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CNS Neuroscience & Therapeutics Mar 2022Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with... (Review)
Review
Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with multiple sclerosis (MS). This systematic review aimed to provide a comprehensive overview of both in vitro and in vivo studies describing the pharmacokinetics, efficacy, safety, and mechanism of LA in MS-related experiments and clinical trials. A total of 516 records were identified by searching five databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane Library. Overall, we included 20 studies reporting LA effects in cell and mouse models of MS and 12 studies reporting LA effects in patients with MS. Briefly, cell experiments revealed that LA protected neurons by inhibiting the expression of inflammatory mediators and activities of immune cells. Experimental autoimmune encephalomyelitis mouse experiments demonstrated that LA consistently reduced the number of infiltrating immune cells in the central nervous system and decreased the clinical disability scores. Patients with MS showed relatively stable Expanded Disability Status Scale scores and better walking performance with few adverse events after the oral administration of LA. Notably, heterogeneity of this evidence existed among modeling methods, LA usage, MS stage, and trial duration. In conclusion, this review provides evidence for the anti-inflammatory and antioxidative effects of LA in both in vitro and in vivo experiments; therefore, patients with MS may benefit from LA administration. Whether LA can be a routine supplementary therapy warrants further study.
Topics: Animals; Antioxidants; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Multiple Sclerosis; Thioctic Acid
PubMed: 34964271
DOI: 10.1111/cns.13793 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983 -
Acta Neurologica Belgica Apr 2022Multiple Sclerosis (MS) is a disease determined by inflammatory demyelination and neurodegeneration in the Central Nervous System (CNS). Despite the extensive... (Review)
Review
INTRODUCTION AND AIM
Multiple Sclerosis (MS) is a disease determined by inflammatory demyelination and neurodegeneration in the Central Nervous System (CNS). Despite the extensive utilization of Complementary and Alternative Medicine (CAM) in MS, there is a need to have comprehensive evidence regarding their application in the management of MS symptoms. This manuscript is a Systematic Literature Review and classification (SLR) of CAM therapies for the management of MS symptoms based on the International Classification of Functioning Disability and Health (ICF) model.
METHOD
Studies published between 1990 and 2020 IN PubMed, Science Direct, Scopus, Pro-Quest, and Google Scholar using CAM therapies for the management of MS symptoms were analyzed.
RESULTS
Thirty-one papers on the subject were analyzed and classified. The findings of this review clearly show that mindfulness, yoga, and reflexology were frequently used for managing MS symptoms. Moreover, most of the papers used mindfulness and yoga as a CAM therapy for the management of MS symptoms, which mostly devoted to mental functions such as fatigue, depression, cognition, neuromuscular functions such as gait, muscle strength, and spasticity, and sensory function such as balance, in addition to, reflexology is vastly used to management of mental functions of MS patients.
CONCLUSION
Evidence suggested that CAM therapies in patients with MS have the potential to target and enhancement numerous elements outlined in the ICF model. Although the use of CAM therapies in MS symptom management is promising, there is a need for strict clinical trials. Future research direction should concentrate on methodologically powerful studies to find out the potential efficacy of CAM intervention.
Topics: Complementary Therapies; Fatigue; Gait; Humans; Multiple Sclerosis; Muscle Strength
PubMed: 35060096
DOI: 10.1007/s13760-021-01847-3 -
Multiple Sclerosis and Related Disorders Aug 2021Many studies have been conducted investigating a range of environmental factors which have been implicated in the pathogenesis of multiple sclerosis (MS). We collated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have been conducted investigating a range of environmental factors which have been implicated in the pathogenesis of multiple sclerosis (MS). We collated available data about exposure to domestic animals before symptom onset in MS to perform a systematic review and meta-analysis.
METHODS
Medline, Embase and Cinahl were searched for relevant articles, based on pre-defined inclusion and exclusion criteria and reference lists were hand-searched. Data were extracted and critical analysis was conducted using the Newcastle-Ottawa criteria. Meta-analysis used random effects.
RESULTS
Study heterogeneity was high and study quality was variable. Random effects meta-analysis showed no associations with any pet ownership and development of MS.
CONCLUSION
It is not possible to draw definitive conclusions from this work. The studies included had a high level of heterogeneity. There are many variables involved in pet ownership and exposure and the nature of the way these have been studied makes the analysis challenging.
Topics: Animals; Child; Humans; Multiple Sclerosis; Ownership
PubMed: 34090130
DOI: 10.1016/j.msard.2021.103046 -
Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. Siponimod (BAF312) is an oral treatment, a selective sphingosine-1-phosphate (S1P) receptor modulator, for the treatment of adults with relapsing forms of MS including active, secondary progressive MS with relapses.
OBJECTIVES
To assess the benefits and adverse effects of siponimod as monotherapy or combination therapy versus placebo or any active comparator for people diagnosed with MS.
SEARCH METHODS
On 18 June 2020, we searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Trials Register, which contains studies from CENTRAL, MEDLINE and Embase, and the trials registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). We also handsearched relevant journals and screened the reference lists of published reviews and retrieved articles and searched reports (2004 to June 2020) from the MS societies in Europe and America.
SELECTION CRITERIA
We included randomised parallel controlled clinical trials (RCTs) that evaluated siponimod, as monotherapy or combination therapy, versus placebo or any active comparator in people with MS. There were no restrictions on dose or administration frequency.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We discussed disagreements and resolved them by consensus among the review authors. Our primary outcomes wereworsening disability , relapse and adverse events, and secondary outcomes were annualised relapse rate, gadolinium-enhancing lesions, new lesions or enlarged pre-existing lesions and mean change of brain volume. We independently evaluated the certainty of evidence using the GRADE approach. We contacted principal investigators of included studies for additional data or confirmation of data.
MAIN RESULTS
Two studies (1948 participants) met our selection criteria, 608 controls and 1334 treated with siponimod. The included studies compared siponimod with placebo. Overall, all studies had a high risk of bias due to selective reporting and attrition bias. Comparing siponimod administered at a dose of 2 mg to placebo, we found that siponimod may reduce the number of participants with disability progression at six months (56 fewer people per 1000; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.65 to 0.94; 1 study, 1641 participants; low-certainty evidence) and annualised relapse rate (RR 0.43, 95% CI 0.34 to 0.56; 2 studies, 1739 participants; low-certainty evidence). But it might lead to little reduction in the number of participants with new relapse (166 fewer people per 1000; RR 0.38, 95% CI 0.15 to 1.00; 1 study, 94 participants; very low-certainty evidence). We observed no evidence of a difference due to adverse events for siponimod at 2 mg compared to placebo (14 more people per 1000; RR 1.52, 95% CI 0.85 to 2.71; 2 studies, 1739 participants, low-certainty evidence). In addition, due to the high risk of inaccurate magnetic resonance imaging (MRI) data in the two included studies, we could not combine data for active lesions on MRI scans. Both studies had high attrition bias resulting from the unbalanced reasons for dropouts among groups and high risk of bias due to conflicts of interest. Siponimod may reduce the number of gadolinium-enhancing T1-weighted lesions at two years of follow-up (RR 0.14, 95% CI 0.10 to 0.19; P < 0.0001; 1 study, 1641 participants; very low-certainty evidence). There may be no evidence of a difference between groups in the number of participants with at least one serious adverse event excluding relapses (113 more people per 1000; RR 1.80, 95% CI 0.37 to 8.77; 2 studies, 1739 participants; low-certainty evidence) at six months. No data were available regarding cardiac adverse events. In terms of safety profile, the most common adverse events associated with siponimod were headache, back pain, bradycardia, dizziness, fatigue, influenza, urinary tract infection, lymphopenia, nausea, alanine amino transferase increase and upper respiratory tract infection. These adverse events have dose-related effects and rarely led to discontinuation of treatment.
AUTHORS' CONCLUSIONS
Based on the findings of the RCTs included in this review, we are uncertain whether siponimod interventions are beneficial for people with MS. There was low-certainty evidence to support that siponimod at a dose of 2 mg orally once daily as monotherapy compared with placebo may reduce the annualised relapse rate and the number of participants who experienced disability worsening, at 6 months. However, the certainty of the evidence to support the benefit in reducing the number of people with a relapse is very low. The risk of withdrawals due to adverse events requires careful monitoring of participants over time. The duration of all studies was less than 24 months, so the efficacy and safety of siponimod over 24 months are still uncertain, and further exploration is needed in the future. There is no high-certainty data available to evaluate the benefit on MRI outcomes. We assessed the certainty of the body of evidence for all outcomes was low to very low, downgraded due to serious study limitations, imprecision and indirectness. We are uncertain whether siponimod is beneficial for people with MS. More new studies with robust methodology and longer follow-up are needed to evaluate the benefit of siponimod for the management of MS and to observe long-term adverse effects. Also, in addition to comparing with placebo, more new studies are needed to evaluate siponimod versus other therapeutic options.
Topics: Adult; Azetidines; Benzyl Compounds; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
PubMed: 34783010
DOI: 10.1002/14651858.CD013647.pub2 -
Nutrients Jun 2023Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS).... (Meta-Analysis)
Meta-Analysis Review
Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.
Topics: Adult; Female; Humans; Dietary Supplements; Fatigue; Multiple Sclerosis; Vitamin D; Male
PubMed: 37447189
DOI: 10.3390/nu15132861 -
Outcome in chronic inflammatory demyelinating polyneuropathy: A systematic review and meta-analysis.Muscle & Nerve Oct 2023Outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) have been reported in longitudinal and cross-sectional studies. A considerable variation in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION/AIMS
Outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) have been reported in longitudinal and cross-sectional studies. A considerable variation in long-term disease outcome has appeared in those reports. To overcome this uncertainty, a systematic review and meta-analysis was conducted on CIDP outcomes, including the parameters of case fatality rate, ambulation, physical ability, and remission.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was conducted in PubMed and EMBASE (OVID) for reports with at least 2 years of follow-up on patients with active or previously active CIDP that were published no later than May 12, 2022. Studies were appraised for quality using the Joanna Briggs Institute Critical Appraisal Checklist for studies reporting prevalence data. Pooled analyses were conducted and the results were visualized using forest plots. The study protocol was registered prospectively on PROSPERO (CRD42021266903).
RESULTS
A total of 1290 titles were identified. Sixty-nine full-text articles were screened and 21 studies with 1199 patients were selected for the data analysis. The pooled case fatality rate was 3.3% (95% confidence interval [CI], 1.9% to 5.7%). The pooled fraction of nonambulatory patients was 8.2% (95% CI, 5.7% to 11.6%) and, overall, 47.1% (95% CI, 39.5% to 54.9%) of CIDP patients had a good outcome without disability. The pooled rate of remission was 40.8% (95% CI, 30.6% to 51.8%).
DISCUSSION
Future research is warranted on how to prevent long-term impairment in CIDP. Care should be taken in developing clinical strategies to avoid immunomodulating therapy in the many patients in remission.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Cross-Sectional Studies; Prevalence
PubMed: 36928889
DOI: 10.1002/mus.27820 -
European Addiction Research 2021Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties,...
INTRODUCTION
Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive.
METHODS
We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019.
RESULTS
Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers' levels.
DISCUSSION
Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators' levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.
Topics: Analgesics; Cannabis; Humans; Inflammation Mediators; Multiple Sclerosis
PubMed: 32726782
DOI: 10.1159/000508840 -
Neurodegenerative Disease Management Oct 2022Many neurodegenerative conditions are chronic disorders and result in a range of debilitating symptoms, with many people turning to complementary therapies. A systematic... (Meta-Analysis)
Meta-Analysis Review
Many neurodegenerative conditions are chronic disorders and result in a range of debilitating symptoms, with many people turning to complementary therapies. A systematic review and meta-analysis were conducted to investigate the evidence on effectiveness of aromatherapy and reflexology on all neurodegenerative conditions. We identified nine eligible studies (total sample n = 504 participants) all of which were on multiple sclerosis only. A meta-analysis was conducted including data from six studies, which demonstrated no significant benefit of aromatherapy/reflexology; however, the sample sizes were small and of low quality. This systematic review confirmed that it is not possible to draw conclusions regarding the effectiveness of reflexology and aromatherapy in multiple sclerosis. Larger high-quality studies are required to test these widely used therapies.
Topics: Aromatherapy; Humans; Massage; Multiple Sclerosis; Musculoskeletal Manipulations; Neurodegenerative Diseases
PubMed: 35770590
DOI: 10.2217/nmt-2021-0056