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Howard Yonas, Sue Patre and Robert J. White

✓ An anomaly of the anterior spinal artery in association with a berry aneurysm is reported. The embryological basis for this previously unreported combination is reviewed.

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Howard Yonas, David Gur, Barbara C. Good, Richard E. Latchaw, Sidney K. Wolfson Jr., Walter F. Good, Glenn S. Maitz, James G. Colsher, J. Edward Barnes, Kristine G. Colliander and Bruce C. Teeter

✓ Xenon computerized tomography (Xe CT) blood flow studies were conducted in 25 patients referred for a possible extracranial-intracranial bypass procedure for occlusive vascular disease in one or more extra- or intracranial vessels. These studies were helpful in selecting eight candidates for surgery. The Xe CT studies were performed at one or two brain levels using a prototype Xe CT system for measurement of cerebral blood flow which was designed in collaboration with the General Electric Co., and adapted for the GE 9800 scanner. In those patients selected to undergo operation, Xe CT demonstrated compromise of flow reserve regionally, globally, and/or in the watershed area. All eight patients who underwent the procedure showed a favorable clinical response postoperatively, and seven had a dramatic increase in flow. The 17 patients whose baseline CT studies showed no reduction of flow with the Xe CT method were not selected for surgery. All 25 patients have remained neurologically stable to date. Case studies of three of the eight patients undergoing bypass surgery are presented.

This limited but consistent experience suggests that Xe CT blood flow mapping makes possible the recognition of brain regions in which flow reserves are compromised. This is due to the relatively high degree of spatial resolution that this technique provides and to the fact that mapping can be correlated directly with the anatomy. Used in combination with a careful clinical examination and an accurate medical history, this study method appears to be a useful guide in the selection of patients who are most at risk from hemodynamic instability and those who are most likely to benefit from flow-augmentation surgery.

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Howard Yonas, David Gur, Diana Claassen, Sidney K. Wolfson Jr. and John Moossy

✓ When the lateral striate arteries of the baboon are temporarily occluded for either 20 or 60 minutes, a near-cessation of blood flow is followed by a dramatic, transient local increase in blood flow values. These findings are evident from serial xenon (Xe)-computerized tomography (CT) measurement of cerebral blood flow (CBF). In this study, 20 minutes of vessel occlusion resulted in brief (< 1 hour) hyperemia, with no subsequent CT alteration and minimal random neuronal injury. Sixty minutes of occlusion resulted in a more prolonged hyperemia, a low-density area on CT images within 3 hours of reperfusion, and infarction of all cellular elements within the anterior lentiform nucleus. The Xe-CT method provides a sensitive, noninvasive technique for examining sequential alterations of CBF in small regions deep within the brain. This method of recording CBF also permits correlative studies of cerebral infarction, both clinically and experimentally, and allows reasonable inference about the probabilities of neuronal tissue damage with or without reperfusion.

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Donald W. Marion, Joseph Darby and Howard Yonas

✓ To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 61 CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) ≤ 7). The measurements were made within 7 days after injury, 43% in the first 24 hours. During the 1st day, patients with an initial GCS score of 3 or 4 and no surgical mass had significantly lower flows than did those with a higher GCS score or mass lesions (p < 0.05): in the first 1 to 4 hours, those without surgical mass lesions had a mean CBF of 27 cc/100 gm/min, which rose to 44 cc/100 gm/min by 24 hours. Patients without surgical mass lesions who died tended to have a lower global CBF than did those with better outcomes. Mass lesions were associated with a high global CBF and bihemispheric contusions with the lowest flows. By 24 hours after injury, global blood flow increased in groups that originally had low flows and decreased in those with very high initial flows, such that by 36 to 48 hours, most patients had CBF values between 32 and 55 cc/100 gm/min. Lobar, basal ganglion, and brain-stem blood flow values frequently differed by 25% or more from global averages. Brain-stem CBF varied the most but did not correlate with clinical signs of brain-stem dysfunction. Double studies were performed at two different pCO2 values in 10 patients with various posttraumatic lesions, and the CO2 vasoresponsivity was calculated. Abnormal CO2 vasoresponsivity was found with acute subdural hematomas and defuse cerebral swelling but not with epidural hematomas. In patients without surgical mass lesions, the findings suggest that CBF in the first few hours after injury is often low, followed by a hyperemic phase that peaks at 24 hours. Global CBF values vary widely depending on the type of traumatic brain injury, and brain-stem flow is often not accurately reflected by global CBF values. These findings underscore the need to define regional CBF abnormalities in victims of severe head injury if treatment is intended to prevent regional ischemia.

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Mark E. Linskey, Joseph A. Horton, Gutti R. Rao and Howard Yonas

✓ The authors report the clinical course, radiographic findings, and gross and microscopic pathology of a patient with fatal rupture of the supraclinoid segment of the left internal carotid artery during transluminal angioplasty for subarachnoid hemorrhage-induced vasospasm. The rupture most likely resulted from a small portion of aneurysm neck which remained unclipped, thereby leaving an area of structural weakness in the arterial wall at the site of clipping. The area of structural weakness predisposed the artery to rupture upon the addition of transmural pressure induced by balloon inflation during transluminal angioplasty. Caution is advised when performing transluminal angioplasty in the region of aneurysm clipping since the vessel lumen “recreated” during the clipping procedure may contain some residual and structurally incomplete aneurysm neck in the vessel wall.

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Mark E. Linskey, Laligam N. Sekhar, Joseph A. Horton, William L. Hirsch Jr. and Howard Yonas

✓ Of 43 cavernous sinus aneurysms diagnosed over 6½ years, 23 fulfilled indications for treatment; of these 19 were treated, eight surgically and 11 with interventional radiological techniques. Six small and two giant aneurysms were treated surgically: four were clipped, two were repaired primarily, and two were trapped with placement of a saphenous-vein bypass graft. Seven large and four giant aneurysms were treated with interventional radiological techniques: in five cases the proximal internal carotid artery (ICA) was sacrificed; one aneurysm was trapped with detachable balloons; and five were embolized with preservation of the ICA lumen. The mean follow-up period was 25 months. At follow-up examination, three patients in the surgical group were asymptomatic, two had improved, and three had worsened. Three of these patients had asymptomatic infarctions apparent on computerized tomography (CT) scans. At follow-up examination, four radiologically treated patients were asymptomatic, five had improved, two were unchanged, and none had worsened. One patient had asymptomatic and one minimally symptomatic infarction apparent on CT scans; both lesions were embolic foci after aneurysm embolization with preservation of the ICA.

It is concluded that treatment risk depends more on the adequacy of collateral circulation than on the size of the aneurysm. A multidisciplinary treatment protocol for these aneurysms is described, dividing patients into high-, moderate-, and low-risk groups based on pretreatment evaluation of the risk of temporary or permanent ICA occlusion using a clinical balloon test occlusion coupled with an ICA-occluded stable xenon/CT cerebral blood flow study. Radiological techniques are suggested for most low-risk patients, while direct surgical techniques are proposed for most moderate- and high-risk patients.

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Howard Yonas, Holly A. Smith, Susan R. Durham, Susan L. Pentheny and David W. Johnson

✓ The authors sought to determine risk for stroke in individuals with symptomatic carotid stenosis or occlusion based upon an assessment of cerebral blood flow (CBF) reserves. Vascular reserve was assessed by two consecutive xenon/computerized tomography (Xe/CT) CBF studies with intravenous acetazolamide introduced 20 minutes prior to the second study. Patients were assigned to one of two vasoreactivity groups. Group 2 included individuals who experienced a CBF reduction of more than 5% in at least one vascular territory and had a baseline flow of 45 cc/100 gm/min or less. Group 1 included all other individuals. Any territory with volume loss on CT of more than 50% was eliminated from analysis.

Sixty-eight individuals were followed at 6-month intervals for a mean of 24 months. In Group 1 two strokes were observed contralateral to the side with lowest reserve, for a stroke incidence of 4.4%; in Group 2 eight strokes were observed ipsilateral to the side with lowest reserve, for a stroke incidence of 36%. The latter group had a 12.6 times greater chance of stroke (p = 0.0007). History of stroke, history of transient ischemic attacks, baseline CBF, and degree of stenosis were not associated with an increased stroke rate. In this study, significantly compromised vascular reserves accompanied by relatively low initial flow identified individuals who subsequently demonstrated a significantly increased rate of ipsilateral stroke.

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Joseph M. Darby, Howard Yonas, Elizabeth C. Marks, Susan Durham, Robert W. Snyder and Edwin M. Nemoto

✓ The effects of dopamine-induced hypertension on local cerebral blood flow (CBF) were investigated in 13 patients suspected of suffering clinical vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The CBF was measured in multiple vascular territories using xenon-enhanced computerized tomography (CT) with and without dopamine-induced hypertension. A territorial local CBF of 25 ml/100 gm/min or less was used to define ischemia and was identified in nine of the 13 patients. Raising mean arterial blood pressure from 90 ± 11 mm Hg to 111 ± 13 mm Hg (p < 0.05) via dopamine administration increased territorial local CBF above the ischemic range in more than 90% of the uninfarcted territories identified on CT while decreasing local CBF in one-third of the nonischemic territories. Overall, the change in local CBF after dopamine-induced hypertension was correlated with resting local CBF at normotension and was unrelated to the change in blood pressure. Of the 13 patients initially suspected of suffering clinical vasospasm, only 54% had identifiable reversible ischemia.

The authors conclude that dopamine-induced hypertension is associated with an increase in flow in patients with ischemia after SAH. However, flow changes associated with dopamine-induced hypertension may not be entirely dependent on changes in systemic blood pressure. The direct cerebrovascular effects of dopamine may have important, yet unpredictable, effects on CBF under clinical pathological conditions. Because there is a potential risk of dopamine-induced ischemia, treatment may be best guided by local CBF measurements.

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Brent L. Clyde, Andrew D. Firlik, Anthony M. Kaufmann, MichaelP. Spearman and Howard Yonas

✓ Reports of intraarterial papaverine infusion as treatment for cerebral vasospasm are few and documented complications are uncommon. The authors report the case of a patient with paradoxical aggravation of cerebral arterial narrowing during selective intraarterial papaverine infusion intended to treat vasospasm following aneurysmal subarachnoid hemorrhage (SAH). A 48-year-old man presented to the authors' service with symptomatic vasospasm 10 days after experiencing an SAH. The ruptured anterior communicating artery aneurysm was surgically obliterated the following day, and thereafter maximum hypervolemic and hypertensive therapies were used. However, the patient remained lethargic, and a stable xenon—computerized tomography (CT) cerebral blood flow (CBF) study revealed CBF to be 15 cc/100 g/minute in the left anterior cerebral artery (ACA) and 25 cc/100 g/minute in the right ACA territories. Cerebral arteriography demonstrated diffuse severe left ACA and mild left middle cerebral artery (MCA) vasospasm. In response intraarterial papaverine was infused into the internal carotid artery just proximal to the ophthalmic artery. During the infusion the patient became aphasic and exhibited right hemiplegia. Arteriography performed immediately after the intraarterial papaverine infusion revealed diffuse exacerbation of vasospasm in the distal ACA and MCA territories. A repeat xenon—CT CBF study showed that CBF in the left ACA and the MCA had drastically decreased (2 cc/100 g/minute and 10 cc/100 g/minute, respectively). Despite aggressive management, infarction ultimately developed.

This is the first clinical case to illustrate a paradoxical effect of intraarterial papaverine treatment for vasospasm following aneurysmal SAH. The possible mechanisms of this paradoxical response and potential therapeutic reactions are reviewed.

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Richard Klementavicius, Edwin M. Nemoto and Howard Yonas

✓ Previously the authors showed that hypothermia exerts a greater effect on the cerebral metabolic rate for oxygen (CMRO2) that is associated with the maintenance of cellular viability, or “basal” CMRO2, than on electroencephalogram (EEG)-associated CMRO2 or “functional” CMRO2. On the basis of their findings, the authors hypothesized that the ratio of CMRO2 over a 10°C temperature range (Q10) for basal CMRO2 was greater than that for functional and total CMRO2. They tested their hypothesis by determining the Q10 for basal CMRO2 from 38°C to 28°C. They measured whole-brain cerebral blood flow (CBF) and CMRO2 in six rats during progressive hypothermia at a brain temperature of 38°C and, after induction of an isoelectric EEG signal (50 µV/cm) with thiopental sodium, they repeated the measurements at 38°C, 34°C, 30°C, and 28°C. In a control group (five rats), six sequential measurements of CBF and CMRO2 were made while the animals were anesthetized by 0.5% isoflurane/70% N2O/30% O2 at a brain temperature of 38°C over a time span equivalent to the hypothermic group, that is, approximately 3 hours. The Q10 for basal CMRO2 calculated over 38°C to 28°C was 5.2 ± 0.92. However, the decrease in basal CMRO2 between 38°C and 28°C was nonlinear on a log plot, revealing a two-component response: a high temperature sensitivity component between 38°C and 30°C with a Q10 of 12.1, and a lower temperature sensitivity component between 30°C and 28°C with a Q10 of 2.8. The combined overall Q10 for basal CMRO2 between 38° and 28°C was 5.2. The energy-requiring processes associated with these high and low temperature sensitivity components of basal CMRO2 have yet to be identified.