Multiple Sclerosis Research Articles

Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies.

Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited. To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20. Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023. Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID. In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.

Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction

Multiple sclerosis (MS) is an autoimmune disease mediated by T helper cells, which is characterized by neuroinflammation, axonal or neuronal loss, demyelination, and astrocytic gliosis. Histone deacetylase inhibitors (HDACis) are noted for their roles in easing inflammatory conditions and suppressing the immune response. Panobinostat, an HDACi, is now being used in treating multiple myeloma. Nevertheless, the effect of panobinostat on autoimmune diseases remains largely unclear. Thus, our research endeavored to determine if the administration of panobinostat could prevent experimental autoimmune encephalomyelitis (EAE) in mice, one of the most commonly used animal models of MS, and further explored the underlying mechanisms. The EAE mice were generated and then administered continuously with panobinostat at a dosage of 30 mg/kg for 16 days. The results indicated that panobinostat markedly alleviated the clinical symptoms of EAE mice, inhibiting demyelination and loss of oligodendrocytes in the central nervous system (CNS). Moreover, panobinostat decreased inflammation and the activation of microglia and astrocytes in the spinal cords of EAE mice. Mechanistically, treatment with panobinosat significantly suppressed M1 microglial polarization by blocking the activation of toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/interferon regulatory factor 5 (IRF5) pathway. Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.

Engineered Immune Constructs Alter Antigen-Specific Immune Tolerance and Confer Durable Protection in Myelin-Driven Autoimmunity.

Autoimmune diseases are broadly characterized as a failure in immune tolerance. In multiple sclerosis (MS), autoreactive immune cells attack the protective myelin sheath lining neurons in the central nervous system. Therapeutic strategies that selectively and durably restore immune tolerance without broad immunosuppression are urgently needed for MS. Our lab has developed assemblies of immune constructs built entirely from myelin antigen (MOG35-55 or PLP139-151) and regulatory innate immune cues (GpG) using layer-by-layer self-assembly. Here, we present mechanistic and translational data showing these assemblies confer therapeutic benefits in a range of clinically relevant disease contexts, including progressive disease in male mice and in relapsing-remitting disease that mimics the intermittent bouts of disease and remission most MS patients initially experience. Here, the antigen component in the complexes is matched to the disease-causing antigen, resulting in a decrease in paralysis in these models. We show that subcutaneous delivery of assemblies durably prevents diseases and drives tolerance by regulatory remodeling of the draining lymph node. Importantly, we show that subcutaneously delivered assemblies recruit and expand antigen-specific regulatory T cells (TREGS) in draining lymph nodes. Finally, we find a shift of these recruited TREGS from a resting to an activated phenotype. Taken together, these data inform the design of therapeutics for antigen-specific tolerance that could combat autoimmunity by exploiting the role of innate pathways in a disease.

Resting state functional magnetic resonance imaging in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hemopoietic stem cell transplantation

BACKGROUND: Multiple sclerosis is a chronic autoimmune disease characterized by multifocal foci of demyelination in the central nervous system, usually affecting people of working age. The disease causes damage to the blood-brain barrier, the development of multifocal inflammation, destruction of the myelin sheath of axons and various degrees of damage. It is clinically manifested by restriction of motor activity, visual acuity, as well as other symptoms leading to loss of performance and disability of the patient. AIM: determination of changes in the functional connectivity of brain neural networks in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation by performing functional magnetic resonance imaging at rest. MATERIALS AND METHODS: The data of functional magnetic resonance imaging of patients with multiple sclerosis were analyzed in dynamics before and after the use of high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation. The study involved 25 patients with a verified diagnosis of multiple sclerosis. Each underwent complex magnetic resonance imaging at two time points (before and after high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation) with a difference of 12 months, which included structural magnetic resonance imaging - in order to exclude the presence of pathological foci in the brain (in addition to foci of multiple sclerosis) and functional magnetic resonance imaging.-resonance imaging at rest — to assess functional connectivity. Also, according to the method generally accepted in classical neurology, a clinical neurological examination was performed. RESULTS: At the stage of comparing data on the two groups obtained using functional magnetic resonance imaging at rest, changes in functional activity were detected in various parts of the brain, presumably responsible for clinical differences in the studied groups. CONCLUSION: Currently, the links between brain structures and morphological changes that cause cognitive impairment in multiple sclerosis are being studied. To predict the progression of the disease, the development of biomarkers, including those based on functional magnetic resonance imaging, is required. Evaluating changes in the functional connectivity of brain neural networks can help personalize therapeutic and rehabilitation approaches.

Patients with multiple sclerosis have higher rates of worsening following total hip arthroplasty: a propensity-matched analysis.

The progressive nature of multiple sclerosis (MS) may adversely affect outcomes following total hip arthroplasty (THA). As patient-reported outcome measures (PROMs) in this specific group are not well defined, this study aimed to compare the clinical outcomes and the rates of achieving the minimal clinically important difference for improvement (MCID-I) and worsening (MCID-W) between patients with MS and those without MS undergoing THA. We conducted a retrospective analysis of 375 THAs, including 75 MS patients and 300 propensity-matched non-MS patients (4:1), performed between 2016 and 2022. Collected PROMs included Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Mental and Physical, PROMIS Physical Function short form 10-a (PF-10a), and Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS). Preoperative and postoperative PROMs and MCID-I/MCID-W rates were compared. A total of 375 THAs, including 75 MS and 300 matched non-MS patients, were analysed. MS patients had higher 90-day postoperative complication rates (9.3% vs. 2.3%, p = 0.012) and infection rates (4.0% vs. 0.3%, p = 0.006). The rates of achieving MCID-I and MCID-W were similar for PROMIS Global Mental, PROMIS Global Physical, and HOOS-PS, but MS patients had a higher rate of experiencing MCID-W for PROMIS PF-10a compared to non-MS patients (16.7% vs. 6.5%, p = 0.022). Additionally, MS patients had a longer mean hospital stay (2.4 vs. 1.9 days, p = 0.005) and lower rates of being discharged home (82.7% vs. 94.3%, p < 0.001). The present study found that MS patients experience similar rates of MCID-I and MCID-W in most PROMs but have a higher rate of MCID-W for PROMIS PF-10a and increased postoperative complications. These findings highlight the need for careful consideration of postoperative risks despite potential improvements. Further research is needed to explore the impact of MS progression on PROMs and perioperative outcomes.

Changes in the sensory regions of the brain in patients with multiple sclerosis after complex neurorehabilitation according to resting functional magnetic resonance imaging

BACKGROUND: Multiple sclerosis is the one of leading causes of non-traumatic disability in young adult patients. An in-depth understanding of the processes of neuroplasticity underlying rehabilitation measures will ensure full and effective recovery of patients with this disease. AIM: To evaluate changes in the brain connectome in patients with multiple sclerosis in response to complex rehabilitation. MATERIALS AND METHODS: A prospective cohort study included 20 patients with relapsing-remitting multiple sclerosis (EDSS 1.5–6.5) in remission. All patients underwent comprehensive inpatient neurorehabilitation in a volume corresponding to individual rehabilitation needs for 5 weeks. To assess changes in the connectome, resting-state functional magnetic resonance imaging (rs-fMRI) was performed at three points: before the start of rehabilitation, immediately after its completion, and one month after discharge from the hospital. Statistical analysis is carried out using the CONN 7 (based on MathLab). Clinical neurological examination included examination using functional tests, passing questionnaires, and determining scores on the EDSS scale before and after rehabilitation. RESULTS: A total of 20 patients were examined, 13 of them at three control points. According to rs-fMRI data, clusters of decreased connectivity were identified between the left parahippocampal gyrus and the lateral cortex of the right occipital lobe, and between the right parahippocampal gyrus and the precuneus (p-FWE, p-FDR of cluster size and mass 0.05). Clusters of increased connectivity were determined between the left inferior temporal gyrus and the lateral occipital cortex of the left hemisphere, between the left middle temporal gyrus and the right frontal field, between the pole of the left temporal lobe and the lateral cortex of the left hemisphere (p-FWE, p-FDR of cluster size and mass 0.05). Other clusters of sufficient size demonstrated borderline statistical significance (individual adjusted p values for cluster size and mass exceeded 0.05). CONCLUSION: The identified changes indicate a functional reorganization of brain structures responsible for the perception of complex visual information, the functioning of executive control systems, as well as the implementation of memory and sequential action planning.

Automated assessment of brain MRIs in multiple sclerosis patients significantly reduces reading time.

Assessment of multiple sclerosis (MS) lesions on magnetic resonance imaging (MRI) is tedious, time-consuming, and error-prone. We evaluate whether assessment of new, expanding, and contrast-enhancing MS lesions can be done more time-efficiently by radiologists with assistance of artificial intelligence (AI). Baseline and three follow-up (FU) MRIs of thirty-five consecutive patients diagnosed with MS were assessed by a radiologist manually, and with assistance of an AI-tool. Results were discussed with a consultant neuroradiologist and time metrics were evaluated. The mean reading time for the resident radiologist was 9.05min (95CI: 6.85-11:25). With AI-assistance, the reading time was reduced by 2.83min (95CI: 3.28-2.41, p < 0.001). The reading decreased steadily from baseline to FU3 for the resident radiologist (9.85min baseline, 9.21 FU1, 8.64 FU2 and 8.44 FU3, p < 0.001). Assistance of AI further remarkably decreased reading times during follow-ups (3.29min FU1, 3.92 FU2, 3.79 FU3, p < 0.001) but not at baseline (0.26min, p = 0.96). The baseline reading time of the resident radiologist was 5.04min (p < 0.001), with each lesion adding 0.14min (p < 0.001). There was a substantial decrease in the baseline reading time from 5.04min to 1.59min (p = 0.23) with AI-assistance. Discussion of the reading results of the resident with the neuroradiology consultant (as usual in clinical routine) was exemplary done for FU-3 MRIs and added another 3min (CI:2.27-3.76) to the reading time without AI-assistance. We found that AI-assisted reading of MRIs of patients with MS may be faster than evaluating these MRIs without AI-assistance.

Sensor-Derived Measures of Motor and Cognitive Functions in People With Multiple Sclerosis Using Unsupervised Smartphone-Based Assessments: Proof-of-Concept Study.

Smartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem. This analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS). The proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated. A total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|<0.5). SDMs extracted from the manual dexterity tests showed either fair correlation (0.25≤|ρ|<0.5) or were not correlated (|ρ|<0.25) with the in-clinic 9-hole peg test and EDSS scores. Most selected SDMs from mobility tests showed fair correlation with the in-clinic timed 25-foot walk test and fair to moderate-to-good correlation (0.5<|ρ|≤0.75) with EDSS scores. SDM correlations with relevant patient-reported outcomes varied by functional domain, ranging from not correlated (cognitive test SDMs) to good-to-excellent correlation (|ρ|>0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely. Reported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials.

Altered Steroidome in Women with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ5 androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach.

Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine's impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (rs = -0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R2β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine's capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

Features of the vaginal microbiota in women with relapsing-remitting multiple sclerosis

Introduction. Multiple sclerosis (MS) is a chronic disease of the central nervous system predominantly affecting women of reproductive age. It is known that there is a high incidence of low urinary tract infections in MS. However, information about microbiology of the genital tract in women with MS is extremely limited.Aim. To study the qualitative and quantitative composition of the vaginal microflora in patients with MS.Materials and methods. 19 patients with relapsing-remitting MS of the main group and 19 healthy women of the control group, the qualitative and quantitative composition of the microflora in the vaginal secretion was determined using the polymerase chain reaction method in real time (a set of reagents was used to study the biocenosis of the urogenital tract in women, Femoflor 16, DNA-Technology, Moscow), a gynecological smear from the vagina was performed. The neurological status was assessed using the EDSS scale and The questionnaire on pelvic organ function. The following statistical indicators were determined: frequency, spread, average and χ² test.Results. A status of normocenosis was observed in the majority of women with MS (14 subjects, 73.7%), Lactobacillus bacteria were found in 16 subjects (84.2%), and an increased number of facultative anaerobes was identified in 7 subjects (37.4%), there were no significant differences with the comparator group. Bacteriological examination findings from vaginal smears did not show any signs of inflammation in either group. A high incidence of vaginal infections in anamnesis was reported in women with neurogenic lower urinary tract dysfunction (16 subjects, 84.2%).Conclusion. Data on the state of the vaginal biocenosis of women with MS has been presented for the first time. It was found the preservation of normocenosis with a tendency to shift the balance towards dysbiotic processes in the vagina.

Adalimumab induced CNS demyelination in a patient with multiple pre-existing autoimmune diseases; treatment contemplation.

Anti-TNF agents like Adalimumab are safe and effective for rheumatologic disorders, but they have been reported to cause demyelinating diseases like Multiple Sclerosis (MS). A 47-year-old woman with left hand weakness was evaluated. She had a previous medical history of Intermediate Uveitis (IU) and Rheumatoid arthritis (RA). anti-TNF-α treatment was initiated with adalimumab two years before this visit. MRI showed numerous T2-hyperintense lesions in bilateral periventricular, juxtacortical, and subcortical areas, which were absent in her scan before anti-TNF therapy. She was diagnosed with MS, and Adalimumab was discontinued. IV glucocorticoids (GCs) were administered with marked improvement. She was then started on anti-CD20 therapy with Rituximab. A year later, she was symptom-free, and her follow-up Brain MRI showed no new lesions. The link between MS and TNF-α inhibitors is poorly understood, but several hypotheses have been proposed. Discontinuing anti-TNF therapy alone may not be enough to prevent further demyelinating disease activity, and it is essential to consider the necessity of starting a disease-modifying treatment. Autoimmunity plays a significant role in rheumatologic and neurological diseases, and as personalized medicine advances, understanding genetic risk is crucial for selecting appropriate therapeutic targets. A thorough evaluation of a patient's family background is recommended before therapeutic decision-making, especially in patients with multiple autoimmune disorders, and the question of whether TNF-α is a suitable therapeutic target in patients with multiple autoimmune disorders is raised.

Reliability and Validity of the L Test in Persons With Multiple Sclerosis.

The L Test has been developed to assess balance and gait disorders. Our aim in this study was to estimate the test-retest reliability and validity of the L Test when used with 82 persons with multiple sclerosis (PwMS). For these participants, we examined the degree of agreement between the results of a first and second administration of the L Test (separated by one day), using Bland-Altman analysis and intra-class correlation coefficients (ICCs). We computed minimal detectable change (MDC) and standard error of measurement (SEM) values for the L Test and evaluated concurrent validity by correlating L Test results with the Timed Up and Go test (TUG) and the 10-minute Walk Test (10MWT). Prior to administering these measurements, we randomized the sequence of the test administrations to our participants. The Bland-Altman analysis showed that L Test was reproducible, with upper and lower limits of agreement of 0.99 and -1.45 seconds, respectively. The L Test demonstrated excellent test-retest reliability, with an ICC value of 0.996 (95% CI: 0.994-0.998). Cronbach's alpha coefficient was 0.996. The performance of the L Test is measured by seconds required to complete the task, and we found the L Test SEM value to be 0.35 seconds, and its MDC value to be 0.97 seconds. The L Test showed a strong correlation with both the TUG test (rho = 0.936; p < .001) and the 10MWT (rho = 0.925; p < .001). We concluded that the L Test is a reliable and valid \ tool for assessing functional mobility and balance in PwMS.

Decreased Expression of the EAAT5 Glutamate Transporter at Photoreceptor Synapses in Early, Pre-Clinical Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis

Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis. Methodology: In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites. Results: We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas. Conclusions: Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations.

Psychiatric considerations of multiple sclerosis

Multiple sclerosis is a degenerative neuroinflammatory disease that affects the central nervous system with a wide range of neurological and psychiatric symptoms. A correct differential diagnosis is crucial for the management of pathology and there are specific diagnostic methods. This study presents the case of a 53-year-old patient diagnosed with Strumpell-Lorrain disease resistant to psychopharmacological treatment for depression and anxiety who, after the change of diagnosis and therapy to multiple sclerosis, showed clinical improvement in psychiatric symptoms.

Emerging MRI biomarkers for the diagnosis of multiple sclerosis.

The need to improve diagnostic precision in multiple sclerosis (MS) is widely recognized. In recent years, several novel magnetic resonance imaging (MRI) biomarkers have been proposed to enhance diagnostic specificity and reduce misdiagnosis. Some of these imaging biomarkers are deemed highly specific for MS and are likely ready to enter the MS diagnostic work-up, while others are still in their exploratory phase. In addition, new synthetic MRI contrasts and artificial intelligence-based diagnostic algorithms are being tested to reduce the time burden related to imaging data acquisition and analysis. In this review, we summarize the most recent advancement in the field, focusing on the adoption of these novel MRI biomarkers-whether used alone or in combination-for the differential diagnosis of MS.

Development and initial validation of the Cognitive Change Scale (CCS).

Cognitive impairment is common in neurologic diseases. Precise measurement of cognitive change over time is necessary for isolating disease-related patterns from normal age-related decline. Existing measures of subjective cognition, however, focus on present status. There is, to our knowledge, no currently available self-report measure of cognitive change. We therefore developed the Cognitive Change Scale (CCS), which assesses perceived cognitive change in neurologic populations. A systematic mixed-methods process was followed for the scale design and validation. Associations of CCS responses to demographics, mood, and fatigue were examined in 131 persons with multiple sclerosis. A total of 46 participants also completed a cognitive test battery. Correlations of test scores with CCS responses were calculated. The 17-item CCS showed good reliability and validity. Results of exploratory and confirmatory factor analyses supported a four-factor structure, with items reflecting change in (1) general cognition, (2) language and executive function, (3) external feedback, and (4) use of coping strategies. Positive relationships of CCS scores with fatigue, depression, and anxiety were observed. Correlations of CCS scores with cognitive test performance did not reach significance. The CCS may be a useful cognitive outcome tool for treatment trials in neurologic populations.

Effectiveness and Feasibility of Blood Flow Restriction Training for People with Multiple Sclerosis: A Systematic Review

Effectiveness and Feasibility of Blood Flow Restriction Training for People with Multiple Sclerosis: A Systematic Review

Evaluation of the volume of brain structures in patients with multiple sclerosis at the disease onset as a marker of radiological specificities of its course

Evaluation of the volume of brain structures in patients with multiple sclerosis at the disease onset as a marker of radiological specificities of its course

All roads lead to cholesterol: Modulating lipid biosynthesis in multiple sclerosis patient-derived models

Studies from Ionescu etal.1 and Clayton etal.2 using multiple sclerosis (MS) patient-derived cell models underscore cholesterol metabolism's role in inflammatory and dysfunctional cell phenotypes in the disease. Inhibiting cholesterol biosynthesis ameliorated critical cellular phenotypes, emphasizing the need to further investigate this pathway as a potential target for MS treatment.