Normal Perfusion Pressure Breakthrough

Definition

Normal perfusion pressure breakthrough (NPPB) can be defined as the occurrence of multifocal areas of hemorrhage associated with unexplained cerebral edema after the resection of high-flow arteriovenous malformations (AVMs). Various theories have been proposed to explain the hemodynamic basis for this phenomenon.

In 1978, Spetzler and colleagues first introduced the theory of NPPB. They suggested that hypoperfusion of the brain parenchyma surrounding an AVM (caused by an increased blood flow through the low-resistance vascular nidus) could induce local vessels surrounding the AVM nidus to chronically dilate, predisposing them to vasomotor paralysis. Upon restoration of normal perfusion following AVM resection, this impaired autoregulatory capacity may then be unable to compensate for increases in arterial flow and ultimately cause hyperemia, edema, or intracerebral hemorrhage.

However, both the existence and clinical relevance of this theory of NPPB in brain AVMs remain a matter of debate. The incidence of this type of postoperative complication is reported to be lower than 5%.

Pathophysiology

AVMs are vascular lesions characterized by direct connections between feeding arteries and draining veins without an intervening capillary network. The missing capillary bed creates a low-resistance condition, causing a high flow through the AVM and a hypotensive zone in its immediate vicinity, where the AVM feeders and neighboring normal vessels share the same proximal arterial origin and capillary perfusion pressure is relatively low. This is termed “intracerebral steal,” where the increased blood flow through a low-resistance vascular bed diverts flow away from the adjacent brain.

Spetzler et al., in their theory of NPPB, proposed that the parenchyma surrounding high-flow AVMs is chronically hypoperfused (due to intracerebral steal) and has an impaired autoregulation mechanism that renders it vulnerable to the restoration of normal perfusion pressure following resection of the AVM. The combination of disturbed autoregulation and normal perfusion pressure results in disruption of local capillary beds, with subsequent hemorrhage and edema.

In NPPB, the capillaries in the adjacent brain parenchyma undergo neovascularization in response to chronic cerebral ischemia through increased capillary density and absent foot processes, making them prone to mechanical weakness, instability, and disruption of the blood–brain barrier, contributing to edema and hemorrhage.

Apart from the NPPB theory, the postoperative hemorrhage and edema following AVM resection have been explained by various other hypotheses. An alternative theory, called the “occlusive hyperemia” theory, proposed a mechanism involving both the arterial feeders and the venous drainage systems, accounting for the postoperative complications. Both the stagnant arterial flow in the former AVM feeders with subsequent worsening of existing hypoperfusion and ischemia, and the venous outflow obstruction in the adjacent parenchyma causing passive hyperemia, engorgement, and further arterial stagnation, contribute to the postoperative hemorrhage and edema significantly. An impairment of the venous drainage system has been noted in up to 75% of the patients with high-flow AVMs.

Such venous overload is seen not only after surgical excision of AVMs but also after embolization of high-flow lesions. Occlusion of the draining venous system in the brain, adjacent to the AVM by a glue embolus, may result in venous outflow obstruction, passive hyperemia, and stagnation in the feeding artery, with subsequent postoperative hemorrhage and edema.