Pathophysiology of pseudotumor.
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Biomedical subjects
Publications and source records attributed to M E Raichle.
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Regional cerebral blood flow (rCBF) and regional cerebral oxygen utilization (rCMRO2) were measured before and after surgery in nine patients undergoing a superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis to bypass cerebrovascular lesions not amenable to extracranial operative procedures. The objective of these studies was to determine whether measurements of this type could provide objective criteria for surgery as well as assess the effect of surgery. The preliminary data, although limited, suggest that measurements of regional cerebral hemodynamics and metabolism in these patients before and after surgery provide valuable data upon which to develop criteria and assess results. For example, 1) a significant depression of rCBF and rCMRO2 in patients in whom a major cerebral infarction has not occurred, or 2) relative preservation of rCMRO2 despite depressed rCBF seem to be favorable indications for establishing a functioning STA-MCA anastomosis. In such patients, STA-MCA anastomosis can be followed by a return of rCBJ and rCMRO2 to virtually normal levels. Relatively normal rCBF and rCMRO2 in the presence of an occluded internal carotid artery in asymptomatic patients indicates satisfactory collateral circulation and is probably a contraindication to surgery.
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Emission tomography can be used to monitor, in vivo and regionally, the utilization of metabolic substrates labeled with positron-emitting radioisotopes produced by a cyclotron. The concept was validated by measuring brain glucose utilization with carbon--11-labeled glucose in rhesus monkeys.
The brain vasculature, especially capillaries, may function in a very dynamic fashion under neuroendocrine control to regulate the internal environment of the brain. This is exemplified by new observations on the regulation of brain water permeability using the tracer H215O in vivo in adult rhesus monkeys. These studies reveal that brain water permeability, and hence brain water content and volume, are, at least in part, under the influence of the central noradrenergic system and centrally released vasopressin.
A comprehensive analysis of cerebral hemodynamics and metabolism was carried out in 14 patients with pseudotumor cerebri. Tracer techniques were employed to measure cerebral blood flow (CBF) and vascular reactivity to acute changes in arterial carbon dioxide tension and blood pressure, cerebral blood volume (CBV), and the cerebral metabolic rate for oxygen and glucose. There was a small reduction (p less than 0.01) in CBF (44 +/- 7 ml/100 gm/min; normal, 54 +/- 9) with normal vascular reactivity; an increase (p less than 0.005) in CBV (4.8 +/- 0.8 ml/100 gm; normal, 3.6 +/- 0.5), and normal cerebral metabolism. We conclude that an abnormality of the cerebral microvasculature is responsible for an elevation in CBV, but the intracranial hypertension can be explained only by tissue swelling due to an increase in water content. The relationship between the vascular abnormality and the tissue swelling remains to be defined.
The technique of positron emission tomography was used to measure cerebral blood volume (CBV) in 10 normal right-handed human volunteers following inhalation of trace quantities of cyclotron-produced, 11C-labeled carbon monoxide. In scans obtained 4 cm above the orbitomeatal line, CBV was 4.3 ml per 100 gm of tissue, whereas in scans obtained 8 cm above the orbitomeatal line, CBV was significantly less (3.3 ml per 100 gm; p less than 0.001). This difference reflects the greater proportion of gray matter in the lower scan. Furthermore, the CBV was significantly larger (p less than 0.001) in the left cerebral hemisphere in the tomographic scans obtained 4 cm above the orbitomeatal line. These scans include the region of the superior surface of the temporal lobe (planum temporale), which is thought to be larger in individuals with left cerebral dominance for speech. This observation is the first in vivo demonstration of a structural correlate of a known functional difference in the cerebral hemispheres of man.
The brain is critically dependent for its moment to moment function and survival on an adequate supply of oxygen. The enzyme carbonic anhydrase (EC 4.2.1.1) may play an important role in oxygen delivery to brain tissue by facilitating the hydration of metabolically produced carbon dioxide in erythrocytes in brain capillaries, thus permitting the Bohr effect to occur. We examined the effect of 30 mg/kg i.v. acetazolamide, a potent inhibitor of carbonic anhydrase, upon cerebral blood flow and oxygen consumption in lightly anesthetized, passively ventilated rhesus monkeys. Cerebral blood flow and oxygen consumption were measured with oxygen-15-labeled water and oxygen-15-labeled oxyhemoglobin, respectively, injected into the internal carotid artery and monitored externally. Acetazolamide produced an immediate and significant increase in cerebral blood flow (from a mean of 64.7 to 83.8 ml/100 g per min), an increase in arterial carbon dioxide tension (from a mean of 40.7 to 47.5 torr), and a decrease in cerebral oxygen consumption (from a mean of 4.16 to 2.82 ml/100 g per min). Because the change in cerebral oxygen consumption occurred within minutes of the administration of acetazolamide, we believe that this effect probably was not due to a direct action on brain cells but was achieved by an interference with oxygen unloading in brain capillaries. A resultant tissue hypoxia might well explain part of the observed increase in cerebral blood flow.
A cyclotron target system for the production of anhydrous [18F] fluoride ion has been developed and used for the synthesis of carrier-free [18F]-3-deoxy-3fluoro-D-glucose (3-FDG). The synthesis is sufficiently rapid and efficient to allow production of usable amounts of 3-FDG with a 6-MeV cyclotron. Preliminary animal studies show that 3-FDG is in fact a glucose analog.
Patients with dementia had significant decreases in cerebral blood flow and cerebral oxygen utilization and a mild, but not significant, increase in cerebral blood volume. These studies were not useful in distinguishing patients with cerebral atrophy from patients with normal pressure hydrocephalus, as similar changes in cerebral circulation and metabolism were seen in both groups. Changes in cerebral blood flow after acute decrease in the intracranial pressure also were not helpful differentiating patients with normal pressure hydrocephalus from patients with cerebral atrophy.
Forty-five studies of regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional cerebral oxygen utilization (rCMRO2) were performed in 30 patients undergoing diagnostic cerebral angiography for evaluation of a subarachnoid hemorrhage due to a ruptured intracranial aneurysm. Tracer methods employing radioactive oxygen-15 were used to measure rCBV, rCBF, and rCMRO2. The patient studies were divided into groups based on their neurological status and the presence or absence of cerebral vasospasm. Subarachnoid hemorrhage, with and without vasospasm, produced significant decreases in CBF and CMRO2. In general, patients with more severe neurological deficits, and patients with more severe degrees of vasospasm, had a more marked depression of CBF and CMRO2. The most striking finding was a significant (p less than 0.001) increase in CBV (to 58% above normal) in patients with severe neurological deficits associated with severe cerebral vasospasm. This large increase suggests that cerebral vasospasm consists of constriction of the large, radiographically visible extraparenchymal vessels accompained by a massive dilation of intraparenchymal vessels.
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