OBSERVATIONS ON CYCLIC NUCLEOTIDE CONCENTRATIONS IN HUMAN CEREBROSPINAL-FLUID

The concentration of c[cyclic]AMP and cGMP in CSF, brain or both are increased by melanotropic peptides, catecholamines, and cholinergic agents. The concentrations of cAMP, cGMP and melanotropic activity were measured in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF concentrations (mean .+-. standard deviation) were: cAMP, 21 .+-. 8 mM; cGMP, 2.4 .+-. 0.5 mM; and melanotropic activity, 17 .+-. 6 units/100 ml. Concentrations of cAMP, cGMP and melanotropic activity did not differ significantly (P < .05) from normal in the following categories of adult and pediatric patients: back pain due to vertebral disease; seizures, headache or vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor or subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These 2 variables were significantly correlated in the entire series of CSF samples (r = +0.55, P < .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide level rose as high as 50 .times. normal when ventricular pressure exceeded 300 mm H2O). The concentration of ventricular cGMP was proportional to that of ventricular pressure (r = +0.76, P < .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient or the nature of the underlying disease.