Multiple Sclerosis Plaques Research Articles

A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for Pathogenesis

Background: Multiple sclerosis (MS) is characterized by white matter demyelinating plaques, which can be classified as active, chronic active, or chronic inactive based on the extent of demyelination, cellularity, and inflammation. Microglia and macrophages play a central role in these processes. This study aimed to investigate the morphological characteristics of HLA-DR-immunopositive cells in these plaques to improve our understanding of the roles of these cells in MS plaques. Methods: This study is a retrospective post-mortem histopathological study. We analyzed 90 plaques from 6 MS cases. Of the plaques studied, 77 were grouped into three categories: 28 active, 34 chronic active, and 15 chronic inactive. Additionally, five vacuolated white matter lesions, two axonal degeneration lesions, and six lesions with mixed histological features were included. Six control cases were also examined to assess HLA-DR-immunopositive cell expression across various age groups. The cells were classified based on their morphology into two types: round cells without processes (macrophages) and cells with varying processes and shapes (ramified microglia). Results: Both macrophages and ramified microglia were present in all lesion types, with a focus on identifying the predominant cell type. Of the 28 active plaques, macrophages were the primary cell type in 25 plaques, while ramified microglia predominated in 3. In the center of 49 chronic plaques, scattered ramified microglia were observed in 46, with three plaques showing a predominance of macrophages. Among the 34 chronic active lesions, ramified microglia were the main cell type in the periphery of 32 plaques, with the remaining two predominantly exhibiting macrophages. Conclusions: The predominance of macrophages in active lesions and the presence of scattered ramified microglia in the center of chronic plaques are consistent with the phagocytic role of macrophages. Meanwhile, the prevalence of ramified microglia at the periphery of chronic active lesions suggests a potential protective function in maintaining lesion stability.

Cervical Spondylosis Severity and Its Correlation with Clinical Parameters and Cervical Lesions in Multiple Sclerosis: A Cross-Sectional MRI Study

Background: The co-occurrence of multiple sclerosis (MS) and cervical spondylosis (CS) may not only intensify symptoms but also complicate the management of these disorders. Magnetic resonance imaging (MRI) is the preferred modality for detecting spinal cord lesions; however, there is limited evidence assessing myelopathy in concurrent CS and MS. Objectives: This study aims to evaluate the association between CS and its effects on the spinal cord, as well as their impact on enhancing MS cervical lesions. Methods: This cross-sectional study was conducted on 104 MS patients between 2019 and 2021. Data collected included age, gender, duration and phenotype of MS, and the Extended Disability Status Scale (EDSS). Magnetic resonance imaging images were obtained and analyzed for the presence of cervical spondylosis and demyelinated cervical plaques (active/inactive). Multiple sclerosis plaques were evaluated based on their extension, enhancement, and cervical location. Cervical spondylosis was categorized into four grades using the Muhle scale. Additionally, the spinal cord cross-sectional area (SC - CSA) was measured at the C2 - C3 cervical spine level. Results: The severity of cervical spondylosis was associated with older age (P-value < 0.001), longer duration of MS (P-value = 0.04), more severe EDSS scores (P-value = 0.03), and a lower C2 - C3 CS-CSA (P-value < 0.001). However, no significant associations were found with gender (P-value = 0.90), MS plaques activity (P-value = 0.25), or extension (P-value = 0.13). Conclusions: The study findings indicate that the severity of CS is associated with age, MS duration, EDSS, and the C2 - C3 cervical spine cross-sectional area. However, the study did not find evidence supporting a relationship between CS and the extension or activity of MS plaques.

Apparent Diffusion Coefficient in the Diagnosis and Follow-up of Multiple Sclerosis: Role of Magnetic Resonance Imaging

Background: Chronic Multiple Sclerosis (MS) modifies the apparent diffusion coefficient (ADC) value due to severe pathological changes. After trauma, it is the second most common cause of brain injury in healthy young adults. MRI is considered the initial imaging modality for MS diagnosis and follow-up. Objective: To assess the significance of the ADC in the diagnosis and follow-up of MS plaques across various disease subtypes. Methods: Forty MS patients were included in a case-control study at Ibn-Sina Teaching Hospital, Mosul Province, between June 1, 2022 and February 28, 2023. The patients had diffusion-weighted and traditional MR imaging with ADC measurement in plaques, and the normal white matter value of controls was compared to the patients' results. Results: The ADC values were higher in cases that were acute or secondary-progressive than in relapsing-remitting cases or normal white matter. In both types of newly generated plaques, there was an initial non-significant increase in ADC values compared to existing plaques. Overall, the ADC sensitivity, specificity, and accuracy in diagnosing MS were 85.7%, 95.2%, and 90.5% in acute cases, and 85.7%, 83.3%, and 84.6% in chronic cases, respectively, with no significant difference between active and inactive lesions. Conclusions: The apparent diffusion coefficient value can be included in the imaging protocol for the diagnosis and follow-up of various subtypes of MS.

Niacin produces an inconsistent treatment response in the EAE model of multiple sclerosis

Niacin was found in the lysolecithin model of multiple sclerosis (MS) to promote the phagocytic clearance of debris and enhance remyelination. Lysolecithin lesions have prominent microglia/macrophages but lack lymphocytes that populate plaques of MS or its experimental autoimmune encephalomyelitis (EAE) model. Thus, the current study assessed the efficacy of niacin in EAE. We found that niacin inconsistently affects EAE clinical score, and largely does not ameliorate neuropathology. In culture, niacin enhances phagocytosis by macrophages, but does not reduce T cell proliferation. We suggest that studies of niacin for potential remyelination in MS should include a therapeutic that targets adaptive immunity.

Dual Inversion Recovery Magnetic Resonance Imaging's Diagnostic Value for Estimating the Overall Load of Multiple Sclerosis Lesions and its Anatomical Distribution

B Background: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double inversion recovery pulse pattern was recently proposed to improve the detectability of multiple sclerosis lesions. Objectives: To evaluate the diagnostic value of double inversion recovery sequence in the detection of cortical and white matter multiple sclerosis plaques in different brain anatomical locations. Subjects and methods: A total of 37 patients with an established diagnosis of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2 and FLAIR sequences. The number of lesions was counted and compared in the three sequences. Results: Dual Inversion Recovery sequence was highly significant and superior to both T2 and FLAIR sequences (P < 0.001) in depicting the lesions regardless of anatomical distribution. Dual Inversion Recovery was significantly superior to T2 (P =<0.001) and FLAIR (P =<0.001) in detecting lesions in cortical and juxtacortical. However, Dual Inversion Recovery shows less periventricular and deep white matter lesions in comparison to T2 and FLAIR sequences. Conclusion: The Dual Inversion Recovery sequence detected more multiple sclerosis lesions in cortical, subcortical and infratentorial than the traditional T2W and FLAIR sequences. It also demonstrated greater delineation between the white matter, grey matter, and multiple sclerosis lesions, which became more easily visualized.

The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.

Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of TDAG8, as opposed to GPR4 or OGR1, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human in vitro and in vivo models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research.

Torben Fog – A Danish pioneer in a multi-faceted spectrum of multiple sclerosis research

Torben Fog was committed to multiple sclerosis (MS) research for more than four decades, starting before the defence of his thesis in 1948 and lasting until his death in 1987. His research was multi-facetted, making him one of the great pioneers in the study of essential parts of the pathology, immunology and treatment of MS. He has contributed with meticulous studies of the MS plaques, documenting the perivenous distribution of plaques in the spinal cord. He constructed a scoring system for the disability in MS and used a computer programme to calculate a total neurological deficit. Together with his co-workers, Fog in 1972 was the first to report the association between MS and the human leukocyte antigen system. Fog can be considered as the father of immunomodulatory therapy in MS, treating MS patients with the first transfer factor, and as early as 1980, he was the first to treat MS with intramuscular natural interferon.

Diagnostic Contribution of Additional Sequences to the Evaluation of Cord Lesions in Patients with Cervical Spinal Multiple Sclerosis in Turkey: A Retrospective Study.

Multiple Sclerosis (MS) is the most common cause of non-traumatic disability in young adults. Spinal cord involvement is observed in 55-75% of patients with MS. To identify the strengths and shortcomings of sagittal phase-sensitive inversion recovery (PSIR), sagittal proton density/T2-weighted (PD/T2W), and axial turbo inversion recovery magnitude (TIRM) sequences in the detection of cervical MS plaques by comparing with routine sequences (axial and sagittal T2W, sagittal T1W, sagittal TIRM, fat-suppressed contrast T1W) and therefore determine their diagnostic contributions. A total of 48 patients in whom additional magnetic resonance imaging (MRI) sequences were obtained for the diagnosis of cervical MS were retrospectively identified and included in the study. A total of 111 MS plaques were analyzed in terms of visibility, number, size, border sharpness, and intensity ratio based on the routine and additional MRI sequences. The evaluation of the images was independently undertaken by two radiologists. The highest visibility was provided by sagittal PSIR, sagittal TIRM, and axial TIRM sequences (P < 0.05 for all additional sequences). Seven lesions in PD/T2W and four lesions in axial T2W sequences were unable to be detected. Lesions seen in sagittal and axial TIRM sequences were larger than the others. The sharpest borders were determined in the axial TIRM sequence, and the most diffuse borders in the PD/T2W sequence. In intensity ratio, the sagittal PSIR sequence revealed the most significant contrast difference. The sagittal PSIR sequence may improve the detection of cervical MS plaques due to the improved visibility and intensity ratios. The axial TIRM sequence may be more useful than routine axial T2W in the evaluation of visibility, border sharpness, and size measurement of MS plaques.

3D U-Net for automated detection of multiple sclerosis lesions: utility of transfer learning from other pathologies.

Deep learning algorithms for segmentation of multiple sclerosis (MS) plaques generally require training on large datasets. This manuscript evaluates the effect of transfer learning from segmentation of another pathology to facilitate use of smaller MS-specific training datasets. That is, a model trained for detection of one type of pathology was re-trained to identify MS lesions and active demyelination. In this retrospective study using MRI exams from 149 patients spanning 4/18/2014 to 7/8/2021, 3D convolutional neural networks were trained with a variable number of manually-segmented MS studies. Models were trained for FLAIR lesion segmentation at a single timepoint, new FLAIR lesion segmentation comparing two timepoints, and enhancing (actively demyelinating) lesion segmentation on T1 post-contrast imaging. Models were trained either de-novo or fine-tuned with transfer learning applied to a pre-existing model initially trained on non-MS data. Performance was evaluated with lesionwise sensitivity and positive predictive value (PPV). For single timepoint FLAIR lesion segmentation with 10 training studies, a fine-tuned model demonstrated improved performance [lesionwise sensitivity 0.55 ± 0.02 (mean ± standard error), PPV 0.66 ± 0.02] compared to a de-novo model (sensitivity 0.49 ± 0.02, p = 0.001; PPV 0.32 ± 0.02, p < 0.001). For new lesion segmentation with 30 training studies and their prior comparisons, a fine-tuned model demonstrated similar sensitivity (0.49 ± 0.05) and significantly improved PPV (0.60 ± 0.05) compared to a de-novo model (sensitivity 0.51 ± 0.04, p = 0.437; PPV 0.43 ± 0.04, p = 0.002). For enhancement segmentation with 20 training studies, a fine-tuned model demonstrated significantly improved overall performance (sensitivity 0.74 ± 0.06, PPV 0.69 ± 0.05) compared to a de-novo model (sensitivity 0.44 ± 0.09, p = 0.001; PPV 0.37 ± 0.05, p = 0.001). By fine-tuning models trained for other disease pathologies with MS-specific data, competitive models identifying existing MS plaques, new MS plaques, and active demyelination can be built with substantially smaller datasets than would otherwise be required to train new models.

Clinical Types of Movement Disorders in Patients with Multiple Sclerosis

Background Little is known about the true prevalence and clinical characteristics of movement disorders in early multiple sclerosis (MS), associated clinical disability and their effect on QOL. We conducted a cross sectional study to fill this knowledge gap. Objectives to study the prevalence of movement disorders in early stages of multiple sclerosis, presence of other clinical disability and their effect on QOL. Patients and method This is a cross sectional observational study. The patients group included 250 patients with RRMS whom were recruited consecutively from the MS clinic of Ain Shams and Nasr institute hospitals. Each eligible patient was interviewed and examined for presence of movement disorders, Patients were divided into 2 groups, group A without movement disorders and group B showing movement disorders. General and neurological examination including Expanded Disability Status Scale (EDSS) score at time of interview for both groups. Magnetic resonance imaging (MRI) of brain and cervical spinal cord (with contrast whenever available) obtained at the time of interview with documentation of MS plaques involvement for both groups. RRMS patients with movement disorders (group B) are subjected to different assessment for depression by Beck Depression Inventory (BDI), cognitive assessment by Montreal Cognitive Assessment (MOCA) scale, disability and quality of life (QOL) by the Short Form 36 Health Survey Questionnaire. Results This study included 250 RRMS. onset of their movement disorders was 2.69 ± 2.34 years from MS diagnosis with mean EDSS 3.515 ± 1.04. Cerebellar signs are present in 97% of total number of movement disorders and 26% of total sample, regarding tremors, 36 patients in this study showed tremors representing 53.7% of movement disorders patients, 14.4% of total sample of RRMS patients. This study showed presence of 5 cases of restless leg syndrome 7.5% of total number of MD. 4 cases of dystonia are present in this study representing 6% of MD patients. Patients with MD showed presence of depressive symptoms and cognitive affection with negative impact on QOL. Tremors severity is not correlated with either cognition or depression scores where ataxia is correlated with depression score only. MRI assessment of patients with MD showed higher lesion load and involvement of infratentorial structures especially cerebellum and its connections and cerebellum. Conclusion Movement disorders are common to occur than previously known especially ataxia and tremors early in the course of the disease. Presence of MD is related to high lesion load and strategic location of these lesions. special assessment of movement disorders as independent cause of disability with concomitant depression and cognitive impairment especially early in the disease course should be taken in consideration due to their negative impact on QOL.

Relationship between disability and psychiatric outcome in multiple sclerosis patients and its determinants

BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating central nervous system disease with diverse clinical manifestations. The present study aimed to compare the psychiatric outcomes of MS patients with full ambulatory versus impaired ambulatory function and identify the potential risk factors for disability in MS. Seventy MS patients were classified into two groups based on their Expanded Disability Status Scale (EDSS) scores, Group A: full ambulatory (EDSS ≤ 4.5) (N = 48), Group B: impaired ambulatory (EDSS ≥ 5) (N = 22). All participants were evaluated by the Socioeconomic Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Brief Psychiatric Rating Scale, and The Pittsburgh Sleep Quality Index.ResultsIn the total cohort (N = 70), females represented (77.1%). The mean age was 31.16 ± 6.46, the mean age of onset was 26 ± 6.083, and the mean disease duration was 5.33 ± 3.653 years which was less in Group A than in Group B. Relapsing–remitting multiple sclerosis (RRMS) was the most common presentation (80%), representing 93.6% of Group A. Group A reported more severe depression and anxiety, while Group B had more poor sleep quality. Correlation analysis showed increased relapses, progressive-relapsing multiple sclerosis (PRMS), cervical or dorsal plaques, sensory or motor manifestations, and precipitancy increased disability, while RRMS type decreased disability.ConclusionsFull ambulatory MS patients had high anxiety and depression, while impaired ambulatory MS patients had poor sleep quality. Associated factors for disability were frequent relapses, plaque location, MS subtype, sphincter, and sensory symptoms.Trial registration clinicaltrials.gov, NCT05029830. Registered: September 01, 2021, https://clinicaltrials.gov/ct2/show/NCT05029830

Introducing radiomics model to predict active plaque in multiple sclerosis patients using magnetic resonance images

Multiple Sclerosis (MS) is the most common non-traumatic disabling disease in young people. The prediction active plaque has the potential to offer new biomarkers for assessing the activity of MS disease. Consequently it supports patient management in the clinical setting and trials. This study aims to investigate the predictive capability of radiomics features for identifying active plaques in these patients using T2 FLAIR (Fluid Attenuated Inversion Recovery) images. For this purpose, a dataset images from 82 patients with 122 lesions was analyzed. Feature selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) method. Six different classifier algorithms, namely K-Nearest Neighbors (KNN), Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM), Naive Bayes (NB), and Random Forest (RF), were employed for modeling. The models were evaluated using 5-fold cross-validation, and performance metrics including sensitivity, specificity, accuracy, area under the curve (AUC), and mean squared error were computed. A total of 107 radiomics features were extracted for each lesion, and 11 robust features were identified through the feature selection process. These features consisted of four shape features (elongation, flatness, major axis length, mesh volume), one first-order feature (energy), one Gray Level Co-occurrence Matrix feature (correlation), two Gray Level Run Length Matrix features (gray level non-uniformity, gray level non-uniformity normalized), and three Gray Level Size Zone Matrix features (low gray level zone emphasis, size zone non-uniformity, small area low gray level emphasis). The NB classifier demonstrated the best performance with an AUC, sensitivity, and specificity of 0.85, 0.82, and 0.66, respectively. The findings indicate the potential of radiomics features in predicting active MS plaques in T2 FLAIR images.

The Effect of Sagittal STIR and FLAIR Sequences Compared to Sagittal T2-W for Characterizing MS Lesions in Cervical Spine MRI

Purpose: Multiple Sclerosis (MS) is an acute, autoimmune, and inflammatory disease in the central nervous system. This study investigated the effect of sagittal Short Tau Inversion Recovery (STIR) and T2-W Fluid Attenuated Inversion Recovery (FLAIR) sequences rather than sagittal T2-W as complementary sequences in patients with cervical spinal cord lesions and suspected MS.&#x0D; Materials and Methods: This cross-sectional study was performed on all individuals referred to the Shahid Ghazi MRI center in Sanandaj for six months. Sixty patients with a cervical spine MRI request that were suspected of having MS were examined. The number of MS plaques in the sagittal T2-W FSE, sagittal STIR, and sagittal T2-W FLAIR were recorded separately. A comparison between routine sequences and sequence supplementation has been made for characterizing MS plaque in the spine.&#x0D; Results: Results showed that the greatest agreement was related to sagittal STIR, and sagittal FLAIR (Cohen’s kappa = 0.56). Whereas the least agreement values were from sagittal T2-W and sagittal FLAIR, STIR and FLAIR, T2-W and FLAIR, T2-W and STIR (Cohen’s kappa = 0.20, 0.33, 0.48, 0.55), respectively. Sagittal STIR and sagittal FLAIR were excellent predictors for MS plaques diagnosis due to the area under the ROC curve = 0.56; sensitivity (95% CI) = [0.85 (0.73426 to 0.929044)] and specificity (95% CI) = [0.46 (0.336699 to 0.600035)].&#x0D; Conclusion: Results show that FLAIR T2-W images in sagittal sequence are appropriate for detecting lesions around spinal cord lesions. Furthermore, using thresholds obtained via statistical analysis, plaques in the cervical spinal cord can be identified in sagittal STIR images.

TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury.

During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. Axonal damage includes swelling, defects in transport, and failure to clear damaged intracellular proteins, all of which affect recovery and compromise neuronal integrity. The clearance of damaged cell components is important to maintain normal turnover and restore homeostasis. In this study, we used mass spectrometry to identify insoluble proteins within high-speed/mercaptoethanol/sarcosyl-insoluble pellets from purified white matter plaques isolated from the brains of individuals with relapsing-remitting MS (RRMS). We determined that the transmembrane protein 106B (TMEM106B), normally lysosome-associated, is insoluble in RRMS plaques relative to normal-appearing white matter from individuals with Alzheimer's disease and non-neurologic controls. Relative to wild-type mice, hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Additionally, the corpora callosa from cuprizone-challenged hypomorphic mice fail to clear lipid droplets efficiently during remyelination, suggesting that when TMEM106B is compromised, protein and lipid clearance by the lysosome is delayed. As TMEM106B contains putative lipid- and LC3-binding sites, further exploration of these sites is warranted.

The Diversity of Astrocyte Activation during Multiple Sclerosis: Potential Cellular Targets for Novel Disease Modifying Therapeutics.

Neuroglial cells, and especially astrocytes, constitute the most varied group of central nervous system (CNS) cells, displaying substantial diversity and plasticity during development and in disease states. The morphological changes exhibited by astrocytes during the acute and chronic stages following CNS injury can be characterized more precisely as a dynamic continuum of astrocytic reactivity. Different subpopulations of reactive astrocytes may be ascribed to stages of degenerative progression through their direct pathogenic influence upon neurons, neuroglia, the blood-brain barrier, and infiltrating immune cells. Multiple sclerosis (MS) constitutes an autoimmune demyelinating disease of the CNS. Despite the previously held notion that reactive astrocytes purely form the structured glial scar in MS plaques, their continued multifaceted participation in neuroinflammatory outcomes and oligodendrocyte and neuronal function during chronicity, suggest that they may be an integral cell type that can govern the pathophysiology of MS. From a therapeutic-oriented perspective, astrocytes could serve as key players to limit MS progression, once the integral astrocyte-MS relationship is accurately identified. This review aims toward delineating the current knowledge, which is mainly focused on immunomodulatory therapies of the relapsing-remitting form, while shedding light on uncharted approaches of astrocyte-specific therapies that could constitute novel, innovative applications once the role of specific subgroups in disease pathogenesis is clarified.

Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis

Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44hiCD4+ Tcells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-ɑ (IL-3Rɑ). Astrocytic and Tcell IL-3 elicited an immune migratory and chemotactic program by IL-3Rɑ+ myeloid cells that enhanced CNS immune cell infiltration, exacerbating MS and its preclinical model. Multiregional snRNA-seq of human CNS tissue revealed the appearance of IL3RA-expressing myeloid cells with chemotactic programming in MS plaques. IL3RA expression by plaque myeloid cells and IL-3 amount in the cerebrospinal fluid predicted myeloid and Tcell abundance in the CNS and correlated with MS severity. Our findings establish IL-3:IL-3RA as a glial-peripheral immune network that prompts immune cell recruitment to the CNS and worsens MS.

A backpack-based myeloid cell therapy for multiple sclerosis

Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS. We developed monocyte-adhered microparticles ("backpacks") for activating myeloid cell phenotype to an anti-inflammatory state through localized interleukin-4 and dexamethasone signals. We demonstrate that backpack-laden monocytes infiltrated into the inflamed CNS and modulated both the local and systemic immune responses. Within the CNS, backpack-carrying monocytes regulated both the infiltrating and tissue-resident myeloid cell compartments in the spinal cord for functions related to antigen presentation and reactive species production. Treatment with backpack-monocytes also decreased the level of systemic pro-inflammatory cytokines. Additionally, backpack-laden monocytes induced modulatory effects on TH1 and TH17 populations in the spinal cord and blood, demonstrating cross talk between the myeloid and lymphoid arms of disease. Backpack-carrying monocytes conferred therapeutic benefit in EAE mice, as quantified by improved motor function. The use of backpack-laden monocytes offers an antigen-free, biomaterial-based approach to precisely tune cell phenotype invivo, demonstrating the utility of myeloid cells as a therapeutic modality and target.

Inflammation and Epstein-Barr Virus at the Crossroads of Multiple Sclerosis and Post-Acute Sequelae of COVID-19 Infection.

Recent studies have strengthened the evidence for Epstein-Barr Virus (EBV) as an important contributing factor in the development of multiple sclerosis (MS). Chronic inflammation is a key feature of MS. EBV+ B cells can express cytokines and exosomes that promote inflammation, and EBV is known to be reactivated through the upregulation of cellular inflammasomes. Inflammation is a possible cause of the breakdown of the blood-brain barrier (BBB), which allows the infiltration of lymphocytes into the central nervous system. Once resident, EBV+ or EBV-specific B cells could both plausibly exacerbate MS plaques through continued inflammatory processes, EBV reactivation, T cell exhaustion, and/or molecular mimicry. Another virus, SARS-CoV-2, the cause of COVID-19, is known to elicit a strong inflammatory response in infected and immune cells. COVID-19 is also associated with EBV reactivation, particularly in severely ill patients. Following viral clearance, continued inflammation may be a contributor to post-acute sequelae of COVID-19 infection (PASC). Evidence of aberrant cytokine activation in patients with PASC supports this hypothesis. If unaddressed, long-term inflammation could put patients at risk for reactivation of EBV. Determining mechanisms by which viruses can cause inflammation and finding treatments for reducing that inflammation may help reduce the disease burden for patients suffering from PASC, MS, and EBV diseases.

Marburg Variant of Multiple Sclerosis: A Case Report

Multiple sclerosis (MS) is a demyelinating disorder with central nervous system (CNS) involvement, leading to varied presentations. It is an autoimmune disease characterised by chronic inflammation, demyelination, gliosis (plaques or scarring) and neuronal loss with relapsing or progressive course. MS plaques typically develop at different times and in different CNS locations (i.e., MS is said to be disseminated in time and space). The clinical course is extremely variable, ranging from a relatively benign condition to a rapidly evolving and incapacitating disease requiring profound lifestyle adjustments. MacDonald’s criteria are frequently used to diagnose MS. Rapidly, evolving severe forms of MS such as Marburg’s variant and Balo’s concentric sclerosis account for &lt;4% of total incidence of MS. The clinical course is rapid and often fatal. The exact aetiology behind this malignant nature of Marburg’s variant MS is unknown. In this case report, we will be discussing one such rare presentation of Marburg variant of MS.

Role of Diffusion Weighted Imaging and Apparent Diffusion Coefficient Value in Diagnosis of Asymptomatic / Inactive Multiple Sclerosis Plaques

Role of Diffusion Weighted Imaging and Apparent Diffusion Coefficient Value in Diagnosis of Asymptomatic / Inactive Multiple Sclerosis Plaques