James D. Weinstein

Cerebral vasomotor paralysis produced by intracranial hypertension

THE SIGNS and symptoms of increased intracranial pressure and cerebral compression have occupied the interest of numerous investigators since earliest times. Although changes in vital signs in response to alterations in intracranial dynamics have long been recognized, the importance of these changes in the diagnosis and management of patients with expanding intracranial lesions has been questioned. In particular, the arterial hypertension which is readily produced experimentally by increased intracranial pressure has been considered to be of limited clinical significance because it has been assumed that blood pressure does not increase until the intracranial pressure approaches the diastolic pressure and that this rarely occurs. This conclusion was based primarily on periodic recording of the lumbar subarachnoid pressnre and thus requires the additional assumption that the spinal fluid pressure at all times approximates the intracranial pressure. In a previous report we presented experimental evidence that obstruction at the tentorial incisura during expansion of a supratentorial mass prevents communication of pressure to the posterior fossa and spinal cana1.l Also, as the pressure gradient across the incisura increases, the vasopressor threshold decreases, and arterial hypertension may then occur, with absolute intracranial pressures far below the diastolic pressure.? The first purpose of the present experiments was to extend these observations in an attempt to determine the sequence of events which ultimately lead to neurological deterioration and death during gradual expansion of an intracranial mass lesion. The history of the investigation of cerebral compression before 1900 was reviewed by

CEREBRAL BLOOD FLOW WITH INTRACRANIAL HYPERTENSION.

IN A PREVIOUS REPORT we advanced the hypothesis that a progressive rise in intracranial pressure ultimately causes vasomotor paralysis and brain swelling, the latter due primarily to an increase in cerebral blood volume.1 This process was termed cerebrovascular decompensation and was divided into 4 successive stages. The development of this hypothesis was, in part, dependent on the demonstration of the relationship of increased pressure to volume within the intracranial space. We confirmed previous observations that spatial compensation for an expanding mass occurs by expression of fluid from the intracranial space, and a rise in pressure occurs only when the volume added exceeds the volume of fluid displaced. However, when displaceable fluid has been eliminated, a slight further increase in the volume of the mass causes a great rise in intracranial pressure, due to the fact that the skull approaches a closed, rigid container. Thus, during the period of spatial compensation (stage 1) the volume-pressure curve is essentially horizontal, with volume on the abscissa and pressure on the ordinant, then rises abruptly, nearly vertical to the abscissa, after displaceable volume has been eliminated. Indirect evidence also was presented that increased intracranial pressure, produced by expansion of an extradural balloon, causes cerebral vasodilation and an increase in intracranial blood volume, which is further augmented by a rise in systemic arterial pressure when the intracranial pressure reaches the vasopressor threshold. The most likely cause of the initial cerebra1 vasodilation is anoxia and carbon dioxide retention due to diminished blood flow. If this secondary rise in intracranial volume and tension is sufficient to cause additional elevation of the arterial pressure, both pressures rise together as a pressure wave, often to an intracranial pressure in excess of 100 mm. Hg (stage 2) . After repeated pressure waves the vasopressor response begins to fail, and, as the intracranial pressure approaches the arterial pressure, severe cerebral ischemia ensues. This leads to further vascular dilation due to ischemic vasomotor paralysis, and progressive brain swelling develops as cerebral blood volume increases (stage 3) . Ultimately the vasomotor paralysis is complete, and when the mass is suddenly evacuated the intracranial pressure falls and then rebounds quickly to the level of the arterial pressure. Pressure is equal everywhere now within the intracranial space, the decompensation process is complete and irreversible, and we postulated that at this time cerebral blood flow has ceased (stage 4). In the present experiments changes in cerebral blood flow have been measured continuously during the stages of cerebrovascular decompensation, and the results support the concept that vasomotor paralysis is the essential feature of the decompensation process.

The effect of dexamethasone on brain edema in patients with metastatic brain tumors

Eight consecutive patients with severe neurol o g i c deficits (table I ) from documented metastatic brain tumors were studied before and during dexamethasone therapy. Patients were evaluated for changes in: (1) neurologic status, (2) cerebrospinal fluid (CSF) pressure, (3) CSF protein, (4) cerebral angiography, and ( 5 ) regional cerebral blood flow (rCBF). Cerebrospinal fluid pressure and protein were measured by lumbar punctures before and every three to seven days during treatment. Carotid angiography was obtained in all patients before treatment, and in four patients, repeat studies were done during the course of therapy. Three of these four had serial regional cerebral blood flow measurements a t the time of angiography. Regional cerebral blood flow was determined by the intracarotid xenon 133 washout method’ and has been previously reported in detaiL8 ,9 In this laboratory, normal values are: 54.4 t 5.8 cc per 100 gin per minute for each individual area and 54.4 t 2.7 cc per 100 gm per minute for the hemisphere as a whole, calculated as the average value of all areas. A change of more than 20 percent for any area or 7 percent in the mean hemispheric flow between studies is considered significant.’ ’ Dexamethasone (16 mg) was given intramuscularly in four divided doses each day, except for one patient (case 2) who received 24 mg daily. Attempts were made t o decrease the dosage t o minimize potential side effects after favorable clinical response had been obtained.

VASOPRESSOR RESPONSE TO INCREASED INTRACRANIAL PRESSURE.

THE MEANS whereby increased intracranial pressure produces a systemic arterial pressor response has been the subject of numerous investigations because of its possible significance in the pathology of intracranial hypertension. Three different mechanisms have been proposed to explain the vasopressor response, namely, brain ischemia, direct pressure on cerebral blood vessels activating mechanical receptors, and distortion of the brain. Cushingl-3 observed that a vasopressor response did not occur in anesthetized dogs until the intracranial pressure reached the level of the systemic blood pressure; on this basis he postulated that the pressor response was due to medullary ischemia and represented a compensatory mechanism to restore cerebral blood flow. Subsequently, Forster4 demonstrated that this vasopressor response could be elicited after destruction of the cerebral hemispheres and progressive maceration of the brainstem to the level of the superior border of the inferior olivary body. Destruction of medulla below this point caused the response to disappear. I t also has been shown that the vasopressor effect is dependent on the thoracic sympathetic chain.5 In more recent experiments, the ischemic hypothesis has been tested by controlled perfusion of the isolated dog head, and an increase in systemic arterial pressure was quantitated with progressive degrees of ischemia.6 A vasopressor response to ischemia also has been demonstrated experimentally in primates with progressive occlusion of carotid and vertebral arteries and also the middle cerebral artery.7 The significance of Cushing’s observations in relation to clinical states of increased intracranial pressure has been questioned by Browder and Meyerss79 and Evans and associateslg

Ophthalmic Artery Pressure Response To Carotid Occlusion

DIRECT CANNULATION of the frontal branch of the ophthalmic artery in the rhesus monkey has enabled us to measure the effects of carotid artery occlusions on ophthalmic artery pressure. The data gained by using this technique in conjunction with occlusions of the common, external, and internal carotid arteries will be presented and discussed in this paper. The work to be reported was done with the full consideration that there may be anatomic variations between the monkey and the human being and, of course, between individual animals.1 However, the results of experimental work done thus far have been sufficiently consistent to warrant a report at this time.