- Provides guidelines on when to consider alternate diagnosis rather than MS
- The full article reviewed provides a rational approach to the differential diagnosis based on the clinical setting and basic imaging studies in individual patients.
- Every patient need not have testing for each of the many possible disorders in the differential diagnosis.
PLEASE NOTE: Each article is selected by faculty on the scientific merits of the new data. It is one part of a bundled series of articles that, as a group, provide a full and balanced perspective.
Multiple sclerosis (MS) is sometimes difficult to accurately diagnose due to the fact that it has clinical features that are similar to those seen in other diseases. For example, patients with infectious, neoplastic, congenital, metabolic or vascular disease, or non-MS idiopathic inflammatory demyelinating disease (IIDD), can exhibit symptoms that are similar to those seen in patients with MS. Excluding other possible diseases that share symptoms of MS is difficult because there is presently no conceptual framework from which a differential diagnosis can be made. This has often resulted in the diagnosis of MS being made when there is "no better explanation" for a suspected MS presentation. The goal of the present review article was to provide a summary of a guide to the interpretation of clinical, laboratory, and imaging data to guide in the differential diagnosis of MS. With this information, it is expected that practitioners will be better suited to make an early, accurate diagnosis, which is crucial to patient care, therapy design, and treatment outcome.
The authors, an array of experts in the field of demyelinating disease, convened at the Task Force on Differential Diagnosis in MS. The goal of this meeting was to provide an expert-opinion-based, diagnostic approach for the proper diagnosis of patients presenting with suspected central nervous system white matter diseases, including guidance for appropriate diagnostic testing to exclude alternative diagnoses, and the development of a tool for neurologists that could guide disease management. The Task Force was divided into subgroups to focus on three key areas. The first subgroup focused on the identification of ways to exclude potential alternatives to an MS diagnosis. A series of "red flags" were identified that were likely to suggest a diagnosis other than MS. A 79-item table was developed, and based on rankings given by the members of the Task Force, "major," "intermediate," and "minor" red flags were categorized and ranked based on how strongly they are suggestive of an alternative diagnosis to MS. Of these, 36 major red flags were identified, and these strongly suggest a diagnosis other than MS.
Examples of red flags include:
- Major red flags: bone lesions, lung involvement, and multiple cranial neuropathies or polyradiculopathy
- Intermediate red flags: hydrocephalus, punctiform parenchymal enhancement, and Sicca syndrome
- Minor red flags: brainstem syndrome, no MRI enhancement, and myelopathy alone
For a complete list of red flags, see the article
A second subgroup focused on defining and diagnosing common clinically isolated syndromes (CIS) that are typical presentations of MS (eg, optic neuropathy, brain stem and spinal cord syndromes), and CIS features that commonly precede MS were contrasted to those that are atypical of MS and warrant further evaluation. Because the present definition of CIS can be considered ambiguous, the Task Force members more closely defined the term as a monophasic presentation with suspected underlying inflammatory demyelinating disease, which implies a single clinical episode that is of rapid onset. A total of five types of CIS were described, four of which were defined based on whether or not the monophasic clinical presentation has mono or multifocal clinical or magnetic resonance imaging (MRI) features.
Finally, a third subgroup focused on differentiating MS and non-MS IIDD. Demographic and paraclinical factors were considered that differentiate prototypical MS from variants, such as neuromyelitis optica (NMO) and acute disseminated encephalomyelitis (ADEM), and criteria that include specific imaging features and biomarkers were proposed for their diagnoses.
A limitation of this review is that the classification proposed has not yet been validated in the clinic. Also, although the existing literature on this topic was considered, the authors note that the recommendations are mostly consensus-driven. The sensitivity, specificity, and accuracy of the red flags that might suggest a disease other than MS have not been investigated. Also, the discussion of the characteristics for this guide was based on the Western population, and the authors caution that it may not be as applicable to other populations.
In summary, the authors review their classification of the clinical presentation of suspected MS into those features that are typical of MS and suggest that MS is likely, and those that are atypical of MS and suggest an alternative diagnosis. The identification of red flags that suggest a diagnosis other than MS, diagnosis and a refined definition of CIS, and differentiation of MS and non-MS IIDD are the first steps toward an established protocol in MS differential diagnosis. While these guidelines have not yet been validated and lack empirical evidence of their effectiveness, the discussion presented here can assist MS and non-MS specialist neurologists in achieving diagnostic accuracy and precision in suspected cases of MS.
Miller DH, Weinshenker BG, Filippi M, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler. 2008;14:1157-1174.