The pathogenesis is unclear, but it appears to involve mitochondrial dysfunction that inhibits oxidative phosphorylation and fatty-acid beta-oxidation in a virus-infected, sensitized host. The host has usually been exposed to mitochondrial toxins, most commonly salicylates (>80% of cases). Some have postulated that salicylates stimulate the expression of inducible nitric oxide synthase (iNOS) because of findings of iNOS stimulation in African children with fatal malaria. Malaria causes symptoms similar to those of Reye syndrome and is often treated with aspirin.
Histologic changes include cytoplasmic fatty vacuolization in hepatocytes, astrocyte edema and loss of neurons in the brain, and edema and fatty degeneration of the proximal lobules in the kidneys. All cells have pleomorphic, swollen mitochondria that are in reduced number, along with glycogen depletion and minimal tissue inflammation. Hepatic mitochondrial dysfunction results in hyperammonemia, which is thought to induce astrocyte edema, resulting in cerebral edema and increased intracranial pressure (ICP).
- Stage I
- Stage II
- Stage III
- Stage IV
- The ever-deepening coma
- Large pupils with minimal response to light
- Minimal but still present hepatic dysfunction
- Stage V