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H. Lee Finney, Theodore S. Roberts and Robert E. Anderson

✓ The authors describe a giant intracranial internal carotid aneurysm in a patient with Marfan's syndrome. Treatment consisted of internal carotid ligation with subsequent thrombosis of the lesion. The patient's course was complicated by carotid arterial dissection and possible laminar thrombosis within the aneurysm increasing the size of the lesion. Three clinical syndromes, Marfan's, Ehlers-Danlos, and pseudoxanthoma elasticum, are discussed. The literature is reviewed with reference to the hazards of treatment of vascular pathology in patients with these connective tissue disorders.

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The Nd:YAG laser in neurosurgery

Part 2. Clinical studies: an adjunctive measure for hemostasis in resection of arteriovenous malformations

Robert E. Wharen Jr., Robert E. Anderson and Thoralf M. Sundt Jr.

✓ The Nd:YAG laser has been used safely to aid in the resection of 10 cases of parenchymal arteriovenous malformations (AVM's). The laser was, found helpful for: 1) defining the plane between the AVM and the brain; 2) coagulating any dural component of the AVM; and 3) achieving hemostasis of the bed following resection of the lesion. However, its overall benefit in the resection of AVM's remains to be determined, as it could not arrest active high-flow bleeding from the thin-walled vessels feeding the deep portion of the AVM. This was attributed to the inherent characteristics of these vessels, since the instrument has been effective in non-AVM arteries of similar dimensions containing contractile elements in the vessel walls. Future refinements in focusing instrumentation and operative technique should enhance its capabilities and usefulness. When used within the recommended power range, the Nd:YAG laser is safe and its penetration predictable. The fiberoptic cable light delivery system allows excellent mobility of the handpiece, but the protective eyewear laser-light filters reduce the available light to the surgeon. The instrument appears promising but more work is required.

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Bernard A. Coert, Robert E. Anderson and Fredric B. Meyer

Object. A nitric oxide (NO) donor that has been successfully used in the treatment of myocardial infarction, 3-morpholinosydnonimine (SIN-1), may be a potential neuroprotective agent. Production of NO in brain microsomes is dependent on the pH. The purpose of this study was to determine the efficacy of SIN-1 and its dependence on pH in vivo during periods of focal cerebral ischemia.

Methods. At 0.1 or 1 mg/kg, SIN-1 was administered to 54 Wistar rats 30 minutes before a 2-hour period of focal cerebral ischemia under moderate hypo-, normo-, and hyperglycemic conditions. Measurements of brain intracellular pH (pHi); regional cortical blood flow, and the redox state of nicotinamide adenine dinucleotide were obtained in three additional animals to confirm the effects of the serum glucose manipulations. The animals were killed at 72 hours after the ischemic period to obtain infarction volumes. Administration of SIN-1 significantly reduced infarction in normoglycemic animals and, to a lesser extent, in hyperglycemic animals, indicating that SIN-1 was less effective under hyperglycemic conditions. At either dose SIN-1 had no significant effect on infarction volume in moderately hypoglycemic animals because moderate hypoglycemia in itself significantly (p < 0.005) reduced infarction volume.

Conclusions. The NO donor SIN-1 may be a useful intraoperative cerebral protective agent. Furthermore, it is hypothesized that a mechanism that could explain the published discrepancies regarding the effects of NO donors in vivo may be affected by differences in ischemic brain acidosis.

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Bert A. Coert, Robert E. Anderson and Fredric B. Meyer

Object. A critical review of the literature indicates that the effects of nitric oxide synthase (NOS) inhibitors on focal cerebral ischemia are contradictory. In this experiment the authors methodically examined the dose-dependent effects of two NOS inhibitors and two NO donors on cortical infarction volume in an animal model of temporary focal cerebral ischemia simulating potential ischemia during neurovascular interventions.

Methods. Ninety-two Wistar rats underwent 3 hours of combined left middle cerebral artery and bilateral common carotid artery occlusion after having been anesthetized with 1% halothane. A nonselective NOS inhibitor, NG-nitro-l-arginine-methyl-ester (l-NAME), and two NO donors, 3-morpholinosydnonimine hydrochloride and NOC-18, DETA/NO, (Z)-1-[2(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, were administered intravenously 30 minutes before ischemia was induced. A selective neuronal NOS inhibitor, 7-nitroindazole (7-NI), was administered intraperitoneally in dimethyl sulfoxide (DMSO) 60 minutes before ischemia was induced. Two ischemic control groups, to which either saline or DMSO was administered, were also included in this study. Seventy-two hours after flow restoration, the animals were perfused with tetrazolium chloride for histological evaluation.

Cortical infarction volume was significantly reduced by 71% in the group treated with 1 mg/kg l-NAME when compared with the saline-treated ischemic control group (27.1 ± 37 mm3 compared with 92.5 ± 26 mm3, p < 0.05). The NOS inhibitor 7-NI significantly reduced cortical infarction volume by 70% and by 92% at doses of 10 and 100 mg/kg: 35.2 ± 32 mm3 (p < 0.05) and 9 ± 13 mm3 (p < 0.005), respectively, when compared with the DMSO-treated ischemic control group (119 ± 43 mm3). There was no significant difference between the saline-treated and DMSO-treated ischemic control groups. Treatment with NO donors did not significantly alter cortical infarction volume.

Conclusions. These results support an important role for NO in ischemic neurotoxicity and indicate that neuronal NOS inhibition may be valuable in reducing cortical injury in patients suffering temporary focal cerebral ischemia during neurovascular procedures.

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Robert E. Anderson, Alice M. Bowron and Thoralf M. Sundt Jr.

✓ A combination of the Sundt-Kees reinforcing aneurysm clip applied to a Drake aneurysm clip in a piggyback fashion was studied for possible defects due to corrosion and or tissue toxicity. These two clips, which are made of similar metal (301 stainless steel), showed little or no defects when immersed in 5% saline or when implanted in rats for 6 months. This study demonstrates that clips made of similar metals can be used piggyback in patients without ill effects provided that they are carefully handled to avoid any abrasion or misbends which could conceivably lead to corrosion.

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Brian A. Iuliano, Robert E. Anderson and Fredric B. Meyer

✓ The authors examined the effects of both intermittent reperfusion and nitric oxide synthase (NOS) inhibition, caused by NG-nitro-l-arginine methyl ester (l-NAME) during episodes of focal cerebral ischemia induced to simulate the neurosurgical setting. Seventy-eight Wistar rats underwent single (60 minutes of ischemia) or repetitive (four 15-minute periods of ischemia separated by 5 minutes of reperfusion) episodes of middle cerebral artery occlusion while under anesthesia (1.0% halothane). Twenty-four hours after the procedure, the animals were given neurological examinations and then sacrificed for histological preparation and examination. The intermittent reperfusion groups tended to have smaller mean cortical infarctions. There was also a trend showing a decrease in infarction size in groups given l-NAME. The combination of intermittent reperfusion and preischemic administration ofl-NAME (10 mg/kg) resulted in a 65% reduction in infarction size (p < 0.05) when compared to that caused by 60 minutes of single occlusion without l-NAME. The use of NOS inhibition combined with intermittent reperfusion may be a technique to provide intraoperative cerebral protection during neurovascular procedures that require temporary vascular occlusion.

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Jonathan A. Friedman, Robert E. Anderson and Fredric B. Meyer

Understanding the physiological mechanisms of cerebral blood flow (CBF) is of great importance to neurosurgeons engaged in the management of patients with cerebrovascular disease. Over the past 50 years, techniques to measure CBF and mathematical methods to calculate CBF have evolved substantially. For the cerebrovascular surgeon, intra-operative CBF monitoring is an important adjunct in certain intra- and extracranial procedures. The authors review current techniques in use for the intraoperative measurement of CBF.

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Marc S. Goldman, Robert E. Anderson and Fredric B. Meyer

✓ There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 ± 0.89 sq mm), 90-minute (1.08 ± 1.02 sq mm), and 120-minute (8.72 ± 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 ± 3.10 sq mm), 90-minute (11.54 ± 2.68 sq mm), or 120-minute (30.43 ± 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair.

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M. Peter Heilbrun, O. Howard Reichman, Robert E. Anderson and Theodore S. Roberts

✓ Regional cerebral blood flow (rCBF) studies were performed during the postoperative period on 16 patients with internal carotid occlusions and inaccessible stenoses, and middle cerebral artery occlusion and stenoses, who underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses. The intra-arterial xenon method with selective application of the xenon bolus through the internal carotid and the newly established superficial temporal channel has allowed comparison of the flow provided by the pathological input with flow through the new input. The results show that initial rCBF (rCBF1) was globally reduced in all patients to a mean of 28.4 ± 11.9 ml/100 gm/min at a mean pCO2 of 29.6 ± 9.55 mm Hg. Patients with transient ischemic attacks (TIA) and minor strokes with minimal residua (RIND) had a mean rCBF1 of 30.4 ± 11.6 ml/100 gm/min at a mean pCO2 of 30 ± 10 mm Hg, while patients with completed strokes had a mean rCBF1 of 25.0 ± 12.4 ml/100 gm/min at a mean pCO2 of 29.1 ± 8.8 mm Hg. There was no significant difference between these two groups. This finding suggests that in this small group of patients with TIA's and RIND's, the cause of the stroke is probably related more to decreased perfusion than embolus, and may explain why these patients' symptoms improve after STA-MCA anastomosis. The results of this study suggest that in addition to an inaccessible lesion, global or focal decreased rCBF is a necessary criterion in the definition of indications for intracranial revascularization procedures.