Multiple sclerosis treatments a review of current biomedical engineering approaches.

Multiple Sclerosis (MS) is an autoimmune condition targeting the central nervous system (CNS) characterized by focal demyelination with inflammation, causing neurodegeneration and gliosis. This is accompanied by a refractory period in relapsing MS or chronic progression in primary progressive MS. Current MS treatments target disease relapses and aim to reduce further demyelination and disability. These include the treatment of acute exacerbations through global immunomodulation upon corticosteroid administration, which are accompanied by adverse reactions. Disease modifying therapies (DMTs) which provide targeted immunosuppression of T and B cells, and sequestration of leukocytes out of CNS, have led to further improvements in demyelination prevention and disease burden reduction. Despite their efficacy, DMTs are ineffective in remyelination, pathology reversal and have minimal effects in progressive MS. The advent of modern biomedical engineering approaches in combination with a better understanding of MS pathology, has led to the development of novel, regenerative approaches to treatment. Such treatments utilize neural stem cells (NSCs) and can reduce disease relapses and reverse damage caused by the disease through localized tissue regeneration. While at initial stages, pre-clinical and clinical studies utilizing NSCs and immune modulation have shown promising outcomes in tissue regeneration, creating a potential new era in MS therapy.

Long-term effects of siponimod on cardiovascular and autonomic nervous system in secondary progressive multiple sclerosis.

Background: Siponimod, a second-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, represents an important therapeutic choice for active secondary progressive multiple sclerosis (SPMS). Besides the beneficial immunomodulatory effects, siponimod impacts cardiovascular function through S1PR1 modulation. Short-term vagomimetic effects on cardiac activity have proved to be mitigated by dose titration. However, long-term consequences are less known. Objectives: This study aimed to investigate the long-term impact of siponimod on cardiac autonomic modulation in people with SPMS (pwSPMS). Methods: Heart rate variability (HRV) and vascular hemodynamic parameters were evaluated using Multiple Trigonometric Regressive Spectral analysis in 47 pwSPMS before siponimod therapy and after one, three, six and 12 months of treatment. Autonomic activation tests (tilt test for the sympathetic and deep breathing test for the parasympathetic cardiac modulation) were performed at each examination. Results: pwSPMS preserved regular cardiovascular modulation responses during the autonomic tests reflected in the variation of several HRV parameters, such as RMSSD, pNN50, total power of HRV, high-frequency and low-frequency bands of the spectral domain or hemodynamic vascular parameters (Cwk, Zao, TPR, MAP) and baroreflex sensitivity (BRS). In the long-term follow-up, RMSSD, pNN50, total power, BRS and CwK presented a significant decrease, underlining a reduction of the parasympathetic and a shift towards sympathetic predominance in cardiac autonomic modulation that tends to stabilise after 1 year of treatment. Conclusion: Due to dose titration, the short-term effects of siponimod on cardiac autonomic modulation are mitigated. The long-term impact on cardiac autonomic modulation is similar to fingolimod. The autonomic activation tests showed normal cardiovascular responses during 1-year follow-up in pwSPMS, confirming the safety profile of siponimod. Further research on autonomic function could reveal whether the observed sympathetic activation is a compensatory response to S1P signaling intervention or a feature of the disease, while also shedding light on the role of S1PR modulation in MS.

Effects of robotic rehabilitation on fatigue experience, disability, and quality of life in patients with multiple sclerosis (MS): A systematic review and meta-analysis.

Background: Rehabilitation plays an important role in improving symptoms in patients with multiple sclerosis (MS). There are studies evaluating the effects of robotic rehabilitation in patients with MS, but the results varied between the studies. So, we designed this systematic review and meta-analysis to estimate pooled effects of robotic rehabilitation on fatigue, disability, and quality of life in subjects with MS. Methods: We systematically searched PubMed, Scopus, EMBASE, Web of Science, Google Scholar, and also gray literature including references of the included studies, and also conference abstracts on October 1th 2022. Data regarding the total number of participants, first author, publication year, country of origin, mean age, EDSS, and results of fatigue and quality of life were recorded. Results: The first literature search revealed 6878 results, after deleting duplicates, 5019 studies remained. Two researchers, evaluated the titles and abstracts, and finally 77 full texts were assessed. For meta-analysis, we included 11 studies. The pooled Standardized Mean Difference (SMD) of Kurtzke Expanded Disability Status Scale (EDSS) (after-before) estimated as -0.56 (95%CI: -0.89,-0.23). The pooled SMD of Fatigue Severity Scale (FSS) estimated as -0.54(95%CI: -1.06, -0.01) (I2=66.7%, P=0.01). The pooled SMD of physical health subscale of multiple sclerosis quality of life (MSQOL-54) estimated as 0.36(95%CI:-0.23, 0.96) (I2=51.4%, P=0.1). The pooled SMD of mental health subscale of MSQOL54 estimated as 0.48 (95%CI: 0.07, 0.88) (I2=0%, P=0.6). Conclusions: The results of this systematic review and meta-analysis show that robotic rehabilitation has positive effects on fatigue, and disability in patients with MS.

Multiple sclerosis in a patient with Takayasu's Arteritis: A case report.

Background: Multiple sclerosis (MS) and Takayasu's arteritis (TAK) are two autoimmune diseases that affect the Central nervous system (CNS), but the relationship between them has not been established. Case Presentation: Here we report the emergence of MS during treatment. Takayasu's arteritis in a 24-year-old Iranian woman with a severe presentation. She was treated aggressively with IV methylprednisolone 1 g/day for 3 days and continued with oral prednisolone, also IV cyclophosphamide monthly. After 2 months, loss of vision led to a diagnosis of Optic neuritis (ON) caused by concomitant MS. Conclusion: Differentiating CNS vasculitis associated with Takayasu's arthritis from coexisting MS affecting the CNS is challenging and what is important is to avoid giving a TNF inhibitor.

Exploring the effectiveness of circuit training rehabilitation on balance, gait, and fatigue in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: People with Multiple Sclerosis (PwMS) often experience imbalance, gait dysfunction, and fatigue. Circuit Training (CT) can be viable for improving balance, gait, and fatigue in MS. To the author's knowledge, no studies have systematically reviewed the existing literature evaluating the effectiveness of CT in PwMS. OBJECTIVES: To investigate the effectiveness of CT in improving balance, gait, and reducing fatigue in PwMS and provide a quantitative and qualitative synthesis of Randomized Controlled Trials (RCTs). DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Google Scholar, and PEDro Database (Dec 2021 to May 2024). STUDY SELECTION: RCTs using CT in PwMS including balance, gait, or fatigue outcomes. DATA SYNTHESIS: Search inclusion criteria were: i) available full text, ii) CT rehabilitation, iii) balance, gait, or fatigue measured as outcomes, and iv) articles in English. Full text articles were analyzed by two screeners. If there was disagreement regarding inclusion, a further reviewer was consulted. No discrepancies were found. RESULTS: We identified 878 studies, 14 studies were eligible including 716 PwMS with a mean (standard deviation) age of 49.9 (10.9) years, disease duration of 10.8 (7.2) years, and Expanded Disability Status Scale score of 4.3 (0.9) points. RevMan 5.4.1 was used to run the meta-analysis. We found a significant overall effect on Berg Balance Scale (Mean Difference (MD) = 6.07 points, 95%CI:1.40,10.75; p = 0.01) and in Fatigue Severity Scale (MD = 0.98 points, 95%CI:0.30,1.66; p = 0.005) in favor of CT. We did not find a significant effect in Timed Up and Go (MD = 0.46 second, 95%CI:-0.04,0.96; p = 0.07), in Six-Minute Walk Test (MD = 17.46 m, 95%CI:-8.06,42.97; p = 0.18), and in Modified Fatigue Impact Scale (MD = 3.34 points, 95%CI:-0.41,7.09; p = 0.08) in favor of CT. We assessed methodological quality using RoB 2.0, and quality of evidence using GRADE. LIMITATIONS: Small number of studies, all identifying having some risk of bias. CONCLUSION: Circuit training can have positive effects on PwMS in terms of increasing balance, gait, and reducing fatigue. Further research is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021286834. CONTRIBUTION OF THE PAPER.

Living With Multiple Sclerosis: The Rainbow of Inspiring Experiences and Resilience in the Face of the Disease.

INTRODUCTION: Multiple sclerosis (MS), a leading cause of disability in young adults worldwide, including in Iran, affects their whole life so common care is no longer effective. In this regard, context-based approaches should be considered for a holistic care delivery that accords with the patients' inputs. We aimed to explore patients' understanding of MS and their personal experiences of living with this disease. METHODS: A qualitative descriptive study was conducted. The data were collected through in-depth, semi-structured interviews with 17 patients. These patients were selected using a purposive sampling method, and the data were analyzed using a conventional content analysis approach. FINDINGS: Three main categories and nine subcategories were identified: Thunder and Lightning strike in the form of Displeasure, Social wrong beliefs, Experiences of Constraints, Interference with Life Stages and Dark Spots on the Horizon of the Future; Subtle Beam consisting of Extrinsic Light Radiation, Reflection of Individual Effort and Formation of a Rainbow by Resilience and Hope for a Bright Future. CONCLUSION: By offering multidimensional support, patients reported a shift from fear to a vibrant life. Although research often focuses on the negative aspects of MS, this study recognizes both positive and negative aspects. These findings can contribute to future interventional research. PATIENT OR PUBLIC CONTRIBUTION: During the explanation of research goals and consent acquisition, participants were reminded that sharing their experiences could provide valuable insights benefiting others coping with or at risk of the same disease. Additionally, during data analysis, codes extracted were reviewed and improved with active participant involvement.

The Effectiveness of Vitamin D Intake in Improving Symptoms and Relapses of Multiple Sclerosis: A Systematic Review.

There are disagreements over the effectiveness of vitamin D supplementation in treating multiple sclerosis (MS) patients' symptoms and reducing relapses. The goal of this systematic review is to assess the effect of vitamin D supplements on improving symptoms and relapses in MS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted by searching eight databases: Embase, PubMed, Cochrane Library, MEDLINE, CINAHL, Web of Science, Scopus, and Google Scholar. The RoB 2 tool was used to evaluate the quality of the studies that were included in the analysis. From the 1,345 studies identified, 16 randomized controlled trials were selected. All studies reported that vitamin D administration significantly increased the mean serum 25(OH)D compared with the placebo group. Also, most included studies revealed a significant improvement in magnetic resonance imaging (MRI) brain lesion markers. However, most studies showed that being treated with vitamin D instead of placebo showed no significant effect on relapse rates, fatigue, Expanded Disability Status Scale (EDSS), serum neurofilament light chain (NfL), calcium, and cytokine levels, except for quality-of-life transforming growth factor beta (TGF-ß). This systematic review shows that the effect of vitamin D supplements on improving symptoms and relapses during treatment in MS patients remains inconclusive.

Corticosteroid-induced bradycardia following high-dose methylprednisolone administration: a case report.

Introduction: Besides their wide use in the clinical field due to their anti-inflammatory and immune-modulating effect, corticosteroids still have a lot of adverse effects. The most common adverse effects are hyperglycemia, hypertension, osteoporosis, psychosis, immunosuppression, weight gain, and hyperlipidemia. Another important side effect is cardiac arrhythmias. Case presentation: We report a case of a 43-year-old woman with multiple sclerosis who developed symptomatic bradycardia after 3 days of treatment with a high dose of methylprednisolone. The patient received a dose of atropine and her bradycardia resolved after 36 h of stopping methylprednisolone. Discussion: While tachyarrhythmias are more common, bradyarrhythmias such as bradycardia and premature atrial or ventricular contraction are rare but crucial to be considered. Conclusion: Corticosteroid-induced bradycardia is usually in sinus rhythm and has an unknown etiology, possibly occurring at high and low doses. The majority of cases in the literature were asymptomatic and resolved spontaneously.

Female sexual dysfunctions in multiple sclerosis patients with lower urinary tract symptoms: an Italian case-control study.

Background: Multiple sclerosis (MS) is a recurrent, autoimmune, and inflammatory demyelinating chronic disease that typically manifests in young adulthood and exerts adverse effects on sexual functions. Aim: The study evaluated the prevalence of sexual dysfunctions (SDs) and the relationship with neurological disability, depression, and lower urinary tract symptoms (LUTS) in a cohort of MS female patients, comparing these results with those of healthy women. Methods: From January 2023 to January 2024, consecutive premenopausal female patients with MS, were recruited and the examination included urinalysis, ultrasonography and a urodynamic test according to the International Continence Society standard. Outcomes: Descriptive statistics were reported as mean and standard deviation for continuous variables (analyzed by independent samples Mann-Whitney U test and independent samples Kruskal-Wallis test) while categorical variables were reported as frequency and percentage (analyzed by chi-square test with Fisher's exact test). Results: Female Sexual Function Index (FSFI) total score and all FSFI subscales scores were significantly lower in patients with MS vs healthy control subjects (P < .001); FSFI total scores and all FSFI subscale scores were statistically significantly lower in patients with MS with an International Prostate Symptom Score ≥20 (P < .001) and considering a cutoff for Beck Depression Inventory-II score ≥17, depression was present in 61% (n = 47 of 77) of patients with MS and completely absent in the control group. Clinical Translation: The knowledge that SDs are a common problem in MS and in other chronic illnesses can alleviate the feeling of stigma and talking openly of sexual problems can be helpful for the patients and so the doctor-patient relationship can be reinforced. Strengths and Limitations: The sample was drawn from a single center, and larger multicenter studies that include both genders are needed to obtain strong results. Conclusion: Our findings confirm the idea of a polygenic and multifactorial etiology of female SDs in MS. Therefore, women with MS should be evaluated in terms of SDs during follow-ups.

Pectin-stabilized nanoceria double coated with lactoferrin/chitosan for management of experimental autoimmune encephalomyelitis.

Cerium oxide nanoparticles are a unique antioxidant mimicking the activity of natural antioxidant enzymes. Previous research showed its' promising effect mitigating free radical damage in neurodegenerative disorders. However, there is still unmet therapeutic needs due to poor BBB penetration, a high accumulation in liver, kidney and spleen. This study aimed to synthesize and optimize nanoceria stabilized by natural bioactive polymers suitable for intranasal administration to manage multiple sclerosis. Among the different employed biopolymers, pectin-stabilized nanoceria exhibited the ideal properties with small particles size 87.20 ±â€¯3.43 nm, high zeta potential -56.37 ±â€¯2.39 mV and high free radical scavenging activity 85.27 ±â€¯0.07 %. Then coating was achieved for the first time by two biopolymers: lactoferrin and chitosan producing a double coated cationic nanoceria. Biological assessment involved using experimental autoimmune encephalomyelitis animal model treated in a dose of 1 mg/kg nanoceria for 15 days. Motor function testing in rats revealed 6- and 17-folds increase in latency time in rotating rod and hanging wire tests, respectively. Biochemical analysis revealed significant reduction in lipid peroxidation along with about 1-fold upgrading of the intrinsic antioxidant system. Moreover, histologic examination disclosed decreased degeneration of the brain and spinal cord of treated rats and much decreased liver toxicity.

The cost-of-illness of multiple sclerosis in Jordan.

BACKGROUND: Multiple Sclerosis (MS) imposes a significant financial burden on health-care systems. This study aims to determine the cost-of-illness (COI) for MS in Jordan, a country where data on the economic impact of MS are scarce. METHODS: Data were collected for one year, annual COI was estimated using a cross-sectional snowball sampling design. Eligible patients completed a self-reported questionnaire to provide sociodemographic, physician visit, and diagnostic and laboratory test data. Indirect costs were estimated using an adjusted Human Capital Approach. RESULTS: This study included 383 patients, (73% females, 61% between 26-45). Eighty % took disease-modifying therapies (DMTs), and 40% had relapses in that year. One-third use non-DMTs and equipment for assistance. The average annual cost per patient was $11,719 (direct costs=$11,252, indirect costs=$467). The total annual cost for all participants was $748,299. The estimated cost of non-DMT, medical tools, diagnostic tests, and hospitalization per patient was $53, 51, 99, and 235 respectively. CONCLUSION: High costs of DMTs state the necessity of resource optimization in Jordan public healthcare facilities. Such findings yield policy-informing actionable insights, suggesting strategic investments in more cost-effective DMTs with potential improvement in accessibility and reduction in the overall economic burden faced by both patients and governments.

Clinical Problem-Solving: A 19-Year-Old Woman With Progressive Neurological Decline and Multiple Intracranial Lesions.

The differential diagnosis for multiple intracranial lesions in a young adult is broad and includes demyelinating, neoplastic, and infectious etiologies. In this report, we describe the case of a 19-year-old immunocompetent woman presenting with progressive headaches and aphasia. MRI of the brain revealed multiple, large supratentorial lesions with concentric bands of alternating T2 signal intensities and peripheral contrast enhancement. Cerebrospinal fluid (CSF) analysis was overall bland with negative oligoclonal bands. Serum antibody testing for neuromyelitis optica (NMO) and myelin-oligodendrocyte associated disease (MOGAD) were negative. A broad infectious work-up was also unrevealing. A definitive diagnosis was ultimately obtained after brain biopsy and the patient was started on appropriate therapy. This case highlights a diagnostic framework in evaluating immunocompetent patients presenting with multiple intracranial lesions and progressive neurological decline. The main differential diagnoses for this constellation of radiological and clinical findings are discussed and a literature review is performed on the revealed diagnosis. Lastly, both acute and long-term therapeutic approaches are reviewed.

Cutaneous infection with Mycobacterium chelonae in a patient with multiple sclerosis.

Cutaneous infections caused by Mycobacterium chelonae can present with a variety of clinical symptoms, depending on the patient's immune status. Here, we report a case involving a 46-year-old woman with multiple sclerosis who developed a cutaneous infection caused by M. chelonae. The initial presentation included skin discoloration on her right wrist, which progressed to a granuloma. Following surgical intervention, the infection led to tissue atrophy and the formation of a deep cavity at the site. Upon identification of the causative pathogen, a treatment regimen consisting of clarithromycin and moxifloxacin was initiated and continued for seven months. The patient showed signs of recovery, with the swelling and deep cavity resolving; however, some redness at the site persists. The patient remains under treatment.

Microstructural Changes in the Corpus Callosum in Neurodegenerative Diseases.

The corpus callosum, the largest white matter structure in the brain, plays a crucial role in interhemispheric communication and cognitive function. This review examines the microstructural changes observed in the corpus callosum across various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). New neuroimaging studies, mainly those that use diffusion tensor imaging (DTI) and advanced tractography methods, were put together to show how changes have happened in the organization of white matter and the connections between them. Some of the most common ways the corpus callosum breaks down are discussed, including less fractional anisotropy, higher mean diffusivity, and atrophy in certain regions. The relationship between these microstructural changes and cognitive decline, motor dysfunction, and disease progression is explored. Additionally, we consider the potential of corpus callosum imaging as a biomarker for early disease detection and monitoring. Studies show that people with these disorders have lower fractional anisotropy and higher mean diffusivity in the corpus callosum, often in ways that are specific to the disease. These changes often happen before gray matter atrophy and are linked to symptoms, which suggests that the corpus callosum could be used as an early sign of neurodegeneration. The review also highlights the implications of these findings for understanding disease mechanisms and developing therapeutic strategies. Future directions, including the application of advanced imaging techniques and longitudinal studies, are discussed to elucidate the role of corpus callosum degeneration in neurodegenerative processes. This review underscores the importance of the corpus callosum in understanding the pathophysiology of neurodegenerative diseases and its potential as a target for therapeutic interventions.

Acute Hemorrhagic Leukoencephalitis in a Patient With Hepatitis B.

Acute hemorrhagic leukoencephalitis (AHLE), also known as Weston-Hurst syndrome or Hurst disease, is a rare and rapidly progressive form of acute disseminated encephalomyelitis. It is characterized by severe inflammation, hemorrhage, and necrosis within the white matter of the brain. AHLE often follows an upper respiratory infection or other systemic illnesses, suggesting a potential post-infectious autoimmune mechanism. The disease is associated with a high mortality rate and significant disability among survivors. We present the case of a 46-year-old Indian woman with a history of chronic hepatitis B (HBV) who presented with an insidious onset of right-sided limb weakness and bi-frontal headaches. Initial brain MRIs showed features of tumefactive demyelination. Despite aggressive treatment with intravenous (IV) methylprednisolone, IV immunoglobulin, and anti-edema measures, the patient's condition rapidly deteriorated, leading to a diagnosis of AHLE following the emergence of hemorrhagic white matter lesions on repeat MRI. Remarkably, with continued treatment, the patient survived and showed gradual neurological improvement, although she remained significantly debilitated at the time of discharge. AHLE represents one of the most severe forms of demyelinating diseases, often resulting in rapid neurological decline and high mortality. This case highlights the potential link between chronic HBV infection with a high viral load and the onset of AHLE. The patient's recovery underscores the importance of early recognition and aggressive treatment in improving outcomes, even in conditions with traditionally poor prognosis. Clinicians should maintain a high index of suspicion for AHLE in patients with chronic viral infections presenting with neurological symptoms. Prompt and aggressive management can be life-saving, and ongoing research is needed to better understand the pathogenesis and optimal treatment strategies for this rare but devastating condition.

A cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS).

INTRODUCTION: There is a high prevalence of cognitive difficulties in MS, but despite this, there are few programmes targeting cognition that focus on the ability to function well in everyday life. The Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS), an occupation-focused cognitive intervention, was developed to address this. It addresses both the functional difficulties and the wide-ranging symptoms that present in MS. OBJECTIVE: Here we report on the results of a cluster-randomised controlled feasibility trial (ISRCTN11462710; registered 4th September 2019) evaluating the COB-MS in terms of feasibility and initial efficacy as a cognitive intervention for people with MS. METHOD: The eight-session COB-MS intervention was delivered remotely by occupational therapists to participants with MS in the intervention group. Following the end of the trial the COB-MS was delivered to the wait-list control group. Data was collected from people with MS experiencing cognitive difficulties at baseline, post-intervention, 12-weeks, and 6-month follow-up. The primary outcome measure was the Goal Attainment Scaling at 12 weeks. Data was also collected in the domains of cognition, quality of life, and mood. RESULTS: One hundred and eighteen people with MS and cognitive difficulties were randomised to either usual care (n = 60) or COB-MS intervention (n = 58). Ninety-four participants were retained at 6-month follow-up. The COB-MS was found to be feasible, including trial procedures and protocol. Data indicates that the COB-MS is accepted by participants and had positive impacts on daily life. Those allocated to the COB-MS group had a significant improvement in the primary outcome compared to the control condition. Progression criteria set for the feasibility trial have been met therefore further testing of the COB-MS at a definitive trial is supported by the results. CONCLUSION: The results provide a strong basis for a pathway to a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. TRIAL REGISTRATION: ISRCTN11462710 Date of registration: 4th September 2019.

Disease-Modifying Symptomatic Treatment (DMST): The Potential Role of Vortioxetine in the Treatment of Depression in Patients with Multiple Sclerosis.

In multiple sclerosis (MS), alongside the physical symptoms, individuals often grapple with anxiety and depressive symptoms as prevalent comorbidity. Mood disturbances, frequently undertreated in clinical practice, significantly impact the quality of life of individuals with MS, exacerbating disability and hindering overall well-being. Furthermore, traditional antidepressant therapies are often associated with adverse events, such as sexual side effect, weight gain, which could limit their use in these patients. Vortioxetine is one of the most innovative antidepressant drugs in the current pharmacopeia. Its pharmacological profile includes serotonin reuptake inhibition, antagonism for hydroxytryptamine (HT) receptors 5-HT3, 5-HT1D and 5-HT7, partial agonism for 5-HT1B, and agonism for 5-HT1A. It has been shown to have a beneficial effect on depression-related cognitive dysfunction, as well as on anxiety, depression, anhedonia and emotional blunting. Recently a potential anti-inflammatory action was also described. Limited clinical studies have specifically explored the efficacy of vortioxetine in treating depressive symptoms in MS. However, extrapolating from existing research in major depressive disorder, it is plausible that vortioxetine's multimodal mechanism could provide a favorable therapeutic approach. This position paper, which summarizes the output of annual clinical meeting held by the DMSTs in MS Italian Study Group, is focused on the possible role that vortioxetine could play as symptomatic treatment (ST) of depressed patients with MS, hypothesizing a direct impact on the clinical course of the disease.

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (ß = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: ß = -0.020, P = 7.203 × 10-5; right: ß = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: ß = -0.030, P = 2.175 × 10-8; right: ß = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (ß = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

Algorithms for the first-line management of bladder, bowel and sexual dysfunction in multiple sclerosis: Present and future.

INTRODUCTION: Neurogenic lower urinary tract (NLUTD), bowel (NBD), and sexual dysfunction (SD) are commonly observed in patients with (pw) multiple sclerosis (MS) and diminish the patients' quality of life (QoL). This systematic review aim to evaluate and discuss the current algorithms for the management of these issues. METHODS: A systematic review was conducted on the PubMed in June 2024. The primary search criterion was the presence of the term 'algorithm/s' or 'management/ing' in the title and/or abstract, followed by the MeSH term 'multiple sclerosis' and a combination of free-text keywords referring to NLUTD, NBD or SD. RESULTS: Fifteen articles regarding NLUTD were considered eligible, only one regarding SD while none addressed NBD. DISCUSSION: Numerous studies emphasize the profound impact of urinary and bowel symptoms on the QoL and morbidity in pwMS. Few algorithms addressing NLUTD are designed for first-line physicians and addresses the key priorities in MS care. Specific approaches to NBD management in pwMS are lacking. Screening for SD requires a structured assessment to deliver appropriate solutions. CONCLUSION: NLUTD, NBD, and SD are underdiagnosed and undertreated. The implementation of straightforward algorithms for first-line physicians could enhance the management of these common issues, improve the QoL, reduce costs, and ensure appropriate referral to specialists.

Pediatric inflammatory leukoencephalopathies.

Acquired demyelinating syndromes (ADS) represent acute neurologic illnesses characterized by deficits persisting for at least 24hours and involving the optic nerve, brain, or spinal cord, associated with regional areas of increased signal on T2-weighted images. In children, ADS may occur as a monophasic illness or as a relapsing condition, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Almost all young people with MS have a relapsing-remitting course with clinical relapses. Important strides have been made in delineating MS from other ADS subtypes. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin 4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) were once considered variants of MS; however, studies in the last decade have established that these are in fact distinct entities. Although there are clinical phenotypic overlaps between MOGAD, AQP4-NMOSD, and MS, cumulative biologic, clinical, and pathologic evidence allows discrimination between these conditions. There has been a rapid increase in the number of available disease-modifying therapies for MS and novel treatment strategies are starting to appear for both MOGAD and AQP4-NMOSD. Importantly, there are a number of both inflammatory and noninflammatory mimics of ADS in children with implications of management for these patients in terms of treatment.