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Multiple sclerosis is a neurodegenerative disease that causes balance deficits, even in early stages. Evidence suggests that people with multiple sclerosis (PwMS) rely more on vision to maintain balance, and challenging balance with optical flow perturbations may be a practical screening for balance deficits. Whether these perturbations affect standing balance in PwMS is unknown. Therefore, the purpose of this study was to examine how optical flow perturbations affect standing balance in PwMS. We hypothesized that perturbations would cause higher variability in PwMS compared with matched controls during standing and that standing balance would be more susceptible to anterior–posterior (A–P) perturbations than medial–lateral (M–L) perturbations. Thirteen PwMS and 13 controls stood under 3 conditions: unperturbed, M–L perturbation, and A–P perturbations. A–P perturbations caused significantly higher A–P trunk sway variability in PwMS than controls, although both groups had similar center-of-pressure variability. Both perturbations increased variability in A–P trunk sway and center of pressure. Trunk variability data supported the hypothesis that PwMS were more susceptible to optical flow perturbations than controls. However, the hypothesis that A–P perturbations would affect balance more than M–L perturbations was partially supported. These results suggest potential for optical flow perturbations to identify balance deficits in PwMS. [ABSTRACT FROM AUTHOR]

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. MOG-specific T cells are required in MOG EAE, and while anti-MOG Abs can exacerbate EAE and CNS demyelination, those Abs are neither necessary nor sufficient to cause EAE. Knowledge regarding the spectrum of MOGAD clinical and radiologic presentations is advancing rapidly, yet our grasp of MOGAD pathogenesis is incomplete. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis.

Multiple sclerosis (MS) is a chronic and debilitating neurological disease that results in inflammatory demyelination. While endogenous remyelination helps to recover function, this restorative process tends to become less efficient over time. Currently, intense efforts aimed at the mechanisms that promote remyelination are being considered promising therapeutic approaches. The M1 muscarinic acetylcholine receptor (M1R) was previously identified as a negative regulator of oligodendrocyte differentiation and myelination. Here, we validate M1R as a target for remyelination by characterizing expression in human and rodent oligodendroglial cells (including those in human MS tissue) using a highly selective M1R probe. As a breakthrough to conventional methodology, we conjugated a fluorophore to a highly M1R selective peptide (MT7) which targets the M1R in the subnanomolar range. This allows for exceptional detection of M1R protein expression in the human CNS. More importantly, we introduce PIPE-307, a brain-penetrant, small-molecule antagonist with favorable drug-like properties that selectively targets M1R. We evaluate PIPE-307 in a series of in vitro and in vivo studies to characterize potency and selectivity for M1R over M2-5R and confirm the sufficiency of blocking this receptor to promote differentiation and remyelination. Further, PIPE-307 displays significant efficacy in the mouse experimental autoimmune encephalomyelitis model of MS as evaluated by quantifying disability, histology, electron microscopy, and visual evoked potentials. Together, these findings support targeting M1R for remyelination and support further development of PIPE-307 for clinical studies.

This study aimed to determine whether choroid plexus volume (CPV) could differentiate multiple sclerosis (MS) from its mimics. A secondary analysis of two previously enrolled studies, 50 participants with MS and 64 with alternative diagnoses were included. CPV was automatically segmented from 3T magnetic resonance imaging (MRI), followed by manual review to remove misclassified tissue. Mean normalized choroid plexus volume (nCPV) to intracranial volume demonstrated relatively high specificity for MS participants in each cohort (0.80 and 0.76) with an area under the receiver-operator characteristic curve of 0.71 (95% confidence interval (CI) = 0.55-0.87) and 0.65 (95% CI = 0.52-0.77). In this preliminary study, nCPV differentiated MS from its mimics.

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.

In the United States, patients with chronic conditions experience disparities in health outcomes across the care continuum. Among patients with multiple sclerosis, diabetic retinopathy, and lung cancer, there is a lack of evidence summarizing interventions to improve care and decrease these disparities. The aim of this rapid literature review was to identify interventions among patients with these chronic conditions to improve health and reduce disparities in screening, diagnosis, access to treatment and specialists, adherence, and retention in care. Using structured search terms in PubMed and Web of Science, we completed a rapid review of studies published in the prior five years conducted in the United States on our subject of focus. We screened the retrieved articles for inclusion and extracted data using a standard spreadsheet. The data were synthesized across clinical conditions and summarized. Screening was the most common point in the care continuum with documented interventions. Most studies we identified addressed interventions for patients with lung cancer, with half as many studies identified for patients with diabetic retinopathy, and few studies identified for patients with multiple sclerosis. Almost two-thirds of the studies focused on patients who identify as Black, Indigenous, or people of color. Interventions with evidence evaluating implementation in multiple conditions included telemedicine, mobile clinics, and insurance subsidies, or expansion. Despite documented disparities and a focus on health equity, a paucity of evidence exists on interventions that improve health outcomes among patients who are medically underserved with multiple sclerosis, diabetic retinopathy, and lung cancer.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.