Pediatric Hydrocephalus Etiology
see also Hydrocephalus Etiology.
Etiologies in one series of pediatric patients
1. congenital
a) Chiari Type 2 malformation and/or myelomeningocele (MM) (usually occur together)
b) Chiari Type 1 malformation: Hydrocephalus may occur with fourth ventricle outlet obstruction
c) Primary aqueductal stenosis (usually presents in infancy, rarely in adulthood)
d) Secondary aqueductal gliosis: due to intrauterine infection or germinal matrix hemorrhage
e) Dandy Walker malformation: atresia of foramina of Luschka & Magendie. The incidence of this in patients with HCP is 2.4%
f) X-linked inherited disorder: rare
Acquired
a) infectious (the most common cause of communicating HCP)
● post-meningitis; especially purulent and basal, including TB, cryptococcus
b) post-hemorrhagic (2nd most common cause of communicating HCP)
● post-SAH
● post-intraventricular hemorrhage (IVH): many will develop transient HCP. 20–50% of patients with large IVH develop permanent HCP, requiring a shunt
Congenital (without myelomeningocele) 38%
Congenital (with myelomeningocele) 29%
Perinatal hemorrhage 11%
Trauma/subarachnoid hemorrhage 4.7%
Tumor 11%
Previous infection 7.6%
c) secondary to masses
● non neoplastic: e.g. vascular malformation
● neoplastic: most produce obstructive hydrocephalus by blocking CSF pathways, especially tumors around aqueduct (e.g. medulloblastoma). A colloid cyst can block CSF flow at the foramen of Monro.
Pituitary tumor: suprasellar extension of tumor or expansion from pituitary apoplexy
d) post-op: 20% of pediatric patients develop permanent hydrocephalus (requiring shunt) following p-fossa tumor removal. May be delayed up to 1 yr
f) “constitutional ventriculomegaly”: asymptomatic. Needs no treatment
g) associated with spinal tumors: ? due to ↑ protein?, ↑ venous pressure?, previous hemorrhage in some?
Hydrocephalus has many causes:
Posthemorrhagic hydrocephalus.
Neurofibromatosis type 1 related hydrocephalus
Congenital hydrocephalus, most commonly involving aqueductal stenosis, has been linked to genes that regulate brain growth and development.
Newborn infants with germinal matrix hemorrhage.
Hydrocephalus can also be acquired, mostly from pathological processes that affect ventricular outflow, subarachnoid space function, or cerebral venous compliance.
Aneurysmal subarachnoid hemorrhage.
see Hydrocephalus after intraventricular hemorrhage
Hydrocephalus after decompressive craniectomy.
Terminal deletion of chromosome 6q is a rare chromosomal abnormality associated with intellectual disabilities and various structural brain abnormalities.
Iwamoto et al. presented a case of 6q terminal deletion syndrome with unusual magnetic resonance imaging (MRI) findings in a neonate.
The neonate, who was prenatally diagnosed with dilation of both lateral ventricles, was born at 38 weeks of gestation. MRI demonstrated abnormal membranous structure continuing to the hypertrophic massa intermedia in the third ventricle that had obscured the cerebrospinal fluid pathway, causing hydrocephalus. G-band analysis revealed a terminal deletion of 6q with the karyotype 46, XY, add(6)(q25.3) or del(6)(q26). He underwent ventriculoperitoneal shunt successfully, and his head circumference has been stable.
6q terminal deletion impacts the molecular pathway, which is an essential intracellular signaling cascade inducing neurological proliferation, migration, and differentiation during neuronal development. In patients with hydrocephalus in association with hypertrophy of the massa intermedia, this chromosomal abnormality should be taken into consideration. This case may offer an insight into the hydrocephalus etiology in this rare chromosomal abnormality 1).
Molecular mechanisms
The underlying molecular mechanisms remain unknown. Ju et al. performed proteomics of cerebrospinal fluid (CSF) from 7 congenital hydrocephalus and 5 arachnoid cyst patients who underwent surgical treatment. Differential expression of proteins (DEPs) were identified by label-free Mass Spectrometry followed by differential expression analysis. The GO and GSEA enrichment analysis was performed to explore the cancer hallmark pathways and immune-related pathways affected by DEPs. Then, network analysis was applied to reveal the location of DEPs in the human protein-protein interactions (PPIs) network. Potential drugs for hydrocephalus were identified based on drug-target interaction. They identified 148 up-regulated proteins and 82 down-regulated proteins, which are potential biomarkers for clinical diagnosis of hydrocephalus and arachnoid cyst. Functional enrichment analysis revealed that the DEPs were significantly enriched in the cancer hallmark pathways and immune-related pathways. In addition, network analysis uncovered that DEPs were more likely to be located in the central regions of the human PPIs network, suggesting DEPs may be proteins that play important roles in human PPIs. Finally, they calculated the overlap of drug targets and the DEPs based on drug-target interaction to identify the potential therapeutic drugs of hydrocephalus. The comprehensive proteomic analyses provided valuable resources for investigating the molecular pathways in hydrocephalus, and uncovered potential biomarkers for clinical diagnosis and therapy 2).