The relationship of free and conjugated catecholamines in plasma and cerebrospinal fluid in cerebral and meningeal disease.

The concentration of free and conjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) were measured by a modified radio-enzymatic assay in the plasma and in the cerebrospinal fluid (CSF) of 45 patients with normal and in 21 patients with disturbed blood-CSF barriers. In patients with an undisturbed blood-CSF barrier the free NE and E in CSF were 128 +/- 45 ng/l and 27 +/- 20 ng/l (mean values +/- S.E.), respectively, and represented about 50% of the average plasma values. Mean DA was not different in plasma (47 +/- 22 ng/l) and in CSF (41 +/- 19 ng/l). Both in plasma and in CSF, considerable higher free catecholamine (CA) levels were measured in patients with dysfunction of the blood-CSF barrier. In one patient with bacterial meningitis twofold higher concentrations of free NE and DA in CSF as compared with plasma were detectable. Sulfate conjugates of catecholamines are predominant in plasma and CSF. The contribution of conjugated CA to total CA in plasma from patients with normal blood-CSF barrier averaged 69.7%, 63.1% and 98.1% for NE, E and DA, respectively and was significantly lower in the CSF (p less than 0.001). In patients with disturbed blood-CSF barrier, the increases of conjugated CA were more pronounced in CSF than in plasma. Further, the contribution of conjugated NE and E to total NE and E in CSF was not only increased in patients with bacterial meningitis, but also in patients with renal insufficiency compared to the "control" patients (p less than 0.02 and p less than 0.001 resp.). Free and conjugated NE, E and DA in the plasma and CSF were related significantly (p less than 0.01 resp.) with stronger correlation for conjugated CA (p less than 0.001 resp.). These results together with findings in the literature, suggest that there is little or no rostral-caudal gradient in CSF CA conjugate concentrations and that even in patients with intact blood-CSF barrier plasma conjugated CA concentrations influence those in CSF. Thus only free CA levels in CSF may reflect the central adrenergic activity.