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European Journal of Medical Research Sep 2022Hydrocephalus 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... (Review)
Review
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.
Topics: Adult; Child; Humans; Hydrocephalus; Incidence; Infant
PubMed: 36050779
DOI: 10.1186/s40001-022-00798-6 -
European Journal of Medical Genetics Aug 2014Hydrocephalus is a common but complex condition caused by physical or functional obstruction of CSF flow that leads to progressive ventricular dilatation. Though... (Review)
Review
Hydrocephalus is a common but complex condition caused by physical or functional obstruction of CSF flow that leads to progressive ventricular dilatation. Though hydrocephalus was recently estimated to affect 1.1 in 1000 infants, there have been few systematic assessments of the causes of hydrocephalus in this age group, which makes it a challenging condition to approach as a scientist or as a clinician. Here, we review contemporary literature on the epidemiology, classification and pathogenesis of infantile hydrocephalus. We describe the major environmental and genetic causes of hydrocephalus, with the goal of providing a framework to assess infants with hydrocephalus and guide future research.
Topics: Animals; Humans; Hydrocephalus; Infant
PubMed: 24932902
DOI: 10.1016/j.ejmg.2014.06.002 -
Cancer Control : Journal of the Moffitt... Jan 2017Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue.
BACKGROUND
Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue.
METHODS
Key points on the physiology of CSF as well as the diagnostic and treatment options for hydrocephalus are discussed.
RESULTS
Understanding the fundamentals of the production, absorption, dynamics, and pathophysiology of CSF is crucial for addressing hydrocephalus. Shunts and endoscopic third ventriculostomy have changed the therapeutic landscape of hydrocephalus.
CONCLUSIONS
The treatment of hydrocephalus in adults and children represents a large part of everyday practice for the neurologist, both in benign cases and cancer-related diagnoses.
Topics: Adult; Cerebrospinal Fluid; Humans; Hydrocephalus
PubMed: 28178707
DOI: 10.1177/107327481702400102 -
Neurology India 2021Post-traumatic hydrocephalus (PTH) is a sequel of traumatic brain injury (TBI) that is seen more often in patients undergoing decompressive craniectomy (DC). It is... (Review)
Review
BACKGROUND
Post-traumatic hydrocephalus (PTH) is a sequel of traumatic brain injury (TBI) that is seen more often in patients undergoing decompressive craniectomy (DC). It is associated with prolonged hospital stay and unfavorable outcomes.
OBJECTIVE
To study the incidence and risk factors for development of PTH in patients undergoing DC in our institution and to review the literature on PTH with respect to incidence, risk factors, pathophysiology, and outcomes of management.
METHODS
Data from 95 patients (among 220 patients who underwent DC for TBI and fulfilled the inclusion criteria) over a 5-year period at Christian Medical College, Vellore were collected and analyzed to study the incidence and possible risk factors for development of PTH. A review of the literature on PTH was performed by searching PUBMED resources.
RESULTS
Thirty (31.6%) out of 95 patients developed post-traumatic ventriculomegaly, of whom seven (7.3%) developed symptomatic PTH, necessitating placement of ventriculoperitoneal shunt (VPS). No risk factor for development of PTH could be identified. The reported incidence of PTH in the literature is from 0.07% to 29%, with patients undergoing DC having a higher incidence. Younger age, subarachnoid hemorrhage, severity of TBI, presence of subdural hygroma, and delayed cranioplasty after DC are the main risk factors reported in the literature.
CONCLUSIONS
PTH occurs in a significant proportion of patients with TBI and can lead to unfavorable outcomes. PTH has to be distinguished from asymptomatic ventriculomegaly as early as possible so that a CSF diversion procedure can be planned early during development of PTH.
Topics: Decompressive Craniectomy; Humans; Hydrocephalus; Incidence; Postoperative Complications; Ventriculoperitoneal Shunt
PubMed: 35102998
DOI: 10.4103/0028-3886.332264 -
Nature Neuroscience Apr 2022Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF...
Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain-CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.
Topics: Animals; Biomechanical Phenomena; Brain; Cerebrospinal Fluid; Humans; Hydrocephalus; Mice; Neurogenesis; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Exome Sequencing
PubMed: 35379995
DOI: 10.1038/s41593-022-01043-3 -
Nature Medicine Nov 2020Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby...
Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
Topics: Brain; Cerebral Ventricles; Exome; Female; Genetic Predisposition to Disease; Humans; Hydrocephalus; Male; Mutation; Neural Stem Cells; Neurogenesis; Neuroglia; Transcription Factors; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Exome Sequencing
PubMed: 33077954
DOI: 10.1038/s41591-020-1090-2 -
European Review For Medical and... Aug 2022Encephalocele is a rare congenital neural tube defect (NTD) characterized by herniation of intracranial contents through a defect in the skull. In our study,...
OBJECTIVE
Encephalocele is a rare congenital neural tube defect (NTD) characterized by herniation of intracranial contents through a defect in the skull. In our study, encephalocele was diagnosed in our clinic and its association with hydrocephalus was evaluated. The effect of this association on the prognosis was discussed.
PATIENTS AND METHODS
Patients who underwent surgery and follow-up with the diagnosis of encephalocele in the neurosurgery clinic of our hospital in an 8-year period from 2013 to 2021 were retrospectively examined.
RESULTS
Patient records were obtained from the case notes of patients who underwent excision and repair for encephalocele. Of the 78 patients included in the study, 88.4% underwent surgery in the neonatal period. Moreover, 47% of the patients are male, and 31% are female. Encephalocele was present in 62.8% of patients and meningocele in 37.2%. Furthermore, 82.1% of encephalocele sacs were located in the occipital region. Chiari type 3 malformation was present in 57.6% of patients. Hydrocephalus developed in 56.4% of patients. There was an additional syndrome in 10.3% of the cases. The most common additional syndromes were corpus callosum dysgenesis with 39.7% and colpocephaly with 29.5%. The additional disease was present in 43.6% of patients. Preoperative and postoperative examination findings of more than half of patients were normal, but 33.3% were apathetic. Furthermore, 67.9% of patients, who underwent complete repair, survived, and 32.1% died. Hydrocephalus was present in 73.5% of patients with encephalocele (p<0.05). Hydrocephalus developed in 77.8% of patients with Chiari type 3 malformation (p<0.05). Hydrocephalus was found in 88.0% of patients with Ex (p<0.05).
CONCLUSIONS
Encephalocele, which is a subgroup of NTD, differs clinically by its location and accompanying additional anomalies. In encephaloceles, the risk of morbidity and mortality can only be reduced with the multidisciplinary approach. Hydrocephalus and Chiari type 3 malformation are common in patients with encephalocele. These associations adversely affect the prognosis of the disease. Further research should be conducted on the evaluation of risk factors of NTD and methods of prevention from NTD. In this regard, we recommend that the training be repeated at certain intervals and that people's awareness should be raised.
Topics: Encephalocele; Female; Humans; Hydrocephalus; Infant, Newborn; Male; Neural Tube Defects; Prognosis; Retrospective Studies
PubMed: 35993634
DOI: 10.26355/eurrev_202208_29407 -
Neurology India 2021This paper highlights the hydrocephalus research efforts undertaken at AIIMS, New Delhi, supporting progress in the field. (Review)
Review
OBJECTIVE
This paper highlights the hydrocephalus research efforts undertaken at AIIMS, New Delhi, supporting progress in the field.
MATERIAL
Over a period of three decades, basic research, clinical investigations, and multicentric studies were undertaken. This report will review the work mainly to emphasize the need for future generations to pursue further research. Studies that impacted hydrocephalus care (mainly in India) are described, and some of these findings may be useful in other resource-challenged situations.
RESULTS
Investigative studies on the effect of shunting on brainstem auditory evoked responses (BAER), transcranial Doppler (TCD), and CT-SPECT were published offering management options for patients. Participation in the International Infant Hydrocephalus Study (IIHS) study offered opportunities to compare our approaches and develop modifications in patient care. This effort proved shunting was equal or better for young children with congenital aqueductal stenosis. Shunt infection protocols and changes made in a systematic manner helped develop local protocols to reduce postoperative shunt infections.
CONCLUSIONS
Hydrocephalus research over three decades at AIIMS, New Delhi was productive and educational, confirming that locally performed investigative work can help in decision making. Further studies and active participation in international efforts are necessary to advance the field.
Topics: Child; Child, Preschool; Humans; Hydrocephalus; Infant; Neurosurgical Procedures; Postoperative Complications; Postoperative Period; Ultrasonography, Doppler, Transcranial
PubMed: 35102975
DOI: 10.4103/0028-3886.332258 -
EBioMedicine Apr 2022Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular... (Review)
Review
Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular and subarachnoid hemorrhage, traumatic brain injuries, brain tumors, craniectomy or may be idiopathic, as in the case of normal pressure hydrocephalus. Irrespective of its prevalence and significant impact on quality of life, neurosurgeons still rely on invasive cerebrospinal fluid shunt systems for the treatment of hydrocephalus that are exceptionally prone to failure and/or infection. Further understanding of this process at a molecular level, therefore, may have profound implications for improving treatment and quality of life for millions of individuals worldwide. The purpose of this article is to review the current research landscape on hydrocephalus with a focus on recent advances in our understanding of cerebrospinal fluid pathways from an evolutionary, genetics and molecular perspective.
Topics: Heart Ventricles; Humans; Hydrocephalus; Infant; Quality of Life; Subarachnoid Hemorrhage
PubMed: 35306341
DOI: 10.1016/j.ebiom.2022.103931 -
Human Genomics Mar 2023Congenital hydrocephalus is characterized by ventriculomegaly, defined as a dilatation of cerebral ventricles, and thought to be due to impaired cerebrospinal fluid...
BACKGROUND
Congenital hydrocephalus is characterized by ventriculomegaly, defined as a dilatation of cerebral ventricles, and thought to be due to impaired cerebrospinal fluid (CSF) homeostasis. Primary congenital hydrocephalus is a subset of cases with prenatal onset and absence of another primary cause, e.g., brain hemorrhage. Published series report a Mendelian cause in only a minority of cases. In this study, we analyzed exome data of PCH patients in search of novel causal genes and addressed the possibility of an underlying oligogenic mode of inheritance for PCH.
MATERIALS AND METHODS
We sequenced the exome in 28 unrelated probands with PCH, 12 of whom from families with at least two affected siblings and 9 of whom consanguineous, thereby increasing the contribution of genetic causes. Patient exome data were first analyzed for rare (MAF < 0.005) transmitted or de novo variants. Population stratification of unrelated PCH patients and controls was determined by principle component analysis, and outliers identified using Mahalanobis distance 5% as cutoff. Patient and control exome data for genes biologically related to cilia (SYScilia database) were analyzed by mutation burden test.
RESULTS
In 18% of probands, we identify a causal (pathogenic or likely pathogenic) variant of a known hydrocephalus gene, including genes for postnatal, syndromic hydrocephalus, not previously reported in isolated PCH. In a further 11%, we identify mutations in novel candidate genes. Through mutation burden tests, we demonstrate a significant burden of genetic variants in genes coding for proteins of the primary cilium in PCH patients compared to controls.
CONCLUSION
Our study confirms the low contribution of Mendelian mutations in PCH and reports PCH as a phenotypic presentation of some known genes known for syndromic, postnatal hydrocephalus. Furthermore, this study identifies novel Mendelian candidate genes, and provides evidence for oligogenic inheritance implicating primary cilia in PCH.
Topics: Female; Pregnancy; Humans; Multifactorial Inheritance; Mutation; Hydrocephalus; Consanguinity; Databases, Factual
PubMed: 36859317
DOI: 10.1186/s40246-023-00464-w