The Kappa Free Light Chains Index and Central Vein Sign: Two New Biomarkers for Multiple Sclerosis Diagnosis

Abstract

At the last European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting, Montalban and the experts' panel announced the 2024 revision of the McDonald criteria. The optic nerve has been added as a fifth dissemination in space (DIS) criteria topography among the main changes. Multiple sclerosis (MS) can be diagnosed in patients with radiologically isolated syndrome (RIS) if specific biomarkers are added to at least two of the five DIS criteria. Among the particular MS biomarkers, the kappa free light chain index (kFLC index) positivity will be added to oligoclonal band (OCB) detection to fulfill intrathecal immunoglobulin synthesis, and the central vein sign (CVS) will be able to ensure the specificity of the lesions detected on MRI scans. This review summarises the knowledge on the kFLC index and the CVS in people with MS and RIS, allowing them to be incorporated into the proposed revision of the McDonald criteria.

Keywords: Central vein sign; Kappa free light chains index; Multiple sclerosis; Radiologically isolated syndrome.

Fig. 1

Central vein sign assessment on 3T MRI scan. A Axial 3D FLAIR (on the left) and SWAN-venule (on the right) MR images from a 46-year-old woman with MS (two distinct clinical events: sensitive myelitis and diplopia). The 3D FLAIR images highlights typical MS lesions (i.e. Dawson’s fingers lesion in the top left image and U-fiber lesion in the bottom left image). This patient had also brainstem, and cervical spinal cord lesion, with 2 enhanced-lesions on T1-weighted gadolinium sequences. SWAN-venule sequences showed a positive CVS MR scan (more than 6 CVS positive lesions). She also had positive OCB and kFLC index testing. However, according to the NAIMS criteria, both selected images should not be considered for CVS assessment (confluent or non-ovoid lesion on 3D FLAIR sequences). B Axial 3D FLAIR (on the left) and SWAN-venule (all 3 images on the right) MR images from a 48-year-old asymptomatic woman, diagnosed with RIS. The SWAN-venule sequences shows typical ovoid lesions, most of them harboring a CVS (last image on the right). 3D FLAIR images also show typical periventricular, brainstem and cervical spinal cord lesions. The SWAN-venule sequence showed a positive CVS MR scan (more than 6 CVS positive lesions). She also had positive OCB and kLFC index. This asymptomatic patient presenting with typical lesions in 3 of the 5 DIS topography, and having intrathecal Ig synthesis and a CVS positive MR scan, fulfill 2024 McDonald criteria of preclinical MS. C Axial 3D FLAIR (on the left) and SWAN-venule (on the right) MR images from a 46-year-old woman presenting with fatigue and dizziness. She suffers from rheumatoid arthritis and high blood pressure. 3D FLAIR sequences showed no periventricular, brainstem, cerebellar or spinal cord lesions. No ovoid lesions harboured a CVS on SWAN-venule sequences. She was diagnosed as having small cerebral vessel disease