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Regenerative Therapy Dec 2024Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and... (Review)
Review
Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and molecular events makes the lesion chronic. Recently, cell-based clinical trials as a new procedure have been gradually tested to improve the symptoms of patients. Each treatment method is associated with different adverse events. Based on the PRISMA flow diagram of the identified records, and after multistep screening, finally in 76 reviewed studies with 1633 cases and 189 controls, 64 types of adverse events in 12 categories were recorded in 45 studies. The most common adverse events were transient backache and meningism (90%) and cord malacia (80%). The cell therapy method in which the treatment was associated with more adverse events was Olfactory ensheathing cell and bone marrow mesenchymal stem cell combination therapy in 55%, and the adverse events were less with the embryonic stem cell in 2.33% of patients. In a meta-analysis, the total prevalence of adverse events in cell therapy was 19% and the highest pulled effect size belonged to urinary tract and localized adverse events. Also, the total prevalence of adverse events in 14 cell therapy methods was 18% and four cell types (neural stem cell, bone marrow hematopoietic stem cell, embryonic stem cell, and umbilical cord mesenchymal stem cell) had the most effect. None of the adverse events were reported on the 4 (life-threatening consequences) and 5 (death) grading scales. We concluded that the frequency of life-threatening adverse events following cell therapy clinical trials in chronic spinal cord injury patients is very scarce and can be ignored.
PubMed: 38694447
DOI: 10.1016/j.reth.2024.03.012 -
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 -
Neuropsychology Review Mar 2024Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating... (Review)
Review
Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.
Topics: Humans; Brain; Cognition; Olfaction Disorders; Olfactory Training; Smell
PubMed: 36725781
DOI: 10.1007/s11065-022-09573-0 -
Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
Translational Research : the Journal of... Oct 2022Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of... (Review)
Review
Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. In addition to targeting local tissue like the olfactory epithelium, it provides minimally invasive access to various organ systems, including the central nervous system and the respiratory tract. Through a systematic literature review, a total of 53 articles that investigated the intranasal application of AAVs were identified, included, and summarized in this manuscript. Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.
Topics: Administration, Intranasal; Dependovirus; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans
PubMed: 35597541
DOI: 10.1016/j.trsl.2022.05.002 -
The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Chinese Medical Sciences Journal =... Mar 2022Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory...
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb (OB), which eventually damages the structure of the olfactory epithelium, leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Methods Two investigators independently searched four databases consisting of PubMed, ProQuest, Scopus, and Web of Science for relevant records as of November 11, 2020 with no time, space, and language restrictions. Google Scholar was also searched for the related resources within the time limit of 2020. All the found articles were reviewed based on the PRISMA flow diagram. Qualitative studies, case reports, editorials, letters, and other non-original studies were excluded from this systematic analysis. Results Initial search yielded 434 records. After reviewing the titles and abstracts, we selected 74 articles; finally, 8 articles were depicted to be investigated and read in full text. The obtained results showed an increase in the width and volume of the olfactory cleft (OC), complete or partial destruction of OC, and complete occlusion of OC in COVID-19 patients. Deformation and degeneration as well as a subtle asymmetry were evident in the OBs. Computed tomography (CT), meganetic resonance imaging (MRI), and positron emission tomography (PET) were used to detect the outcomes of anosmia in these studies. Conclusions The changes in OC are greater than those in OB in patients with COVID-19, mainly due to the inflammatory and immune responses in OC. However, fewer changes in OB are due to neurological or vascular disorders. Topical steroid therapy and topical saline can be helpful.
PubMed: 35256044
DOI: 10.24920/003982 -
Brain Structure & Function Jan 2022Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired...
Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired anosmia may exhibit different structural characteristics. A systematic review was undertaken to compare brain structural features between patients with congenital and acquired anosmia. A systematic search was conducted using PubMed/MEDLINE and Scopus electronic databases to identify eligible reports on anosmia and structural changes and reported according to PRISMA guidelines. Reports were extracted for information on demographics, psychophysical evaluation, and structural changes. Then, the report was systematically reviewed based on various aetiologies of anosmia in relation to (1) olfactory bulb, (2) olfactory sulcus, (3) grey matter (GM), and white matter (WM) changes. Twenty-eight published studies were identified. All studies reported consistent findings with strong associations between olfactory bulb volume and olfactory function across etiologies. However, the association of olfactory function with olfactory sulcus depth was inconsistent. The present study observed morphological variations in GM and WM volume in congenital and acquired anosmia. In acquired anosmia, reduced olfactory function is associated with reduced volumes and thickness involving the gyrus rectus, medial orbitofrontal cortex, anterior cingulate cortex, and cerebellum. These findings contrast to those observed in congenital anosmia, where a reduced olfactory function is associated with a larger volume and higher thickness in parts of the olfactory network, including the piriform cortex, orbitofrontal cortex, and insula. The present review proposes that the structural characteristics in congenital and acquired anosmia are altered differently. The mechanisms behind these changes are likely to be multifactorial and involve the interaction with the environment.
Topics: Anosmia; Brain; Gray Matter; Humans; Magnetic Resonance Imaging; Olfaction Disorders
PubMed: 34635958
DOI: 10.1007/s00429-021-02397-3 -
Brain Sciences Jul 2021Olfactory decline is an early symptom of Alzheimer's disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could... (Review)
Review
Olfactory decline is an early symptom of Alzheimer's disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could reflect AD-related atrophy of structures related to the sense of smell. The aim of this study was to verify whether the presence of a clinical diagnosis of AD or MCI is associated with a volumetric decrease in the olfactory bulbs (OB) and the primary olfactory cortex (POC). We conducted two systematic reviews, one for each region and a meta-analysis. We collected articles from PsychNet, PubMed, Ebsco, and ProQuest databases. Results showed large and heterogeneous effects indicating smaller OB volumes in patients with AD (k = 6, = -1.21, 95% CI [-2.19, -0.44]) and in patients with MCI compared to controls. There is also a trend for smaller POC in patients with AD or MCI compared to controls. Neuroanatomical structures involved in olfactory processing are smaller in AD and these volumetric reductions could be measured as early as the MCI stage.
PubMed: 34439629
DOI: 10.3390/brainsci11081010 -
Korean Journal of Radiology Nov 2021Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19.
MATERIALS AND METHODS
A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality.
RESULTS
A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings.
CONCLUSION
Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.
Topics: Brain; COVID-19; Humans; Magnetic Resonance Imaging; Neuroimaging; SARS-CoV-2
PubMed: 34269530
DOI: 10.3348/kjr.2021.0127