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 a ge after neonatal encephalopathy (NE) in infants with severe neurodevelopme ntal impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potentia l. Forty three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinatio ns were obtained: 25 aged <2 wk, 16 aged greater than or equal to ? to less than or equal to 4 wk, 25 aged >4 to less than or equal to 30 wk, and 11 a ged >30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infan ts had a normal outcome and 26 infants had an abnormal outcome. Using univa riate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pH( i)) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome gro up or age at rime of study. Between outcome groups, there were significant differences for lactate/Cr measured at <2 wk (p = 0.005) and >4 to less tha n or equal to 30 wk Co = 0.01); Pi/PCr measured at (<2 wk (p < 0.001); pH, measured at <2 wk (p < 0.001), greater than or equal to 2 to less than or e qual to 4 wk; (p = 0.02) and >4 to less than or equal to 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at greater than or equal to 2 to less than or equal to 4 wk (p = 0.03) and >4 to less than or equal to 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alk alosis are a prolonged change in redox state within neuronal cells, the pre sence of phagocytic cells, the proliferation of glial cells, or altered buf fering mechanisms. These findings may have implications for therapeutic int ervention.