicion of MS.
“People rely too heavily on MRIs with diagnosis,” Solomon contends. “There are a lot of causes of an abnormal brain MRI.”
The result, according to a number of studies, is that an average of 10% of patients diagnosed with MS do not actually have the disease. Re-examination found a number of alternative diagnoses, including rheumatologic disorders, migraine and, most commonly, psychiatric disorders.
A 2012 study headed by Solomon surveyed 122 MS specialists nationwide. Almost 95% had seen one patient within the previous year who had been misdiagnosed with MS by another provider. Almost three-quarters said they had seen at least three patients during that time who they believe had been misdiagnosed. Among the 122 MS specialists, as many as 600 patients were believed to be misdiagnosed.1
Even patients suspected of being misdiagnosed are not always re-evaluated, however. According to Solomon’s studies, there are well-documented psychological and institutional barriers in the medical field preventing an in-depth discussion of errors. Physicians sometimes shy away from probing too deeply into whether a colleague has made a mistake.
Solomon noted that even neurologists won’t always raise questions about a diagnosis, adding, “The first step is to realize that we could all be wrong.”
Strict adherence to diagnostic criteria and an understanding of how those criteria were developed can help eliminate misdiagnoses, according to Solomon, who added, “I think some physicians are not using our diagnostic criteria as stringently as they should.”
Studies conducted by him and others have shown that physicians are overreliant on imaging to strengthen a diagnosis.
“Patients with psychiatric disease can present with numbness and tingling and have an abnormal MRI, but that abnormality might not relate to their psychiatric disease. It could be from smoking or high blood pressure,” Solomon pointed out, but also can be mistaken for MS.
One indicator physicians should take into account, he added, is cerebrospinal fluid (CSF). A meta-analysis of MS patients, published in 2013, found that 87% had oligoclonal bands (OCB) in their CSF. OCB is not found in many of the diseases frequently mistaken for MS, including migraine, small vessel ischemic disease and psychiatric disease.2
“If someone has normal spinal fluid, that’s a red flag,” Solomon said.
Physicians should constantly be on the lookout for these signs, he explained, asking questions such as: Are patients presenting with symptoms that cannot be shown on scans? Are imaging tests coming back normal or inconclusive?
Diagnosis in the Future
The hope is that biomarkers soon will be identified that could provide that hard yes or no for an MS diagnosis, Solomon explained. There’s also the possibility that MRI metrics could be developed — different ways of imaging the brain that could show something specific in MS that could not be mistaken for another disease.
In the meantime, sometimes the best way to confirm whether a patient has MS is to wait and see. More symptoms might appear, or current symptoms could retreat, leading to a clearer diagnosis, although this does not always come in time to help the patient.
“I had a patient who developed what looked like MS, but she subsequently developed weakness,” Solomon said. “We re-imaged her and her MRI showed a brain tumor, unfortunately.”
This is one of the cases when a misdiagnosis can prevent a patient from receiving treatment for the condition they actually have. In other cases, patients could be exposed to MS treatments that, for them, may be harmful.
In fact, the damage caused by misdiagnoses can be considerable. An estimated $500 million is spent annually on disease-modifying MS treatment for misdiagnosed patients. There’s also the unknown impact that misdiagnosed patients are having on research; research findings could be skewed without anyone ever realizing why.
The health cost to patients is impossible to estimate, meanwhile. Like Solomon’s patient with the brain tumor, there are an unknown number of misdiagnosed patients going untreated for a disease that will eventually kill them.
Psychological damage also can occur from correcting a misdiagnosis, Solomon noted.
“Being undiagnosed can be pretty devastating for some people,” Solomon said. “Many patients are involved in support groups and identify as people with MS. There’s a risk of loss of social support, risk of loss of identity if you’re questioning a diagnosis.”
It also can affect their peace of mind and rip away a part of their identify.
The consequences of misdiagnosis can potentially be even more devastating for veterans.
“What if they’re service-connected and rely on disability benefits?” Solomon asked. “What impact will a re-evaluation of their diagnosis have?”
Until the diagnostic testing improves, physicians will likely continue to face these ethical quandaries, Solomon said. In the meantime, he emphasized, the best course of action for clinicians is strict adherence to guidelines, keeping a careful watch for red flags and the willingness to believe that they or their colleagues might have made a mistake.
1 Solomon AJ, Klein EP, Bourdette D. “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS. Neurology. 2012 Jun 12;78(24):1986-91. doi: 10.1212/WNL.0b013e318259e1b2. Epub 2012 May 11. PubMed PMID: 22581930; PubMed Central PMCID: PMC3369504.
2 Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):909-14. doi: 10.1136/jnnp-2012-304695. Epub 2013 Feb21. Review. PubMed PMID: 23431079.