Insight 10

Stay with us on this journey of exploration and knowledge as Insight Ten becomes your monthly beacon, illuminating the most noteworthy research in MS and NMO.

1. Environmental Risk Factors & Genetics in Multiple Sclerosis (MS)

The interplay between environmental risk factors, genetic predispositions, and their influence on Multiple Sclerosis (MS) phenotypes has been a focus of recent research, offering new insights into disease mechanisms and potential therapeutic avenues. Bellucci et al. (2024) have made significant strides in elucidating this relationship through their innovative study. They established a "MS-Mendelian network" by testing for enrichment of MS-associated variants within genes known for Mendelian disorders, uncovering a substantial overlap. Their analysis revealed that out of 617 MS-associated loci, there's a significant enrichment with genes implicated in Mendelian diseases, especially those related to immune, neurologic, metabolic, and visual functions. This groundbreaking approach not only sheds light on the complex genetic landscape of MS but also proposes a novel phenotypical framework that could revolutionize the classification of MS endophenotypes and guide the development of new, more targeted therapies.

In a parallel vein, the study by Zhang et al. (2024) explores the causal links between coffee consumption and neurological diseases through a Mendelian randomization (MR) study. Leveraging genetic variants associated with coffee intake as instrumental variables, they analyzed data from the UK Biobank. The MR analysis, using 40 SNPs as instrumental variables, revealed a compelling genetic evidence of a causal relationship between increased coffee consumption and a reduced risk of migraine, with an odds ratio (OR) of 0.528 (95% CI: 0.342-0.817, P=0.004) for migraine and an OR of 0.374 (95% CI: 0.208-0.672, P=0.001) for migraine with aura. This finding is particularly relevant for neurologists, as migraines are a frequent comorbidity in MS patients, suggesting that dietary recommendations regarding coffee intake could potentially serve as a preventive strategy for certain patients.

Lastly, the research conducted by Üremiş MM et al. (2024) on the effects of acrylamide (ACR) exposure during pregnancy on myelination processes adds a crucial dimension to our understanding of environmental risk factors in MS. Their study on rats demonstrated that ACR exposure significantly decreased the levels of key myelin-related proteins (MBP, MAG, and MOG), highlighting the toxin's potential role in the etiopathogenesis of demyelinating diseases. Importantly, the administration of vitamin E was found to mitigate the negative effects of ACR, underscoring the potential of antioxidant-rich diets in supporting myelination and protecting against neurotoxic environmental exposures.

References

Bellucci G, et al. Disentangling multiple sclerosis phenotypes through Mendelian disorders: A network approach. Mult Scler. 2024; (unknown volume):13524585241227119. doi: 10.1177/13524585241227119.

Zhang J, et al. Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study. Eur J Clin Nutr. 2024; 78:114-119. doi: 10.1038/s41430-023-01355-y.

Üremiş MM, et al. Acrylamide, Applied During Pregnancy and Postpartum Period in Offspring Rats, Significantly Disrupted Myelination by Decreasing the Levels of Myelin-Related Proteins: MBP, MAG, and MOG. Neurochem Res. 2024; 49:617-635. doi: 10.1007/s11064-023-04053-0.

2. EAE & Disease Mechanisms in Multiple Sclerosis

In a pivotal study published in Annals of Neurology (2024), Chomyk et al. have significantly advanced our understanding of the role microglia/macrophages play in the progression of Multiple Sclerosis (MS), particularly focusing on their behavior at the borders of demyelinated lesions within cerebral white matter and cortex. The study illuminates the contrasting profiles of microglia/macrophages associated with chronic white matter lesions versus those adjacent to subpial gray matter lesions, offering insights that could potentially reshape therapeutic strategies for progressive MS.

Using laser capture microscopy, the researchers meticulously compared the morphology and transcript profiles of these cells at the lesion borders. This approach enabled the isolation of cells for RNA sequencing, complemented by immunocytochemistry to trace the distribution of specific transcripts upregulated in white matter line (WM line) microglia.

The findings reveal that WM line cells exhibit an activated state, characterized by shorter processes and larger cell bodies, indicative of their involvement in lesion expansion and disability progression in MS. Conversely, microglia at the borders of subpial gray matter lesions (GM line) appear more homeostatic, with smaller cell bodies and multiple thin processes. Transcript profiling further differentiates these cells, identifying 176 genes differentially expressed in WM lines and 111 in GM lines. Specifically, WM line microglia showed increased expression of genes related to immune activation and iron homeostasis, while GM line microglia exhibited elevated levels of genes within the canonical Wnt signaling pathway. This nuanced understanding of microglia/macrophage function and gene expression at lesion borders underscores the complexity of MS pathology and points to the possibility of targeted therapies that address the distinct mechanisms of lesion expansion and disease progression. The study posits that the increased expression of the Fc epsilon receptor, spleen tyrosine kinase, and Bruton's tyrosine kinase, in particular, plays a critical role in the regulation of microglia/macrophage activity in chronic active white matter lesions. Such insights open new avenues for research and therapeutic intervention, aiming to modulate these key pathways to halt or slow the progression of MS.

References

Chomyk A, et al. Transcript Profiles of Microglia/Macrophage Cells at the Borders of Chronic Active and Subpial Gray Matter Lesions in Multiple Sclerosis. Ann Neurol. 2024; doi: 10.1002/ana.26877.

3. Randomized Clinical Trials & Observational Studies in Multiple Sclerosis

Recent research in the field of MS has been notably enriched by findings from both randomized clinical trials and observational studies, focusing on treatment efficacies and safety profiles.

The study by Benallegue et al. (2024) published in JAMA Neurology delves into the effectiveness of highly effective therapies (HETs) as a first-line treatment for pediatric-onset multiple sclerosis (POMS), a critical area where consensus on treatment strategies has been elusive. Their retrospective cohort study, leveraging data from the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort, sheds light on the real-world impact of HET compared with moderately effective therapies (METs). The study included 530 treatment-naive children, showing that HET significantly reduced the risk of first relapse by 54% and exhibited superior tolerability and a lower rate of treatment discontinuation compared to METs. This pivotal finding underscores the potential of HET in managing POMS, suggesting a paradigm shift towards prioritizing HET as initial treatment to improve midterm outcomes, albeit with a call for further long-term safety studies.

Concurrently, Androdias G et al. (2024) in their study published in Neurology Neuroimmunology & Neuroinflammation, explore the impact of immune checkpoint inhibitors (ICIs) on MS progression, a pertinent inquiry given the rising use of ICIs in cancer treatment and their potential to exacerbate MS. This multicentric French study, collecting both retrospective and prospective data, identified 18 patients with MS treated with ICIs post-cancer diagnosis. Preliminary findings indicated an increased risk of MS activity post-ICI initiation in a subset of patients, particularly those younger than 50 years with a relapsing-remitting course. This investigation into the intersection of cancer treatment and MS management highlights the nuanced balance between treating malignancies and mitigating the risk of exacerbating underlying autoimmune conditions.

References:

Benallegue N, et al. Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis. JAMA Neurol. 2024. doi: 10.1001/jamaneurol.2023.5566.

Androdias G, et al. Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024; 11:e200202. doi: 10.1212/NXI.0000000000200202.

4. Rehabilitation, Psychology, & Cognition in Multiple Sclerosis

The intricate relationship between multiple sclerosis (MS) and cognitive functions such as apathy and the risk of dementia has been the subject of recent studies, shedding light on the profound impact MS has on mental health and cognitive abilities.

The study by Tazza et al. (2024) in Mult Scler focuses on the clinical and radiological correlates of apathy in people with MS (PwMS), a condition linked to fronto-striatal dysfunction across various neurological disorders but understudied within the context of MS. Through the evaluation of clinical variables and the microstructural integrity of fronto-striatal grey and white matter structures using diffusion tensor imaging (DTI), the researchers identified that a significant portion of PwMS (32.5%) exhibited apathy. These apathetic PwMS were characterized by lower education levels, higher scores in depression, anxiety, and fatigue assessments (HADS, MFIS), and greater white matter lesion volumes than their non-apathetic counterparts. Crucially, DTI metrics revealed significant differences in the middle frontal, anterior cingulate, superior frontal prefrontal cortex (PFC) subregions, and caudate nuclei, along with alterations in the right cingulum and left striatal-frontorbital tracts. These findings underscore the association of apathy in MS with higher levels of physical disability, psychological distress, and specific microstructural damage, providing a clearer understanding of the pathological substrate of apathy in MS.

Further expanding the exploration of cognitive impairment in MS, Fleming NH et al. (2024) in Mult Scler Relat Disord investigated the risk of dementia in older veterans diagnosed with MS. While cognitive dysfunction is a well-recognized consequence of MS, the progression to dementia remains a contentious issue. This study aims to bridge the gap in understanding by examining the prevalence and risk factors associated with dementia in this population.

Together, these studies highlight critical aspects of cognitive impairment in MS, from apathy driven by specific brain structural changes to the broader risk of dementia. These insights are pivotal for neurologists and rehabilitation specialists focusing on MS, as they emphasize the need for comprehensive cognitive assessments and tailored rehabilitation strategies. Addressing apathy and the potential progression to dementia requires an integrated approach that encompasses both physical and psychological interventions, highlighting the significance of mental health and cognitive preservation in the overall management of MS.

References

Tazza F, et al. Clinical and radiological correlates of apathy in multiple sclerosis. Mult Scler. 2024; 30:247-256. doi: 10.1177/13524585231217918.

Fleming NH, et al. Risk of dementia in older veterans with multiple sclerosis. Mult Scler Relat Disord. 2024; 82:105372. doi: 10.1016/j.msard.2023.105372.

5. Pregnancy and Multiple Sclerosis

In the landscape of Multiple Sclerosis (MS) treatment, the management of disease-modifying therapies (DMTs) during pregnancy has been a critical area of concern, particularly because MS frequently affects women of childbearing age. The comprehensive nationwide study by Swital et al. (2024) in France, spanning from 2010 to 2021, sheds significant light on the evolving practices and trends in the use of DMTs among pregnant women with MS, reflecting the increasing availability and variety of DMTs over the past decade.

This pivotal research, leveraging data from the nationwide Mother-Child Register EPI-MERES, constructed from the French National Health Data System, captured 20,567 pregnancies in women with MS, of which 7,587 were exposed to DMTs. The study documented a striking increase in DMT-exposed pregnancies, from 1,079 in the 2010-2012 period to 2,413 in 2019-2021, marking a 124% rise. This surge is notably attributed to the escalated use of glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20 therapies.

A key aspect of the study's findings is the management of DMTs around the pregnancy period. Among women on DMTs six months before pregnancy, 78.0% discontinued the treatment, while 7.6% switched to a different DMT, predominantly before or during the first trimester (33.0% and 77.0% before pregnancy, respectively, and 58.3% and 17.8% during the first trimester, respectively). Notably, the rate of DMT discontinuation showed a decreasing trend, from 84.0% in 2010-2012 to 72.4% in 2019-2021, with discontinuation being less frequent among women aged ≥35 years and those socioeconomically disadvantaged.

These findings underscore a significant shift in therapeutic management strategies during pregnancy in women with MS, reflecting a nuanced approach towards balancing disease control with the safety of both the mother and the fetus. The increase in DMT exposure during pregnancy, especially with treatments whose safety profiles are not yet fully established, points to the pressing need for ongoing research and updated guidelines to navigate the complex decisions surrounding DMT use in pregnant patients with MS. This study not only highlights the evolving landscape of MS treatment during pregnancy but also calls attention to the disparities in treatment discontinuation rates, suggesting a potential area for targeted interventions and support.

References:

Swital M, et al. Use of multiple sclerosis disease-modifying therapies during pregnancy in France: Nationwide study between 2010 and 2021. Mult Scler. 2024; 30:227-237. doi: 10.1177/13524585231223395

6. MRI Biomarkers in Multiple Sclerosis

Recent advancements in magnetic resonance imaging (MRI) have ushered in a new era of diagnosing and understanding multiple sclerosis (MS), with a particular focus on identifying biomarkers that correlate with disease progression, treatment response, and underlying pathophysiology. These biomarkers not only enhance our comprehension of MS but also hold promise for improving patient care through more precise diagnostics and tailored treatment strategies.

The study by Galbusera et al. (2024) published in Neurology highlights the discovery and clinical relevance of juxtacortical paramagnetic rims (JPRs) in MS patients. By employing quantitative susceptibility mapping (QSM) and magnetization-prepared 2 rapid acquisition gradient-echo (MP2RAGE) images, the research team identified JPRs in approximately 10% of an in vivo cohort of 165 MS patients. These rims were associated with an increased cortical lesion load and were histologically linked to the accumulation of activated iron-laden phagocytes, pointing to a novel MRI biomarker of focal cortical demyelination. This finding is significant as it relates to global cortical pathology, suggesting potential utility in diagnostic and stratification processes in clinical settings.

Niehaus et al. (2024), in their work published in Talanta, explored the molecular and elemental landscape of MS lesions using cutting-edge spectroscopic and mass spectrometric techniques. Through the post-mortem analysis of MS brains, significant variances in concentrations of various elements and specific lipid species were observed in MS lesions compared to surrounding white matter. This comprehensive molecular and atomic mapping offers a high-resolution view into the bio-indicative entities of MS, potentially complementing current understandings of MS pathophysiology and aiding in the development of targeted therapies.

Ravano et al. (2024), featured in J Neurol, demonstrated the utility of quantitative MRI in conducting tract-wise microstructural analysis of white matter (WM) tracts in MS patients. This approach revealed that T1 tissue alterations in normal-appearing WM and the presence of lesions in specific WM tracts could better predict disability evolution and current disability, respectively. Such tract-wise analyses underscore the importance of location and extent of microstructural changes in understanding and monitoring MS progression, offering a promising direction for personalized treatment plans.

These studies collectively underscore the potential of MRI biomarkers in revolutionizing the diagnosis, understanding, and treatment of multiple sclerosis. From identifying novel biomarkers like JPRs to employing advanced molecular and elemental mapping techniques, and conducting microstructural analyses of WM tracts, the research provides crucial insights into MS pathology. These advancements not only promise to refine diagnostic criteria and treatment approaches but also pave the way for personalized medicine in MS care, ultimately aiming to improve patient outcomes.

References:

Galbusera R, et al. Characteristics, Prevalence, and Clinical Relevance of Juxtacortical Paramagnetic Rims in Patients With Multiple Sclerosis. Neurology. 2024; 102:e207966. doi: 10.1212/WNL.0000000000207966.

Niehaus P, et al. Multimodal analytical tools for the molecular and elemental characterisation of lesions in brain tissue of multiple sclerosis patients. Talanta. 2024; 270:125518. doi: 10.1016/j.talanta.2023.125518.

Ravano V, et al. Tract-wise microstructural analysis informs on current and future disability in early multiple sclerosis. J Neurol. 2024; 271:631-641. doi: 10.1007/s00415-023-12023-3.

7. Laboratory Biomarkers in Multiple Sclerosis

The realm of laboratory biomarkers in Multiple Sclerosis (MS) has seen pivotal advancements, aiming to enhance diagnosis, prognostication, and understanding of disease mechanisms. Two recent studies contribute significantly to this field, offering insights into complement activation's role in MS pathology and the potential of combined protein biomarkers in predicting MS diagnosis and outcomes.

Oechtering et al. (2024) delve into the association between complement activation and MS severity. Their research, published in Neurology Neuroimmunology & Neuroinflammation, underscores the elevated levels of complement components (CCs) and complement activation products (CAPs) in the cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS) and MS, particularly those with intrathecal IgM synthesis. The study presents a compelling link between increased complement activation within the CSF and higher disease activity and progression, marked by Expanded Disability Status Scale (EDSS) scores, MS Severity Score (MSSS), and neurofilament light chain (NfL) levels. This underscores the potential of complement inhibition as a therapeutic target to mitigate MS severity and progression.

Kodosaki et al. (2024), in their work published in the Journal of Neuroinflammation, explore the efficacy of combining protein biomarkers to predict MS diagnosis and outcomes. By analyzing 24 fluid biomarkers in blood and CSF, their study demonstrates that predictions using combinations of biomarkers significantly outperform those based on single biomarkers. This approach not only improves diagnostic accuracy against other neurological disorders but also enhances prognostication for MS patients, particularly in terms of time to first relapse and reaching disability milestones.

These studies collectively signify a shift towards a more nuanced understanding of MS pathophysiology and its prognostic assessment. Oechtering et al.'s findings on complement activation present a novel perspective on the molecular underpinnings of MS severity, suggesting a targeted approach for therapeutic intervention. On the other hand, Kodosaki et al.'s research on combined biomarkers offers a promising strategy for refining MS diagnosis and predicting disease course, potentially leading to personalized treatment plans.

The emphasis on CSF biomarkers and the exploration of multi-biomarker models highlight the complexity of MS pathology and the need for comprehensive diagnostic and prognostic tools. As these biomarkers become integrated into clinical practice, they hold the promise of transforming MS management, tailoring therapies to individual disease profiles, and ultimately improving patient outcomes.

References

Oechtering J, et al. Complement Activation Is Associated With Disease Severity in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024; 11:e200212. doi: 10.1212/NXI.0000000000200212.

Kodosaki E, et al. Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes. J Neuroinflammation. 2024; 21:52. doi: 10.1186/s12974-024-03036-4.

8. Neurophysiological Biomarkers in Multiple Sclerosis and Related Disorders

Recent advancements in the field of neurophysiological biomarkers have shed light on the intricate dynamics of synaptic interactions and their implications for demyelinating diseases, specifically in the context of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Two pivotal studies from Li et al. (2024) and Yang et al. (2024) provide groundbreaking insights into the neurophysiological mechanisms underlying these conditions, offering new avenues for diagnosis, monitoring, and potentially therapeutic interventions.

Li et al. (2024) explore the role of synaptic input and calcium activity in zebrafish oligodendrocyte precursor cells (OPCs), highlighting their significant contribution to myelin sheath formation. The study, published in Nature Neuroscience, elucidates the presence of neuron-glial synapses between neurons and OPCs, focusing on the in vivo functions and downstream signaling pathways of these synaptic interactions. Through in vivo microscopy in zebrafish spinal cords, the research identifies the postsynaptic molecules PSD-95 and gephyrin in OPCs, which play critical roles in the dynamic assembly of synapses during early development and their decrease upon OPC differentiation. This research provides a novel understanding of myelination processes, potentially influencing therapeutic strategies for demyelinating diseases like MS.

Yang et al. (2024), on the other hand, delve into the realm of resting-state electroencephalography (rs-EEG) oscillations in patients with NMOSD, a condition closely related to MS. Published in Brain Research Bulletin, their study marks the first investigation into rs-EEG features of NMOSD patients, assessing the potential of rs-EEG as a biomarker for functional impairments, disease monitoring, and neuromodulation treatment. The study reveals significant differences in rs-EEG power spectra between NMOSD patients and healthy controls, particularly in increased slow oscillations (delta and theta power) and the association of alpha and gamma oscillation power with anxiety, depression, and fatigue symptoms. These findings suggest rs-EEG power spectra as potential biomarkers for NMOSD, offering insights into the neurophysiological impacts of the disease and associated complications.

Together, these studies contribute significantly to the understanding of neurophysiological biomarkers in demyelinating diseases. Li et al.'s work provides foundational knowledge on the synaptic mechanisms involved in myelination, while Yang et al. introduce rs-EEG as a promising tool for the evaluation and management of NMOSD. These advancements underscore the importance of neurophysiological research in developing more effective diagnostic and therapeutic strategies for MS and related disorders.

References:

Li J, et al. Synaptic input and Ca^2+ activity in zebrafish oligodendrocyte precursor cells contribute to myelin sheath formation. Nat Neurosci. 2024; 27:219-231. doi: 10.1038/s41593-023-01553-8.

Yang L, et al. Exploring resting-state EEG oscillations in patients with Neuromyelitis Optica Spectrum Disorder. Brain Res Bull. 2024; 208:110900. doi: 10.1016/j.brainresbull.2024.110900.

9. Wearable Devices

Recent advances in wearable technology have opened new avenues for monitoring and managing multiple sclerosis (MS), offering more precise and ecologically valid assessments of symptoms and disease progression. Two studies, one focusing on gait assessment through smartphone technology and the other on sleep health via wearable devices, exemplify this trend.

Regev et al. (2024) introduce the Mon4t® app, a novel digital tool leveraging sensors in standard smartphones to analyze gait parameters in MS patients. Their study of 100 MS patients and age-matched healthy controls utilized the app alongside traditional human raters to perform various motor tasks. The findings underscore the app's efficacy in distinguishing between MS patients and healthy controls, as well as among MS patients with varying levels of disability, based on gait parameters. Significant differences were observed in tasks like the Timed Up and Go (TUG) and tandem walk, with specific metrics correlating closely with the Expanded Disability Status Scale (EDSS) scores. This research highlights the potential of smartphone-based gait assessment in enhancing disease monitoring and clinical decision-making, providing a convenient and relevant tool for detecting early gait impairments in MS patients.

On the other hand, Turner et al. (2024) explore the multidimensional sleep health of individuals with MS, Huntington's disease (HD), and healthy controls, using wearable devices for the first time to gather comprehensive sleep data. Through actigraphy and various sleep quality indices, the study assesses seven domains of sleep health, revealing distinct patterns among the groups. Notably, the HD group exhibited higher sleep regularity but lower sleep rhythmicity compared to the MS and control groups, with no significant differences in the composite sleep health score across groups. These findings suggest unique sleep challenges in neurodegenerative diseases, with implications for understanding and managing sleep-related issues in MS.

Together, these studies illustrate the significant potential of wearable devices and smartphone technology in advancing the understanding and management of MS. By providing detailed insights into gait and sleep patterns, these technologies offer valuable tools for personalized monitoring and intervention, reflecting a broader trend towards integrating digital health solutions into neurology.

References:

Regev K, et al. Smartphone-based gait assessment for multiple sclerosis. Mult Scler Relat Disord. 2024; 82:105394. doi: 10.1016/j.msard.2023.105394.

Turner M, et al. The multidimensional sleep health of individuals with multiple sclerosis, Huntington's disease and healthy controls. J Clin Sleep Med. 2024; (unknown volume):(unknown pages). doi: 10.5664/jcsm.11052.

10. Neuromyelitis Optica and Late-Onset MOGAD: Advances in Understanding and Management

Recent studies have shed light on the complex pathophysiology and varied clinical presentations associated with neuromyelitis optica (NMO) and late-onset myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), contributing significantly to the field of neurology, particularly in the understanding and management of autoimmune diseases affecting the central nervous system.

Afzali et al. (2024) explore the pivotal role of B cells in orchestrating tolerance to the NMO autoantigen AQP4. NMO is recognized as a paradigmatic autoimmune disorder where the immune system erroneously targets AQP4, a critical water-channel protein in the central nervous system. This groundbreaking study, published in Nature, uncovers the intricate mechanisms by which B cells contribute to the immune tolerance of AQP4. By elucidating these processes, the research offers potential pathways for novel therapeutic interventions aimed at modulating B cell activity to restore tolerance to AQP4 and prevent the autoimmune attack characteristic of NMO.

On a related note, Huang et al. (2024) delve into the clinical and imaging features of late-onset MOGAD, highlighting the unique aspects of this condition when it manifests later in life. Through a retrospective analysis of 110 MOGAD patients, including 21 with onset age ≥50 years, the study published in Mult Scler Relat Disord identifies several distinguishing characteristics of late-onset MOGAD. Compared to younger patients, those with late-onset MOGAD tend to have a milder disease onset, a more monophasic course, fewer relapses, and distinct imaging features, such as fewer lesions in the basal ganglia, thalamus, and cerebellum but more in the white matter and periventricular area. These findings not only enhance our understanding of the age-dependent variability in MOGAD presentation but also underscore the importance of considering age and potential comorbidities in diagnosis and treatment planning.

Together, these studies represent significant strides in the comprehension of NMO and MOGAD, offering insights into the underlying immune mechanisms and the influence of age on disease manifestation. By advancing our knowledge of these complex disorders, Afzali et al. and Huang et al. contribute to the development of more targeted and effective treatments, improving outcomes for patients across the spectrum of disease onset ages.

References:

Afzali AM, et al. B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4. Nature. 2024; doi: 10.1038/s41586-024-07079-8.

Huang Y, et al. Clinical and imaging features of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease. Mult Scler Relat Disord. 2024; 82:105405. doi: 10.1016/j.msard.2023.105405.