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BMC Neurology Mar 2018Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population.... (Review)
Review
BACKGROUND
Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS.
METHODS
The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice.
RESULTS
The revised International Pediatric MS group diagnostic criteria improved the accuracy of diagnosis. Identification of red flags and mimickers (e.g. acute disseminated encephalomyelitis and neuromyelitis optica) are vital before establishing a definitive diagnosis. Possible etiology and mechanisms including both environmental and genetic risk factors are highlighted. Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age. Although no therapeutic randomized clinical trials were conducted in pediatric cohorts, open-label multi-center studies reported efficacy and safety results with beta interferons, glatiramer acetate and natalizumab in similar adult cohorts. Several randomized clinical trials assessing the efficacy and safety of oral disease-modifying therapies are ongoing in pediatric MS patients.
CONCLUSION
Pediatric MS has been increasingly recognized to have a more inflammatory course with frequent infratentorial presentations at onset, which would have important implications in the future management of pediatric cohorts while awaiting the results of ongoing clinical trials.
Topics: Adolescent; Child; Female; Humans; Male; Multiple Sclerosis; Risk Factors
PubMed: 29523094
DOI: 10.1186/s12883-018-1026-3 -
Seminars in Immunopathology Nov 2019Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting... (Review)
Review
Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting multiple sclerosis (RRMS), the most common initial presentation (85%) among which, if not treated, about half will transform, into the secondary progressive multiple sclerosis (SPMS) and the primary progressive MS (PPMS) (15%) that is directly progressive without superimposed clinical relapses. Inflammation is present in all subsets of MS. The relapsing/remitting form could represent itself a particular interest for the study of inflammation resolution even though it remains incomplete in MS. Successful resolution of acute inflammation is a highly regulated process and dependent on mechanisms engaged early in the inflammatory response that are scarcely studied in MS. Moreover, recent classes of disease-modifying treatment (DMTs) that are effective against RRMS act by re-establishing the inflammatory imbalance, taking advantage of the pre-existing endogenous suppressor. In this review, we will discuss the active role of regulatory immune cells in inflammation resolution as well as the role of tissue and non-hematopoietic cells as contributors to inflammation resolution. Finally, we will explore how DMTs, more specifically induction therapies, impact the resolution of inflammation during MS.
Topics: Animals; Biomarkers; Disease Management; Disease Susceptibility; Humans; Immune System; Immunomodulation; Inflammation; Multiple Sclerosis
PubMed: 31732775
DOI: 10.1007/s00281-019-00765-0 -
ASN Neuro 2015The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not... (Review)
Review
The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.
Topics: Animals; Dietary Supplements; Gastrointestinal Tract; Humans; Life Style; Microbiota; Multiple Sclerosis; Nutritional Physiological Phenomena; Rats
PubMed: 25694551
DOI: 10.1177/1759091414568185 -
BMJ (Clinical Research Ed.) Apr 2015
Review
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Diagnosis, Differential; Disease Progression; Humans; Immunosuppressive Agents; Multiple Sclerosis; Prognosis; Recurrence; Risk Factors
PubMed: 25872511
DOI: 10.1136/bmj.h1765 -
American Family Physician May 2013
Review
Topics: Humans; Multiple Sclerosis; Prognosis; Risk Factors
PubMed: 23939450
DOI: No ID Found -
Multiple Sclerosis and Related Disorders Sep 2016We present international consensus recommendations for improving diagnosis, management and treatment access in multiple sclerosis (MS). Our vision is that these will be... (Review)
Review
INTRODUCTION
We present international consensus recommendations for improving diagnosis, management and treatment access in multiple sclerosis (MS). Our vision is that these will be used widely among those committed to creating a better future for people with MS and their families.
METHODS
Structured discussions and literature searches conducted in 2015 examined the personal and economic impact of MS, current practice in diagnosis, treatment and management, definitions of disease activity and barriers to accessing disease-modifying therapies (DMTs).
RESULTS
Delays often occur before a person with symptoms suggestive of MS sees a neurologist. Campaigns to raise awareness of MS are needed, as are initiatives to improve access to MS healthcare professionals and services. We recommend a clear treatment goal: to maximize neurological reserve, cognitive function and physical function by reducing disease activity. Treatment should start early, with DMT and lifestyle measures. All parameters that predict relapses and disability progression should be included in the definition of disease activity and monitored regularly when practical. On suboptimal control of disease activity, switching to a DMT with a different mechanism of action should be considered. A shared decision-making process that embodies dialogue and considers all appropriate DMTs should be implemented. Monitoring data should be recorded formally in registries to generate real-world evidence. In many jurisdictions, access to DMTs is limited. To improve treatment access the relevant bodies should consider all costs to all parties when conducting economic evaluations and encourage the continuing investigation, development and use of cost-effective therapeutic strategies and alternative financing models.
CONCLUSIONS
The consensus findings of an international author group recommend a therapeutic strategy based on proactive monitoring and shared decision-making in MS. Early diagnosis and improved treatment access are also key components.
Topics: Brain; Humans; Multiple Sclerosis; Time Factors
PubMed: 27640924
DOI: 10.1016/j.msard.2016.07.003 -
BMC Neurology Mar 2014There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of... (Review)
Review
Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis.
BACKGROUND
There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials.
METHODS
We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.
RESULTS
For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).
CONCLUSIONS
Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.
Topics: Clinical Trials as Topic; Disability Evaluation; Humans; Multiple Sclerosis; Psychometrics
PubMed: 24666846
DOI: 10.1186/1471-2377-14-58 -
Behavioural Neurology 2018
Topics: Cognitive Dysfunction; Humans; Multiple Sclerosis
PubMed: 29576817
DOI: 10.1155/2018/4831647 -
Cold Spring Harbor Perspectives in... Jun 2018The microbiome can be defined as the sum of the microbial and host's genome. Recent information regarding this complex organ suggests that in animal models of multiple... (Review)
Review
The microbiome can be defined as the sum of the microbial and host's genome. Recent information regarding this complex organ suggests that in animal models of multiple sclerosis (MS), the composition of the gut microbiome can be altered, giving rise to both the effector and regulatory phases of central nervous system (CNS) demyelination. Experimental findings during the past decade in animal models of MS have provided clear evidence for the significant role of gut microbes in both the effector and regulatory phase of this condition. There is mounting evidence in preliminary human studies suggesting that a dysbiotic MS gut microbiome could affect disease progression. We propose considering the gut microbiome as a key organ for the regulation of tolerance mechanisms and speculate that the gut microbiome is the major environmental risk factor for CNS demyelinating disease. Accordingly, we hypothesize that intervention of the gut microbiome could result in safer novel therapeutic strategies to treat MS.
Topics: Animals; Disease Progression; Gastrointestinal Microbiome; Humans; Multiple Sclerosis; Neuroimmunomodulation
PubMed: 29311123
DOI: 10.1101/cshperspect.a029017 -
Multiple Sclerosis (Houndmills,... Oct 2023Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem.
BACKGROUND
Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem.
OBJECTIVE
Describe the prevalence, determinants and consequences of delayed diagnoses.
METHODS
This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures.
RESULTS
Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores ( = 0.03; = 0.034) and greater -score of the blood neurofilament light chain ( = 0.35; = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis ( = 63; 43.2%) had a trend towards greater EDSS scores ( = 0.06; = 0.006) and number of total ( = 0.13; = 0.040) and periventricular ( = 0.06; = 0.039) brain lesions.
CONCLUSION
Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.
Topics: Adult; Humans; Multiple Sclerosis; Delayed Diagnosis; Prevalence; Multiple Sclerosis, Relapsing-Remitting; Recurrence; Magnetic Resonance Imaging; Brain
PubMed: 37840276
DOI: 10.1177/13524585231197076