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World Neurosurgery Jun 2022Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI). However, findings of these studies are contradictory.
OBJECTIVE
The present study aims to conduct a systematic review and meta-analysis of animal studies evaluating the effects of administration of growth factor gene-modified cells on locomotion recovery after SCI.
METHODS
A search of the MEDLINE, Embase, Scopus, and Web of Science databases was conducted, including all animal studies until the end of 2020. Two researchers screened search results, summarized relevant studies and assessed risk of bias, independently.
RESULTS
Thirty-three studies were included in the final analysis. Transplantation of growth factor gene-modified cells in the injured spinal cord resulted in a significant improvement in locomotion of animals compared with nontreated animals (standardized mean difference = 1.86; 95% confidence interval, 1.39-2.33; P < 0.0001)] and non-genetically modified cell-treated animals (standardized mean difference = 1.30; 95% confidence interval, 0.80-1.79; P < 0.0001). Transplantation efficacy of these cells failed to achieve significance in moderate lesions (P = 0.091), when using modified neural stem/progenitor cells (P = 0.164), when using synthetic neurotrophins (P = 0.086) and when the number of transplanted cells was less than 1.0 × 10 cells per animal (P = 0.119).
CONCLUSIONS
The results showed that transplantation of growth factor gene- modified cells significantly improved locomotion in SCI animal models. However, there is a major concern regarding the safety of transplantation of genetically modified cells, in terms of overexpressing growth factors. Further studies are needed before any effort to perform a translational and clinical study.
Topics: Animals; Humans; Locomotion; Models, Animal; Neural Stem Cells; Recovery of Function; Spinal Cord; Spinal Cord Injuries
PubMed: 35276395
DOI: 10.1016/j.wneu.2022.03.012 -
Journal of Neurology Jan 2023To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine.
METHODS
Neuroimaging studies published from origin to August 1, 2021 were searched in six databases including PubMed, Web of Science, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP. Study selection, quality assessment, and data extraction were conducted by two independent researchers. Anisotropic effect size-signed differential mapping (AES-SDM) and activation likelihood estimation (ALE) were used to perform the meta-analysis of available studies reporting whole-brain gray matter (GM) structural data in migraine patients. Clinical variables correlation analysis and migraine subgroup analysis were also conducted.
RESULTS
40 articles were included after the strict screening, containing 1616 migraine patients and 1681 matched healthy subjects (HS) in total. Using the method of AES-SDM, migraine patients showed GM increase in the bilateral amygdala, the bilateral parahippocampus, the bilateral temporal poles, the bilateral superior temporal gyri, the left hippocampus, the right superior frontal gyrus, and the left middle temporal gyrus, as well as GM decrease in the left insula, the bilateral cerebellum (hemispheric lobule IX), the right dorsal medulla, the bilateral rolandic operculum, the right middle frontal gyrus, and the right inferior parietal gyrus. Using the method of ALE, migraine patients showed GM increase in the left parahippocampus and GM decrease in the left insula. The results of correlation analysis showed that many of these brain regions were associated with migraine headache frequency and migraine disease duration. Migraine patients in different subtypes (such as migraine without aura (MwoA), migraine with aura (MwA), episodic migraine (EM), chronic migraine (CM), vestibular migraine (VM), etc.), and in different periods (in the ictal and interictal periods) presented not entirely consistent GM alterations.
CONCLUSION
Migraine patients have GM alterations in multiple brain regions associated with sensation, affection, cognition, and descending modulation aspects of pain. These changes might be a consequence of repeated migraine attacks. Further studies are required to determine how these GM changes can be used to diagnose, monitor disease progression, or exploit potential therapeutic interventions for migraine patients.
Topics: Humans; Brain; Gray Matter; Frontal Lobe; Prefrontal Cortex; Migraine without Aura; Magnetic Resonance Imaging
PubMed: 36098838
DOI: 10.1007/s00415-022-11363-w -
Cells Oct 2021The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person's... (Meta-Analysis)
Meta-Analysis
The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person's quality of life. There is an unmet clinical need for a treatment which will prevent progression of the injury, allowing improved axonal regeneration and functional recovery to occur. The initial mechanical insult, followed by a cascade of secondary mechanisms, leads to the exacerbation and remodelling of the lesion site, thus inhibiting neurological recovery. Oedema rapidly accumulates following SCI and contributes to the detrimental pathophysiology and worsens functional outcomes. This study systematically reviewed the current experimental treatments being explored in the field of SCI, which specifically target oedema. Abiding by PRISMA guidelines and strict inclusion criteria, 14 studies were identified and analysed from three online databases (PubMed, Web of Science and EMBASE). As a result, we identified three key modalities which attenuate oedema: selective inhibition of the main water channel protein, aquaporin 4 (AQP4), modulation of inflammation and surgical interventions. Collectively, however, they all result in the downregulation of AQP4, which crucially leads to a reduction in oedema and improved functional outcomes. We concluded that trifluoperazine (TFP), a calmodulin kinase inhibitor which prevents the cell-surface localisation of AQP4, was the most efficacious treatment, significantly eliminating oedema within 7 days of administration. To date, this study is the most concise analysis of current experimental treatments for oedema, exposing its molecular mechanisms and assessing potential therapeutic pathways for future research.
Topics: Animals; Blood-Brain Barrier; Edema; Humans; Motor Activity; Publication Bias; Rats; Recovery of Function; Risk; Spinal Cord Injuries; Treatment Outcome
PubMed: 34685662
DOI: 10.3390/cells10102682 -
Journal of Clinical Neuroscience :... Jun 2022To investigate the incidence of cervical spine deformity and instability after posterior cervical spinal cord tumor (CSCT) resection without fusion or fixation in adults... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the incidence of cervical spine deformity and instability after posterior cervical spinal cord tumor (CSCT) resection without fusion or fixation in adults and examine relevant risk factors by reviewing and summarizing previously reported studies.
METHODS
We selected peer reviewed articles published between January 1990 and December 2020 from the MEDLINE and Cochrane Library databases using relevant key words. Articles in which the authors mainly described spinal cord tumor resection through posterior surgery without fusion or fixation in adults were selected for analysis. Patient's data including age, sex, extensive number of laminectomy levels, laminectomy at C2, C3, or C7, multilevel facetectomy, facet destruction, preoperative cervical kyphosis, and preoperative motor deficit were documented. Comparable factors were assessed using the odds ratio (OR) and weighted mean difference (WMD) of 95% confidence intervals (CI).
RESULTS
Among 133 articles identified, 18 met selection criteria. Overall incidence of deformity and instability after CSCT surgery was 0%-41.7% and 0%-20.5%, respectively. Younger age (WMD, -5.5; 95% CI, -10.52 ∼ -0.49; P = 0.03), C2 laminectomy (OR, 5.33; 95% CI, 2.39 ∼ 11.91; P < 0.0001), more laminectomy level (WMD, 2.77; 95% CI, 1.78 ∼ 3.76; P < 0.00001) were identified as risk factors for deformity and instability after CSCT surgery.
CONCLUSION
Patients undergoing CSCT resection should receive careful follow-up for postoperative spinal deformity and instability. Younger age, C2 laminectomy, and more laminectomy level were significantly associated with occurrence of deformity and instability after CSCT surgery. Upfront spinal fixation at the time of resection should be considered in selected patients.
Topics: Adult; Cervical Cord; Cervical Vertebrae; Humans; Kyphosis; Laminectomy; Postoperative Complications; Spinal Cord Neoplasms; Spinal Fusion
PubMed: 35472680
DOI: 10.1016/j.jocn.2022.04.005 -
Neurology India 2020Cervical split cord malformations are extremely rare with less than 75 cases reported in the literature worldwide. The widely different terminologies used to describe... (Review)
Review
Cervical split cord malformations are extremely rare with less than 75 cases reported in the literature worldwide. The widely different terminologies used to describe the same pathoanatomy make the documentation of all reported cases a difficult task. We conducted a systematic review of 71 cases documented over 38 reports from 1889 to 2016. The controversy regarding prophylactic surgery in asymptomatic individuals remains. We advocate prophylactic surgery in all asymptomatic individuals to preclude severe neurological deficit following trivial trauma in future. The results of surgery in asymptomatic individuals are excellent while those in symptomatic individuals are good as well.
Topics: Humans; Spinal Cord
PubMed: 33109840
DOI: 10.4103/0028-3886.299132 -
Journal of Neurotrauma Aug 2022Epidural spinal cord stimulation (eSCS) has been recently recognized as a potential therapy for chronic spinal cord injury (SCI). eSCS has been shown to uncover residual... (Review)
Review
Epidural spinal cord stimulation (eSCS) has been recently recognized as a potential therapy for chronic spinal cord injury (SCI). eSCS has been shown to uncover residual pathways within the damaged spinal cord. The purpose of this review is to summarize the key findings to date regarding the use of eSCS in SCI. Searches were carried out using MEDLINE, EMBASE, and Web of Science database and reference lists of the included articles. A combination of medical subject heading terms and keywords was used to find studies investigating the use of eSCS in SCI patients to facilitate volitional movement and to restore autonomic function. The risk of bias was assessed using Risk Of Bias In Non-Randomized Studies of Interventions tool for nonrandomized studies. We were able to include 40 articles that met our eligibility criteria. The studies included a total of 184 patient experiences with incomplete or complete SCI. The majority of the studies used the Medtronic 16 paddle lead. Around half of the studies reported lead placement between T11- L1. We included studies that assessed motor ( = 28), autonomic ( = 13), and other outcomes ( = 10). The majority of the studies reported improvement in outcomes assessed. The wide range of included outcomes demonstrates the effectiveness of eSCS in treating a diverse SCI population. However, the current studies cannot definitively conclude which patients benefit the most from this intervention. Further study in this area is needed to allow improvement of the eSCS technology and allow it to be more widely available for chronic SCI patients.
Topics: Epidural Space; Humans; Movement; Spinal Cord; Spinal Cord Injuries; Spinal Cord Stimulation
PubMed: 35403432
DOI: 10.1089/neu.2022.0007 -
The Journal of Spinal Cord Medicine Jul 2015Employment rates in individuals with spinal cord injury (SCI) are approximately 35%, which is considerably lower than that of the general population. In order to improve... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Employment rates in individuals with spinal cord injury (SCI) are approximately 35%, which is considerably lower than that of the general population. In order to improve employment outcomes a clear understanding of what factors influence employment outcomes is needed.
OBJECTIVE
To systematically review factors that are consistently and independently associated with employment outcomes in individuals with SCI, and to understand the magnitude of their influence.
METHODS
Through an electronic search of MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, Social Science Abstracts and Social Work databases, we identified studies published between 1952-2014 that investigated factors associated with employment outcomes following SCI. Exclusion criteria included: (1) reviews (2) studies not published in English (3) studies not controlling for potential confounders through a regression analysis, or (4) studies not providing an effect measure in the form of OR, RR, or HR. Data were categorized based on the International Classification of Functioning, Disability and Health framework, with each domain sub-categorized by modifiability. First author, year of publication, sample size, explanatory and outcome variables, and effect measures were extracted.
RESULTS
Thirty-nine studies met the inclusion criteria. Twenty modifiable and twelve non-modifiable factors have been investigated in the context of employment following SCI. Education, vocational rehabilitation, functional independence, social support, and financial disincentives were modifiable factors that have been consistently and independently associated with employment outcomes.
CONCLUSION
A number of key modifiable factors have been identified and can inform interventions aimed at improving employment outcomes for individuals with SCI. Future research should focus on determining which factors have the greatest effect on employment outcomes, in addition to developing and evaluating interventions targeted at these factors.
Topics: Employment; Humans; Spinal Cord Injuries
PubMed: 25989899
DOI: 10.1179/2045772315Y.0000000031 -
Spine May 2018Systematic review. (Review)
Review
STUDY DESIGN
Systematic review.
OBJECTIVE
The aim of this study was to investigate, quantify, compare, and compile the various mesenchymal stem cell (MSC) tissue sources within human spinal tissues to act as a compendium for clinical and research application.
SUMMARY OF BACKGROUND DATA
Recent years have seen a dramatic increase in academic and clinical understanding of human MSCs. Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta, and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research.
METHODS
The PubMED, MEDLINE, EMBASE, and Cochrane databases were searched for articles relating to the harvest, characterization, isolation, and quantification of human MSCs from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites.
RESULTS
Human MSC levels varied widely between spinal tissues. Yields for intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500 to 61,875 cells/0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000 to 500,000 cells/g of tissue. Annulus fibrosus fluorescence activated cell sorting treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584 to 234,137 MSCs per gram of tissue.
CONCLUSION
Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human MSCs. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of MSCs, and may prove comparable to that of bone marrow.
LEVEL OF EVIDENCE
5.
Topics: Animals; Bone Marrow; Cell Differentiation; Humans; Intervertebral Disc; Ligamentum Flavum; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Periosteum; Spinal Cord
PubMed: 28885289
DOI: 10.1097/BRS.0000000000002401 -
Magnetic Resonance Insights 2015To assess the use of fMRI of the spinal cord in measuring noxious stimulation. (Review)
Review
OBJECTIVE
To assess the use of fMRI of the spinal cord in measuring noxious stimulation.
METHODS
The Scopus, Medline, EMBASE, and Web of Science databases were searched, along with the reference lists of included articles. Two independent reviewers screened abstracts, full-text articles, and extracted data. Original research was included if fMRI of the human spinal cord was used to measure responses to noxious stimulation.
RESULTS
Of the 192 abstracts screened, 19 met the search criteria and were divided according to their focus: investigating pain responses (n = 6), methodology (n = 6), spinal cord injury (n = 2), or cognition-pain interactions (n = 5). All but one study appear to have observed activity in ipsilateral and dorsal gray matter regions in response to noxious stimuli, although contralateral or ventral activity was also widely observed.
CONCLUSIONS
Although nociception can be investigated using spinal fMRI, establishing reliability, standardizing methodology, and reporting of results will greatly advance this field.
PubMed: 26543372
DOI: 10.4137/MRI.S23556 -
Cellular and Molecular Neurobiology Apr 2023Pre-clinical studies place tumor necrosis factor (TNF) as a central player in the inflammatory response after spinal cord injury (SCI), and blocking its production... (Review)
Review
Pre-clinical studies place tumor necrosis factor (TNF) as a central player in the inflammatory response after spinal cord injury (SCI), and blocking its production and/or activity has been proposed as a possible treatment option after SCI. This systematic review provides an overview of the literature on the temporal and cellular expression of TNF after SCI and clarifies the potential for its therapeutic manipulation in SCI. A systematic search was performed in EMBASE (Ovid), MEDLINE (Ovid), and Web of Science (Core Collection). The search terms were the MeSH forms of tumor necrosis factor and spinal cord injury in the different databases, and the last search was performed on February 3, 2021. We found twenty-four articles examining the expression of TNF, with most using a thoracic contusive SCI model in rodents. Two articles described the expression of TNF receptors in the acute phase after SCI. Twenty-one articles described the manipulation of TNF signaling using genetic knock-out, pharmaceutical inhibition, or gain-of-function approaches. Overall, TNF expression increased rapidly after SCI, within the first hours, in resident cells (neurons, astrocytes, oligodendrocytes, and microglia) and again in macrophages in the chronic phase after injury. The review underscores the complexity of TNF's role after SCI and indicates that TNF inhibition is a promising therapeutic option. This review concludes that TNF plays a significant role in the inflammatory response after SCI and suggests that targeting TNF signaling is a feasible therapeutic approach.
Topics: Humans; Tumor Necrosis Factor-alpha; Spinal Cord Injuries; Neurons; Microglia; Macrophages; Spinal Cord
PubMed: 35604578
DOI: 10.1007/s10571-022-01229-0