Implications of Diagnosing and Misdiagnosing Multiple Sclerosis

Alise Carlson, MD

The current standard in the diagnosis of multiple sclerosis (MS) relies on the appropriate application of the McDonald criteria to patients who present with typical signs and symptoms of the disease. Although revisions to the diagnostic criteria have allowed for earlier diagnosis and initiation of disease modifying therapies over time, diagnostic inaccuracy continues to be a widely recognized issue. This is largely due to the fact that the diagnosis is still made primarily based on clinical factors, which are often subjective. Rates of MS misdiagnosis (the incorrect assignment of an MS diagnosis) are quoted to occur at rates of approximately 20-30% in the literature.^1-5 The misdiagnosis of MS leads to several long-term consequences, including unnecessary exposure to immunosuppressive therapies, economic and psychosocial stress on patients, and stress on health care systems. MS misdiagnosis also has potential implications for research, as these patients may attempt to enroll in clinical trials (potentially exposing them to therapies with potential for harm and/or skewing of trial data).

Over time, revisions of the MS diagnostic criteria have aimed to simplify the diagnostic process, and lead to a more timely diagnosis for these patients. With each iteration there has been continued and increased emphasis on promoting the appropriate application of the criteria to reduce rates of misdiagnosis. Numerous studies spanning the past several years have aimed to identify both clinical and radiographic “red flags” which may help to detect patients with diseases that mimic MS. As the differential diagnosis for MS continues to expand, there has been greater emphasis on the need to develop additional strategies to avoid MS misdiagnosis. Studies to evaluate and validate MRI-based biomarkers, such as the central vein sign (CVS), are currently underway. These novel tools may serve as more sensitive and specific diagnostic markers for MS, and aid in differentiating MS from other conditions which may mimic it.

In addition to the clinical implications of accurately diagnosing MS, clinicians must consider the significant social and psychological impacts that are had on these patients. It is also important to consider the ethical problems which arise when it comes to revising an incorrect diagnosis.

Patients often present to MS specialists after receiving a diagnosis of MS from another provider, who after further evaluation may not meet criteria for the disease (or may be found to have a different condition entirely). Misdiagnoses come in many different forms, including medically inaccurate diagnoses, indeterminate diagnoses, and therapeutic mislabeling (the intentional or conscious, inappropriate mislabeling of MS to describe another condition that is explained (often psychogenic) or unexplained, which the clinician knows is not related to MS).⁶ Because an MS diagnosis often becomes a core part of these patient’s identities due to the substantial financial, physical, and emotional toll the long-term management of this disease may incur, challenging or un-doing an inaccurate diagnosis may be distressing for both patient’s and providers.

The need for improved diagnostic methods is clear. Additional prospective studies are needed to establish diagnostic algorithms that may be widely applied in clinical settings. Although recent advancements in identifying and validating biomarkers for the diagnosis of MS will undoubtedly lead to fewer misdiagnoses in the future, it is crucial that we as clinicians are judicious about appropriately labeling patients from the time of the first encounter, as questioning or un-doing an inaccurate diagnosis may ultimately be more damaging to the patient than the initial diagnosis was in the first place. Nonetheless, misdiagnoses should not be reinforced, and Neurologists should be open to discussing uncertainties with patients. Neurologists with expertise in MS remain essential to the appropriate assessment and management of this patient population.

REFERENCES

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