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Hydrocephalus is a common disorder of cerebral spinal fluid (CSF) physiology resulting in abnormal expansion of the cerebral ventricles. Infants commonly present with progressive macrocephaly whereas children older than 2 years generally present with signs and symptoms of intracranial hypertension. The classic understanding of hydrocephalus as the result of obstruction to bulk flow of CSF is evolving to models that incorporate dysfunctional cerebral pulsations, brain compliance, and newly characterised water-transport mechanisms. Hydrocephalus has many causes. Congenital hydrocephalus, most commonly involving aqueduct stenosis, has been linked to genes that regulate brain growth and development. Hydrocephalus can also be acquired, mostly from pathological processes that affect ventricular outflow, subarachnoid space function, or cerebral venous compliance. Treatment options include shunt and endoscopic approaches, which should be individualised to the child. The long-term outcome for children that have received treatment for hydrocephalus varies. Advances in brain imaging, technology, and understanding of the pathophysiology should ultimately lead to improved treatment of the disorder.

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation — driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways — contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia–lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.In this Review, Karimy et al. discuss the mechanisms by which inflammation can contribute to the pathogenesis of acquired hydrocephalus and highlight targets for therapeutic intervention.

Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K + , accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K + transporters, particularly the Na + , K + , Cl − , and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K + clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K + clearance through the ChP in the critical period during postnatal neurodevelopment in mice. Abnormal CSF accumulation in the brain can lead to hydrocephalus. The mechanisms regulating CSF clearance during early development are unclear. Here, the authors show that NKCC1 regulates the clearance of both CSF K + and fluid volume through the choroid plexus during postnatal development in mice.

Background Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007–2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012–2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery ( i.e., initial CSF shunt placement and revisions) in children. Methods A retrospective observational cohort study at 6 tertiary care children’s hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. Results A total of 1723 children underwent initial shunt placement between 2007–2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82–1.81, p  = 0.3) and AICs (OR 0.91, 95% CI 0.56–1.49, p  = 0.7) compared to standard care. Conclusion In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk ( i.e., initial or revision) shunt surgeries.

Background Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother’s arsenic exposure, folic acid, and spina bifida risk in Bangladesh. Methods We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure. Results We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother’s arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p  = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52–2.29, p  = 0.82). Conclusions Mother’s arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries.

A randomized trial involving 100 Ugandan infants with postinfectious hydrocephalus compared endoscopic third ventriculostomy plus choroid plexus cauterization with conventional ventricular shunting and found no difference in cognitive outcomes at 1 year.

IntroductionManaging paediatric hydrocephalus with shunt placement is especially risky in resource-limited settings due to risks of infection and delayed life-threatening shunt obstruction. This study evaluated a new evidence-based treatment algorithm to reduce shunt-dependence in this context.MethodsA prospective cohort design was used. The CURE Protocol employs preoperative and intraoperative data to choose between endoscopic treatment and shunt placement. Data were prospectively collected for 730 children in Uganda (managed by local neurosurgeons highly experienced in the protocol) and, for external validation, 96 children in Nigeria (managed by a local neurosurgeon trained in the protocol).ResultsThe age distribution was similar between Uganda and Nigeria, but there were more cases of postinfectious hydrocephalus in Uganda (64.2% vs 26.0%, p<0.001). Initial treatment of hydrocephalus was similar at both centres and included either a shunt at first operation or endoscopic management without a shunt. The Nigerian cohort had a higher failure rate for endoscopic cases (adjusted HR 2.5 (95% CI 1.6 to 4.0), p<0.001), but not for shunt cases (adjusted HR 1.3 (0.5 to 3.0), p=0.6). Despite the difference in endoscopic failure rates, a similar proportion of the entire cohort was successfully treated without need for shunt at 6 months (55.2% in Nigeria vs 53.4% in Uganda, p=0.74).ConclusionUse of the CURE Protocol in two centres with different populations and surgeon experience yielded similar 6-month results, with over half of all children remaining shunt-free. Where feasible, this could represent a better public health strategy in low-resource settings than primary shunt placement.

Background and significanceThe third Sustainable Development Goal for child health, which aims to end preventable deaths of newborns and children less than 5 years of age by 2030, cannot be met without substantial reduction of infection-specific neonatal mortality in the developing world. Neonatal infections are estimated to account for 26% of annual neonatal deaths, with mortality rates highest in sub-Saharan Africa (SSA). Reliable and comprehensive estimates of the incidence and aetiology surrounding neonatal sepsis in SSA remain incompletely available. We estimate the economic burden of neonatal sepsis in SSA.MethodsData available through global health agencies and in the medical literature were used to determine population demographics in SSA, as well as to determine the incidence, disease burden, mortality and resulting disabilities associated with neonatal sepsis. The disability-adjusted life years (DALY) associated with successful treatment or prevention of neonatal sepsis in SSA for 1 year were calculated. The value of a statistical life (VSL) methodology was estimated to evaluate the economic burden of untreated neonatal sepsis in SSA.ResultsWe conservatively estimate that 5.29–8.73 million DALYs are lost annually in SSA due to neonatal sepsis. Corresponding VSL estimates predict an annual economic burden ranging from $10 billion to $469 billion.ConclusionsOur results highlight and quantify the scope of the public health and economic burden posed by neonatal sepsis in SSA. We quantify the substantial potential impact of more successful treatment and prevention strategies, and we highlight the need for greater investment in strategies to characterise, diagnose, prevent and manage neonatal sepsis and its long-term sequelae in SSA.