Cytotoxic cerebral edema

Cytotoxic cerebral edema refers to a type of cerebral edema, most commonly seen in cerebral ischemia, in which extracellular water passes into cells, resulting in their swelling. 

The term is frequently used in clinical practice to denote the combination of true cytotoxic edema and ionic cerebral edema. As the pathophysiology of these two types of edema is different, as is their imaging, they are discussed separately. The remainder of this article is concerned with true cytotoxic edema, also known as cellular edema ⁸.

Pathology

Cytotoxic edema is the result of cells being unable to maintain ATP-dependent sodium/potassium (Na+/K+) membrane pumps which are responsible for high extracellular and low intracellular Na+ concentration ⁶. When energy fails, as is the case in cerebral ischemia, these pumps cease to operate and Na+ accumulates within the cell, drawing with it chloride (Cl-) and water along an osmotic gradient. This, in turn, results in cellular swelling and a reduction in the extracellular volume ⁹. These are the primary reasons for increased restricted diffusion on MRI. 

This intracellular edema mainly affects grey matter but also involves white matter as astrocytes are also involved.

In contrast to vasogenic cerebral edema, in which the blood-brain barrier is compromised, cytotoxic edema does not involve endothelial dysfunction or changes in capillary permeability. 

Radiographic features

CT

In true isolated cytotoxic edema little change is evident on CT as a mere redistribution of water from extracellular to intracellular compartments does not result in attenuation changes. The changes colloquially ascribed to 'cytotoxic edema' are in fact mostly due to ionic edema and are described separately. This is why brain CT is often normal in patients with an acute ischemic stroke.

MRI

As cytotoxic edema represents the redistribution of water from extracellular to intracellular compartments, without a change in local constituents it stands to reason that no T1 or T2 changes are evident. As is the case with CT, the changes colloquially ascribed to 'cytotoxic edema' are in fact mostly due to ionic edema and are described separately.

The one sequence which is able to identify cytotoxic edema, and was thus responsible for a revolution in the imaging of acute ischemic stroke, is diffusion weighted imaging (DWI). As cells swell due to inward shift of water, there is a commensurate decrease in diffusion, identified as high signal on DWI and low signal on ADC.

These changes persist into the subacute phase until about two weeks when the ADC signal begins to rise above the normal parenchyma and eventually becomes hyperintense.

Treatment and prognosis

Treatment generally focuses on the underlying cause of cerebral edema. Steroids are not beneficial in the treatment of cytotoxic edema secondary to stroke, and may, in fact, be harmful in cytotoxic edema from trauma ⁷.