All cases of acute supratentorial cerebral infarction which came to postmortem examination over the past 10 years at the Philadelphia General Hospital were reviewed. Of a total of 353 such cases, 45 showed severe brain swelling. Seventy-eight percent of these 45 patients died within seven days of the acute infarction. The rapidly fatal outcome appeared to be directly related to the acute brain swelling with transtentorial herniation and brain-stem edema or hemorrhage. In those patients who survived longer than one week following onset of the ictus (22%), clinical and anatomic findings suggested that increased intracranial pressure probably did not develop until later in the course of the illness. A second massive infarct was probably superimposed upon an earlier one and produced the acute brain swelling noted at the time of postmortem examination. Complicating visceral diseases were more common in this group and seemed to contribute to death in the majority of these patients. Although it has been established that a large cerebral infarct may produce sufficient brain swelling and simulate an acutely expanding lesion, this is not widely recognized as playing an important part in determining the patient's clinical outcome. The role of increased intracranial pressure resulting from acute brain swelling should not be overlooked in the management of patients with severe strokes.

Levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), a major metabolite of norepinephrine, were measured in human CSF by gas-liquid chromatography. MHPG concentrations were similar in both ventricular and lumbar CSF samples ; about 30 per cent of the MHPG from either source occurred as the sulphate conjugate. There was relatively little entry of intravenously infused [14C]MHPG into lumbar spinal fluid. Both a-methylparatyrosine, an inhibitor of tyrosine hydroxylase, and fusaric acid, an inhibitor of dopamine-,%hydroxylase, significantly diminished MHPG values. On the other hand, doses of L-DOPA or probenecid, sufficient to substantially elevate CSF levels of the dopamine metabolite, hornovanillic acid, failed to alter the spinal fluid content of MHPG. CSF concentrations of MHPG in patients with Parkinson's disease or the other central nervous system disorders studied did not differ significantly from control levels. The results suggest that MHPG values in CSF may provide an index to norepinephrine metabolism in the central nervous system of man.CEREBROSPINAL fluid (CSF) levels of monoamine metabolites have been used extensively to estimate dopamine and serotonin metabolism in the human CNS. The rationale for this approach derives from observations suggesting that the CSF content of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the principal degradation products of these monoamines, reflect levels in CNS tissues (GULDBERG and YATES, 1968; ECCLESTON et al., 1968). Recently a sensitive and specific method has been developed to measure CSF concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) (WILK, DAVIS and THACKER, 1971 ; GORDON and OLIVER, 1971), a major product of norepinephrine metabolism (SCHANBERG et al., 1968; MAAS and LANDIS, 1968; BREESE et d., 1969; SUGDEN and ECCLESTON, 1972). Here we report the application of this technique to the study of noradrenergic function in patients with various CNS disorders and during the administration of centrally active drugs. MATERIALS A N D M E T H O D SLumbar CSF samples were obtained from 67 patients (29 males and 38 females, ages 8-67 yr). Included were 13 with idiopathic parkinsonism, five with dystonia musculorum deformans, three with acquired dystonia, seven with Huntington's chorea, six with Down's syndrome, eight with diseases involving the spinal cord, 14 with miscellaneous central or peripheral nervous system disorders and 11 control subjects who were free of nervous system disease. In addition, ventricular CSF samples were obtained from nine patients with various CNS disorders via chronically indwelling, subcutaneous reservours (RATCHESON and OMMAYA, 1968).Lumbar punctures were ordinarily performed at 0900 hours with the patients kept fasting and recumbent in bed during the preceding 10-12 h. CSF samples from individuals receiving orally Abbreviations used: HVA, homovanillic acid; MHPG, 3-methoxy-4hydroxyphenylethylene glycol ; 581 5-HIAA, 5-hydroxyindoleacetic acid.

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