Pathology of CSF Circulation and Hydrocephalus in Children

Authors

Andrew Jea, M.D.

Abhaya V. Kulkarni, M.D.

Section Editor

Shlomi Constantini, M.D.

Editor in Chief

Rick Abbott, M.D.

Pathophysiology

Hydrocephalus most commonly results from impaired CSF absorption.  Excessive functioning choroid plexus tissue in choroid plexus “hypertrophy” or papilloma remains the sole exception of CSF overproduction as the cause for hydrocephalus.

Communicating hydrocephalus

Impairment of CSF absorption in communicating hydrocephalus may occur at the arachnoid villus, the lymphatic channels associated with cranial and spinal nerves, or the arachnoid membrane. The result is enlargement of all of the interior CSF spaces of the brain.

Axial CT Scan of Communicating Hydrocephalus: Shown are dilated lateral and third ventricles.

Axial CT Scan of Communicating Hydrocephalus: Shown is an enlarged fourth ventricle as well as dilated temporal horns of the lateral ventricles.

• Obstruction of the basal cisterns: There may exist an inability of CSF to reach the arachnoid villi with a delay in emptying from the ventricles.
• Occlusion or atresia of the arachnoid villi: Obstruction of the terminal CSF pathways results in a failure of the absorption of CSF into the venous sinuses. It is postulated that hydrocephalus may result from a congenital absence of these structures.
• Increased sagittal sinus pressure: Increased pressure in the venous sinuses, particularly the superior sagittal sinus, has significant effects on ICP and CSF absorption. The pressure in the intracranial compartment must rise to at least 5 mm Hg above the pressure within the sinuses, or no absorption of CSF will occur. This may be the mechanism of hydrocephalus in vein of Galen malformations, severe congenital heart disease with very high right atrial pressures, achondroplasia, and complex syndromic and nonsyndromic craniosynostosis.

Obstructive hydrocephalus

Impairment of CSF bulk flow in obstructive hydrocephalus may occur at any point along the pathway of CSF flow.

Sagittal T2-weighted MRI of Obstructed Hydrocephalus: Midsagittal T2-weighted MRI of the brain demonstrates the presence of a tectal glioma associated with aqueductal stenosis and enlarged lateral and third ventricles out of proportion to the size of the fourth ventricle.

• Foramen of Monro: Occlusion of the foramen of Monro is an unusual cause of obstruction of CSF flow. Congenital atresia or stenosis of the foramen of Monro is quite rare. Tumors and non-neoplastic mass lesions such as craniopharyngioma, hypothalamic astrocytoma, subependymal giant cell astrocytoma, and colloid cyst may grow to such a size that they occlude one or both of the foramina.
• Aqueduct of Sylvius: Aqueductal stenosis is a congenital malformation that is sex-linked, occurring only in boys. A tectal glioma may lead to an acquired aqueductal stenosis, resulting in obstruction of CSF flow at any age.
• Outlet foramina of the fourth ventricle (Luschka and Magendie): The inability of CSF to exit the fourth ventricle usually results from a posterior fossa tumor that occludes the exit foramina of the fourth ventricle. Severe infections of the CSF pathways can also lead to scarring and obstruction of the outlet foramina of the fourth ventricle. 

Molecular/Genetic Pathology

X-linked hydrocephalus

• Aqueductal stenosis: An inheritable form of aqueductal stenosis has been described that occurs only in males and is transmitted from one generation to the next by a female carrier (X-linked hydrocephalus).
• 4% of hydrocephalus cases: X-linked hydrocephalus comprises less than 4% of all cases of hydrocephalus but accounts for 8–15% of primary hydrocephalus in boys (15).
• Xq28 locus: The abnormal gene is located on Xq28 (6, 9), and its effect is a deficiency of the L1 cell adhesion molecule.
• Manifestations on examination: X-linked hydrocephalus is frequently associated with mental retardation, corpus callosum hypoplasia, adducted thumbs, and lower limb spasticity.

Histopathology

Obstruction of the CSF pathways, by whatever cause, results in a wide variety of pathological findings that depend on the age of the patient, the pliability of the skull, and the type and duration of hydrocephalus.

Pathological effects of hydrocephalus

• Atrophy of white matter: A primary destruction of axons, a secondary loss of myelin, and chronic astrogliosis are found. Neurons are selectively spared because of a more luxurious blood supply to the gray matter.
• Multiple anomalies within ventricles: Fibrosis of the choroid plexuses and stretching and denuding of the ependymal epithelium can be seen along with diverticula within the ventricles. The septum pellucidum can become fenestrated.
• Anomalies in surrounding brain: Spongy edema can develop in the surrounding brain, and there can be thinning and elongation of the interhemispheric commissures.