Differential diagnosis of multiple sclerosis

Abstract

Multiple sclerosis (MS) is determined as a central nervous system (CNS) disease with multiple demyelination that disseminates in time (DIT) and space (DIS). The CNS includes brain, spinal cord, and optic nerves, in which myelin is produced by oligodendrocytes. The term “demyelination” denotes that myelin is selectively destructed. The strict definition of MS therefore requires the histological validation of these features : The definitive diagnosis of MS can only be made with the histological proof as such obtained with brain biopsies.

In reality, however, the clinical diagnosis of MS is made according to the McDonald criteria. The diagnosis criteria is an international consensus for the determination of “CNS demyelination with DIT and DIS” by the use of magnetic resonance imaging (MRI), in order to avoid the invasive biopsy procedure. The most recent McDonald criteria (the 2010 revision) adopted the Swanton MRI criteria, of which sensitivity and specificity for MS reported to be 77% and 92%, respectively, within the European countries. As neuromyelitis optica–spectrum disorder (NMOSD), the major MS–mimic, is relatively more frequent in Japan compared to the European countries, the specificity may be reduced and it may be reasonable to speculate the misdiagnosis rate of MS to be around 10 to 20% in Japan.

How can we reduce the possibility of misdiagnosing MS? Firstly, we must understand the technical limitation of the McDonald criteria upon making MS diagnosis and secondly, we must be aware of major patterns of alternative diagnosis in MS practice. As for the former, for example, “T2-lesions” are considered to be demyelinated lesions in the McDonald criteria, albeit the fact that the T2 signal is not specific to myelin. In order to make more correct speculation that a T2 lesions is likely to be a demyelinated lesion, we may need to focus on the location of such lesion : Accumulating pathological evidence suggested that MS shows a unique pattern of lesion distribution. For the latter, several previous studies provided a list of the major alternative diagnosis in MS practice.

This article reviews and summarizes the practical approach for the differential diagnosis of MS and its mimics.