In severe cases, there is coma. Seizures often intercede, both generalized and focal, and coma can last for several days. Gross autopsy findings in patients who died with cerebral malaria include opacification of the leptomeninges, dusky discoloration of the grey matter, edema, congestion, and petechial hemorrhages. Histologic examination reveals blockage of cerebral capillaries by erythrocytes, many of which are parasitized in various stages of maturation. Hemorrhages are found throughout, but are more common in the white matter and may surround necrotic arterioles and veins.
Glial proliferation occurs in the ischemic parenchyma.
There also may be a monocytic inflammatory infiltrate. Cytoadherence is the primary underlying pathophysiologic event that results in cerebral dysfunction. Electron dense membrane protrusions, or knobs, are expressed on erythrocyte membranes and consist of histidine rich parasite-derived proteins. The knobs increase in number as the parasites become more mature and subsequently are able to form focal junctions with adjacent erythrocytes and endothelial cells resulting in microvascular obstruction. Most obstruction is reversible and neurologic abnormalities resolve completely in most who recover from cerebral malaria.