Paediatric hydrocephalus.

Hydrocephalus is classically considered as a failure of cerebrospinal fluid (CSF) homeostasis that results in the active expansion of the cerebral ventricles. Infants with hydrocephalus can present with progressive increases in head circumference whereas older children often present with signs and symptoms of elevated intracranial pressure. Congenital hydrocephalus is present at or near birth and some cases have been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. Acquired hydrocephalus can develop at any time after birth, is often caused by central nervous system infection or haemorrhage and has been associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. Treatments for hydrocephalus mainly include surgical CSF shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization. In utero treatment of fetal hydrocephalus is possible via surgical closure of associated neural tube defects. Long-term outcomes for children with hydrocephalus vary widely and depend on intrinsic (genetic) and extrinsic factors. Advances in genomics, brain imaging and other technologies are beginning to refine the definition of hydrocephalus, increase precision of prognostication and identify nonsurgical treatment strategies.

Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus".

The Hydrocephalus Association (HA) workshop, Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus, was held on November 4 and 5, 2019 at Washington University in St. Louis. The workshop brought together a diverse group of basic, translational, and clinical scientists conducting research on multiple hydrocephalus etiologies with select outside researchers. The main goals of the workshop were to explore areas of potential overlap between hydrocephalus etiologies and identify drug targets that could positively impact various forms of hydrocephalus. This report details the major themes of the workshop and the research presented on three cell types that are targets for new hydrocephalus interventions: choroid plexus epithelial cells, ventricular ependymal cells, and immune cells (macrophages and microglia).

Inpatient healthcare burden and variables influencing hydrocephalus-related admissions across the lifespan.

OBJECTIVE: The aims of this study were to quantify inpatient healthcare costs, describe patient demographics, and analyze variables influencing costs for pediatric and adult hydrocephalus shunt-related admissions in the US. METHODS: A cross-sectional study was performed using the 2019 Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) and National Inpatient Sample (NIS), nationally representative weighted data sets of hospital discharges for pediatric and adult patients, respectively. International Classification of Diseases, 10th Revision, Clinical Modification and Procedure Coding System (ICD-10-CM/PCS) code filters for data extraction were queried for admission information. Age at admission was categorized into five groups (≤ 28 days, 29 days to < 1 year, 1-18 years, 19-64 years, and ≥ 65 years). RESULTS: In 2019, there were 36,898 shunt-related hospital admissions accounting for 495,138 hospital days and a total cost of more than $2.06 billion. Initial shunt placements accounted for 53.5% of all admissions and nearly 60% of the total cost. The median cost per admission was $22,700 and the median length of stay was 5 days. Admissions for shunt infection requiring revision had the highest median cost at $71,300 (p < 0.001) and the longest median length of stay at 25 days (p < 0.001) compared with initial shunt placements. By age, admissions that occurred in the first 28 days of life cost almost 5 times more than the median, $110,500 versus $22,700, respectively, and resulted in hospital stays that were 8 times longer than the median, 41 versus 5 days, respectively. Individuals aged ≥ 65 years accounted for 28% of the total shunt-related admissions. Almost two-thirds (65.3%) of shunt-related admissions were classified as nonelective. The median cost of nonelective procedures was double that of elective admissions, $33,900 versus $15,100, respectively (p < 0.001), and resulted in almost 5 times longer hospital stays, 9 versus 2 days, respectively (p < 0.001). Shunt-related admissions were predominantly male across all age groups (54.7%-57.4% male) except the 19- to 64-year age group. In the 19- to 64-year age group, females accounted for 51.1% of admissions. Insurance status was largely age dependent. Of all admissions, 33.1% used private insurance, 32.9% Medicare, and 27.7% Medicaid. CONCLUSIONS: This is the first study to quantify the patient demographics and cost of hydrocephalus shunt-related admissions across the entire age spectrum. Shunt-related admissions cost the US more than $2.06 billion dollars per year and represent only a fraction of the total cost of hydrocephalus care.

Establishing ranked priorities for future hydrocephalus research.

OBJECTIVE: The aim of this initiative was to develop a ranked list of hydrocephalus research priorities as determined by the hydrocephalus patient community in conjunction with the healthcare and scientific community. METHODS: Using the validated methodology published by the James Lind Alliance (JLA), the Hydrocephalus Association (HA) administered two surveys and hosted a final prioritization workshop. Survey One solicited open-ended responses from the community. From these responses, a long list of priority statements was developed. This list was then consolidated into a short list of research priority statements, which, after a nonsystematic literature review, were verified as being research uncertainties. Survey Two asked the community members to select their top 10 priorities from the short list. The final prioritization leading to a final ranked top 20 list of hydrocephalus research priorities took place at a virtual workshop led by a team of trained facilitators, by means of an iterative process of consensus building. RESULTS: From Survey One, 3703 responses from 890 respondents were collected, leading to a long list of 146 priority statements. The consolidated short list contained 49 research priority statements, all of which were verified as uncertainties in hydrocephalus research. From an analysis of Survey Two responses, the top 21 research priority statements were determined. A consensus on these statements was reached at the virtual workshop, leading to a final ranked top 20 list of hydrocephalus research priorities, within which needs were apparent in several areas: development of noninvasive and/or one-time therapies, reduction of the burden of current treatments, improvement of the screening and diagnosis of hydrocephalus, improved quality of life, and improved access to care. CONCLUSIONS: By gathering extensive input from the hydrocephalus community and using an iterative process of consensus building, a ranked list of the top 20 hydrocephalus research priorities was developed. The HA will use this ranked list to guide future research programs and encourages the healthcare and scientific community to do the same.

Anterior versus posterior entry site for ventriculoperitoneal shunt insertion: a randomized controlled trial by the Hydrocephalus Clinical Research Network.

OBJECTIVE: The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS: The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS: The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98-1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS: This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

The quality of YouTube videos on endoscopic third ventriculostomy and endoscopic third ventriculostomy with choroid plexus cauterization procedures available to families of patients with pediatric hydrocephalus.

OBJECTIVE: YouTube has become an important information source for pediatric neurosurgical patients and their families. The goal of this study was to determine whether the informative quality of videos of endoscopic third ventriculostomy (ETV) and endoscopic third ventriculostomy with choroid plexus cauterization (ETV + CPC) is associated with metrics of popularity. METHODS: This cross-sectional study used comprehensive search terms to identify videos pertaining to ETV and ETV + CPC presented on the first 3 pages of search results on YouTube. Two pediatric neurosurgeons, 1 neurosurgery resident, and 2 patient families independently reviewed the selected videos. Videos were assessed for overall informational quality by using a validated 5-point Global Quality Score (GQS) and compared to online metrics of popularity and engagement such as views, likes, likes/views ratio, comments/views ratio, and likes/dislikes ratio. Weighted kappa scores were used to measure agreement between video reviewers. RESULTS: A total of 58 videos (47 on ETV, 7 on ETV + CPC, 4 on both) of 120 videos assessed met the inclusion criteria. Video styles included "technical" (62%), "lecture" (24%), "patient testimonial" (4%), and "other" (10%). In terms of GQS, substantial agreement was seen between surgeons (kappa 0.67 [95% CI 0.55, 0.80]) and excellent agreement was found between each surgeon and the neurosurgical resident (0.77 [95% CI 0.66, 0.88] and 0.89 [95% CI 0.82, 0.97]). Only fair to moderate agreement was seen between professionals and patient families, with weighted kappa scores ranging from 0.07 to 0.56. Academic lectures were more likely to be rated good or excellent (64% vs 0%, p < 0.001) versus surgical procedure and testimonial video types. There were significant associations between a better GQS and more likes (p = 0.01), views (p = 0.02), and the likes/dislikes ratio (p = 0.016). The likes/views ratio (p = 0.31) and comments/views ratio (p = 0.35) were not associated with GQS. The number of likes (p = 0.02), views (p = 0.03), and the likes/dislikes ratio (p = 0.015) were significantly associated with video style (highest for lecture-style videos). CONCLUSIONS: Medical professionals tended to agree when assessing the overall quality of YouTube videos, but this agreement was not as strongly seen when compared to parental ratings. The online metrics of likes, views, and likes/dislikes ratio appear to predict quality. Neurosurgeons seeking to increase their online footprint via YouTube would be well advised to focus more on the academic lecture style because these were universally better rated.

Observations from Social Media Regarding the Symptomatology of Adult Hydrocephalus Patients.

BACKGROUND: Patients with hydrocephalus experience symptoms related to hydrocephalus in an age-dependent manner. However, prevalence estimates of hydrocephalus symptoms in young and middle-aged (YMA) adult patients are rare and variable. Highlighting the importance of hydrocephalus symptom management, the persistence and intensity of headache or gait disturbance have been associated with signs of brain white matter integrity loss, including in treated YMA adult patients. Thus, it is important to ascertain which symptoms adult patients with hydrocephalus report most to confirm their relative importance. METHODS: Observations of symptom complaints were made from publicly viewable online responses to an inquiry posted by the Hydrocephalus Association to 2 Facebook webpages. RESULTS: Within 7 days of inquiry posting, 381 complaints of signs and symptoms were identified in 82 online responses. Headache, cognitive deficits (cognition and memory), and mobility issues (dizziness, balance, or gait problems) were most commonly reported by 63%, 45%, and 40% of respondents, respectively. Results were highly similar for the subgroup of 53 patients reported as treated. For self-identified YMA patients (<60 years old), results were similar, but with fewer mobility complaints. Not previously reported, hypersensitivity to external stimuli was reported by one-half of the patients that reported headache. CONCLUSIONS: The current results provide further quantitative support for the prioritization of study of headache, cognitive deficits, and mobility issues in YMA adult patients with hydrocephalus. Warranting further study, cranial hypersensitivity to external stimuli may represent a novel outcome measure, and treated YMA adult hydrocephalus patients continue to report symptoms associated with signs of brain damage.

Perinatal Breathing Patterns and Survival in Mice Born Prematurely and at Term.

Infants born prematurely, often associated with maternal infection, frequently exhibit breathing instabilities that require resuscitation. We hypothesized that breathing patterns during the first hour of life would be predictive of survival in an animal model of prematurity. Using plethysmography, we measured breathing patterns during the first hour after birth in mice born at term (Term 19.5), delivered prematurely on gestational day 18.5 following administration of low-dose lipopolysaccharide (LPS; 0.14 mg/kg) to pregnant dams (LPS 18.5), or delivered on gestational day 18.7 or 17.5 by caesarian section (C-S 18.5 and C-S 17.5, respectively). Our experimental approach allowed us to dissociate effects caused by inflammation, from effects due to premature birth in the absence of an inflammatory response. C-S 17.5 mice did not survive, whereas mortality was not increased in C-S 18.5 mice. However, in premature pups born at the same gestational age (day 18.5) in response to maternal LPS injection, mortality was significantly increased. Overall, mice that survived had higher birth weights and showed eupneic or gasping activity that was able to transition to normal breathing. Some mice also exhibited a "saw tooth" breathing pattern that was able to transition into eupnea during the first hour of life. In contrast, mice that did not survive showed distinct, large amplitude, long-lasting breaths that occurred at low frequency and did not transition into eupnea. This breathing pattern was only observed during the first hour of life and was more prevalent in LPS 18.5 and C-S 18.5 mice. Indeed, breath tidal volumes were higher in inflammation-induced premature pups than in pups delivered via C-section at equivalent gestational ages, whereas breathing frequencies were low in both LPS-induced and C-section-induced premature pups. We conclude that a breathing pattern characterized by low frequency and large tidal volume is a predictor for the failure to survive, and that these characteristics are more often seen when prematurity occurs in the context of maternal inflammation. Further insights into the mechanisms that generate these breathing patterns and how they transition to normal breathing may facilitate development of novel strategies to manage premature birth in humans.

Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop.

The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on July 25 and 26, 2016 at the National Institutes of Health. The workshop brought together a diverse group of researchers including pediatric neurosurgeons, neurologists, and neuropsychologists with scientists in the fields of brain injury and development, cerebrospinal and interstitial fluid dynamics, and the blood-brain and blood-CSF barriers. The goals of the workshop were to identify areas of opportunity in posthemorrhagic hydrocephalus research and encourage scientific collaboration across a diverse set of fields. This report details the major themes discussed during the workshop and research opportunities identified for posthemorrhagic hydrocephalus. The primary areas include (1) preventing intraventricular hemorrhage, (2) stopping primary and secondary brain damage, (3) preventing hydrocephalus, (4) repairing brain damage, and (5) improving neurodevelopment outcomes in posthemorrhagic hydrocephalus.

The physiological determinants of sudden infant death syndrome.

It is well-established that environmental and biological risk factors contribute to Sudden Infant Death Syndrome (SIDS). There is also growing consensus that SIDS requires the intersection of multiple risk factors that result in the failure of an infant to overcome cardio-respiratory challenges. Thus, the critical next steps in understanding SIDS are to unravel the physiological determinants that actually cause the sudden death, to synthesize how these determinants are affected by the known risk factors, and to develop novel ideas for SIDS prevention. In this review, we will examine current and emerging perspectives related to cardio-respiratory dysfunctions in SIDS. Specifically, we will review: (1) the role of the preBötzinger complex (preBötC) as a multi-functional network that is critically involved in the failure to adequately respond to hypoxic and hypercapnic challenges; (2) the potential involvement of the preBötC in the gender and age distributions that are characteristic for SIDS; (3) the link between SIDS and prematurity; and (4) the potential relationship between SIDS, auditory function, and central chemosensitivity. Each section underscores the importance of marrying the epidemiological and pathological data to experimental data in order to understand the physiological determinants of this syndrome. We hope that a better understanding will lead to novel ways to reduce the risk to succumb to SIDS.

Cardiorespiratory coupling in health and disease.

Cardiac and respiratory activities are intricately linked both functionally as well as anatomically through highly overlapping brainstem networks controlling these autonomic physiologies that are essential for survival. Cardiorespiratory coupling (CRC) has many potential benefits creating synergies that promote healthy physiology. However, when such coupling deteriorates autonomic dysautonomia may ensue. Unfortunately there is still an incomplete mechanistic understanding of both normal and pathophysiological interactions that respectively give rise to CRC and cardiorespiratory dysautonomia. Moreover, there is also a need for better quantitative methods to assess CRC. This review addresses the current understanding of CRC by discussing: (1) the neurobiological basis of respiratory sinus arrhythmia (RSA); (2) various disease states involving cardiorespiratory dysautonomia; and (3) methodologies measuring heart rate variability and RSA.

Central and peripheral factors contributing to obstructive sleep apneas.

Apnea, the cessation of breathing, is a common physiological and pathophysiological phenomenon. Among the different forms of apnea, obstructive sleep apnea (OSA) is clinically the most prominent manifestation. OSA is characterized by repetitive airway occlusions that are typically associated with peripheral airway obstructions. However, it would be an oversimplification to conclude that OSA is caused by peripheral obstructions. OSA is the result of a dynamic interplay between chemo- and mechanosensory reflexes, neuromodulation, behavioral state and the differential activation of the central respiratory network and its motor outputs. This interplay has numerous neuronal and cardiovascular consequences that are initially adaptive but in the long-term become major contributors to morbidity and mortality. Not only OSA, but also central apneas (CA) have multiple, and partly overlapping mechanisms. In OSA and CA the underlying mechanisms are neither "exclusively peripheral" nor "exclusively central" in origin. This review discusses the complex interplay of peripheral and central nervous components that characterizes the cessation of breathing.