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.

Pathogenesis and management of low-pressure hydrocephalus: A narrative review.

Patients diagnosed with low-pressure hydrocephalus typically present with enlarged ventricles and unusually low intracranial pressure, often measuring below 5 cmH2O or even below atmospheric pressure. This atypical presentation often leads to low recognition and diagnostic rates. The development of low-pressure hydrocephalus is believed to be associated with a decrease in the viscoelasticity of brain tissue or separation between the ventricular and subarachnoid spaces. Risk factors for low-pressure hydrocephalus include subarachnoid hemorrhage, aqueduct stenosis, prior cranial radiotherapy， ventricular shunting, and cerebrospinal fluid leaks. For potential low-pressure hydrocephalus, diagnostic criteria include neurological symptoms related to hydrocephalus, an Evans index >0.3 on imaging, ICP ≤ 5 cm H2O, symptom improvement with negative pressure drainage, and exclusion of ventriculomegaly caused by neurodegenerative diseases. The pathogenesis and pathophysiological features of low-pressure hydrocephalus differ significantly from other types of hydrocephalus, making it challenging to restore normal ventricular morphology through conventional drainage methods. The primary treatment options for low-pressure hydrocephalus involve negative pressure drainage and third ventriculostomy. With appropriate treatment, most patients can regain their previous neurological function. However, in most cases, permanent shunt surgery is still necessary. Low-pressure hydrocephalus is a rare condition with a high rate of underdiagnosis and mortality. Early identification and appropriate intervention are crucial in reducing complications and improving prognosis.

Post-traumatic hydrocephalus: An overview of classification, diagnosis, treatment, and post-treatment imaging evaluation.

The syndrome of post-traumatic hydrocephalus (PTH) has been recognized since Dandy's report in 1914. The pathogenesis of PTH has not been fully clarified. At present, it is believed that the obstacles of cerebrospinal fluid (CSF) secretion, absorption and circulation pathways are the reasons for the development of PTH. However, recent studies have also suggested that the osmotic pressure load of CSF and the pathological changes of CSF dynamics are caused by the development of hydrocephalus. Therefore, a better understanding of the definition, classification, diagnostic criteria, treatment, and evaluation of post-treatment effects of PTH is critical for the effective prevention and treatment of PTH. In this paper, we reviewed the classification and diagnosis of PTH and focused on the treatment and the imaging evaluation of post-treatment effects of PTH. This review might provide a judgment criterion for diagnosis of PTH and a basis for the effective prevention and treatment of PTH in the future.

Intracranial Pressure Monitoring and Management in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage is a medical condition that can lead to intracranial hypertension, negatively impacting patients' outcomes. This review article explores the underlying pathophysiology that causes increased intracranial pressure (ICP) during hospitalization. Hydrocephalus, brain swelling, and intracranial hematoma could produce an ICP rise. Although cerebrospinal fluid withdrawal via an external ventricular drain is commonly used, ICP monitoring is not always consistently practiced. Indications for ICP monitoring include neurological deterioration, hydrocephalus, brain swelling, intracranial masses, and the need for cerebrospinal fluid drainage. This review emphasizes the importance of ICP monitoring and presents findings from the Synapse-ICU study, which supports a correlation between ICP monitoring and treatment with better patient outcomes. The review also discusses various therapeutic strategies for managing increased ICP and identifies potential areas for future research.

Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus.

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K+] and triggered cytosolic calcium activity in ChP epithelial cells, which was followed by NKCC1 activation. ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity. These data demonstrate that intraventricular blood triggered a trans-choroidal, NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF [K+] fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to mitigate intracranial fluid accumulation following hemorrhage.

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy.

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFß1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.

Endoscopic Lavage for the Treatment of Multiple Shunt Failures in Children.

AIM: To compare the efficacy of neuroendoscopic lavage (NEL) and shunt revision (SR) in the treatment of multiple shunt failures in children with hydrocephalus. MATERIAL AND METHODS: The data of 56 pediatric patients who underwent surgeries for the treatment of shunt failure were retrospectively reviewed. Patients were divided into two groups, i.e., the simple SR (Group A) and the NEL+SR (Group B) cohorts. Demographic characteristics, co-morbidities, surgical interventions, cerebrospinal fluid analyzes, and complications were recorded and statistically compared between the groups. RESULTS: Among the 56 enrolled patients, 51 presented with shunt dysfunction caused by infectious debris or clots at different times. Moreover, 28 of these 51 patients (54.9%) were female and 23 (45%) were male. The mean age was 7.3 months. Simple SR was performed in 30 cases (Group A), and NEL and simultaneous SR were performed in 21 patients (Group B). The risk of shunt dysfunction was significantly lower in Group B (p < 0.05).The risk of infection was elevated in Group A; however, this difference was not statistically significant (p > 0.05). CONCLUSION: Simultaneous endoscopic lavage and SR was an effective method for the treatment of shunt dysfunction in children. It was also superior to simple SR regarding the risk of shunt dysfunction. Additional clinical studies are needed to verify this outcome.

Is ventricular lavage a novel treatment of neonatal posthemorrhagic hydrocephalus? a meta analysis.

INTRODUCTION: Intraventricular hemorrhage (IVH) may produce obliterative arachnoiditis, which disrupts the flow and absorption of cerebrospinal fluid (CSF), resulting in posthemorrhagic hydrocephalus (PHH). PHH gives a high risk of neurofunctional impairment. Ventricular lavage is the treatment of choice for PHH in neonates with IVH for decades. It is developing with the combination of fibrinolytic therapy, also called drainage, irrigation, and fibrinolytic therapy (DRIFT), and with the use of neuroendoscopic apparatus, also called neuroendoscopic lavage (NEL). METHODS: This review is a meta-analysis using the PRISMA method guideline, including the clinical studies comparing ventricular lavage (VL) with standard treatment of PHH between 2000 and 2021. RESULTS: VL group reduced the shunt dependency compared to standard treatment (OR = 0.22; 95CI 0.05 to 0.97; p = 0.05). VL group has less infection risk compared to the standard treatment group (RR = 0.20; 95CI 0.07 to 0.59; p < 0.05). The severe neurofunctional outcome is similar between the two groups (OR = 0.99; 95CI 0.13 to 7.23; p = 0.99). The early approach treatment group may give better neurofunctional outcomes compared to the late approach (OR = 0.14; 95CI 0.06 to 0.35; p < 0.05). CONCLUSION: VL reduce the shunt dependency on the PHH, decreasing the shunt's related infection rate. The early ventricular lavage may give benefit for the neurocognitive outcome.

The ASPECT Hydrocephalus System: a non-hierarchical descriptive system for clinical use.

In patients with hydrocephalus, prognosis and intervention are based on multiple factors. This includes, but is not limited to, time of onset, patient age, treatment history, and obstruction of cerebrospinal fluid flow. Consequently, several distinct hydrocephalus classification systems exist. The International Classification of Diseases (ICD) is universally applied, but in ICD-10 and the upcoming ICD-11, hydrocephalus diagnoses incorporate only a few factors, and the hydrocephalus diagnoses of the ICD systems are based on different clinical measures. As a consequence, multiple diagnoses can be applied to individual cases. Therefore, similar patients may be described with different diagnoses, while clinically different patients may be diagnosed identically. This causes unnecessary dispersion in hydrocephalus diagnostics, rendering the ICD classification of little use for research and clinical decision-making. This paper critically reviews the ICD systems for scientific and functional limitations in the classification of hydrocephalus and presents a new descriptive system. We propose describing hydrocephalus by a system consisting of six clinical key factors of hydrocephalus: A (anatomy); S (symptomatology); P (previous interventions); E (etiology); C (complications); T (time-onset and current age). The "ASPECT Hydrocephalus System" is a systematic, nuanced, and applicable description of patients with hydrocephalus, with a potential to resolve the major issues of previous classifications, thus providing new opportunities for standardized treatment and research.

Survey of Quaternary Neonatal Management of Posthemorrhagic Hydrocephalus.

OBJECTIVE: This study aimed to determine clinical care practices for infants at risk for posthemorrhagic hydrocephalus (PHH) across level IV neonatal intensive care units (NICUs). STUDY DESIGN: Cross-sectional survey that addressed center-specific surveillance, neurosurgical intervention, and follow-up practices within the Children's Hospitals Neonatal Consortium. RESULTS: We had a 59% (20/34 sites) response rate, with 10 sites having at least two participants. Respondents included neonatologists (53%) and neurosurgeons (35%). Most participants stated having a standard guideline for PHH (79%). Despite this, 42% of respondents perceive inconsistencies in management. Eight same-center pairs of neonatologists and neurosurgeons were used to determine response agreement. Half of these pairs disagreed on nearly all aspects of care. The greatest agreement pertained to a willingness to adopt a consensus-based protocol. CONCLUSION: Practice variation in the management of infants at risk of PHH in level IV NICUs exists despite the perception that a common practice is available and used. KEY POINTS: · Practice variation exists despite the perception that common practices are available/used for PHH.. · Our survey had same-center pairs of neonatologist and neurosurgeons to determine response agreement.. · The greatest agreement pertained to a willingness to adopt a consensus-based protocol..

[Ommaya Reservoir and the External Ventricular Drainage].

Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of hydrocephalus pathologies, treatment options are limited. It is difficult for pediatric neurosurgeons to select and perform appropriate surgical procedures for neonates and infants. Treatment options for hydrocephalus are broadly divided into permanent and temporary. Permanent treatments include cerebrospinal fluid shunt and endoscopic third ventriculostomy; temporary treatment entails cerebrospinal fluid drainage using lumbar puncture and intermittent cerebrospinal fluid drainage with an Ommaya reservoir, ventricular drainage, and ventriculosubgaleal shunt. This article describes in detail Ommaya reservoir placement and ventricular drainage as representative procedures for temporarily treating hydrocephalus.

Hydrocephalus: historical analysis and considerations for treatment.

Hydrocephalus is a serious condition that affects patients of all ages, resulting from a multitude of causes. While the etiologies of hydrocephalus are numerous, many of the acute and chronic symptoms of the condition are shared. These symptoms include disorientation and pain (headaches), cognitive and developmental changes, vision and sleep disturbances, and gait abnormalities. This collective group of symptoms combined with the effectiveness of CSF diversion as a surgical intervention for many types of the condition suggest that the various etiologies may share common cellular and molecular dysfunctions. The incidence rate of pediatric hydrocephalus is approximately 0.1-0.6% of live births, making it as common as Down syndrome in infants. Diagnosis and treatment of various forms of adult hydrocephalus remain understudied and underreported. Surgical interventions to treat hydrocephalus, though lifesaving, have a high incidence of failure. Previously tested pharmacotherapies for the treatment of hydrocephalus have resulted in net zero or negative outcomes for patients potentially due to the lack of understanding of the cellular and molecular mechanisms that contribute to the development of hydrocephalus. Very few well-validated drug targets have been proposed for therapy; most of these have been within the last 5 years. Within the last 50 years, there have been only incremental improvements in surgical treatments for hydrocephalus, and there has been little progress made towards prevention or cure. This demonstrates the need to develop nonsurgical interventions for the treatment of hydrocephalus regardless of etiology. The development of new treatment paradigms relies heavily on investment in researching the common molecular mechanisms that contribute to all of the forms of hydrocephalus, and requires the concerted support of patient advocacy organizations, government- and private-funded research, biotechnology and pharmaceutical companies, the medical device industry, and the vast network of healthcare professionals.

New insights into the management of post-hemorrhagic hydrocephalus.

During the last decade, an increasing number of studies have been conducted to improve the outcome of post-hemorrhagic hydrocephalus (PHH), a complication of severe intraventricular hemorrhage (IVH) in preterm infants. Two randomized controlled trials have shown that treatment should be initiated prior to the onset of clinical symptoms. Ventricular access devices and subgaleal shunts are used as temporary neurosurgical interventions whereas ventriculoperitoneal shunts are performed for infants with progressive hydrocephalus. Recently, techniques such as neuro-endoscopic lavage have also been introduced to eliminate toxic blood products and debris from the cerebral ventricles and have shown promise in early clinical studies. The objective of this review is to provide an update on management of PHVD and PHH in the preterm infant.

Pathogenesis of posthemorrhagic hydrocephalus of prematurity: New horizons.

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a vexing problem for patients, their families, and the healthcare system. The complexity of the pathogenesis of PHHP also presents a unique challenge within the fields of neonatology, neurology and neurosurgery. Here we focus on pathogenesis of PHHP and its impact on the development of CSF dynamics including choroid plexus, ependymal motile cilia and glymphatic system. PHHP is contrasted with infantile hydrocephalus from other etiologies, and with other types of posthemorrhagic hydrocephalus that occur later in life. The important concept that distinguishing ventricular volume from brain health and function is highlighted. The influence of the pathogenesis of PHHP on current interventions is reviewed, with particular emphasis on how the unique pathogenesis of PHHP contributes to the high rate of failure of current existing interventions. Finally, we discuss emerging interventions. A thorough understanding of the pathogenesis of PHHP is essential to developing effective non-surgical therapeutics to prevent the transformation from severe IVH to PHHP.

Treatment of Posthemorrhagic Hydrocephalus.

The incidence of intraventricular hemorrhage (IVH) has overall declined to 15% to 20% of preterm infants with birth weight less than 1500 g. One of the major complications of severe IVH is posthemorrhagic ventricular dilation (PHVD). Nearly 10% of all infants with IVH and 20% of infants with severe IVH will develop progressive PHVD requiring surgical intervention to prevent parenchymal damage in the developing brain. This review focuses on the controversies regarding posthemorrhagic hydrocephalus interventions with a focus on how to interpret recent data from trials that some have seen as heralding a call toward more aggressive intervention.

Hyperbaric Oxygen Therapy Associated with Ventricular-Subcutaneous Shunt Promotes Neuroprotection in Young Hydrocephalic Rats.

Hydrocephalus is characterized by the accumulation of CSF within the cerebral ventricles and the subarachnoid space. Ventricular volume can progressively increase and generate serious damage to the nervous system, with cerebral hypoxia/ischemia as one of the most important factors involved. Hyperbaric oxygen therapy (HBOT) improves oxygen supply to tissues, which can reduce the progression of lesions secondary to ventricular enlargement. We evaluated whether HBOT associated with CSF diversion can promote neuroprotective effects to structures damaged by ventriculomegaly and understand its role. Seven-day-old male Wistar Hannover rats submitted to hydrocephalus by intracisternal injection of 15% kaolin were used. The animals were divided into six groups, with ten animals in each: control, control associated with hyperbaric therapy, hydrocephalic without treatment, hydrocephalic treated with hyperbaric oxygen therapy, hydrocephalic treated with CSF deviation, and hydrocephalic treated with hyperbaric oxygen therapy associated with CSF deviation. To assess the response to treatment, behavioral tests were performed such as modified Morris water maze and object recognition, evaluation by transcranial ultrasonography, histology by Hematoxylin-Eosin and Luxol Fast Blue, immunohistochemistry for GFAP, Ki-67, Caspase-3, COX-2, NeuN and SOD1, and biochemical ELISA assay for GFAP and MBP. The results show that the association of treatments exerts neuroprotective effects such as neurobehavioral improvement, preservation of periventricular structures, antioxidant effect, and reduction of damage resulting from ischemia and the neuroinflammatory process. We conclude that HBOT has the potential to be used as an adjuvant treatment to CSF deviation surgery in experimental hydrocephalus.

Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity.

PURPOSE: Post-hemorrhagic hydrocephalus (PHH) of prematurity is a devastating pathology. Neurodevelopmental disabilities, including cognitive and motor deficits are very commonly seen among this population. Thus, there is interest to delineate the pathophysiology of PHH to uncover potential therapeutic targets. METHODS: We performed a systematic review of the current literature on pathophysiological mechanisms and progressive strategies in the management of post-hemorrhagic hydrocephalus of prematurity. Our literature search identified a total of 58 articles pertaining to the pathophysiology, risk factors and management of post-hemorrhagic hydrocephalus. RESULTS: Presence of high-grade germinal matrix hemorrhage does not always predict PHH and neither does obstruction of pathways seen on ultrasound or MRI scan. We also describe the management options for posthemorrhagic hydrocephalus, including surgical and non-surgical. CONCLUSION: We conclude that pathogenesis of post-hemorrhagic hydrocephalus of prematurity is clearly multifactorial and definitive prediction of who will eventually develop PHH continues to be elusive.

Metastases in the Pineal Region: A Systematic Review of Clinical Features, Management Strategies, and Survival Outcomes.

BACKGROUND: Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases. METHODS: PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed. RESULTS: We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence. CONCLUSIONS: Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.

Hospital incidence and costs of congenital hydrocephalus in Spain: a multicenter retrospective study.

METHODS: Records of hospital admissions of patients with congenital hydrocephalus between 2010 and 2019 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. RESULTS: A third of the patients included in the study were perinatal patients, however, the hospitalization rate in this group was higher to that in patients over 1 year of age. Perinatal patients required more ICU admissions and longer hospital stays, with more frequent surgical interventions and mechanical ventilation. The mean medical cost associated to congenital hydrocephalus was €9610 per admission, with significantly higher costs found in perinatal patients. CONCLUSIONS: This study provides novel data on the hospital costs of congenital hydrocephalus in Spain. The hospital medical costs of this disorder have decreased over the past decade for perinatal patients but not in those aged 1 year and older, which should be considered in upcoming healthcare plans and resource allocation decisions.