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A previous study showed that cerebrospinal fluid from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure contains 15 to 30 nm 3', 5' cyclic adenosine monophosphate. We measured the concentration of this cyclic nucleotide by radioimmunoassay in cerebrospinal fluid from the lateral ventricle of six patients with prolonged coma (20 days or longer) after head trauma (four), or spontaneous intracranial hemorrhage (two). Coma was graded IV to I in order of decreasing severity. Fluid was removed at intervals of six to 72 hours from a Rickham reservoir placed in the lateral ventricle. Concentration of the cyclic nucleotide (mean +/- S.E.M.) in coma of Grades IV, III, II and I was 2.1 +/- 0.3, 4.6 +/- 0.5, 6.3 +/- 1.4 and 12.5 +/- 2.4 nM respectively. After sensorium became normal, cAMP was 21.0 +/- 1.4 nM. Correlation between grade of coma and concentration was -0.89 (P less than 0.01). Thus, prolonged coma appears to be associated with a disturbance of cyclic AMP metabolism within the central nervous system.
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