Increased hypoxanthine concentrations in cerebrospinal fluid of infants with hydrocephalus Hypoxanthine, the end product of purine metabolism, is usually very elevated in body fluids during severe hypoxia. We measured hypoxanthine in the cerebrospinal fluid of hydrocephalic preterm infants (12 with posthemorrhagic, one with congenital hydrocephalus) to determine whether hydrocephalus is associated with anaerobic metabolism of brain tissue. Cerebrospinal fluid hypoxanthine was undetectable in normal infants. In hydrocephalic infants, the concentration of hypoxanthine ranged from 7.5 ~mol/L to 28 izmol (Yc= 14.3 ~mol/L). The hypoxanthine concentrations fell from a mean of 12.8 ilmol/L to a mean of 2.0 izmol/L (P < 0.05) with successful treatment of the ventriculomegaly by lumbar puncture or by ventriculoperitoneal shunt. Patients with acute posthemorrhagic hydrocephalus had similar concentrations of hypoxanthine (Yr = 14.5 ixmol/L) as patients with late or with congenital hydrocephalus (Yr = 13.8 lLmol/L), indicating that brain hypoxia is probably a consequence of the ventriculomegaly and not of the hemorrhagic insult. (J PEDtATR 103:44, 1983) Raul Bejar, M.D., Ola D. Saugstad, M.D., Hector James, M.D., and Louis Giuek, M.D. San Diego, Calif. POSTHEMORRHAGIC HYDROCEPHALUS in preterm infants is associated with a poor neurologic outcome./-3 It is not known whether the abnormal development is a conse- quence of the hemorrhagic insult and the factors that led to the initial bleeding or of the increased intracranial pressure and ventriculomegaly present in posthemorrhagic hydro- cephalus. 4 Studies in hydrocephalic infants and experimen- tal animals have shown that ventriculomegaly is associated with tissue damage, including flattening and disruption of the ependyma, edema and disorganization of the periven- tricular white matter, with myelin and axon destruction. 4-~~ Furthermore, increased lactate and lactate-pyruvate ratios have been found in the cerebrospinal fluid of hydrocephalic infants and animals, indicating that this condition may be associated with brain hypoxia or ischemia. "-~z However, absolute lactate values and lactate-pyruvate ratios are influenced by the CO2 tension and the pH of the tissue. 13-1s From the Departments of Pediatrics and Surgery, University of California. Supported by National Institutes of Health Grant HD 10622, National Foundation/March of Dimes 6Fant C-302, and Fogarty International Fellowship Grant PHS TW02934. Reprint requests: Raul Bejar, M.D., Department of" Pediatrics, H638A, University Hospital, 225 Dickinson St., San Diego, CA 92103. Moreover, lactate can cross the blood-brain barrier and be oxidized by the brain tissue. ~3, ,6 Hypoxanthine concentrations in plasma, urine, and CSF have been used to assess tissue hypoxia?7:27 Theoretically, hypoxanthine concentrations could be employed to evalu- ate the intracellular energy status. In animal experiments, hypoxanthine values in CSF and brain are elevated signif- icantly three minutes after respiratory arrest or after several hours of brain ischemia. 2~, 26Hypoxanthine concen- trations in the CSF also are elevated in children with systemic hypoxia and seizures, z2, 23 I LP Lumbar puncture ] VP shunt Ventriculoperitoneal shunt If progressive ventriculomegaly, even without enlarge- ment of the head, is associated with ischemia of the brain, hypoxanthine concentrations in the CSF should be ele- valed, 'indicating metabolic derangement of the brain tissiae. Hypoxanthine concentrations in CSF should then decrease toward normal when the hydrocephalus is treated adequately. A preliminary study was performed to determine wheth- er these changes in concentrations of hypoxanthine were present in hydrocephalic preterm infants. 44 The Journal of P E D I A T R I C S