Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the "gold standard" for laboratory diagnosis of MS, though presents analytical limitations. Indeed, current protocols for OCBs assay are time-consuming and require an operator-dependent interpretation. In recent years, the quantification of free light chain (FLC) in CSF has emerged to assist clinicians in the diagnosis of MS. This article reviews the current knowledge on CSF biomarkers used in the diagnosis of MS, in particular on the validated assays and on the alternative biomarkers of intrathecal synthesis.

Keywords: biomarkers; cerebrospinal fluid; demyelinating diseases; immunoglobulin light chains; multiple sclerosis; oligoclonal bands.

Figure 1

Symptom patterns that define the subtypes of multiple sclerosis (MS). CIS, clinically isolated syndrome; RRMS, relapsing/remitting multiple sclerosis; PPMS, primary progressive multiple sclerosis; SPMS, secondary progressive multiple sclerosis; PRMS, progressive-relapsing multiple sclerosis.

Figure 2

Diagnosis of multiple sclerosis with analytical differences between detection of CSF kappa free light chains (kFLC) versus oligoclonal bands (OCBs) assay.