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Stereotactic and Functional Neurosurgery 2024Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive meta-analysis and systematic review of four less-invasive treatment modalities for TGN in MS patients, namely, gamma knife radiosurgery (GKRS), glycerol rhizotomy (GR), balloon compression (BC), and radiofrequency ablation (RFA).
METHODS
Single-armed meta-analyses were employed to assess the overall efficacy of each treatment, while double-armed analyses compared the efficacy between different treatment options in double-armed studies. Outcome evaluations included acute pain relief (within 1 month post-procedure), recurrence rates throughout 18 months of follow-up, and reported complication rates.
RESULTS
The meta-analysis revealed diverse outcomes for each intervention. GKRS demonstrated favorable outcomes, achieving a 77% success rate in alleviating pain among a pooled cohort of 863 patients, reinforcing its status as a viable therapeutic option. Additionally, GR, BC, and RFA exhibited efficacy, with success rates of 77%, 71%, and 80%, respectively, based on outcomes observed in 611, 385, and 203 patients. Double-armed analyses highlighted distinctions between the treatments, providing nuanced insights for clinical decision-making.
CONCLUSION
This meta-analysis provides a comprehensive overview of less-invasive treatments for TGN in MS patients. GKRS emerges as a leading option with comparable efficacy and fewer complications. However, the study underscores the nuanced efficacy and considerations associated with GR, BC, and RFA. The findings offer valuable insights for clinicians navigating treatment choices in this challenging patient population, considering acute pain relief, recurrence rates, and complication profiles.
Topics: Trigeminal Neuralgia; Humans; Multiple Sclerosis; Radiosurgery; Treatment Outcome; Rhizotomy; Minimally Invasive Surgical Procedures; Radiofrequency Ablation
PubMed: 38648730
DOI: 10.1159/000538516 -
Clinical Neurophysiology : Official... Jun 2024Electroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to... (Review)
Review
OBJECTIVE
Electroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS).
METHODS
A comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses.
RESULTS
In this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load).
CONCLUSIONS
We highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks.
SIGNIFICANCE
Some of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.
Topics: Humans; Multiple Sclerosis; Electroencephalography; Motor Disorders; Brain; Nerve Net
PubMed: 38643612
DOI: 10.1016/j.clinph.2024.03.024 -
Multiple Sclerosis and Related Disorders Jun 2024Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients...
BACKGROUND
Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established.
METHODS
In accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included.
RESULTS
The overall incidence of clinical relapse during washout periods ranging from 4.4-10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02-0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %.
CONCLUSIONS
This systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.
Topics: Humans; Natalizumab; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Antigens, CD20; Drug Substitution; Leukoencephalopathy, Progressive Multifocal
PubMed: 38640586
DOI: 10.1016/j.msard.2024.105605 -
BMC Neurology Apr 2024Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early...
BACKGROUND
Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized.
METHODS
We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes.
RESULTS
From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization.
CONCLUSION
Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.
Topics: Young Adult; Humans; Adult; Hereditary Autoinflammatory Diseases; Neurologists; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Familial Mediterranean Fever; Cryopyrin-Associated Periodic Syndromes; Fever; Phenotype; Meningitis
PubMed: 38632524
DOI: 10.1186/s12883-024-03621-3 -
PloS One 2024Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls.
METHODS
In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls.
RESULTS
Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls.
CONCLUSION
Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.
Topics: Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Multiple Sclerosis; Insulin-Like Peptides; Insulin-Like Growth Factor Binding Proteins
PubMed: 38630771
DOI: 10.1371/journal.pone.0297091 -
PloS One 2024Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and...
INTRODUCTION
Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and cognitive decline. Currently, there are no specific imaging parameters available for the prediction of longitudinal disability in MS patients. Magnetic resonance imaging (MRI) has linked imaging anomalies to clinical and cognitive deficits in MS. In this study, we aimed to evaluate the effectiveness of MRI in predicting disability, clinical progression, and cognitive decline in MS.
METHODS
In this study, according to PRISMA guidelines, we comprehensively searched the Web of Science, PubMed, and Embase databases to identify pertinent articles that employed conventional MRI in the context of Relapsing-Remitting and progressive forms of MS. Following a rigorous screening process, studies that met the predefined inclusion criteria were selected for data extraction and evaluated for potential sources of bias.
RESULTS
A total of 3028 records were retrieved from database searching. After a rigorous screening, 53 records met the criteria and were included in this study. Lesions and alterations in CNS structures like white matter, gray matter, corpus callosum, thalamus, and spinal cord, may be used to anticipate disability progression. Several prognostic factors associated with the progression of MS, including presence of cortical lesions, changes in gray matter volume, whole brain atrophy, the corpus callosum index, alterations in thalamic volume, and lesions or alterations in cross-sectional area of the spinal cord. For cognitive impairment in MS patients, reliable predictors include cortical gray matter volume, brain atrophy, lesion characteristics (T2-lesion load, temporal, frontal, and cerebellar lesions), white matter lesion volume, thalamic volume, and corpus callosum density.
CONCLUSION
This study indicates that MRI can be used to predict the cognitive decline, disability progression, and disease progression in MS patients over time.
Topics: Humans; Multiple Sclerosis; Brain; Gray Matter; White Matter; Magnetic Resonance Imaging; Atrophy; Multiple Sclerosis, Relapsing-Remitting
PubMed: 38626023
DOI: 10.1371/journal.pone.0300415 -
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 -
Complementary Therapies in Medicine Jun 2024Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients.
METHODS
Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION".
RESULTS
three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation.
CONCLUSIONS
Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.
Topics: Humans; Biomarkers; Exercise; Exercise Therapy; Inflammation; Multiple Sclerosis
PubMed: 38608788
DOI: 10.1016/j.ctim.2024.103040 -
Journal of the Peripheral Nervous... Jun 2024Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid...
Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.
Topics: Humans; Chemokines; Cytokines; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 38600685
DOI: 10.1111/jns.12622 -
Journal of Clinical Medicine Feb 2024Currently, it is essential to adopt physical therapy strategies, such as resistance training, to enhance muscle strength and gait in middle-aged individuals (ages... (Review)
Review
Currently, it is essential to adopt physical therapy strategies, such as resistance training, to enhance muscle strength and gait in middle-aged individuals (ages 45-65) suffering from Multiple Sclerosis. This is crucial in combating the typical symptoms of neurodegenerative diseases associated with functional loss. The objective of this study is to determine the effects of resistance training interventions on walking and muscle strength in middle-aged people with Multiple Sclerosis. A systematic review with meta-analysis was conducted by searching specific keywords in the PubMed, Scopus, Cochrane, and Web of Science databases. For inclusion, studies had to incorporate resistance training as a primary or significant component of the overall intervention for middle-aged patients with MS. Out of the 3675 articles identified, 12 randomized clinical trials met the criteria for inclusion in the review, with resistance training being a consistent feature in all of them. Muscle strength and gait were evaluated as the main variables, with fatigue and the quality of life as secondary variables. This review reveals that resistance training significantly improves muscle strength. Resistance training achieves modest and non-significant improvements in gait. Notably, studies combining resistance training with motor control exercises achieve results of greater clinical significance in terms of gait. However, resistance training yields variable positive effects on perceived fatigue and the quality of life. Resistance training is useful for improving muscle strength; however, walking needs to be combined with motor control training.
PubMed: 38592200
DOI: 10.3390/jcm13051378