Diagnostic challenges of central nervous system tuberculosis.
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ABSTRACT:
SUBMITTER: Christie LJ
PROVIDER: S-EPMC2603083 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose of reviewCentral nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis.Recent findingsInsight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival.SummaryRecent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.
| S-EPMC8283909 | biostudies-literature
Project description:Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area.
| S-EPMC5398760 | biostudies-literature
Project description:IntroductionCentral nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead to certain side effects. Herein, we presented a protocol for a systematic review and meta-analysis to assess the diagnostic efficacy of MRI for CNSTB.Methods and analysisSinoMed, Wanfang database, China National Knowledge Infrastructure, Embase, the Cochrane Library and PubMed will be searched to identify studies reporting on the use of MRI in the diagnosis of CNSTB from database inception to December 2023. The following keywords will be applied: 'Intracranial tuberculosis', 'Cerebral tuberculosis', 'Central nervous system tuberculosis', 'Spinal tuberculous arachnoiditis' and 'Magnetic Resonance Imaging'. Studies that evaluate the diagnostic accuracy of MRI for the diagnosis of CNSTB and report clear reference criteria will be included. Studies from which full true positive, false positive, false negative and true negative values cannot be extracted, those published in languages other than English or Chinese, abstracts not reporting the full text, and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used to evaluate the methodological quality of each included study. Stata V.15.0 and RevMan V.5.3 will be used to perform a meta-analysis and generate forest plots and summary receiver operating characteristic curves. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and meta-regression analyses.Ethics and disseminationThis research is based on public databases and does not require ethical approval. Results will be submitted for publication in a peer-reviewed journal.Prospero registration numberCRD42023415690.
| S-EPMC10565314 | biostudies-literature
Project description:There is currently no convenient way to effectively evaluate whether a miliary tuberculosis patient is complicated with central nervous system (CNS) tuberculosis. We aimed to find such a way by analyzing the clinical data of these patients. Fifty patients with confirmed miliary tuberculosis and 31 patients with confirmed miliary tuberculosis complicated with CNS tuberculosis from 2010 to 2014 were selected. Their general conditions, clinical features and laboratory tests were analyzed. Factors that were significantly different between them were chosen to performed multivariate and univariate logistic regression analyses, and factors with significant P values were used to establish a scoring system. Eight factors, i.e., age, cough, nausea, headache, hemoglobin (HGB), serum albumin (ALB), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were significantly different (P < 0.05). Multivariate logistic regression analysis showed that ALB was the independent risk predictor (HR = 1.29, 95% CI 1.09-1.52, P < 0.01), whereas the others were non-independent predictors except age (P < 0.05). The scoring system was based on a summation of the scores of the assigned values of the seven predictors and had an area under the curve (AUC) of 0.86 to confirm CNS tuberculosis, with a sensitivity of 81.5% and a specificity of 81.4% at a score of 0.75 and with a specificity of 95.3% at a score of 2.75. In contrast, a score below -0.75 excluded CNS tuberculosis, with a sensitivity of 88.9% and a specificity of 62.7%. The scoring system should be useful to evaluate whether a miliary tuberculosis patient is complicated with CNS tuberculosis and could help doctors avoid excessive investigation.
| S-EPMC5439665 | biostudies-literature
Project description: Not available
| S-EPMC7525189 | biostudies-literature
Project description:Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area.
| S-EPMC5667336 | biostudies-literature
Project description:BACKGROUND:Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously. RESULTS:We screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum. CONCLUSIONS:Our findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.
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Project description:A urinary miRNA combination could be a powerful classifier for the detection of patients with brain tumors.
2021-03-31 | GSE145510 | GEO
Project description:[This corrects the article DOI: 10.1371/journal.pone.0176651.].
| S-EPMC5540408 | biostudies-literature
Project description:Existing and emerging viral central nervous system (CNS) infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus (HIV). Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available, including candidate thiazolide and pyrazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antiviral agents and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T lymphocytes has been used in humans and may provide an effective therapy for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies.
| S-EPMC4052367 | biostudies-literature