The production of symptoms by tumor growth is governed by certain principles of mechanics and physiology, some of which were discussed in Chaps. 16 and 29. There it was pointed out that the cranial cavity has a restricted volume, and the three elements contained therein—the brain (about 1,200 to 1,400 mL), cerebrospinal fluid (CSF; 70 to 140 mL), and blood (150 mL)—are relatively but not entirely incompressible, particularly the brain substance, and each is subject to displacement by a localized mass lesion. According to the Monro-Kellie doctrine, the total bulk of the three elements is at all times constant, and any increase in the volume of one of them must be at the expense of the others, as discussed in Chap. 29. A tumor growing in one part of the brain therefore compresses the surrounding brain tissue and displaces CSF and blood; once the limit of this accommodation is reached, the intracranial pressure (ICP) rises. The elevation of ICP and perioptic pressure impairs axonal transport in the optic nerve and the venous drainage from the optic nerve head and retina, manifesting in papilledema.
Only some brain tumors cause papilledema and many others—often quite as large—do not. Thus one may question whether the Monro-Kellie doctrine and its simple implied relationships of intracranial volume and CSF pressure fully account for the development of raised ICP and papilledema with brain tumors. This discrepancy is in part because in a slow process, such as tumor growth, brain tissue is to some degree compressible, as one might suspect from the large indentations of brain produced by massive meningiomas.
The slow growth of most tumors permits accommodation of the brain to changes in cerebral blood flow and ICP. Only in the advanced stages of tumor growth do the compensatory mechanisms fail and CSF pressure and ICP rise, with consequences described in Chap. 29. Once pressure is raised in a particular compartment of the cranium, the tumor begins to displace tissue at first locally and at a distance from the tumor, resulting in a number of false localizing signs, including coma, described in Chap. 16. Indeed, the transtentorial herniations, the paradoxical corticospinal signs of Kernohan and Woltman, sixthand third-nerve palsies, occipital lobe infarcts, midbrain hemorrhages, and secondary hydrocephalus were all originally described in tumor cases (see further on, under “Brain Displacements and Herniations”).
Brain edema is such a prominent feature of cerebral neoplasm that this is a suitable place to summarize what is known about it. With tumor growth, the venules in the cerebral tissue adjacent to the tumor are compressed, with resulting elevation of capillary pressure, particularly in the cerebral white matter where edema is most prominent.
It has been recognized that conditions leading to peripheral edema, such as hypoalbuminemia and increased systemic venous pressure, do not have a similar effect on the brain. By contrast, lesions that alter the blood–brain barrier cause rapid swelling of brain tissue. Klatzo specified two categories of edema: vasogenic and cytotoxic. Fishman added a third, which he called interstitial edema. An example of the latter is the edema that occurs with obstructive hydrocephalus, especially when the ependymal lining is disrupted and CSF seeps into the periventricular tissues in the spaces between cells and myelin. Most neuropathologists use the term interstitial to refer to any increase in the extravascular intercellular compartment of the brain; this would include both vasogenic and interstitial edema.