In many, but not all, cases, the CSF pressure and protein values are elevated; the latter to more than 100 mg/dL, but there is no cellular reaction. Except to exclude primary subarachnoid hemorrhage, lumbar puncture is not needed to establish the diagnosis.
Neuropathologic examination reveals a rather normal-looking brain, but in some cases cerebral swelling, hemorrhages of various sizes, or both will be found. In extreme instances, a cerebellar pressure cone reflects an increased volume of tissue and increased pressure in the posterior fossa; lumbar puncture appears to have only rarely precipitated fatalities. Microscopically there are widespread minute infarcts in the brain, the result of fibrinoid necrosis of the walls of arterioles and capillaries and occlusion of their lumens by fibrin thrombi (Chester et al). This is often associated with zones of cerebral edema. Similar vascular changes are found in other organs, particularly in the retinae and kidneys.
Volhard originally attributed the symptoms of hypertensive encephalopathy to vasospasm. This notion was reinforced by Byrom, who demonstrated, in rats, a segmental constriction and dilatation of cerebral and retinal arterioles in response to severe hypertension. However, the observations of Byrom and of others indicate that overdistention of the arterioles (which have lost their adaptive capacity), rather than excessive constriction, may be responsible for the necrosis of the vessel wall (see reviews of Auer and of Chester et al). The brain edema is the result of active exocytosis of water rather than simply a passive leak from vessels subjected to high pressures. In toxemia or eclampsia, rising levels of the antiangiogenic proteins endoglin, vascular endothelial growth factor, and placental growth factor had been postulated to play a role (Levine et al, 2006) but this has not been fully corroborated. The net result is of various forms of endothelial dysfunction, including presumably, in the brain.
We have been impressed that the distribution of lesions on the MRI differs between eclamptic and older hypertensive patients, suggesting some difference in pathophysiology, or perhaps simply that chronic hypertension in the latter group predisposes to the occipital lesions. The forms of PRES that are induced by chemotherapeutic and other agents are more complex and are discussed in Chap. 41. A few eclamptic women will develop hemolysis, hepatic failure, and thrombocytopenia—HELLP syndrome—an illness that has similarities to TTP and the hemolytic uremic syndrome (HUS). The interplay between eclampsia and HELLP syndrome in relation to cerebral lesions is complex and not fully understood.
In the past, when effective treatment was not available, the outcome was often fatal. Lowering of the blood pressure with antihypertensive drugs may reverse the picture in a day or two. The same can be accomplished by administering magnesium sulfate in the eclamptic woman. However, antihypertensive drugs must be used cautiously; a safe target is a pressure of 150/100 mm Hg or a 20 percent reduction in mean pressure. One may use intravenous sodium nitroprusside, 0.5 to 0.8 mg/kg/min; a calcium channel blocker such as nifedipine, 10 to 20 mg sublingually; or intravenous beta-adrenergic blockers (labetalol, 20 to 40 mg intravenously followed by an infusion at 2 mg/min, or esmolol are favored). Longer-acting antihypertensive agents, such as ACE inhibitors and calcium channel blockers, must follow these. If there is already evidence of brain edema and increased intracranial pressure, dexamethasone, 4 to 6 mg every 6 h, is sometimes added, but its effect, and the use of hyperosmolar therapy, have not been studied systematically; our clinical impression is that they have little effect.