Acute hyperammonemia in the young primate: physiologic and neuropathologic correlates

Infusion-induced acute (less than or equal to 24 h) hyperammonemia to concentrations up to five times normal (0.19 +/- 0.03 versus 0.90 +/- 0.08 mM) was studied in eleven 6-9-month-old Macaca mulatta. The young primates developed a progressive reduction of consciousness that correlated in severity directly with the elevation of blood ammonia concentration. Hyperventilation, electroencephalographic slowing, occasional seizure activity, and, eventually, apneustic breathing also occurred. Intracranial pressure rose from 76 +/- 7 to 167 +/- 12 mmH2O. Arterial oxygen and blood pressure remained within normal limits. Neuropathologic examination showed early astrocytic changes, consisting primarily of swollen perikaryal cytoplasm and processes, and membranous whorls. The absence of neuronal pathology suggests that the acute, limited insult, as occurs in many of the childhood hyperammonemic syndromes, is fully reversible.