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NeuroImage. Clinical 2016A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5... (Review)
Review
BACKGROUND
A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established.
METHODS
A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
RESULTS
A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent.
CONCLUSIONS
State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.
Topics: Animals; Brain Mapping; Diffusion Tensor Imaging; Humans; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Myelin Sheath; Spinal Cord; Spinal Cord Injuries; Translational Research, Biomedical; Water
PubMed: 26862478
DOI: 10.1016/j.nicl.2015.11.019 -
Therapeutic Advances in Neurological... 2021A considerable number of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will experience a relapse, but the effect of maintenance...
BACKGROUND
A considerable number of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will experience a relapse, but the effect of maintenance therapies on re-attack rates is currently unknown.
OBJECTIVE
To investigate the efficacy and safety of immunosuppressive therapy for preventing disease relapses in patients with MOGAD, including rituximab (RTX), mycophenolate mofetil (MMF), and azathioprine (AZA).
METHODS
English-language studies published prior to August 31, 2020, were searched in the NCBI (PubMed), ISI Web of Science, and the Cochrane Library databases. Patient characteristics, treatment regimens, outcome measures, and adverse effects were retrieved.
RESULTS
We enrolled 11 studies in the final meta-analysis, including 346 patients with MOGAD. RTX therapy was demonstrated to result in reduced mean annualized relapse rate (ARR) by 1.35 (95% confidence interval (CI): 0.85-1.85) and reduced mean Expanded Disability Status Scale score by 0.80 (95% CI: 0.53-1.08) in patients with MOGAD. MMF therapy was associated with the mean ARR decreasing by 0.83 (95% CI: 0.31-1.35), and AZA was related to the mean ARR decreasing by 1.71 (95% CI: 0.83-2.58). The reported discontinuation rates of RTX, MMF, and AZA therapy due to adverse effects were 3/197 (1.52%), 3/39 (7.69%), and 4/37 (10.81%), respectively.
CONCLUSION
The study provided evidence to support the efficacy of RTX, MMF, and AZA on the preventive treatment in patients with MOGAD. However, large randomized controlled trials are still needed in the future.
PubMed: 34790259
DOI: 10.1177/17562864211054157 -
International Journal of Molecular... Mar 2022A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During...
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.
Topics: Humans; MicroRNAs; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Sciatic Nerve
PubMed: 35408800
DOI: 10.3390/ijms23073440 -
Multiple Sclerosis (Houndmills,... Jan 2022Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in...
BACKGROUND
Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in progressive MS, causing permanent axonal loss and irreversible disabilities. Strategies aimed at enhancing remyelination are critical to attenuate disease progression.
OBJECTIVE
We systematically reviewed recent advances in neuroprotective and regenerative therapies for MS, covering preclinical and clinical studies.
METHODS
We searched three biomedical databases using defined keywords. Two authors independently reviewed articles for inclusion based on pre-specified criteria. The data were extracted from each study and assessed for risk of bias.
RESULTS
Our search identified 7351 studies from 2014 to 2020, of which 221 met the defined criteria. These studies reported 262 interventions, wherein 92% were evaluated in animal models. These interventions comprised protein, RNA, lipid and cellular biologics, small molecules, inorganic compounds, and dietary and physiological interventions. Small molecules were the most highly represented strategy, followed by antibody therapies and stem cell transplantation.
CONCLUSION
While significant strides have been made to develop regenerative treatments for MS, the current evidence illustrates a skewed representation of the types of strategies that advance to clinical trials. Further examination is thus required to address current barriers to implementing experimental treatments in clinical settings.
Topics: Animals; Axons; Multiple Sclerosis; Myelin Sheath; Nerve Regeneration; Oligodendroglia; Remyelination
PubMed: 33870797
DOI: 10.1177/13524585211008760 -
Cells Jan 2022Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates...
Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "nerve regeneration", considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.
Topics: Fibrin Tissue Adhesive; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Models, Biological; Nerve Regeneration; Nerve Tissue
PubMed: 35053336
DOI: 10.3390/cells11020221 -
International Journal of Clinical and... 2015Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis... (Review)
Review
Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis after TBI. There are two main prognostic models: International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) prognosis calculator and the Corticosteroid Randomization after Significant Head Injury (CRASH) prognosis calculator. The prognosis model has three or four levels: (1) model A included age, motor GCS, and pupil reactivity; (2) model B included predictors from model A with CT characteristics; and (3) model C included predictors from model B with laboratory parameters. In consideration of the fact that interventions after admission, such as ICP management also have prognostic value for outcome predictions and may improve the models' performance, Yuan F et al developed another prediction model (model D) which includes ICP. With the development of molecular biology, a handful of brain injury biomarkers were reported that may improve the predictive power of prognostic models, including neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), S-100β protein, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myelin basic protein (MBP), cleaved tau protein (C-tau), spectrin breakdown products (SBDPs), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), and sex hormones. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. Many substances have been implicated as potential biomarkers for TBI; however, no single biomarker has shown the necessary sensitivity and specificity for predicting outcome. The limited number of publications in this field underscores the need for further investigation. Through fluid biomarker analysis, the advent of multi-analyte profiling technology has enabled substantial advances in the diagnosis and treatment of a variety of conditions. Application of this technology to create a bio-signature for TBI using multiple biomarkers in combination will hopefully facilitate much-needed advances. We believe that further investigations about brain injury biomarkers may improve the predictive power of the contemporary outcome calculators and prognostic models, and eventually improve the care of patients with TBI.
PubMed: 26884899
DOI: No ID Found -
Brain Sciences Jan 2023(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes... (Review)
Review
(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes physical disabilities and cognitive impairment. Functional magnetic resonance imaging (fMRI) is a common neuroimaging technique used in studying MS. Computational methods have recently been applied for disease detection, notably graph theory, which helps researchers understand the entire brain network and functional connectivity. (2) Methods: Relevant databases were searched to identify articles published since 2000 that applied graph theory to study functional brain connectivity in patients with MS based on fMRI. (3) Results: A total of 24 articles were included in the review. In recent years, the application of graph theory in the MS field received increased attention from computational scientists. The graph-theoretical approach was frequently combined with fMRI in studies of functional brain connectivity in MS. Lower EDSSs of MS stage were the criteria for most of the studies (4) Conclusions: This review provides insights into the role of graph theory as a computational method for studying functional brain connectivity in MS. Graph theory is useful in the detection and prediction of MS and can play a significant role in identifying cognitive impairment associated with MS.
PubMed: 36831789
DOI: 10.3390/brainsci13020246 -
Cellular Physiology and Biochemistry :... 2015Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI.
METHODS
Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5.
RESULTS
Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding.
CONCLUSION
SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI.
Topics: Animals; Cell Transplantation; Locomotion; Rats; Schwann Cells; Spinal Cord Injuries
PubMed: 26605538
DOI: 10.1159/000438574 -
Frontiers in Neurology 2020Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be...
Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be impacted early in Parkinson disease (PD). Diffusion magnetic resonance imaging (dMRI) has been used extensively to understand such pathological WM changes, and the focus of this systematic review is to understand both the methods utilized and their corresponding results in the context of early-stage PD. Diffusion tensor imaging (DTI) is the most commonly utilized method to probe WM pathological changes. Previous studies have suggested that DTI metrics are sensitive in capturing early disease-associated WM changes in preclinical symptomatic regions such as olfactory regions and the substantia nigra, which is considered to be a hallmark of PD pathology and progression. Postprocessing analytic approaches include region of interest-based analysis, voxel-based analysis, skeletonized approaches, and connectome analysis, each with unique advantages and challenges. While DTI has been used extensively to study WM disorganization in early-stage PD, it has several limitations, including an inability to resolve multiple fiber orientations within each voxel and sensitivity to partial volume effects. Given the subtle changes associated with early-stage PD, these limitations result in inaccuracies that severely impact the reliability of DTI-based metrics as potential biomarkers. To overcome these limitations, advanced dMRI acquisition and analysis methods have been employed, including diffusion kurtosis imaging and q-space diffeomorphic reconstruction. The combination of improved acquisition and analysis in DTI may yield novel and accurate information related to WM-associated changes in early-stage PD. In the current article, we present a systematic and critical review of dMRI studies in early-stage PD, with a focus on recent advances in DTI methodology. Yielding novel metrics, these advanced methods have been shown to detect diffuse WM changes in early-stage PD. These findings support the notion of early axonal damage in PD and suggest that WM pathology may go unrecognized until symptoms appear. Finally, the advantages and disadvantages of different dMRI techniques, analysis methods, and software employed are discussed in the context of PD-related pathology.
PubMed: 32477235
DOI: 10.3389/fneur.2020.00314 -
PloS One 2024Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression...
Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS.
Topics: Humans; Brain; Depression; Fatigue; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Quality of Life; Adult
PubMed: 38551913
DOI: 10.1371/journal.pone.0299634