Pathology of Aqueductal Stenosis in Children

Pathophysiology

Normal CSF Circulation through the aqueduct

Normally, there is a to-and-fro movement of CSF through the aqueduct that results from the pulsatile forces of blood circulation in the brain with a net outflow of CSF from the brain that matches CSF production.

Anatomy of the aqueduct and its obstruction

In recent years, neuroendoscopy has added further knowledge about the anatomy of the cerebral aqueduct in vivo. Longatti et al. (70) well described the endoscopic anatomy of the sylvian aqueduct as it appears when approaching it with a flexible fiberscope through the third ventricle (70).

• Normal aqueduct: A single layer of ependymal cells lines the internal lumen of the aqueduct. The adytum (or inlet) of the aqueduct shows a characteristic dorsally based triangle shape with two small, ventral protuberances, the rubral eminences, separated by a median sulcus.
• Aqueductal stenosis: In aqueductal stenosis the adytum focally narrows to a funnel-like structure whose constriction is in the caudal third of the canal (see below). Pathological states of denuded ependyma with glia herniating into the lumen, diverticuli, or multiple ependymal cell layers can, however, be found.

Stenosis of the Aqueduct at its inlet

Stenosis of the the inlet of the aqueduct (to left of center at 8 o’clock).

Stenosis of the proximal third of the aqueduct (seen is a normal size inlet and a short distance away at its depth a stenosis of the aqueduct is seen just to right of midline at 1 o’clock).

Stenosis of the distal third of the aqueduct. The endoscope is upside down resulting in a 180 degree rotation of the image. The floor of the third ventricle with a third ventriclostomy is seen at 12 o’clock. A wide opening at the inlet of the Aqueduct is present with its becoming stenotic distally.

• Trapped fourth ventricle: When the fourth ventricle is trapped, the adytum is deformed into a round opening, and the aqueduct caudal to it first narrows due to the protruding superior colliculi and then widens into the aqueduct’s ampulla. There is then a second constriction, due to the inferior colliculus, encountered before the passage enlarges in breadth and then abruptly opens into the fourth ventricle.

Evolution of hydrocephalus due to aqueductal stenosis

• Progressive stenosis: Wall shear stresses lead to progressive gliosis.
• Ventricular dilation due to pulsations: Rebounding pulsations due to aqueductal block damage the supratentorial ventricular walls and dilate the ventricles over time.

Ventricular deformities associated with aqueductal stenosis

• Ventricular dilation: The ventricular dilation seen with aqueductal stenosis can be due to an acute process where the CSF volume is at equilibrium between the CSF unable to reach its absorptive site and the resulting ICP elevation that results from the excess volume of CSF and excessive blood volume due to venous congestion. The dilation progresses due to chronic forces of accumulating CSF in an environment of lessening ICP as the brain’s circulation accommodates to the excessive volume and venous congestion abates (41).
• Focal enlargement of the third ventricle: Bulging of the weak portion of the third ventricle’s walls leads to a characteristic deformation in its shape with bowing of the floor downward and, in severe, longstanding cases, the herniation of the posterior pineal recess into the quadrigeminal and supravermian cisterns.
• Ventricular diverticula: Ventricular diverticula are most frequently seen on the medial side of the trigone and can develop into transtentorial “cysts” involving the ambient and superior vermian cisterns.
• Subependymal cysts: These cysts are due to the separation of the ependyma from the subependymal layers, with progressive growth not uncommon.
• Spontaneous ventriculocisternostomies: Rupture of thinned walls of the third ventricle into adjacent subarachnoid space. Typically, this rupture involves the lamina terminalis or suprapineal recess. More rarely, the rupture can be into the subdural space or a sinus, leading to rhinorrhea.

Etiology

The aqueduct may become stenotic because of compression from mass lesions or as consequence of intrinsic pathology (“non-tumoral aqueductal stenosis”). Intrinsic aqueductal stenosis may be congenital or acquired, idiopathic or secondary to a known etiology. Different etiological factors can be identified in approximately only 25% of cases (51).

Molecular/Genetic Pathology

L1 syndrome

• Point mutation Xq28 locus: Recently, a mutation in the L1CAM gene was discovered, giving rise to the term “L1 syndrome” as a synonym for X-linked hydrocephalus (93). Linkage analysis studies (88) established that a point mutation of the gene for neural cell adhesion molecule L1 is responsible for X-linked hydrocephalus. L1CAM, mainly expressed on neurons and Schwann cells, is involved in the mediation of axon and neurite growth, which are necessary for the development of the nervous system.

Histopathology

Photomicrograph of normal aqueduct:

According to Russell (91), non-tumoral aqueductal stenosis can be classified histopathologically into four types:

• Stenosis: The aqueduct is narrowed or obstructed, and ependyma lines the lumen without gliosis of the surrounding tissue. In cases of “simple stenosis” an abnormally small aqueduct with normal cells is present (image below). In cases of “congenital atresia” the aqueduct may not be visible on gross inspection. This latter form is most likely a consequence of “developmental” errors, in which abnormal infolding of the neural plate results in narrowing of the neural tube with cleaning of the lumen (51).

Stenotic aqueduct: Note that cells surrounding the aqueduct are normal

• Forking: The aqueduct is split into two or more separate channels (images below). These channels can communicate with each other, can enter the ventricle independently, or end blindly. This condition, due to incomplete fusion of the median fissure, usually narrows the aqueductal lumen and/or alters the laminar flow of CSF.

Atresia and forking of aqueduct: Note that more than one lumen is present

Forked aqueduct: Seen are two relatively small channels lined by ependymal cells

• Septum formation: The aqueduct is totally or partly obliterated by a gliotic membrane. This is commonly found at the lower end of the aqueduct and happens when the glial overgrowth, limited to the lower end of the aqueduct, gradually becomes a tiny sheet from prolonged pressure and dilation of the canal above (109).
• Gliosis: Proliferation of glial cells and overproduction of glial fibers determine gliotic stenosis. The residual lumen is not outlined by ependyma (see below) . Glial proliferation is frequently a reaction to hemorrhage, infection, or toxic agents and is often associated with widespread ependymitis of the ventricles. Obstruction of the aqueduct by reactive gliosis has to be differentiated from subependimal astrocytomas (51).

Gliotic stenosis of aqueduct: The lumen of the aqueduct on the right is lined by a thin layer of normal ependymal cells with a thick layer of gliosis below