Figure 15.

Excitotoxic mechanisms play an important role in various diseases in pediatric patients. Glutamate excitotoxicity is the final common pathway resulting in brain injury for many seemingly unrelated diseases. Increased extracellular glutamate is a direct cause of excitotoxic brain injury. In acute excitotoxic injury, increased extracellular glutamate results from increased release, decreased re-uptake, or leakage from the axon. There are two positive feedback loops (yellow arrows): 1) increased extracellular glutamate depolarizes adjacent neurons that release glutamate; and 2) neuronal injury causes leakage of glutamate (Figure 15), which make this mechanism self-propagating.

The distribution of lesions on MRI could be related to various excitotoxic mechanisms in the pediatric brain, especially in status epilepticus (NMDA receptor distribution), and shaken baby syndrome, HIE in early infants, and neonatal herpes encephalitis (post-natal vulnerability to glutamate). DWI is useful in detecting cytotoxic edema due to acute excitotoxic brain injury. MRS is thought to be an important tool to elucidate the pathophysiologic mechanisms of excitotoxic brain injury by directly showing or quantifying the excitatory amine itself. Glutamate receptor antagonists may offer attractive possibilities for future therapy as a neuroprotectant in these diseases.