A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida

Abstract

This work is a modified version of the Casey Holter Memorial prize essay presented to the Society for Research into Hydrocephalus and Spina Bifida, June 29th 2007, Heidelberg, Germany. It describes the origin and consequences of the Chiari malformation, and proposes that hydrocephalus is caused by inadequate central nervous system (CNS) venous drainage. A new hypothesis regarding the pathogenesis, anencephaly and spina bifida is described.Any volume increase in the central nervous system can increase venous pressure. This occurs because veins are compressible and a CNS volume increase may result in reduced venous blood flow. This has the potential to cause progressive increase in cerebrospinal fluid (CSF) volume. Venous insufficiency may be caused by any disease that reduces space for venous volume. The flow of CSF has a beneficial effect on venous drainage. In health it moderates central nervous system pressure by moving between the head and spine. Conversely, obstruction to CSF flow causes localised pressure increases, which have an adverse effect on venous drainage.The Chiari malformation is associated with hindbrain herniation, which may be caused by low spinal pressure relative to cranial pressure. In these instances, there are hindbrain-related symptoms caused by cerebellar and brainstem compression. When spinal injury occurs as a result of a Chiari malformation, the primary pathology is posterior fossa hypoplasia, resulting in raised spinal pressure. The small posterior fossa prevents the flow of CSF from the spine to the head as blood enters the central nervous system during movement. Consequently, intermittent increases in spinal pressure caused by movement, result in injury to the spinal cord. It is proposed that posterior fossa hypoplasia, which has origins in fetal life, causes syringomyelia after birth and leads to damage to the spinal cord in spina bifida. It is proposed that hydrocephalus may occur as a result of posterior fossa hypoplasia, where raised pressure occurs as a result of obstruction to flow of CSF from the head to the spine, and cerebral injury with raised pressure occurs in anencephaly by this mechanism.The current view of dysraphism is that low central nervous system pressure and exposure to amniotic fluid, damage the central nervous system. The hypothesis proposed in this essay supports the view that spina bifida is a manifestation of progressive hydrocephalus in the fetus. It is proposed that that mesodermal growth insufficiency influences both neural tube closure and central nervous system pressure, leading to dysraphism.

Figure 1

The intracranial pressure volume relationship: a graph depicting the effect on intracranial pressure of increasing volume. Central nervous system compliance depends upon intrathecal volume. Redrawn from [5], with permission [Additional file 1].

Figure 2

A hypothetical graph showing the relation between spinal or cranial pressure, and venous volume, with and without Chiari malformation. CSF obstruction at the foramen magnum divides the CSF space into cranial and spinal compartments. The sum of the pressure volume indices of the two spaces would approximate that of the unobstructed CNS. The pressure response to influx of venous volume either in the head or the spine may be enhanced by the presence of Chiari malformation.

Figure 3

Hypothetical graph showing the change in spinal volume and pressure with movement and a space-occupying lesion. Lines a and b represent volume fluctuation with movement, with 'a' representing the normal range and 'b' the range with an uncompensated space occupying lesion. Points 'a' and 'b' on the curve indicate maximal CSF pressures that occur with maximal venous volume.

Figure 4

A simplified flow diagram illustrating the causes of spina bifida and anencephaly.

Figure 5

Hypothetical graph depicting the relation between fetal lateral ventricle size and intracranial pressure and the effect of hindbrain impaction on ventricle size. Hindbrain impaction is caused by a pressure gradient across the foramen magnum. A relatively small intracranial pressure gradient will cause the lateral ventricles to empty. Progressive increase in cerebral pressure will then cause the ventricles to enlarge.

Figure 6

Hypothetical graph showing the effect of posterior fossa size on the frequency of dysraphic lesions at different levels in males and females. Higher, more severe, lesions tend to be more frequent in females who have a smaller posterior fossa as illustrated by the curve on the left. Lower, less severe, lesions are more frequent in males with a larger posterior fossa, as illustrated by the curve on the right.

Figure 7

A simplified flow diagram representing the causes of hydrocephalus and syringomyelia.