Cytotoxic edema

Corticosteroids have been evaluated in several types of cerebral injury, including cerebral infarction. Corticosteroids reduce vasogenic edema, such as that associated with neoplasms, but not cytotoxic edema, the type associated with ischemic stroke. A large meta-analysis found no benefit to the use of corticosteroids in ischemic stroke (or intracerebral hemorrhage), and their use is not recommended, except to treat concomitant conditions that mandate it (e.g., COPD flare). 

AQP4 deletion improves outcome in cytotoxic edema... 

Pathophysiologically, the pronounced ADC decline during ischemia occurs at the same time as anoxic depolarization. Anoxic depolarization is the consequence of energy failure with secondary failure of ion pumps (in particular Na+/K+-ATPase), which are necessary to maintain ion gradients over cell membranes. The resulting influx of Na+-ions is accompanied by a water shift from the extra- to the intracellular space (cytotoxic edema) without a net uptake of water (Fig. 7.1). 

Earliest proof of an ischemic situation on MRI can be obtained within seconds after stroke onset by perfusion imaging (PI), depicting the area of reduced cerebral blood flow (Fig. 8.2 see also Chap. 6). This is followed within minutes by a rapid delineation of the early ischemic injury (cytotoxic edema) on DWI. Focus of this chapter will be on data acquired in animal ischemia models, using PD-w, Tl-w, and T2-w MRI, and their correlation with histopathology. 

J, Meric P (1997) Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 28 419-426 discussion 426-417... 

Cerebral ischemia causes not only reversible and then irreversible loss of brain function, but also cerebral edema (Symon et al. 1979 Hossman 1983). Ischemic edema is partly cytotoxic and partly vasogenic. Cytotoxic edema starts early, within minutes of stroke onset, and affects the gray more than the white matter, where damaged cell membranes allow intracellular water to accumulate. Vasogenic edema, which starts rather later, within hours of stroke onset, affects the white matter more, where the damaged blood-brain barrier allows plasma constituents to enter the extracellular space. Ischemic cerebral edema reaches its maximum in two to four days and then subsides over a week or two. 

Recent studies have demonstrated the usefulness of MRI in patients with suspected TIA, particularly diffusion-weighted imaging (DWI) (Figs. 10.3-10.9) (Schulz et al. 2003 Schulz et al. 2004). This modality relies on changes in the Brownian motion of water molecules to generate contrast. During early ischemia, there is decreased water proton movement caused by cytotoxic edema as water moves from the less-restricted extracellular environment into the more-restricted intracellular environment. Reduced proton diffusion leads to... 

Approximately 25% of patients with TIA have cerebral infarction with transient signs in which DWI positivity corresponds to cytotoxic edema this progresses to permanent parenchymal injury and increased tissue water content visible as a lesion on T2-weighted MRI. Approximately 20% of patients have early DWI abnormality but no evidence of later T2-weighted abnormality. This suggests reversibility of the initial DWI abnormality if blood flow is restored early enough to prevent permanent parenchymal injury, as seen in patients with stroke in whom the DWI-detected lesion may regress with reperfusion. 

In patients with negative DWI, a very brief period of ischemia may have been sufficient to disrupt neuronal activity but insufficient to cause cytotoxic edema. 

Brain edema is defined as an abnormal accumulation of fluid associated with volumetric enlargement of the brain (Klatzo, 1967). Excess fluid can accumulate in the intracellular or extracellular spaces. Two types of brain edema have been defined based on the site of damage and where the fluid accumulates. Cytotoxic edema results in intracellular swelling without alterations in vascular permeability. Vasogenic edema is associated with damage to the BBB leading to flow of water and plasma constituents into the brain. These types of edema rarely exist in isolation typically, one type of edema dominates the other, but both co-exist. 

The forces driving water flow to form cytotoxic edema are osmotic, generated in brain injury conditions (ischemia, trauma, hypoxia) by disturbances in ionic homeostasis due to failure of the Na /K+ ATPase and/or dramatic influx of Na" and Ca " via ionotropic glutamate receptors (excitotoxicity) and other ionic channels. These pathological alterations in cellular ionic homeostasis result in Na" " and water flow from the intravascular and extracellular space into the intracellular compartment. 

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