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International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
Ageing Research Reviews Sep 2022To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical markers of neuroplasticity and the association thereof in healthy young and older adults and in patients with multiple sclerosis, Parkinson's disease, and stroke.
DESIGN
Systematic review and robust variance estimation meta-analysis with meta-regression.
DATA SOURCES
Systematic search of MEDLINE, Web of Science, and CINAHL databases.
RESULTS
Fifty studies with 60 intervention arms and 2283 in-analyses participants were included. Due to the low number of studies, the three patient groups were combined and analyzed as a single group. Overall, low- (g=0.19, p = 0.024) and high-intensity exercise (g=0.40, p = 0.001) improved neuroplasticity. Exercise intensity scaled with neuroplasticity only in healthy young adults but not in healthy older adults or patient groups. Exercise-induced improvements in neuroplasticity were associated with changes in motor but not cognitive outcomes.
CONCLUSION
Exercise intensity is an important variable to dose and individualize the exercise stimulus for healthy young individuals but not necessarily for healthy older adults and neurological patients. This conclusion warrants caution because studies are needed that directly compare the effects of low- vs. high-intensity exercise on neuroplasticity to determine if such changes are mechanistically and incrementally linked to improved cognition and motor function.
Topics: Aged; Biomarkers; Cognition; Exercise; Humans; Multiple Sclerosis; Neuronal Plasticity; Resistance Training
PubMed: 35853549
DOI: 10.1016/j.arr.2022.101698 -
Neuroepidemiology 2015Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS... (Review)
Review
Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies.
Topics: Disease Progression; Female; Humans; Male; Multiple Sclerosis, Relapsing-Remitting; Phenotype; Prognosis; Recurrence; Risk Factors
PubMed: 25997994
DOI: 10.1159/000382130 -
Nutrients Sep 2021Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on...
Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on intermittent fasting and obesity, diabetes, and multiple sclerosis was carried out. The scientific quality of the methodology and the results obtained were evaluated in pairs. Intermittent fasting has beneficial effects on the lipid profile, and it is associated with weight loss and a modification of the distribution of abdominal fat in people with obesity and type 2 diabetes as well as an improvement in the control of glycemic levels. In patients with multiple sclerosis, the data available are too scarce to draw any firm conclusions, but it does appear that intermittent fasting may be a safe and feasible intervention. However, it is necessary to continue investigating its long-term effects since so far, the studies carried out are small and of short duration.
Topics: Diabetes Mellitus, Type 2; Fasting; Glycemic Control; Humans; Multiple Sclerosis; Obesity; Randomized Controlled Trials as Topic
PubMed: 34579056
DOI: 10.3390/nu13093179 -
Journal of Neurology Oct 2021Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder characterised by muscle weakness and impaired sensory function. The present... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder characterised by muscle weakness and impaired sensory function. The present study provides a comprehensive literature review of the burden of illness of CIDP.
METHODS
Systematic literature search of PubMed, Embase, and key conferences in May 2019. Search terms identified studies on the epidemiology, humanistic burden, current treatment, and economic burden of CIDP published since 2009 in English.
RESULTS
Forty-five full texts and nineteen conference proceedings were identified on the epidemiology (n = 9), humanistic burden (n = 7), current treatment (n = 40), and economic burden (n = 8) of CIDP. Epidemiological studies showed incidence and prevalence of 0.2-1.6 and 0.8-8.9 per 100,000, respectively, depending on geography and diagnostic criteria. Humanistic burden studies revealed that patients experienced physical and psychosocial burden, including impaired physical function, pain and depression. Publications on current treatments reported on six main types of therapy: intravenous immunoglobulins, subcutaneous immunoglobulins, corticosteroids, plasma exchange, immunosuppressants, and immunomodulators. Treatments may be burdensome, due to adverse events and reduced independence caused by treatment administration setting. In Germany, UK, France, and the US, CIDP economic burden was driven by direct costs of treatment and hospitalisation. CIDP was associated with indirect costs driven by impaired productivity.
CONCLUSIONS
This first systematic review of CIDP burden of illness demonstrates the high physical and psychosocial burden of this rare disease. Future research is required to fully characterise the burden of CIDP, and to understand how appropriate treatment can mitigate burden for patients and healthcare systems.
Topics: Adrenal Cortex Hormones; Cost of Illness; Humans; Immunoglobulins, Intravenous; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 32583051
DOI: 10.1007/s00415-020-09998-8 -
Multiple Sclerosis (Houndmills,... Feb 2023Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid.
OBJECTIVE
To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off.
METHODS
PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models.
RESULTS
A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1.
CONCLUSION
The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.
Topics: Humans; Multiple Sclerosis; Immunoglobulin kappa-Chains; Oligoclonal Bands; Immunoglobulin G; Demyelinating Diseases; Biomarkers
PubMed: 36453167
DOI: 10.1177/13524585221134213 -
European Journal of Physical and... Dec 2017Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely... (Review)
Review
INTRODUCTION
Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. The aim of this study was to systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option.
EVIDENCE ACQUISITION
The databases PubMed, Scopus, WoS and PEDro were searched to identify relevant reports published from January 1, 2011 to April 30, 2016.
EVIDENCE SYNTHESIS
Of 306 articles identified, only 10 fulfilled the inclusion criteria: 5 randomized controlled, 2 simple randomized quasi-experimental, 1 semi-experimental, 1 blind controlled pilot and 1 pilot.
CONCLUSIONS
Evidence that aquatic treatment improves quality of life in affected patients was very good in two studies, good in four, fair in two and weak in two.
Topics: Exercise Therapy; Humans; Hydrotherapy; Multiple Sclerosis; Quality of Life; Treatment Outcome
PubMed: 28215060
DOI: 10.23736/S1973-9087.17.04570-1 -
The Cochrane Database of Systematic... Sep 2015Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS.
OBJECTIVES
To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so.
MAIN RESULTS
Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing-remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value < 0.01). However, there was significant heterogeneity between trials (I(2) > 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to -0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non-exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly.
AUTHORS' CONCLUSIONS
Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome.
Topics: Adult; Exercise Therapy; Fatigue; Humans; Multiple Sclerosis; Physical Conditioning, Human; Physical Endurance; Randomized Controlled Trials as Topic; Resistance Training; Yoga
PubMed: 26358158
DOI: 10.1002/14651858.CD009956.pub2 -
The Lancet. Neurology Oct 2017Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT.
METHODS
In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots.
FINDINGS
Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01).
INTERPRETATION
The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research.
FUNDING
None.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Optic Neuritis; Retina; Tomography, Optical Coherence; Young Adult
PubMed: 28920886
DOI: 10.1016/S1474-4422(17)30278-8 -
Neurocritical Care Jun 2023Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the...
BACKGROUND
Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates.
METHODS
A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format.
RESULTS
Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication.
CONCLUSIONS
These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.
Topics: Adult; Humans; Guillain-Barre Syndrome; Prognosis; Reproducibility of Results; Respiration, Artificial; Respiratory Insufficiency
PubMed: 36964442
DOI: 10.1007/s12028-023-01707-3