Detecting Multiple Sclerosis Mimics Early

Divya Singhal; Joseph R Berger


Future Neurology. 2012;7(5):547-555. 

In This Article

Abstract and Introduction


Multiple sclerosis (MS) is a chronic autoimmune condition affecting the CNS. Despite recent refinements in diagnostic criteria and the availability of ancillary studies, such as cerebrospinal fluid analysis, MRI, electrophysiological studies and optical coherence tomography, MS remains a clinical diagnosis. Repeated studies have convincingly demonstrated that early treatment is critical in decreasing the rate of disease progression and, therefore, establishing the diagnosis in a timely fashion and initiating treatment is imperative. However, the latter is not always easy and recognizing disorders that may mimic MS is essential in avoiding the administration of costly and, on occasion, potentially risky therapy. Furthermore, it is important to recognize MS mimics to initiate appropriate treatment for those conditions. Prominent MS mimickers, many with features of focal neurological disease separated in both time and space, are discussed in this article. Diagnostic pearls to avoid misdiagnosis have been included.


Multiple sclerosis (MS) is an intriguing disease and a challenging diagnosis to establish – several tools are available to aid a physician in its diagnosis, such as MRI, evoked potentials, optical coherence tomography and cerebrospinal fluid (CSF) analysis; however, there is no single test that is specific enough to help establish diagnosis with certainty. At times, the clinical picture, MRI lesions and CSF findings are so convincing that the diagnosis is virtually certain, but not infrequently, there are elements of the clinical or radiographic or laboratory picture that do not conform precisely with MS. In those instances, the clinician must remain open minded and cautious in labeling the patient with MS. With sophisticated diagnostic studies, the refinement of diagnostic criteria, increased awareness of therapeutic options and temporal changes in incidence and prevalence rates, the time from symptom onset to the time of diagnosis of MS has declined very significantly from 1980 to 2004.[1] Not unexpectedly, the increased alacrity in time to diagnosis has been associated with patients being labeled with MS when they are experiencing symptoms suggestive of a mild form of MS.[1] The drive for early diagnosis has the potential to increase the risk of misdiagnosis. The Dutch proverb that "a handful of patience is worth more than a barrel full of brains" may pertain in the latter instance when the prudent physician couches the diagnosis with uncertainty and relies on careful clinical follow-up examinations and serial MRI studies to increase comfort levels with the diagnosis.

The advent of disease-modifying medications appears to have significantly altered the course of MS. The administration of disease-modifying medications in the clinically isolated syndrome has been repeatedly demonstrated to delay the progression to clinically definite MS.[2,3] Not only may this therapy decrease relapse rates and new MRI lesions, but it may also reduce the development of confirmed disability.[4] This alteration of the natural course of the disease may have a significant impact on the morbidity experienced during the peak years of productivity. In addition, it may be effective in reducing axonal loss that leads to cerebral and spinal cord atrophy in advanced MS. Fortunately, the standard platform therapies, IFN-βs and glatiramir acetate, have been associated with few serious adverse effects; however, the consequences of inappropriate administration include not only the cost, which when coupled with 'diagnostic momentum'[5] often leads to long-term administration until the patient's illness properly declares itself, but also the failure to address the real underlying disorder promptly. On the other hand, the availability of increasingly effective treatments for MS that are associated with greater risk and the potential for their earlier administration in the course of the disease raises the risk of serious harm being done to patients who have been misdiagnosed. The importance of establishing the correct diagnosis is highlighted in Box 1.