Latest developments in MS research:
- Learn about whether postpartum treatment with anti-CD20 mAbs is well-tolerated by both mother and infant
- Lesions associated with memory problems in MS connect to a memory circuit centered on the hippocampus
- Direct MRI mapping of the myelin lipid-protein bilayer reveals highly specific myelin maps in brain tissue from patients with MS
These noteworthy MS news highlights and more are included in our recently published ECTRIMS Research Updates – a 30-day snapshot of global news & publications on MS research, treatment and care.
ECTRIMS Research Updates can be sent to you every month, delivered straight to your inbox, via our free subscription service. Simply select all “topics” that are of interest to you, and when one of those appears in our news & publication cycle you’ll be sure to hear from us.
Clinical
Prognostic value of single-subject grey matter networks in early multiple sclerosis
This study examined whether it was possible to predict 5-year Expanded Disability Status Scale (EDSS) progression in 406 individuals with relapsing-remitting MS (RRMS). Grey matter (GM) atrophy over one year and white matter (WM) lesion load were determined using longitudinal magnetic resonance imaging (MRI). Findings revealed that GM network reorganisation was associated with clinical worsening in individuals with RRMS, an observation that was evident even in the absence of GM atrophy. The authors concluded that early GM restructuring towards lower network efficiency was predictive of disability accumulation in RRMS.
Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions
Ann Clin Transl Neurol | 7 September 2023
Anti-CD20 monoclonal antibodies (mAbs) are increasingly the disease modifying treatment (DMT) of choice in postpartum women with neurological conditions, including MS. This study aimed to determine whether any transfer of anti-CD20 mAbs into breast milk occurs. The median concentration of mAbs in breast milk collected from 57 postpartum women receiving treatment with ocrelizumab or rituximab was low. Concentration peaked 1–7 days post-infusion in most women (77%) and was nearly undetectable after 90 days. These findings confirm that there is minimal transfer of mAbs into breast milk, therefore postpartum treatment with anti-CD20 mAbs appears to be well-tolerated for both mother and infant.
Pathogenesis
Multiple sclerosis lesions that impair memory map to a connected memory circuit
Journal of Neurology | 2 August 2023
This study aimed to explore whether the memory dysfunction that often occurs in individuals with MS is associated with white matter lesions to a specific brain circuit. Using a cross-sectional analysis of standard structural images and verbal memory scores from 431 individuals with MS, the investigators examined associations between total MS lesion volume and memory dysfunction, and between memory dysfunction and lesion intersection with memory circuits. Both total lesion volume and lesion damage to memory circuits were associated with memory dysfunction. The investigators concluded that lesion locations associated with memory dysfunction in MS map onto a specific brain circuit centred on the hippocampus. Lesion damage to this circuit fully mediated associations between lesion volume and memory.
Imaging and Non-imaging Biomarkers
Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids
This cross-sectional study, conducted in Japan, identified 671 patients with suspected myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disease (MOGAD), MS, aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), or another neurological disease for whom paired serum and cerebrospinal fluid (CSF) were available. MOGAD is commonly characterised by the presence of MOG immunoglobulins (IgG) in serum, however, seronegative cases with MOG-Ig identified in CSF have been reported. Multivariate regression was used to analyse the relationship between MOG-IgG in serum or CSF and disease phenotype. While the specificities of MOG-IgG in both serum and CSF were found to be 100% in individuals with MOGAD, the correlation between MOG-IgG in serum and CSF was weak, and was associated with distinctive phenotypes. MOG-Ig in serum was associated with Optic Neuritis and ADEM, while MOG-Ig in CSF was associated with Cortical Cerebral Encephalitis phenotypes and ADEM.
Quantitative magnetic resonance mapping of the myelin bilayer reflects pathology in multiple sclerosis brain tissue
Science Advances | 11 August 2023
Magnetic resonance imaging (MRI) allows visualisation of myelin, however, it has only recently become feasible to access the rapidly decaying resonance signals arising from the myelin lipid-protein bilayer itself. Such non-invasive visualisation of myelin could improve understanding of the mechanisms underlying de- and remyelination and permit monitoring of the efficacy of treatments aimed at regenerating myelin in individuals with MS. In this study, direct MRI mapping of the myelin lipid-protein bilayer yielded highly specific myelin maps in brain tissue from patients with MS. By examining bilayer signal behaviour, it proved possible to reveal pathological alterations in normal-appearing white and grey matter.
Serum glial fibrillary acidic protein in natalizumab-treated relapsing-remitting multiple sclerosis: An alternative to neurofilament light
Multiple Sclerosis Journal | 2 August 2023
This study assessed the value of serum glial fibrillary acidic protein (sGFAP) as a biomarker for clinical disease progression and brain volume measurements in individuals with relapsing-remitting MS (RRMS) treated with natalizumab. sGFAP and neurofilament light (sNfL) were measured in an observational cohort of 88 individuals with RRMS and the relationship between them assessed. sGFAP was also compared between significant clinical progressors and non-progressors, and related to MRIderived brain volumes. sGFAP levels at baseline were higher in individuals with gadolinium enhancement and decreased following 3 months of natalizumab treatment. No association was found between longitudinal sGFAP levels and progressor status, however, sGFAP correlated with sNfL at both baseline and last sample follow-up. The authors concluded that sGFAP levels are related to MRI markers of neuroinflammation and neurodegeneration.
Therapeutics
Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial
JAMA Neurology | 21 August 2023
This study (NCT03122652) investigated the potential of preventing MS by treating individuals with preclinical demyelinating disease using a disease-modifying treatment (DMT). Compared with placebo, a significant reduction of 72% in the risk of clinical MS was demonstrated in those patients treated with the DMT teriflunomide. The observed safety profile was consistent with known outcomes reported in prior pivotal MS studies. According to the authors, findings from this randomised clinical trial provide the first evidence of early treatment intervention with teriflunomide in preventing MS in individuals with radiologically isolated syndrome.
Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis
Multiple Sclerosis Journal | 3 August 2023
This analysis evaluated the effect of ibudilast on thalamic tissue integrity and volume in the SPRINT-MS randomised clinical trial (NCT01982942). A total of 255 individuals with progressive MS were randomised to oral ibudilast or placebo, and thalamic magnetisation transfer ratio (MTR) and normalised thalamic volume over 96 weeks were quantified. Ibudilast showed an effect on thalamic MTR, which was associated with confirmed disability progression, suggesting a clinically relevant effect on thalamic tissue integrity. However, the treatment effect was not observed in thalamic volume, suggesting that thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity.