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Epigenetics Insights 2023Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive... (Review)
Review
Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.
PubMed: 38033465
DOI: 10.1177/25168657231213195 -
Acta Neurologica Belgica Apr 2024Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS, has been explored for its off-label extended interval dosing (EID), suggesting a potential reduction in the risk of progressive multifocal leukoencephalopathy (PML) compared to standard interval dosing (SID). Our objective was to assess the efficacy and safety of EID in comparison to SID for natalizumab treatment in patients with MS.
METHODS
We searched PubMed, Embase, WOS, Scopus, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library. Our assessed outcomes were clinical relapses, MRI activity, change in expanded disability status scale [EDSS], and the risk of PML. The EID group was defined as 5 to 8 weeks [EID (Q5-8W)]. The analysis was conducted using RevMan ver. 5.4. The effect estimates were presented as a risk ratio [RR] or mean difference with 95% confidence intervals [CI] using SID group as the reference for comparisons.
RESULTS
Fourteen studies met our inclusion criteria: 2 RCTs, 1 switched single-arm trial, and 12 observational studies. No significant differences were found in all efficacy outcomes of interest. Risk of clinical relapses [RR = 0.90, (95%CI 0.80, 1.02)], risk of new or newly enlarging T2 hyperintense MRI lesions [RR = 0.78, (95%CI 0.59, 1.04)], risk gadolinium enhancing lesions [RR = 1.30, (95%CI 0.98, 1.72)], change in EDSS [MD = 0.09 (95%CI - 0.57, 0.76)], risk of PML [RR = 1.09, 95%CI (0.24, 4.94)].
CONCLUSION
In summary, our meta-analysis indicates that natalizumab maintains its effectiveness under extended interval dosing [up to 8 weeks], presenting comparable risks for clinical relapses, MRI lesions, EDSS, and PML. Caution is advised given study limitations and heterogeneity. Robust conclusions necessitate well-designed high-quality prospective studies.
Topics: Humans; Natalizumab; Multiple Sclerosis; Prospective Studies; Antibodies, Monoclonal; Leukoencephalopathy, Progressive Multifocal; Recurrence; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Observational Studies as Topic
PubMed: 38457005
DOI: 10.1007/s13760-024-02480-6 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971 -
Human Vaccines & Immunotherapeutics Aug 2023A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the...
A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl's GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.
Topics: Female; Humans; Infant; Diphtheria-Tetanus-Pertussis Vaccine; Guillain-Barre Syndrome
PubMed: 37753771
DOI: 10.1080/21645515.2023.2261199 -
Journal of Neurology Jun 2024Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of... (Review)
Review
BACKGROUND
Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS).
METHODS
Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as "quality of life" were searched in PubMed and ClinicalTrials.gov.
RESULTS
We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1-3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen's d 1.02; IQR 0.3-1.7; median Hedges' g 1.01; IQR 0.3-1.69) and ranged between d 0.14 and 2.91.
CONCLUSIONS
Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS.
Topics: Humans; Quality of Life; Multiple Sclerosis; Randomized Controlled Trials as Topic; Outcome Assessment, Health Care; Immunologic Factors
PubMed: 38625399
DOI: 10.1007/s00415-024-12366-5 -
The Primary Care Companion For CNS... Apr 2024Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS),...
Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS), such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS), offers potential solutions. Among NIBS techniques, theta burst stimulation (TBS) is notable for its ability to modulate cortical activity. The objective of this systematic review is to assess the impact of TBS on MS symptoms. The study conducted rigorous systematic searches in PubMed, Google Scholar, and Scopus databases up to June 2023, using specific Medical Subject Headings terms related to NIBS and MS, such as TMS and TBS, in conjunction with terms like MS or demyelinating disease. Additionally, the bibliographic references of included studies, book chapters, and original articles were manually reviewed. The study selection process involved a 2-tiered screening mechanism, beginning with an evaluation of titles and abstracts, followed by a full-text review of selected articles. Inclusion criteria incorporated randomized controlled trials (RCTs) focusing on TBS with MS patients. Exclusion criteria included non-qualitative, non-MS, and non-TBS studies. Risk of bias assessment was conducted using the 2008 Cochrane Risk of Bias 2 Scale for RCTs. Data extraction was conducted by thoroughly reviewing each research article and systematically recording the relevant information using a standardized data extraction form, ensuring consistency and accuracy throughout the process. In a systematic review encompassing 5 randomized controlled trials involving 117 individuals with relapsing-remitting or secondary progressive MS across Italy, France, and Russia, various forms of TBS were applied. These interventions ranged from intermittent TBS (iTBS) to continuous intermittent TBS (c-iTBS) that demonstrated favorable outcomes. Notably, TBS interventions led to significant reductions in spasticity, fatigue, and pain, with c-iTBS combined with vestibular rehabilitation showing additional improvements in vestibular-ocular reflexes, gait, and balance. While specific protocols varied among the studies, collectively, the results suggest promise for TBS approaches in alleviating MS-related symptoms. The findings of this review suggest that TBS may hold promise in addressing specific MS symptoms, notably fatigue and spasticity. Future research should include a more diverse participant pool to explore TBS effects across different MS subtypes and aim for larger sample sizes to enhance statistical power and result reliability. .
Topics: Humans; Multiple Sclerosis; Transcranial Magnetic Stimulation; Theta Rhythm
PubMed: 38684013
DOI: 10.4088/PCC.23r03645 -
International Journal of Infectious... Jan 2024Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but...
OBJECTIVES
Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children.
METHODS
A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients.
RESULTS
A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis.
CONCLUSION
Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.
Topics: Adult; Humans; Child; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Posterior Leukoencephalopathy Syndrome; Neuroimaging; Systemic Inflammatory Response Syndrome
PubMed: 37944584
DOI: 10.1016/j.ijid.2023.11.006 -
Clinical Neurology and Neurosurgery Mar 2024Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the... (Review)
Review
INTRODUCTION
Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. Our work aims to investigate the incidence of GBS after COVID-19 vaccination, and describe its clinical characteristics and potential confounders.
METHODS
An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports and case series describing after COVID-19 vaccine administration. All published articles from inception until November 1st, 2022 were included. Differences between groups were assessed using Pearson chi-square test. Modified Erasmus GBS Outcome Score (mEGOS) for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS.
RESULTS
About 103 studies describing 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ±18.83 years, with AMSAN occurring in a rather older group (63.88 ±20.87 years, p=0.049). The AstraZeneca vaccine was associated with AIDP (n=38, 21.71%) more than other vaccines, p=0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Dysesthesias was the most reported sensory complication (60%, p=0.349). Most GBS patients survived (96%, p=0.036), however, most patients had low mEGOS scores (4 ±3.57, p<0.01). On average, patients developed GBS at 13.43 ±11.45 days from vaccination (p=0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p<0.01). Intravenous immunoglobulins (p=0.03) along with rehabilitation (p=0.19) were the most commonly used treatment.
CONCLUSION
This work investigates the incidence of Guillain-Barré Syndrome after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca or Pfizer vaccines, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines. No specific predisposing or prognostic factor was identified, and the relation between the COVID-19 vaccines and GBS remain unclear.
Topics: Humans; Adult; Middle Aged; Aged; Guillain-Barre Syndrome; COVID-19 Vaccines; COVID-19; Vaccination; Immunoglobulins, Intravenous
PubMed: 38401232
DOI: 10.1016/j.clineuro.2024.108183 -
European Journal of Physical and... Feb 2024Virtual reality (VR) is an advanced technology that creates simulated environments and conditions. By offering the possibility of combining motor, cognitive, and... (Review)
Review
INTRODUCTION
Virtual reality (VR) is an advanced technology that creates simulated environments and conditions. By offering the possibility of combining motor, cognitive, and well-being in conjunction with the potential to manipulate multi-sensorial features in a safe environment, VR has emerged as a promising powerful rehabilitation tool. Among advanced VR systems, various authors have highlighted promising effects in the rehabilitation of the computer-assisted rehabilitation environment (CAREN - Motekforce Link; Amsterdam, The Netherlands). In our scoping review, we aimed to map the existing evidence on the use of CAREN in the rehabilitation of neurological patients.
EVIDENCE ACQUISITION
This scoping review was conducted following the PRISMA guidelines. A search was carried out for all peer-reviewed articles published until June 30, 2023, using the following databases: PubMed, Embase, Cochrane Database, PeDro and Web of Science. The following terms have been used: ("Cognitive Rehabilitation" OR "Motor Rehabilitation" OR "CAREN" or "Computer-Assisted Rehabilitation Environment") AND ("Virtual Reality" OR "Rehab").
EVIDENCE SYNTHESIS
From the assessed studies, only seven met the inclusion criteria: 1) one study concerned cognitive rehabilitation in patients suffering from Parkinson's Disease (PD); 2) one was on the usability of CAREN in PD patients; 3) two studies related to the influence of emotional components to CAREN rehabilitation; 4) three studies were related to motor rehabilitation using CAREN, and involved individuals with PD, Multiple Sclerosis, TBI, respectively. Generally, the few assessed studies demonstrate that CAREN is a safe and potentially effective tool to treat different symptoms (including gait and vestibular disturbances, executive function, depressive mood, and anxiety) in patients with different neurological disorders.
CONCLUSIONS
The reviewed literature indicated the potential use of CAREN in improving motor and cognitive skills with conflicting results on emotional aspects. However, since the data comes from few and small sample size studies, further research is needed to confirm the effectiveness of the tool in neurorehabilitation.
Topics: Humans; Nervous System Diseases; Parkinson Disease; Virtual Reality; Multiple Sclerosis; Computers
PubMed: 37971719
DOI: 10.23736/S1973-9087.23.08025-5 -
Pediatric Neurology Sep 2023There is an increasing number of cases being reported of neurological manifestations of Coronavirus disease 2019 (COVID-19) infection and Monkeypox (Mpox), both during...
BACKGROUND
There is an increasing number of cases being reported of neurological manifestations of Coronavirus disease 2019 (COVID-19) infection and Monkeypox (Mpox), both during the course of the infection and as a presenting symptom. We aim to review the neurological manifestations of COVID-19 and monkeypox in pediatric patients and their management.
METHODS
We conducted a systematic review that included cohort studies and case series or reports involving a pediatric population of patients with a confirmed COVID-19 or Mpox infection and their neurological manifestations. We searched the following electronic databases: PubMed, EMBASE, and Scopus.
RESULTS
From 1136 articles identified, 127 studies were included. Headache, stroke, Guillain-Barré syndrome, seizure, nerve palsies, and multisystem inflammatory syndrome in children were the most common neurological symptoms caused by COVID-19, whereas encephalitis was commonly seen in patients with Mpox. Rare neurological manifestations of COVID-19 included cerebral venous sinus thrombosis, plexopathies, demyelinating disorders, encephalitis, etc., and rare neurological manifestations of Mpox included headache.
CONCLUSIONS
Our review highlights the importance of investigating possible neurological manifestations and closely monitoring these patients to develop a better understanding of the treatment strategies that can be adopted.
Topics: Humans; Child; COVID-19; Mpox (monkeypox); Nervous System Diseases; SARS-CoV-2; Headache; Encephalitis
PubMed: 37441883
DOI: 10.1016/j.pediatrneurol.2023.05.011