William J. Perkins

Awake craniotomy for aggressive resection of primary gliomas located in eloquent brain

OBJECTIVE To determine with intraoperative neurologic and language examinations the maximal tumor resection achievable with acceptable postoperative neurologic dysfunction in patients undergoing awake stereotactic glial tumor resection in eloquent regions of the brain. PATIENTS AND METHODS Between October 1995 and December 2000, 65 patients underwent frameless stereotactic resection of glial tumors located in functioning tissue. During the resection, continuous examinations by a neurologist and speech pathologist were performed. The goal of surgery was to resect the maximum neurologically permissible tumor volume defined on preoperative T2 imaging. Tumor resection was stopped at the onset of neurologic dysfunction. Novel segmentation software was used to measure tumor cytoreduction based on pre- and postoperative magnetic resonance imaging. All patients underwent 3-month postoperative neurologic examinations to determine functional outcomes. RESULTS The cortical and subcortical white matter tracts at risk for injury were the left frontal operculum in 15 patients, the central lobule in 38, the insula in 11, and the left angular gyrus in 1. Thirty-four (52%) had a greater than 90% reduction in T2 signal postoperatively. In 26 patients thought to have low-grade tumors based on preoperative imaging, 12 proved to have grade 3 gliomas. Forty-eight patients (74%) developed intraoperative deficits; 34 (71%) recovered to a modified Rankin grade of 0 or 1 at 3 months postoperatively, 11 (23%) achieved a modified Rankin grade of 2, and 3 patients (6%) achieved a modified Rankin grade of 3 or 4 at 3-month follow-up. There was no operative mortality; 17 patients (26%) died from tumor progression during the follow-up period. CONCLUSIONS Combining frameless computer-guided stereotaxis with cortical stimulation and repetitive neurologic and language assessments facilitates tumor resection in functioning brain regions. Resecting tumor until the onset of neurologic deficits allows for a good functional recovery. Imaging software can objectively and accurately measure preoperative and postoperative tumor volumes.

The Effects of Dizocilpine Maleate (MK-801), an Antagonist of the N-Methyl-D-Aspartate Receptor, on Neurologic Recovery and Histopathology Following Complete Cerebral Ischemia in Primates

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 μg/kg i.v. over 5 min, followed by an infusion of 150 μg/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.

Remote Cerebellar Hemorrhage after Supratentorial Surgery

OBJECTIVE Remote cerebellar hemorrhage (RCH) is an infrequent and poorly understood complication of supratentorial neurosurgical procedures. We retrospectively compared 42 patients who experienced RCH with a case-matched control cohort, to delineate risk factors associated with the occurrence of this complication. METHODS Between 1988 and 2000, 42 patients experienced RCH after supratentorial neurosurgical procedures at our institution. Diagnoses were made on the basis of postoperative computed tomographic or magnetic resonance imaging findings in all cases. The medical records for these patients were reviewed and compared with those for a control cohort of 43 patients, matched for age, sex, surgical lesion, and type of craniotomy, who were treated during the same period. RESULTS RCH most commonly occurred after frontotemporal craniotomies for unruptured aneurysm repair or temporal lobectomy and was frequently an incidental finding on postoperative computed tomographic scans. However, some cases of RCH were associated with significant morbidity, and two patients died. Preoperative aspirin use and elevated intraoperative systolic blood pressure were significantly associated with RCH (P = 0.026 and P = 0.036, respectively). Pathological findings for two cases demonstrated hemorrhagic infarctions in both. CONCLUSION RCH most commonly follows supratentorial neurosurgical procedures, performed with the patient in the supine position, that involve opening of cerebrospinal fluid cisterns or the ventricular system (such as unruptured aneurysm repair or temporal lobectomy). Preoperative aspirin use and moderately elevated intraoperative systolic blood pressure are potentially modifiable risk factors associated with the development of RCH. Although RCH can cause death or major morbidity, most cases are asymptomatic or exhibit a benign course. Cerebellar “sag” as a result of cerebrospinal fluid hypovolemia, causing transient occlusion of superior bridging veins within the posterior fossa and consequent hemorrhagic venous infarction, is the most likely pathophysiological cause of RCH.

Evaluation of a forced-air system for warming hypothermic postoperative patients.

Thirty adult surgical patients oral temperature ≤35.0°C were randomized into two groups. Group 1 patients were covered with cotton blankets warmed to 37.0°C, and group 2 patients were treated with a forced-air warming system. Mean oral temperature on admission to the recovery room was the same in both groups (34.3°C). Oral temperature and the presence or absence of shivering were recorded at 15-min intervals. After application of the selected warming method, patients in group 2 were warmer at all time intervals. Mean temperatures in the forced-air heating group and in group 1 were, respectively, 34.8°C and 34.3°C (P < 0.05) at 15 min; 35.0°C and 34.2°C (P < 0.01) at 30 min; 35.2°C and 34.5°C (P < 0.05) at 45 min; 35.8°C and 34.7°C (P < 0.001) at 60 min; 36.0°C and 35.0°C (P < 0.01) at 75 min; and 36.0°C and 35.0°C (P < 0.01) at 90 min. The incidence of shivering was significantly greater in group 1 at 15 and 45 min. In addition, time spent in the recovery room was significantly greater in group 1 than in group 2, 156.0 min versus 99.7 min (P < 0.003).

F-actin stabilization increases tension cost during contraction of permeabilized airway smooth muscle in dogs

1 Dynamic actin reorganization involving actin polymerization and depolymerization may play an important functional role in smooth muscle. 2 This study tested the hypothesis that F‐actin stabilization by phalloidin increases tension cost (i.e. ATP hydrolysis rate per unit of isometric force) during Ca2+‐induced activation of Triton X‐100‐permeabilized canine tracheal smooth muscle. 3 Adenosine 5′‐triphosphate (ATP) hydrolysis rate was quantified using an enzyme‐coupled NADH fluorometric technique, regulatory myosin light chain (rMLC) phosphorylation was measured by Western blot analysis, and maximum unloaded shortening velocity (Vmax) was estimated by interpolation of the force‐velocity relationship to zero load during isotonic loading. 4 Maximal activation with 10 μm free Ca2+ induced sustained increases in isometric force, stiffness, and rMLC phosphorylation. However, the increase in ATP hydrolysis rate initially reached peak values, but then declined to steady‐state levels above that of the unstimulated muscle. Thus, tension cost decreased throughout steady‐state isometric force. 5 Following incubation of permeabilized strips with 50 μm phalloidin for 1 h, the increases in isometric force and stiffness were not sustained despite a sustained increase in rMLC phosphorylation. Also, after an initial decline, tension cost increased throughout activation. Phalloidin had no effect on Vmax during steady‐state isometric force or on rMLC phosphorylation. 6 These findings suggest that dynamic reorganization of actin is necessary for optimal energy utilization during contraction of permeabilized airway smooth muscle.

Evaluation of the glutamate antagonist dizocilipine maleate (MK-801) on neurologic outcome in a canine model of complete cerebral ischemia: correlation with hippocampal histopathology

This study was designed to determine if dizocilipine maleate (MK-801), administered following 11 min of complete ischemia in dogs, could favorably alter neurologic outcome and hippocampal damage. Eighteen dogs were anesthetized and subjected to complete cerebral ischemia by temporary occlusion of the ascending aorta and the venae cavae via a thoracotomy. Five min postischemia, 9 dogs were given dizocilipine 150 micrograms/kg, followed by an infusion of 1.25 microgram/kg/min for 8 h. Control dogs were given equal volumes of placebo. Dogs were evaluated neurologically at 24, 48, and 72 h; thereafter, the brains were perfused, fixed and harvested. There was no significant difference in outcome between dizocilipine- and placebo-treated dogs: 5 of 9 given dizocilipine were normal, 1 was mildly injured and 3 were severely injured or dead. In the control animals given placebo, 3 of 9 were normal, 2 were mildly injured and 4 were moderately to severely injured. Histopathologic examination was limited to the hippocampus. CA1 and CA2,3,4 pyramidal neurons were graded according to degree of injury on a 5-point scale. There were no differences in histopathologic grades between the two groups. However, in both groups combined there was a significant correlation between neurologic outcome grade and histopathologic grade. The only notable systemic effect of dizocilipine appeared to be prolonged sedation which extended beyond 24 h postischemia but was not evident at 48 h postischemia. The authors conclude that more outcome studies in more sensitive models are needed.

Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs.

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione

This study tested the hypothesis that the NO donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) in part by a cGMP-independent process that involves reversible oxidation of intracellular thiols. GSNO caused a concentration-dependent relaxation in ACh-contracted strips (EC50 ∼1.2 μM) accompanied by a concentration-dependent increase in cytosolic cGMP concentration ([cGMP]i). The soluble guanylate cyclase inhibitor methylene blue prevented the increase in [cGMP]iinduced by 1 and 10 μM GSNO, but isometric force decreased by 10 ± 4 and 55 ± 3%, respectively. After recovery of [cGMP]i to baseline, GSNO-induced relaxation persisted during continuous ACh stimulation. Dithiothreitol caused a rapid recovery of isometric force to values similar to those obtained with ACh alone in these strips. We conclude that GSNO relaxes CTSM contracted by ACh in part by oxidation of intracellular protein thiols.

Correlation of regional cerebral blood flow with ischemic electroencephalographic changes during sevoflurane-nitrous oxide anesthesia for carotid endarterectomy.

Background Carotid endarterectomy necessitates temporary unilateral carotid artery occlusion. Critical regional cerebral blood flow (rCBF) has been defined as the rCBF below which electroencephalographic (EEG) changes of ischemia occur. This study determined the rCBF50, the rCBF value at which 50% of patients will not demonstrate EEG evidence of cerebral ischemia with carotid cross‐clamping. Methods Fifty‐two patients undergoing elective carotid end‐arterectomy were administered 0.6–1.2% (0.3–0.6 minimum alveolar concentration) sevoflurane in 50% nitrous oxide (N2 O). A 16‐channel EEG was used for monitoring. The washout curves from intracarotid133 Xenon injections were used to calculate rCBF before and at the time of carotid occlusion by the half‐time (t1/2) technique. The quality of the EEG with respect to ischemia detection was assessed by an experienced electroencephalographer. Results Ischemic EEG changes developed in 5 of 52 patients within 3 min of carotid occlusion at rCBFs of 7, 8, 11, 11, and 13 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1. Logistic regression analysis was used to calculate an rCBF50 of 11.5 +/‐ 1.4 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1 for sevoflurane. The EEG signal demonstrated the necessary amplitude, frequency, and stability for the accurate detection of cerebral ischemia in all patients within the range of 0.6–1.2% sevoflurane in 50% N2 O. Conclusions The rCBF50 of 0.6–1.2% sevoflurane in 50% N2 O, as determined using logistic regression analysis, is 11.5 +/‐ 1.4 ml [center dot] 100 g sup ‐1 [center dot] min sup ‐1. Further, in patients anesthetized in this manner, ischemic EEG changes due to carotid occlusion were accurately and rapidly detected.

Airway management in patients who develop neck hematomas after carotid endarterectomy.

BACKGROUND: Progressive airway compromise from neck hematoma and edema is a feared complication of carotid endarterectomy (CEA). Despite this, the relationship of airway management technique to patient outcome has not been systematically studied in this population. We report the rate of successful airway management using various techniques in post-CEA patients. METHODS: A 10-year retrospective analysis was conducted to identify patients requiring airway management for neck exploration within 72 hours after CEA at Mayo Clinic, Rochester, MN. RESULTS: Three thousand two hundred twenty-five patients underwent CEA over a 10-year period at our institution. Forty-four (1.4%) required neck exploration for hematoma, and 42 of these required airway management immediately before neck exploration surgery. (The tracheal tube had not been removed after CEA in the remaining 2 patients.) The average interval between the completion of CEA and return to the operating room for hematoma evacuation was 6.0 ± 6.0 hours (mean ± sd; range, <1-32 hours). Fiberoptic airway management, performed before the induction of anesthesia, was successful in 15 of 20 patients (75%) and, in patients in whom fiberoptic tracheal intubation failed, direct laryngoscopy (DL) was successful in all 5 (3 before and 2 after the induction of general anesthesia). In the remaining 22 patients, DL was used as the initial management technique without a trial of fiberoptic intubation. DL was successful in 5 of 7 patients (71%) when performed before induction of general anesthesia and was successful in 13 of 15 patients (87%) when performed after induction of general anesthesia. Hematoma decompression facilitated DL in 3 of 4 failures of DL; tracheostomy was performed in the remaining patient. An arterial site of bleeding was subsequently identified in 36% of patients in whom no difficulty was encountered during laryngoscopy for hematoma evacuation versus 6% in whom difficulty was noted (P = 0.03). In 36 of 44 patients (82%), the tracheal tube was removed within 24 hours of surgery for neck exploration. No adverse events related to airway management were noted. There were no deaths at 2 weeks after hematoma evacuation. CONCLUSIONS: Multiple techniques resulted in successful airway control both before and after the induction of general anesthesia. Tracheal intubation was accomplished with both fiberoptic visualization and DL. In instances of poor direct visualization of the glottis, decompression of the airway by opening of the surgical incision may facilitate intubation of the trachea.