Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy.

We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged > or = 2 to < or = 4 wk, 25 aged > 4 to < or = 30 wk, and 11 aged > 30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at < 2 wk (p = 0.005) and > 4 to < or = 30 wk (p = 0.01); Pi/PCr measured at < 2 wk (p < 0.001); pHi measured at < 2 wk (p < 0.001), > or = 2 to < or = 4 wk (p = 0.02) and > 4 to < or = 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at > or = 2 to < or = 4 wk (p = 0.03) and > 4 to < or = 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.