How Early Is Early Multiple Sclerosis?

Abstract

The development and further optimization of the diagnostic criteria for multiple sclerosis (MS) emphasize the establishment of an early and accurate diagnosis. So far, numerous studies have revealed the significance of early treatment administration for MS and its association with slower disease progression and better late outcomes of the disease with regards to disability accumulation. However, according to current research results, both neuroinflammatory and neurodegenerative processes may exist prior to symptom initiation. Despite the fact that a significant proportion of individuals with radiologically isolated syndrome (RIS) progress to MS, currently, there is no available treatment approved for RIS. Therefore, our idea of "early treatment administration" might be already late in some cases. In order to detect the individuals who will progress to MS, we need accurate biomarkers. In this review, we present notable research results regarding the underlying pathology of MS, as well as several potentially useful laboratory and neuroimaging biomarkers for the identification of high-risk individuals with RIS for developing MS. This review aims to raise clinicians' awareness regarding "subclinical" MS, enrich their understanding of MS pathology, and familiarize them with several potential biomarkers that are currently under investigation and might be used in clinical practice in the future for the identification of individuals with RIS at high risk for conversion to definite MS.

Keywords: RIS; disease progression; early treatment; laboratory biomarkers; multiple sclerosis; multiple sclerosis prodrome; neuroimaging biomarkers.

Figure 1

The potentially predictive laboratory biomarkers for the progression of radiologically isolated syndrome (RIS) to definite multiple sclerosis (MS) are summarized. Laboratory biomarkers in blue are found in the cerebrospinal fluid (CSF), whereas those in yellow are found in the serum, and the one in green is retrieved from peripheral blood. Concentric circles are used to visualize the predictive value of each biomarker according to the currently available research results. Biomarkers closer to the center have been found to be more strongly associated with RIS progression to definite MS compared to those located in the outer layers of the circle. Biomarkers located outside the circle have not been assessed yet for their predictive value in RIS conversion to MS. Transparent biomarkers have already been assessed and there was no association found.