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Neurology India 2021Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions.... (Review)
Review
BACKGROUND
Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions. Incorrect diagnosis poses a significant risk to patients, it may lead to delays in management, increased morbidity, and also adds to the financial cost.
OBJECTIVE
The aim of this study was to highlight strategies for the efficient differentiation of multiple sclerosis from other diseases which may masquerade as MS clinico-radiologically.
MATERIAL AND METHODS
A systematic literature review was conducted through online databases including PubMed and Medline. Relevant publications on radiological aspects of multiple sclerosis, white matter diseases and mimickers of Multiple sclerosis were included in the analysis.
RESULTS
Common mimickers of MS include small vessel disease, acute disseminated encephalomyelitis, neuromyelitis optica, anti-MOG encephalomyelitis, vasculitis, and CADASIL. Contrast-enhanced MRI study performed using MS protocol on high strength MRI system evaluated following a structured protocol along with clinical correlation is effective in differentiating MS from its mimickers.
CONCLUSIONS
Contrast-enhanced MRI performed on a high strength scanner using MS protocol with structured protocol for evaluation along, with a better collaboration between radiologists and clinicians may help in minimizing errors in diagnosis of multiple sclerosis.
Topics: Encephalomyelitis; Encephalomyelitis, Acute Disseminated; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Neuromyelitis Optica
PubMed: 34979638
DOI: 10.4103/0028-3886.333497 -
Journal of Neuroimmunology Jan 2022Since the emergency use approval of different types of COVID-19 vaccines, several safety concerns have been raised regarding its early and delayed impact on the nervous...
BACKGROUND
Since the emergency use approval of different types of COVID-19 vaccines, several safety concerns have been raised regarding its early and delayed impact on the nervous system.
OBJECTIVE
This study aims to systematically review the reported cases of CNS demyelination in association with COVID-19 vaccination, which has not been performed, to our knowledge.
METHODS
A systematic review was performed by screening published articles and preprints of cases of CNS demyelination in association with COVID-19 vaccines in PubMed, SCOPUS, EMBASE, Google Scholar, Ovid and medRxiv databases, until September 30, 2021. This study followed PRISMA guidelines. Descriptive findings of reported cases were reviewed and stratified by demographic and clinical findings, diagnostic work-up, management, and overall outcome.
RESULTS
A total of 32 cases were identified, with female predominance (68.8%) and median age of 44 years. Eleven cases were reported after Pfizer vaccine, 8 following AstraZeneca vaccine, 6 following Moderna, 5 following Sinovac/ Sinopharm vaccines, and one following each of Sputnik and Johnson&Johnson vaccines. The majority of cases (71.8%) occurred after the first dose of the vaccine, with neurological symptoms manifesting after a median of 9 days. The most common reported presentations were transverse myelitis (12/32) and MS-like pictures (first diagnosis or a relapse) in another 12/32 cases, followed by ADEM- like (5/32), and NMOSD- like (3/32) presentations. History of a previous immune-mediated disease was reported in 17/32 (53.1%) cases. The mRNA-based vaccines resulted in the greatest number of demyelinating syndromes (17/32), followed by viral vector vaccines (10/32), and inactivated vaccines (5/32). Most MS-like episodes (9/12) were triggered by mRNA-based vaccines, while TM occurred following both viral vector and mRNA-based vaccines. Management included high dose methylprednisolone, PLEX, IVIg, or a combination of those, with a favorable outcome in the majority of case; marked/complete improvement (25/32) or stabilized/ partial recovery in the remaining cases.
CONCLUSION
This systematic review identified few cases of CNS demyelination following all types of approved COVID-19 vaccines so far. Clinical presentation was heterogenous, mainly following the first dose, however, half of the reported cases had a history of immune-mediated disease. Favorable outcome was observed in most cases. We suggest long-term post-marketing surveillance for these cases, to assess for causality, and ensure the safety of COVID-19 vaccines.
Topics: COVID-19; COVID-19 Vaccines; Demyelinating Autoimmune Diseases, CNS; Humans; SARS-CoV-2
PubMed: 34839149
DOI: 10.1016/j.jneuroim.2021.577765 -
Multiple Sclerosis and Related Disorders Feb 2018Physical activity may be neuroprotective in multiple sclerosis (MS). One review (2011) of exercise and MS disability was inconclusive, but highlighted the need for more... (Review)
Review
BACKGROUND
Physical activity may be neuroprotective in multiple sclerosis (MS). One review (2011) of exercise and MS disability was inconclusive, but highlighted the need for more studies.
OBJECTIVE
To perform an updated systematic literature review examining the relationship between physical activity and physical ability outcomes in persons with MS.
METHODS
EMBASE and MEDLINE were searched for original interventional studies (2011-2016) evaluating exercise on quantitative outcomes of physical disability in MS. We also assessed any reported adverse outcomes.
RESULTS
Of the 153 articles identified, 12 were included; 3 examined endurance training; 6 resistance training; and 3 explored less conventional exercises, specifically, tai chi, kickboxing, and vestibular rehabilitation, each lasting 5-24 weeks. In total, 568 unique individuals were included, and >10 different scales used to assess outcomes. Endurance training provided benefits in walking ability, while mindfulness exercises (tai chi and vestibular rehabilitation), and dynamic workouts (kickboxing) led to improvements in balance and coordination. Resistance training alone did not improve walking ability, but improved lower limb muscular strength and endurance. When resistance and endurance training were combined, improvements were seen in mobility, balance and coordination. Four studies assessed discontinuation; most reported a return to pre-intervention function. Adverse outcomes were reported in 6 studies, and appeared generally mild, ranging from mild muscle soreness to exacerbation of MS symptoms.
CONCLUSIONS
Physical activity was associated with measurable benefits on ability outcomes, but continuation is likely required to maintain benefits. While adverse events were generally mild, approximately half of studies actually reported safety outcomes.
Topics: Disability Evaluation; Exercise; Humans; Multiple Sclerosis
PubMed: 29414293
DOI: 10.1016/j.msard.2018.01.021 -
BMC Neurology May 2013Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.
METHODS
We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.
RESULTS
We identified 33 case-control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I(2) = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I(2) = 0%) in individual's ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I(2) = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I(2) = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I(2) = 35%). The combined OR of 15 studies (N = 2,380) looking at "surgery" before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I(2) = 71%).
CONCLUSIONS
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.
Topics: Case-Control Studies; Databases, Factual; Humans; Multiple Sclerosis; Risk Factors
PubMed: 23648120
DOI: 10.1186/1471-2377-13-41 -
Multiple Sclerosis and Related Disorders Jan 2023Seizures in people with multiple sclerosis (MS) are reported; however, the risk of epilepsy in adults with MS remains poorly defined. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Seizures in people with multiple sclerosis (MS) are reported; however, the risk of epilepsy in adults with MS remains poorly defined.
METHODS
We performed a systematic review and meta-analysis to evaluate the incidence and prevalence of epilepsy in adults (≥ 18 years) with MS compared to those without. We searched MEDLINE and EMBASE from inception to July 1, 2022 to include observational studies that reported the prevalence or incidence of epilepsy in adults with MS and a comparator group, consisting of adults without MS or the general population. We used the Newcastle Ottawa Scale to evaluate quality of the included studies. We performed random-effects meta-analyses to determine the prevalence and incidence of epilepsy in adults with MS compared to the non-MS group.
RESULTS
We identified 17 studies consisting of 192,850 adults with MS, across nine countries. Most studies were of moderate quality as they did not specify the MS type or type of seizures. Compared to a comparison group, both the prevalence (pooled OR 2.04; 95% confidence interval 1.59-2.63, I = 95.4, n = 12) and the incidence of epilepsy (pooled RR 3.34; 3.17-3.52, I = 4.6%, n = 6) was higher in people with MS. Heterogeneity in estimates was not explained by additional analyses.
CONCLUSIONS
MS is an independent risk factor for both incident and prevalent epilepsy, suggesting variation in grey matter involvement over the disease course. Longitudinal studies are required to help identify patient and disease characteristics associated with epilepsy.
Topics: Adult; Humans; Multiple Sclerosis; Epilepsy; Seizures; Risk Factors; Incidence
PubMed: 36434909
DOI: 10.1016/j.msard.2022.104421 -
Multiple Sclerosis and Related Disorders Mar 2023The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.
METHODS
We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.
RESULTS
Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.
DISCUSSION
EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
Topics: Adult; Humans; Multiple Sclerosis; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Cladribine
PubMed: 36848839
DOI: 10.1016/j.msard.2023.104581 -
Neuroepidemiology 2022The causes of multiple sclerosis (MS) are not fully understood, yet. Genetic predisposition, environmental and lifestyle factors as well as an interplay thereof... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The causes of multiple sclerosis (MS) are not fully understood, yet. Genetic predisposition, environmental and lifestyle factors as well as an interplay thereof constitute relevant factors in the development of MS. Especially early-life risk factors such as having been breastfed may also be of relevance. Breast milk provides the newborn not only with essential nutrients and vitamins but also with numerous immune-active molecules, metabolites, oligosaccharides, and microbial components that are important for the development of the immune system. We present a systematic review and meta-analysis on the influence of having been breastfed during infancy on the risk of developing MS.
METHODS
The databases MEDLINE, Cochrane Library, and Web of Science were systematically searched for studies on breastfeeding and MS published between database inception and May 18, 2022. Observational studies comparing persons with MS to healthy controls with regard to having been breastfed during the first 2 years of life were eligible for inclusion. A random effects meta-analysis was calculated to estimate pooled effect sizes using the Mantel-Haenszel method for dichotomous outcomes. The Newcastle-Ottawa Scale was used for quality analysis.
RESULTS
15 studies (13 case-control, 2 cohort) were included of which 12 were rated as high quality. The meta-analysis of crude odds ratios (ORs) yielded a risk estimate of ORcrude = 0.82 (95% confidence interval [CI]: 0.70-0.96) for MS in breastfed versus non-breastfed individuals with substantial heterogeneity (I2 = 68.2%). Using adjusted OR, when available, reduced heterogeneity (I2 = 48.9%) and resulted in an ORadjusted = 0.86 (95% CI: 0.75-0.99). Restricting the analysis to studies with high-quality scores (i.e., ≥6/9 points) resulted in a combined ORcrude of 0.79 (95% CI: 0.66-0.94) and an ORadjusted = 0.83 (95% CI: 0.71-0.98), respectively.
DISCUSSION/CONCLUSION
The meta-analysis showed a small protective effect of having been breastfed on MS risk. This adds to the knowledge that breastfeeding is beneficial for the immunological health of a child. Future studies on the influence of having been breastfed on MS risk should apply a uniform definition of breastfeeding and investigate possible sex-specific aspects.
Topics: Child; Infant, Newborn; Male; Female; Humans; Breast Feeding; Multiple Sclerosis; Risk Factors; Time Factors
PubMed: 36096115
DOI: 10.1159/000526895 -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
Journal of Neurology Mar 2023Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple sclerosis (PwMS). Systematic synthesis of these findings is crucial in deriving credible conclusions.
METHODS
Five databases were searched from their inception to March 2022. The inclusion criteria for studies were MS-specific and required RNFL and cognitive performance data in order to be analyzed. The selection processes followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The systematic review yielded 31 studies that investigated the association between RNFL thickness and cognitive performance. Twenty-two studies reported positive associations, and nine did not. The meta-analysis included 11 studies with a total of 782 PwMS with mean age of 40.5 years, mean Expanded Disability Status Scale (EDSS) of 2.7, and disease duration of 11.3 years. RNFL thickness was significantly associated Symbol Digit Modalities Test (pooled r = 0.306, p < 0.001), Paced Auditory Serial Addition Test (pooled r = 0.374, p < 0.001) and Word List Generation (WLG, pooled r = 0.177, p < 0.001). RNFL was also significantly correlated with visuospatial learning and memory tests (pooled r = 0.148, p = 0.042) and verbal learning and memory tests (pooled r = 0.245, p = 0.005). Within three eligible studies, no significant association between ganglion cell inner-plexiform layer and SDMT 0.083 (95% CI - 0.186, 0.352) was noted. The heterogeneity was high in all correlation studies (I > 63% and p < 0.008) except for the WLG and visuospatial memory findings.
CONCLUSION
RNFL thickness is associated with cognitive processing speed, verbal learning and memory, visual learning and memory, as well as verbal fluency in PwMS. The number of studies included in the meta-analyses were limited due to non-standardized reporting.
Topics: Humans; Adult; Multiple Sclerosis; Nerve Fibers; Tomography, Optical Coherence; Retina; Cognition
PubMed: 36396812
DOI: 10.1007/s00415-022-11449-5 -
Journal of the Neurological Sciences Nov 2023Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS.
METHODS
We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package.
RESULTS
From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I = 79%, z-score = -1.79, p = 0.073).
CONCLUSION
OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test.
Topics: Humans; Male; Female; Adult; Middle Aged; Multiple Sclerosis; Retinal Ganglion Cells; Tomography, Optical Coherence; Retina; Multiple Sclerosis, Chronic Progressive; Optic Neuritis
PubMed: 37924591
DOI: 10.1016/j.jns.2023.120847