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Thoralf M. Sundt Jr.

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John D. Michenfelder, Roy F. Cucchiara and Thoralf M. Sundt Jr.

✓ Because of a suspicion that intraoperative penicillin antibiotics might be causing early postoperative seizures in craniotomy patients, a deliberate effort was initiated in 1987 to avoid these agents in favor of nonpenicillin antibiotics. This permitted a retrospective comparison of the incidence of early postoperative seizures in craniotomy patients who did and who did not receive intraoperative penicillins. Records of patients treated between July 1, 1984, and July 1, 1985, and between July 1, 1987, and July 1, 1988, were reviewed, for a total of 1316 procedures. There were no seizures in the 323 patients who underwent suboccipital craniectomy. However, among the 993 patients receiving supratentorial procedures there were 30 with seizures within the first 6 hours postoperatively, 19 of which were generalized seizures. The incidence of early seizures was 4.7% (20 cases) of the 427 patients given penicillins and only 1.8% (10 cases) of the 566 not given penicillins (p < 0.01). Since patients undergoing surgery for intractable seizures have a high incidence of early postoperative seizures (11 of 92 in this series, or 12%), creation of a subgroup eliminated these from consideration but did not alter the relationship of penicillins to early seizures (p < 0.02). The authors conclude that intraoperative (and early postoperative) penicillin antibiotic administration should be avoided, if possible, in patients undergoing craniotomy for supratentorial pathology.

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Phyo Kim, Thoralf M. Sundt Jr. and Paul M. Vanhoutte

✓ The purpose of this study was to examine the hypotheses that structural stiffening of the arterial wall contributes to chronic cerebral vasospasm, and that alteration in properties of smooth muscle takes place after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage and subsequent chronic vasospasm were induced in dogs by two cisternal injections of autologous blood (on Day 0 and Day 2). Vasospasm was confirmed by angiography performed on Day 0 and Day 7. Animals in the control group underwent angiography only. On Day 8, the mechanical properties of the basilar arteries were studied in vitro. Passive compliance, measured under total inhibition of spontaneous myogenic tone with diltiazem (10−4 M) plus papaverine (10−4 M) was smaller in the SAH group. The length-contraction curve was shifted to the left and the optimum length for maximum contraction (Lmax) was significantly shorter in the spastic blood vessels. The spontaneous myogenic tone was augmented in the SAH group, resulting in an increase in resting tension at each length. By contrast, the maximum contractions in response to KCl and uridine 5′-triphosphate were markedly reduced in the SAH group, without changes in sensitivity to these agents. These differences in mechanical properties were observed in rings both with and without endothelium. The results indicate that, in chronic vasospasm, stiffening of the noncontractile component of the vasculature takes place as well as alterations in the contractile component, both of which presumably contribute to the shift in resting length-tension relationship and length-contraction relationship of the artery. The decreased distensibility, the increase in resting tension, and the shortening of the Lmax all favor a smaller diameter of the artery after SAH, possibly contributing to vasospasm.

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John L. D. Atkinson, Thoralf M. Sundt Jr., O. Wayne Houser and Jack P. Whisnant

✓ A retrospective angiographic analysis was designed to extrapolate the frequency of angiographically defined asymptomatic intracranial aneurysms in the anterior circulation from a relatively unbiased clinical series. A total of 9295 angiograms were reviewed from January, 1980, to January, 1987, and, based on these, 278 patients with minimal bias for the presence of an aneurysm were selected. Three patients were found to have incidental aneurysms; thus, the angiographic frequency of patients with asymptomatic aneurysms in this series was 1%. This patient population is skewed toward the older age groups and probably over-represents the incidence of these aneurysms in the population at large. Comparing current subarachnoid hemorrhage statistics and the low frequency of asymptomatic aneurysms suggests that a larger percentage of these aneurysms than was previously thought subsequently rupture. This study contrasts sharply with previous reports quoting a high incidence of aneurysms, and significantly alters the concept and treatment of this disease.

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Fredric B. Meyer, Thoralf M. Sundt Jr., Nicolee C. Fode, Michael K. Morgan, Glen S. Forbes and James F. Mellinger

✓ In this study, 24 aneurysms occurring in 23 patients under the age of 18 years (mean 12 years) are analyzed. The male:female ratio was 2.8:1, and the youngest patient was 3 months old. Mycotic lesions and those associated with other vascular malformations were excluded. Forty-two percent of the aneurysms were located in the posterior circulation, and 54% were giant aneurysms. Presenting symptoms included subarachnoid hemorrhage in 13 and mass effect in 11. Several of these aneurysms were documented to rapidly increase in size over a 3-month to 2-year period of observation. All aneurysms were surgically treated: direct clipping was performed in 14; trapping with bypass in four; trapping alone in four; and direct excision with end-to-end anastomosis in two. The postoperative results were excellent in 21 aneurysms (87%), good in two (8%), and poor in one. The pathogenesis of cerebral aneurysms is reviewed.

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Phyo Kim, Robert R. Lorenz, Thoralf M. Sundt Jr. and Paul M. Vanhoutte

✓ The purpose of this study was to determine the cause of the loss of endothelium-dependent relaxation observed in chronic cerebral vasospasm. A bioassay system was developed to measure the release of endothelium-derived relaxing factor (EDRF) from canine basilar arteries. Subarachnoid hemorrhage (SAH) was induced in dogs by two injections of autologous blood into the cisterna magna. Angiograms were performed on the 7th day after SAH to check the presence of chronic vasospasm. The animals were sacrificed on the 8th day, and in vitro experiments were performed on rings harvested from the basilar artery. These confirmed loss of endothelium-dependent relaxation in response to bradykinin and arginine vasopressin in the group with SAH. The basilar arteries were perfused with modified Krebs-Ringer solution. The perfusate was bioassayed with a ring of coronary artery without endothelium (bioassay ring). The release of the EDRF was detected by relaxation of the bioassay ring contracted with prostaglandin F2α. Arginine vasopressin and bradykinin added to the perfusate upstream of the basilar artery caused concentration-dependent release of the EDRF. The direct effect of these peptides on the smooth muscle of the bioassay ring was to cause contraction. The release of the EDRF was identical in basilar arteries from the control and the SAH groups. These results indicate that the release of the EDRF is not impaired during chronic vasospasm, and thus that the loss of the endothelium-dependent relaxation is due to a decreased transfer of the EDRF or a reduced responsiveness of the smooth muscle to the factor.

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Douglas Chyatte, Nicolee C. Fode and Thoralf M. Sundt Jr.

✓ The management results in 244 patients admitted to one institution within 3 days of aneurysmal subarachnoid hemorrhage (SAH) from January, 1979, to December, 1985, were analyzed with respect to the timing of surgical intervention. Twenty-six patients died prior to surgery. Patients surviving to surgery were divided into three groups according to the interval between preadmission SAH and surgery: 0 to 3 days (85 cases), 4 to 9 days (83 cases), and 10 or more days (50 cases). Of the patients who were categorized neurologically into Botterell Grades 1 and 2 (Hunt and Hess Grades I to III) on admission, 87% had an excellent or good result on follow-up evaluation. Patients undergoing surgery 0 to 3 days after SAH had a statistically significant increase in the incidence of postoperative ischemic symptoms (p < 0.005), which was balanced by similar complications preoperatively in the 10-day post-SAH surgical group. Most rebleeds occurred before admission but delaying surgery did increase the risk of rebleeding in the hospital (p < 0.0005). Management morbidity and mortality occurred primarily as a direct result of a severe initial hemorrhage; thus, the measured benefits of early surgery were less than might have been predicted.

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Phyo Kim, Thoralf M. Sundt Jr. and Paul M. Vanhoutte

✓ To investigate the alteration of endothelium-dependent responses in chronic vasospasm after subarachnoid hemorrhage (SAH), experiments were carried out in the double-hemorrhage canine model. After the presence of vasospasm was confirmed by cerebral angiography on Days 0 and 7, pharmacological studies on the basilar artery were conducted in vitro on Day 8. In the SAH group, endothelium-dependent relaxation was abolished in response to arginine vasopressin and was significantly reduced in response to thrombin. Endothelium-independent relaxation in the SAH group was preserved in response to papaverine and was minimally reduced in response to sodium nitroprusside. Endothelium-dependent contraction in response to arachidonic acid, acetylcholine, the calcium ionophore A23187, adenosine diphosphate, mechanical stretching, and hypoxia persisted in the SAH group. The maximal contraction to KCl and uridine triphosphate, which is endothelium-independent, was diminished in the SAH group, but no changes in sensitivity were noted in the concentration-response relationships. A significant correlation was observed between the degree of vasospasm determined angiographically and the loss of endothelium-dependent relaxation. The loss of endothelium-dependent relaxation and the persistence of endothelium-dependent contraction suggest that the deterioration in the endothelium-dependent responses may be an important component in the pathogenesis of cerebral vasospasm.

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Clifford R. Jack Jr., Thoralf M. Sundt Jr., Nicolee C. Fode and Dale G. Gehring

✓ Between 1974 and 1982, an anastomosis between a pedicle of the superficial temporal artery (STA) and a cortical branch of the middle cerebral artery (MCA) was performed in 163 carotid systems in 157 patients for internal carotid artery occlusion in whom postoperative angiograms were available for analysis. The angiographic opacification of the arterial system was correlated with the patient's preoperative neurological function and stroke in the follow-up period.

From this analysis, the following observations were made: 1) 96% of bypasses were patent; 2) 80% of bypasses achieved a high or medium MCA filling score; 3) there was hypertrophy of the STA in 70% of the cases; 4) greater bypass filling occurred in hemispheres with nonvisualized preoperative collateral circulation than in those with readily visualized collateral flow; 5) a meaningful correlation between angiographically assessed postoperative bypass function and stroke rate was not possible because only four patients suffered an ipsilateral hemispheric stroke in the 8-year follow-up period; and 6) patients who were neurologically unstable before the procedure were at greatest risk for a stroke in the follow-up period. It is apparent that objective analysis of the effectiveness of an STA-MCA bypass, or any other form of extracranial bypass, must await the development of new diagnostic studies in which high-resolution three-dimensional quantification of cerebral blood flow is possible. These studies will necessarily be correlated with preoperative and follow-up clinical data.