Hypoxic and ischemic central nervous system disorders in infants and children.

Brain damage from severe hypoxemia and ischemia is involved in many childhood disorders that produce permanent disability. Recent progress in diagnosis and brain imaging as well as in the laboratory has expanded understanding of the pathophysiology of these disorders. They are currently thought to trigger a neurotoxic biochemical cascade that produces permanent cell death over a period of hours to days. A prominent feature of this cascade is synaptic dysfunction and overactivation of excitatory amino acid receptors that carry a majority of the excitatory messages transmitted in the brain. In premature infants the periventricular white matter is especially vulnerable, whereas neuronal structures are more vulnerable at term and at older ages. Numerous drugs are now known to protect the brain from neuronal damage in laboratory models. Application of this new pharmacology will require techniques to monitor cerebral metabolism and blood flow at the bedside in order to ensure that only high-risk infants are included. Although the new medications can be expected to have significant adverse effects as well as benefits, it seems likely that this therapy will be applied to certain high-risk groups over the next decade.