Neurogenic Cerebral Edema: Proposed Mechanism for Vasogenic Cerebral Edema.

Abstract

Global cerebral edema (GCE) is a frequent and devastating manifestation of early brain injury after aneurysmal subarachnoid hemorrhage (aSAH), yet its exact inciting biology and sequence of events remain incompletely explained. In this viewpoint, we propose neurogenic cerebral edema (NCE) as a mechanistic hypothesis for vasogenic edema after aSAH, in which autonomic disequilibrium may amplify blood-brain barrier permeability within otherwise mixed cellular, ionic, and vasogenic edema. We integrate evidence that aSAH perturbs the central autonomic network, producing a sympathetic catecholamine surge that can coexist with parasympathetic system activation. This autonomic disequilibrium may indirectly amplify established neurovascular-unit injury pathways, including sulfonylurea receptor 1 (SUR1)-transient receptor potential melastatin 4 (TRPM4) upregulation and tight-junction dysfunction, thereby increasing the vasogenic component of early cerebral edema. We further highlight a pathophysiological parallel with neurogenic pulmonary edema, wherein neurally mediated hemodynamic and permeability forces culminate in protein-rich extravasation across an endothelial barrier. An analogous process in the brain provides a coherent framework for blood-brain barrier (BBB) breakdown and diffuse edema after aSAH. To illustrate the imaging pattern motivating prospective testing, we present a patient with poor-grade aSAH with malignant edema and diffusely elevated apparent diffusion coefficient values. Because autonomic measurements and direct BBB permeability assessment were not obtained, this case illustrates a vasogenic component but does not establish a neurogenic etiology. Our premise is that both arms of autonomic control must be considered. This hypothesis also emphasizes the need for prospective validation using BBB permeability imaging and translational autonomic biomarkers.