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.

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.

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.

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.

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.

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.

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.