Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population.

Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected for this study were from two paediatric groups. Group 1: controls (n = 44): children without meningitis, no neurological symptoms and from the same geographical region as group 2. Group 2: TBM cases (n = 13): collected from paediatric patients that were admitted to Tygerberg Hospital in South Africa on the suspicion of TBM, mostly severely ill; with a later confirmation of TBM. Untargeted 1H NMR-based metabolomics data of urine were generated, followed by statistical analyses via MetaboAnalyst (v5.0), and the identification of important metabolites. Twenty nine urinary metabolites were identified as characteristic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production-metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide original biological insights into this biosignature of urinary metabolites that can be used to characterize paediatric TBM patients in a South African cohort.

Variables included in cerebral palsy registries globally: A scoping review.

AIM: To identify cerebral palsy (CP) variables collected in CP registries from high-income countries (HICs) and low- and middle-income countries (LMICs) to assist with the development of a regional CP registry relevant to the African region. METHOD: A systematic search of online databases to identify peer-reviewed publications and grey literature about CP risk-factor variables, using Ovid MEDLINE, Embase Ovid, CINAHL, and Google Scholar. RESULTS: A total of 197 studies published from global CP registries between 1990 and 2023 were identified. CP registries both from HICs and from LMICs included variables on prenatal CP risk factors. LMIC registries focused more on socioeconomic factors (the physical structure of the family home [21.1%, n = 8, in LMICs vs 1.7%, n = 2, in HICs]). Prenatal modifiable and non-modifiable risk factors were emphasized in HICs. LMIC registries included more postnatal CP risk-factor variables than HIC registries, including history of postnatal jaundice (15.8%, n = 6, in LMICs vs 6.9%, n = 8, in HICs) and postnatal head trauma (10.5%, n = 4, in LMICs vs 5.2%, n = 6, in HICs). INTERPRETATION: CP registries are currently more available in HICs than in LMICs. Differences in CP risk factors account for most of the differences in variables included in HICs and LMICs. Comparing variables used by CP registries in HICs and LMICs suggests the importance of understanding contextually relevant factors for regional registry design.

An exploratory investigation of the CSF metabolic profile of HIV in a South African paediatric cohort using GCxGC-TOF/MS.

INTRODUCTION:  Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation. AIM AND OBJECTIVE: The aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals. RESULTS: The results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size. CONCLUSIONS: This study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.

Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment.

BACKGROUND: The pathogenesis of tuberculous meningitis (TBM) involves infection by Mycobacterium tuberculosis in the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM. METHOD: We used a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16). FINDINGS: Our metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM. CONCLUSION: These results - which are supported by previous urinary studies of tuberculosis - highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.

Diagnosis and Management of Tuberculous Meningitis in Children- an Update.

UPDATE ON THE DIAGNOSIS AND MANAGEMENT OF TUBERCULOUS MENINGITIS IN CHILDREN: Ronald van Toorn, Regan Solomons Seminars in Pediatric Neurology Volume 21, Issue 1, March 2014, Pages 12-18 Tuberculous meningitis (TBM), the most devastating manifestation of tuberculosis, is often missed or overlooked because of nonspecific symptoms and difficulties in diagnosis. It continues to be an important cause of neurologic handicap in resource-poor countries. Owing to the suboptimal performance of diagnostic tests of TBM, diagnosis relies on thorough history, clinical examination, and relevant investigations. The development of affordable, accurate diagnostic tests for TBM in resource-poor settings remains a priority. Short intensified treatment is safe and effective in both human immunodeficiency virus (HIV)-infected and HIV-uninfected children. Treatment of tuberculous hydrocephalus depends on the level of the cerebrospinal fluid obstruction. Corticosteroids reduce risk of neurodisability and death in HIV-uninfected children. Thalidomide should be considered in children compromised by tuberculosis abscesses and tuberculous-related optochiasmic arachnoiditis. In resource-poor countries, home-based TBM treatment after initial in-hospital stabilization is feasible in carefully selected patients. Early diagnosis and treatment of TBM is the single most important factor determining outcome.

Adar-associated Aicardi Goutières syndrome in a child with bilateral striatal necrosis and recurrent episodes of transaminitis.

Aicardi-Goutières syndrome (AGS) refers to a group of genetic diseases characterised by severe inflammatory encephalopathy that usually present within the first year of life, resulting in progressive loss of cognition, spasticity, dystonia and motor disability. Pathogenic variants in the adenosine deaminase acting on RNA (Adar) enzyme have been linked to AGS type 6 (AGS6, Online Mendelian Inheritance in Man (OMIM) 615010). In knockout mouse models, loss of Adar activates the interferon (IFN) pathway and causes autoimmune pathogenesis in the brain or liver. Bilateral striatal necrosis (BSN) has previously been reported in case series of children with biallelic pathogenic variants in Adar We describe a unique, previously unreported case of a child with AGS6, with clinical manifestations of BSN and recurrent transient episodes of transaminitis. The case highlights the importance of Adar in protecting the brain and liver from IFN-induced inflammation. Adar-related disease should therefore be considered in the differential diagnosis of BSN accompanied by recurrent episodes of transaminitis.

Bacterial meningitis in Africa.

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus), Escherichia coli, and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.

Epileptic spasms: A South African overview of aetiologies, interventions, and outcomes.

AIM: To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource-limited settings. METHOD: This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the Western Cape, South Africa. RESULTS: Of 175 children with epileptic spasms, the median age at onset was 6 months (interquartile range 4-8 months). Structural aetiologies were most common (115 out of 175 [66%]), with two-thirds related to perinatal insults. A lead time to treatment (LTTT) of less than 1 month was more likely in the epileptic encephalopathy/developmental and epileptic encephalopathy (DEE) group: 58 out of 92 (63%), compared to 28 out of 76 (37%) of those with developmental encephalopathy (p = 0.001). Failure to recognize preceding developmental delay was common. Ninety-nine children (57%) received first line hormonal therapy such as adrenocorticotropic hormone. A total of 111 out of 172 children (65%) from the developmental encephalopathy and epileptic encephalopathy/DEE groups had clinical and/or electroencephalogram resolution of spasms within 14 days. In our population, children in whom an aetiology could not be identified were statistically more likely to have moderate to profound developmental delay at 1 year of age: 33 out of 44 (p = 0.001). Based on reported incidence of epileptic spasms, 23 to 58 cases per annum would be expected but a far smaller proportion presented to our centres. INTERPRETATION: Whilst this is the largest cohort of infants with epileptic spasms from sub-Saharan Africa, the study size is less than expected; this may reflect misdiagnosis and failure of referral pathways. Despite a reported shorter LTTT, infants with DEE had worse developmental outcomes compared to international studies. Hormonal therapy was safe and effective in our setting, despite exposure to high levels of tuberculosis and HIV. WHAT THIS PAPER ADDS: The number of unreferred cases of epileptic spasms in South Africa remains high. Caregivers and health care workers in primary care facilities often fail to recognize developmental delay. The burden of disease from hypoxic-ischaemic encephalopathy remains high in our resource-limited setting. Hormonal treatment (e.g. adrenocorticotropic hormone) was safe and effective despite the high prevalence of human immunodeficiency virus and tuberculosis.

Risk factors of poor developmental outcome in children with tuberculous meningitis.

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. RESULTS: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87-6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. CONCLUSION: Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness.

Utility of genetic testing in children with developmental and epileptic encephalopathy (DEE) at a tertiary hospital in South Africa: A prospective study.

OBJECTIVES: The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of rare neurodevelopmental disorders, characterised by early-onset seizures that are often intractable, electroencephalographic abnormalities, and developmental delay or regression. There is a paucity of data from sub-Saharan Africa on the genetic basis of DEE. The aim of this study was to investigate the genetic background of DEE using targeted next generation sequencing (NGS) analysis in a tertiary pediatric neurology outpatient department at Tygerberg Hospital, South Africa. In addition, we assessed the value of the genetic results to the parents and managing physicians. METHODS: A prospective cohort study of 41 consecutive children with DEE (onset before 3 years of age) that were recruited over a 2-year period (2019-2021). Pre- and post-test genetic counselling were offered to all study participants. The results were categorized as either: positive (pathogenic/likely pathogenic variant identified), inconclusive (variant(s) of unknown significance identified), or negative (no variants identified). Result interpretation and careful matching of the variant to the clinical phenotype was performed. Subsequently, questionnaires were administered to both the physicians and the parents. RESULTS: A genetic underlying cause for DEE was identified in 18 of 41 children (diagnostic yield 43.9%). Variants in SCN1A (n=7), KANSL1 (n=2), KCNQ2 (n=2) and CDKL5 (n=2) were identified in more than one patient. Rarer genes included IQSEC2, SMC1A and STXBP1. All of the identified pathogenic variants fully explained and matched the respective phenotypic description of the patient at the time of clinical diagnosis. In 26% of patients the genetic result facilitated precision medicine management changes to anti-seizure medication. Both parents and physicians expressed benefit of genetic testing in patients with DEE. CONCLUSION: Targeted NGS analysis proved an efficient diagnostic tool in detection of a genetic cause of DEE in a large proportion of South African children. The 43.9% diagnostic yield is similar to previously reported international pediatric cohorts. Additionally, the genetic findings proved useful for targeted therapeutic decision-making and accurate genetic counseling.

Comparative Effectiveness of Regimens for Drug-Susceptible Tuberculous Meningitis in Children and Adolescents: A Systematic Review and Aggregate-Level Data Meta-Analysis.

Background: Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown. Methods: To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months' duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes. Results: Of 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%-13.4%) vs 23.9% (95% CI, 17.5%-31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%-99.1%) vs 75.4% (95% CI, 68.7%-81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%-75.3%) vs 36.3% (95% CI, 30.1%-43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen. Conclusions: Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

Validation of host cerebrospinal fluid protein biomarkers for early diagnosis of tuberculous meningitis in children: a replication and new biosignature discovery study.

Purpose: The diagnosis of tuberculous meningitis (TBM) in children is often delayed due to diagnostic difficulties. New tools are urgently needed to improve the diagnosis of the disease in this vulnerable group. The present study aimed to validate the accuracy of recently identified host cerebrospinal (CSF) biomarkers as candidates for the diagnosis of TBM in children.Materials and methods: We collected CSF samples from 87 children aged 3 months to 13 years, that were consecutively admitted at a tertiary hospital in Cape Town, South Africa, on suspicion of having TBM. We evaluated the concentrations of 67 selected host protein biomarkers using a multiplex platform.Results: Previously identified 3-marker (VEGF-A + IFN-γ + MPO) and 4-marker (IFN-γ + MPO + ICAM-1 + IL-8) signatures diagnosed TBM with AUCs of 0.89 (95% CI, 0.81-0.97) and 0.87 (95% CI, 0.79-0.95) respectively; sensitivities of 80.6% (95% CI, 62.5-92.5%) and 81.6% (95% CI, 65.7-92.3%), and specificities of 86.8% (71.9-95.6%) and 83.7% (70.4-92.7%) respectively. Furthermore, a new combination between the analytes (CC4b + CC4 + procalcitonin + CCL1) showed promise, with an AUC of 0.98 (95% CI, 0.94-1.00).Conclusions: We have shown that the accuracies of previously identified candidate CSF biomarkers for childhood TBM was reproducible. Our findings augur well for the future development of a simple bedside test for the rapid diagnosis of TBM in children.

Deciphering Genetic Susceptibility to Tuberculous Meningitis.

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB) that arises when a caseating meningeal granuloma discharges its contents into the subarachnoid space. It accounts for ~1% of all disease caused by Mycobacterium tuberculosis and the age of peak incidence is from 2-4 years. The exact pathogenesis of TBM is still not fully understood and the mechanism(s) by which the bacilli initially invade the blood-brain-barrier are still to be elucidated. This study investigated the involvement of the host genome in TBM susceptibility, by considering common variants (minor allele frequency (MAF) >5%) using microarray genotyping and rare variants (MAF <1%) via exome sequencing. A total of 123 TBM cases, 400 pulmonary TB (pTB) cases and 477 healthy controls were genotyped on the MEGA array. A genome-wide association study (GWAS) comparing 114 TBM cases to 395 healthy controls showed no association with TBM susceptibility. A second analysis comparing 114 TBM cases to 382 pTB cases was conducted to investigate variants associated with different TB phenotypes. No significant associations were found with progression from pTB to TBM. Ten TBM cases and 10 healthy controls were exome sequenced. Gene set association tests SKAT-O and SKAT Common Rare were used to assess the association of rare SNPs and the cumulative effect of both common and rare SNPs with susceptibility to TBM, respectively. Ingenuity Pathway Analysis (IPA) of the top-hits of the SKAT-O analysis showed that NOD2 and CYP4F2 are both important in TBM pathogenesis and highlighted these as targets for future study. For the SKAT Common Rare analysis Centriolar Coiled-Coil Protein 110 (CCP110) was nominally associated (p = 5.89x10-6) with TBM susceptibility. In addition, several top-hit genes ascribed to the development of the central nervous system (CNS) and innate immune system regulation were identified. Exome sequencing and GWAS of our TBM cohort has identified a single previously undescribed association of CCP110 with TBM susceptibility. These results advance our understanding of TBM in terms of both variants and genes that influence susceptibility. In addition, several candidate genes involved in innate immunity have been identified for further genotypic and functional investigation.

Giant cerebral tuberculoma mimicking a high-grade tumour in a child.

We present an 11-year-old girl who manifested with unprovoked right-sided focal motor seizures. CT revealed a large lobulated hypodense mass in the left temporoparietal lobe, with perilesional oedema and postcontrast peripheral enhancement. Diagnostic uncertainty resulted in further neuroimaging, which included MRI with modalities including diffusion-weighted imaging, perfusion imaging, as well as spectroscopy. We discuss the radiological features of the lesion, which steered us in the direction of an infective cause. Definitive diagnosis was achieved by brain needle biopsy, which demonstrated necrotising granulomatous inflammation indicative of tuberculous infection on histology. In addition, GeneXpert yielded a positive result. We believe this unique case highlights the diagnostic dilemma clinicians face in differentiating ring-enhancing lesions on neuroimaging in tuberculosis-endemic regions. It also highlights the potential benefit of a brain needle biopsy (histology and GeneXpert) in cases of uncertainty.

Tuberculous Meningitis in Children: A Forgotten Public Health Emergency.

Tuberculous meningitis (TBM) remains a major cause of morbidity and mortality in children with tuberculosis (TB), yet there are currently no estimates of the global burden of pediatric TBM. Due to frequent non-specific clinical presentation and limited and inadequate diagnostic tests, children with TBM are often diagnosed late or die undiagnosed. Even when diagnosed and treated, 20% of children with TBM die. Of survivors, the majority have substantial neurological disability with significant negative impact on children and their families. Surveillance data on this devastating form of TB can help to quantify the contribution of TBM to the overall burden, morbidity and mortality of TB in children and the epidemiology of TB more broadly. Pediatric TBM usually occurs shortly after primary infection with Mycobacterium tuberculosis and reflects ongoing TB transmission to children. In this article we explain the public health importance of pediatric TBM, discuss the epidemiology within the context of overall TB control and health system functioning and the limitations of current surveillance strategies. We provide a clear rationale for the benefit of improved surveillance of pediatric TBM using a TB care cascade framework to support monitoring and evaluation of pediatric TB, and TB control more broadly. Considering the public health implications of a diagnosis of TBM in children, we provide recommendations to strengthen pediatric TBM surveillance and outline how improved surveillance can help us identify opportunities for prevention, earlier diagnosis and improved care to minimize the impact of TBM on children globally.

Intrapartum Basal Ganglia-Thalamic Pattern Injury and Radiologically Termed "Acute Profound Hypoxic-Ischemic Brain Injury" Are Not Synonymous.

OBJECTIVE: Human cases of acute profound hypoxic-ischemic (HI) injury (HII), in which the insult duration timed with precision had been identified, remains rare, and there is often uncertainty of the prior state of fetal health. STUDY DESIGN: A retrospective analysis of 10 medicolegal cases of neonatal encephalopathy-cerebral palsy survivors who sustained intrapartum HI basal ganglia-thalamic (BGT) pattern injury in the absence of an obstetric sentinel event. RESULTS: Cardiotocography (CTG) admission status was reassuring in six and suspicious in four of the cases. The median time from assessment by admission CTG or auscultation to birth was 687.5 minutes (interquartile range [IQR]: 373.5-817.5 minutes), while the median time interval between first pathological CTG and delivery of the infant was 179 minutes (IQR: 137-199.25 minutes). The mode of delivery in the majority of infants (60%) was by unassisted vaginal birth; four were delivered by delayed caesarean section. The median (IQR) interval between the decision to perform a caesarean section and delivery was 169 minutes (range: 124-192.5 minutes). CONCLUSION: The study shows that if a nonreassuring fetal status develops during labor and is prolonged, a BGT pattern HI injury may result, in the absence of a perinatal sentinel event. Intrapartum BGT pattern injury and radiologically termed "acute profound HI brain injury" are not necessarily synonymous. A visualized magnetic resonance imaging (MRI) pattern should preferably solely reflect the patterns description and severity, rather than a causative mechanism of injury. KEY POINTS: · BGT HI injury pattern on MRI may develop in the absence of a perinatal sentinel event.. · BGT pattern injury may not be synonymous with "acute profound HI brain injury.". · MRI pattern and severity thereof should be described rather than a causative mechanism of injury..

CSF Metabolomics of Tuberculous Meningitis: A Review.

From the World Health Organization's global TB report for 2020, it is estimated that in 2019 at least 80,000 children (a particularly vulnerable population) developed tuberculous meningitis (TBM)-an invariably fatal disease if untreated-although this is likely an underestimate. As our latest technologies have evolved-with the unprecedented development of the various "omics" disciplines-a mountain of new data on infectious diseases have been created. However, our knowledge and understanding of infectious diseases are still trying to keep pace. Metabolites offer much biological information, but the insights they permit can be difficult to derive. This review summarizes current metabolomics studies on cerebrospinal fluid (CSF) from TBM cases and collates the metabolic data reported. Collectively, CSF metabolomics studies have identified five classes of metabolites that characterize TBM: amino acids, organic acids, nucleotides, carbohydrates, and "other". Taken holistically, the information given in this review serves to promote the mechanistic action of hypothesis generation that will drive and direct future studies on TBM.