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Recurrence of Arteriovenous Malformations

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Weekend versus weekday admission mortality

Roberto C. Heros

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The effects of gammahydroxybutyric acid on canine cerebral blood flow and metabolism

Kent W. Baumann, Neal F. Kassell, Julie Olin, and Thoru Yamada

✓ Gammahydroxybutyric acid has been proposed as an alternative to high-dose barbiturate therapy for protecting the brain after ischemic or traumatic insult. The cerebral and systemic metabolic and vascular effects of gammahydroxybutyrate and its lactone analogue, gammabutyrolactone, are addressed in this paper. In anesthetized normal dogs, gammahydroxybutyrate or gammabutyrolactone was infused intravenously at a rate of 1 gm/kg/hr. Cerebral blood flow (CBF) decreased progressively with increasing doses of either agent. Cerebral metabolic rate of oxygen (CMRO2) increased initially with gammahydroxybutyrate, but not following gammabutyrolactone. Reduction in CBF exceeded that of CMRO2 at all doses in both series.

The primary systemic effect noted was a severe, lethal metabolic acidosis resulting from infusion of gammabutyrolactone. Gammahydroxybutyrate did not cause a similar acidosis. The imbalance of the CBF-CMRO2 reduction following gammahydroxybutyrate administration suggests that it has no advantage over barbiturates in the management of patients with cerebral vascular insufficiency or intracranial hypertension.

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Comparison of sodium thiopental and methohexital for high-dose barbiturate anesthesia

David J. Boarini, Neal F. Kassell, and Hans C. Coester

✓ High-dose sodium thiopental is frequently used in neuroanesthesia. The authors performed a study to compare a shorter-acting barbiturate, methohexital, to sodium thiopental in producing high-dose barbiturate anesthesia. In two groups of five mongrel dogs each, regional cerebral blood flow (CBF) was determined using the radioactive-microsphere technique, and cardiovascular parameters were measured before, during, and 1 hour after a 1½hour period of deep barbiturate anesthesia with either sodium thiopental or methohexital. Doses of the barbiturates were adjusted to produce electroencephalogram burst suppression of greater than 30 seconds.

Both agents produced a similar degree of cardiac depression, reduction in CBF, and decrease in cerebral metabolic rate of oxygen (CMRO2). Changes in cerebral and peripheral vascular resistance indicated that methohexital caused less vasoconstriction than sodium thiopental. When the barbiturate infusions were discontinued, CMRO2 and CBF returned more rapidly toward control values in the methohexital group than in the thiopental group. The more rapid recovery time and decrease in cerebral vascular resistance with methohexital suggest that it may have some advantage over sodium thiopental during certain neurosurgical procedures.

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Nature of the vasoactive substance in CSF from patients with subarachnoid hemorrhage

Tomio Sasaki, Takao Asano, Kintomo Takakura, Keiji Sano, and Neal F. Kassell

✓ The purpose of this experiment was to study the nature of vasoactive substance in cerebrospinal fluid (CSF) from patients with aneurysmal subarachnoid hemorrhage. The authors have examined the effects of disulfide bond-reducing agents, a sulfhydryl group oxidizing agent, and specific antagonists of so-called “classical” neurotransmitters on the in vitro isometric contraction of canine basilar arterial strips induced by bloody human CSF. The disulfide bond-reducing agents dithiothreitol (10−4 M) and dithioerythritol (10−4 M) suppressed the contraction induced by bloody CSF by an average of 40.3% and 61.2%, respectively. This suppression was achieved under conditions that did not alter KCl-induced contraction. The sulfhydryl group oxidizing agent, 5,5′-dithiobis-(2-nitrobenzoic acid), 10−4 M, reversed the inhibitory effect of dithioerythritol on the contractile response to bloody CSF. No significant suppression of any response in any preparation was observed with methysergide (10−7 M), mepyramine (10−7 M), phenoxybenzamine (10−5 M), propranolol (10−6 M), or atropine (10−6 M).

These results indicate that disulfide bonds in the arterial smooth-muscle cells are involved in the contractile responses of canine basilar artery to bloody CSF. Prostaglandins, hemoglobin, and lipid hydroperoxides may all be spasmogens in bloody CSF, while serotonin, histamine, norepinephrine, and acetylcholine are probably not involved.

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Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage

Preliminary observations from the Cooperative Aneurysm Study

Neal F. Kassell, James C. Torner, and Harold P. Adams Jr.

✓ Antifibrinolytic therapy remains a controversial issue in the management of subarachnoid hemorrhage (SAH). The relationship of antifibrinolytic therapy with mortality, rebleeding, ischemia, hydrocephalus, and clotting abnormalities was studied in 672 patients in the International Cooperative Study on the Timing of Aneurysm Surgery. The patients with antifibrinolytic therapy had a significantly lower rebleeding rate, but higher rates of ischemic deficits and hydrocephalus. The net result was no difference in mortality in the 1st month following the initial SAH. Further clinical trials are needed to determine the overall effects of antifibrinolytic therapy.

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Vasospasm

Aaron S. Dumont, Michael Chow, and Neal F. Kassell

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Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage

Richard S. Polin, Murad Bavbek, Mark E. Shaffrey, Kevin Billups, Christopher A. Bogaev, Neal F. Kassell, and Kevin S. Lee

Object. The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium.

Methods. A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule—1 (ICAM—1), vascular adhesion molecule—1 (VCAM-1), and L-selectin.

Levels of soluble forms of E-selectin (p = 0.0013), ICAM-1 (p = 0.0001), and VCAM-1 (p = 0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of normal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p = 0.044) were highest in patients who later developed moderate or severe vasospasm.

Conclusions. Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.

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Enhanced endogenous antioxidant activity and inhibition of cerebral vasospasm in rabbits by pretreatment with a nontoxic endotoxin analog, monophosphoryl lipid A

Tomikatsu Toyoda, Aij-Lie Kwan, Murad Bavbek, Neal F. Kassell, John E. Wanebo, and Kevin S. Lee

Object. Monophosphoryl lipid A (MPL) and diphosphoryl lipid (DPL) are derivatives of the lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595. Monophosphoryl lipid A is relatively nontoxic and can stimulate the natural defense or immune system. Diphosphoryl lipid is relatively toxic; however, at higher concentrations, it can also stimulate an immune response. The purpose of the present study was to determine the effects of these endotoxin analogs on cerebral vasospasm after the onset of subarachnoid hemorrhage (SAH) in rabbits.

Methods. Intrathecal administration of MPL or DPL (5 µg/kg) was performed immediately before and 24 hours after induction of SAH in New Zealand White rabbits. Forty-eight hours after induction of SAH, the animals were killed by perfusion fixation for morphometric analyses of vessels or perfused with saline and assayed for superoxide dismutase (SOD) activity. Additional rabbits were administered MPL or DPL and killed 24 hours later for assessment of SOD activity; no SAH was induced in these animals.

Experimental SAH elicited spasm of the basilar arteries in each group. Vasospasm was markedly attenuated in animals treated with MPL (p < 0.01 compared with vehicle-treated animals), but not in animals treated with DPL. A substantial reduction in SOD activity in the basilar artery accompanied the vasospasm; this loss of activity was significantly blocked by treatment with MPL, but not DPL. In animals that were not subjected to experimental SAH, MPL elicited a significant increase in SOD activity over basal levels, whereas DPL was ineffective.

Conclusions. These data provide evidence of a marked protective effect of the endotoxin analog MPL against vasospasm. Although the mechanism(s) responsible for the protective effect of MPL remains to be verified, an enhancement of basal antioxidant activity and an inhibition of SAH-induced loss of this activity are attractive candidates. An MPL-based therapy could represent a useful addition to current therapies for SAH-induced cerebral injury.

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Efficacy of transluminal angioplasty for the management of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Richard S. Polin, Volker A. Coenen, Carolyn Apperson Hansen, Peter Shin, Mustafa K. Baskaya, Anil Nanda, and Neal F. Kassell

Object. Transluminal angioplasty has become a widely used adjunct therapy to medical management of symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH). Despite anecdotal reports of universal, angiographically confirmed reversal of vasospasm and high rates of clinical improvement, no rigorous examination of the efficacy of this procedure has been conducted. In this study the authors assess the efficacy of the aforementioned procedure.

Methods. Thirty-eight patients enrolled as part of the North American trial of tirilazad in aneurysmal SAH underwent transluminal angioplasty for symptomatic cerebral vasospasm. Fifty-three percent of these patients showed good recovery or moderate disability based on their 3-month Glasgow Outcome Scale score.

Among the 38 patients who underwent angioplasty, the severity and type of vasospasm, use of papaverine in addition to balloon angioplasty, timing of treatment, and dose of study drug did not have an effect on the outcome. The results of their neurological examinations improved in only four of the 38 patients immediately after the procedure. A conditional logistic regression analysis was performed in which these patients were compared with individuals matched for age, sex, dose of study drug, admission neurological grade, and modified Glasgow Coma Scale score at the time of angioplasty. No effect on favorable outcomes was found for this procedure.

Conclusions. Transluminal cerebral angioplasty is very effective in reversing angiographically confirmed vasospasm, and anecdotal reports of its clinical utility are numerous. However, in this report the authors conclude that its superiority to medical management for symptomatic cerebral vasospasm is questionable.