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Radiology Case Reports Aug 2024Central nervous system tuberculosis accounts for approximately 1% of all tuberculosis cases. Transverse myelitis is an extremely rare manifestation of central nervous...
Central nervous system tuberculosis accounts for approximately 1% of all tuberculosis cases. Transverse myelitis is an extremely rare manifestation of central nervous system tuberculosis, involving 1 or more vertebral segments of the spinal cord. However, it may extend to involve 3 or more segments of the cord, which would then be designated as longitudinally extensive transverse myelitis. Tubercular transverse myelitis may occur in isolation or in association with adjacent meningitis. We present a case of 39-year-old male, who presented with fever, headache, and bilateral lower limb weakness and was eventually diagnosed with tubercular meningoencephalitis with transverse myelitis. The diagnosis was made based on imaging findings correlated with cerebrospinal fluid analysis and microbiological reports. The patient showed significant clinical and radiological improvement following the antitubercular therapy. This case highlights that tuberculosis should always be considered in our differential diagnosis for any pathology with extensive involvement of the meninges, brain and spinal cord, especially in regions with a high prevalence.
PubMed: 38933654
DOI: 10.1016/j.radcr.2024.05.030 -
Frontiers in Immunology 2024
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Antitubercular Agents; Disease Management
PubMed: 38933279
DOI: 10.3389/fimmu.2024.1433345 -
Frontiers in Immunology 2024B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal...
Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis.
BACKGROUND AND OBJECTIVES
B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.
METHODS
Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model.
RESULTS
The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed.
DISCUSSION
Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Mice; Single-Cell Analysis; Meninges; B-Lymphocytes; Female; Tertiary Lymphoid Structures; Mice, Inbred C57BL; Antibodies, Monoclonal; Transcriptome; Gene Expression Profiling; Antigens, CD20; Cerebrospinal Fluid; Disease Models, Animal; Multiple Sclerosis
PubMed: 38933267
DOI: 10.3389/fimmu.2024.1400641 -
Frontiers in Molecular Neuroscience 2024Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective... (Review)
Review
Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.
PubMed: 38932932
DOI: 10.3389/fnmol.2024.1400808 -
Journal of Medical Virology Jun 2024Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth...
Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.
Topics: Animals; Macaca mulatta; Hand, Foot and Mouth Disease; Disease Models, Animal; Viral Tropism; Viral Load; Enterovirus B, Human; Antibodies, Viral; Antibodies, Neutralizing; Animals, Newborn; Cytokines
PubMed: 38932451
DOI: 10.1002/jmv.29707 -
Vaccines Jun 2024There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine...
There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.
PubMed: 38932357
DOI: 10.3390/vaccines12060628 -
Vaccines Jun 2024Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into...
Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) study design. MenB vaccination rates improved after funding and were in line with previously funded vaccines. Co-administration rates also increased significantly. Timely administration increased, protecting children at an early age. Public funding has a positive impact on vaccine accessibility and early protection. Consistent population characteristics highlight the role of funding.
PubMed: 38932352
DOI: 10.3390/vaccines12060623 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters... (Review)
Review
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.
PubMed: 38931455
DOI: 10.3390/ph17060788 -
Brain Sciences May 2024Invasive dental procedures, such as wisdom teeth removal, have been identified as potential triggers for vascular events due to the entry of oral bacteria into the...
Invasive dental procedures, such as wisdom teeth removal, have been identified as potential triggers for vascular events due to the entry of oral bacteria into the bloodstream, leading to acute vascular inflammation and endothelial dysfunction. This study presents the case of a 27-year-old healthy male who developed ischemic stroke resulting from bacteremia after undergoing wisdom teeth extraction. Initially, the patient experienced fever and malaise, which were followed by right-sided hemiplegia. Diagnostic imaging, including a CT scan, identified a subacute infarction in the posterior crus of the left internal capsule, and MRI findings indicated inflammatory changes in the masticatory muscles. Further investigations involving biopsies of the masticatory muscles, along with blood and cerebrospinal fluid samples, confirmed bacterial meningitis with associated vasculitis. Notably, oral bacteria linked to periodontitis, including , , , and , were found in the biopsies and microbiological analyses. To the best of our knowledge, this is the first reported case showing that bacteremia following dental procedures can lead to such severe neurological outcomes. This case underscores the importance of recognizing bacteremia-induced vasculitis in patients presenting with neurological symptoms post-dental procedures, emphasizing the broader implications of oral infections in such pathologies.
PubMed: 38928550
DOI: 10.3390/brainsci14060550 -
Antibiotics (Basel, Switzerland) May 2024(group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the...
(group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the combined use of penicillin and gentamicin due to the enhanced bactericidal activity. However, high-level gentamicin resistance (HLGR) abrogates the synergism. The rate of HLGR was investigated within a dataset of 433 GBS strains collected from cases of invasive disease in both adults and neonates as well as from pregnant carriers. GBS isolates (n = 20, 4.6%) presented with HLGR (gentamicin MIC breakpoint >1024 mg/L) that was differently diffused between strains from adults or neonates (5.2% vs. 2.8%). Notably, 70% of HLGR GBS strains (14 isolates) were serotype IV. Serotype IV HLGR-GBS isolates were susceptible to all antibiotics tested, exhibited the alpha-C/HvgA/PI-2b virulence string, and belonged to sequence type 1010 (clonal complex (CC) 452). The mobile element that harbored the HLGR (6')-(2)″ gene is a novel integrative and conjugative element (ICE) about 45 kb long, derived from GBS 515 ICE tRNA. The clonal expansion of this HLGR hypervirulent serotype IV GBS CC452 sublineage may pose a threat to the management of infections caused by this strain type.
PubMed: 38927158
DOI: 10.3390/antibiotics13060491