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Neal F. Kassell

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Thomas W. Langfitt and Neal F. Kassell

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Focused ultrasound surgery

W. Jeffrey Elias and Neal F. Kassell

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Transmission of Increased Intracranial Pressure

I. Within the Craniospinal Axis

Thomas W. Langfitt, James D. Weinstein, and Neal F. Kassell

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Tomikatsu Toyoda, Neal F. Kassell, and Kevin S. Lee

Object. Inflammatory responses and oxygen free radicals have increasingly been implicated in the development of ischemic brain injury. In some cases, an attenuation of inflammation or free-radical injury can provide tissue protection. Diphosphoryl lipid A (DPL) is a detoxified derivative of a lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595, which is capable of stimulating the immune system without eliciting direct toxic effects. In this study the authors examined the influence of preconditioning with DPL on ischemia/reperfusion injury in rats.

Methods. Sprague—Dawley rats were injected intravenously with either DPL or vehicle. Twenty-four hours later, some animals were tested for superoxide dismutase (SOD) activity. Others were subjected to a 3-hour period of focal cerebral ischemia and, after a reperfusion period of 24 hours, were killed. Infarction volume, SOD activity, and myeloperoxidase (MPO) activity were assayed in the postischemic animals.

Pretreatment with DPL produced significant reductions in cerebral infarction and MPO activity in the ischemic penumbra. A significant enhancement of basal SOD activity was observed 24 hours after DPL treatment (that is, before ischemia), and a further enhancement of SOD activity was seen in the ischemic penumbra 24 hours after reperfusion.

Conclusions. These data provide the first evidence of a neuroprotective effect of preconditioning with DPL in an in vivo model of cerebral ischemia. Although the precise mechanisms through which DPL exerts its neuroprotective influence remain to be established, an inhibition of the complex inflammatory response to ischemia and an enhancement of endogenous antioxidant activity are leading candidates.

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Unruptured aneurysms

Aaron S. Dumont, Giuseppe Lanzino, and Neal F. Kassell

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Giuseppe Lanzino, Neal F. Kassell, and the Participants

Object. To test the safety and efficacy of high-dose (15 mg/kg/day) tirilazad mesylate in women suffering from aneurysmal subarachnoid hemorrhage (SAH), a prospective randomized, double-blind, vehicle-controlled trial (parallel to the one conducted in Europe, Australia, New Zealand, and South Africa) was performed at 65 North American neurosurgical centers.

Methods. Of the 832 patients who were randomized, 823 received at least one dose of tirilazad (410 patients) or placebo vehicle containing citrate (413 patients). The two groups were similar with respect to their prognostic factors for overall outcome and delayed cerebral ischemia. There were no differences in medical and surgical interventions including hyperdynamic therapy (intentional hypervolemia, induced hypertension, and/or hemodilution) between the two treatment groups.

In contrast to the accompanying study, the protocol for the North American study was formally amended, in that a sequential analysis of the primary efficacy end point, mortality rate at 91 days postdosing, was performed. This analysis revealed a statistically significant difference in mortality rates, favoring the study drug, among patients who were neurological Grade IV or V at admission (24.6% compared with 43.4% in the placebo-treated group, p = 0.016). No significant differences, however, were found when the entire patient population was considered (15.6% in the placebo-treated group and 13% in the tirilazad-treated group). Other major and secondary end points, which included rate of favorable outcome (74% in the placebo-treated group and 71% in the tirilazad-treated group); symptomatic vasospasm (38% in the placebo-treated group and 35% in the tirilazad-treated group); and vasospasm severity (severe symptomatic vasospasm in 14% of patients in both groups), were also not significantly different between the two groups. In patients with neurological Grades I through III, rates of favorable outcome advantageous to the vehicle-treated group were observed (83.3% compared with 76.7%, p = 0.04).

Conclusions. High-dose tirilazad mesylate is well tolerated in women with aneurysmal SAH. Sequential analysis revealed a significant reduction in mortality rates among patients with neurological Grades IV and V, favoring the study drug and confirming the same effect observed in male patients in previous large studies. No beneficial effect was observed in patients who were in a good neurological grade at admission.

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Marc N. Pilipuf, John C. Goble, and Neal F. Kassell

✓ The authors have developed a noninvasive head immobilization system for use in neuroimaging (magnetic resonance imaging, computerized tomography, single photon emission computerized tomography, and projection angiography), neurosurgical planning, and neurosurgery. These diagnostic and surgical procedures require patient immobilization, reproducible patient positioning, and anatomical localization. The thermoplastic system described in this technical note addresses each of these requirements with a high degree of accuracy and with no bone fixation. The reproducibility of positioning and effectiveness of immobilization were evaluated using nine healthy volunteers during repeated sessions of magnetic resonance imaging. The mean axial displacement for repeated positioning was 0.6 mm (variance 0.1 mm); the mean displacement during robust patient motion in the axial direction was 1.8 mm (variance 0.9 mm).

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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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Nader Pouratian, Neal F. Kassell, and Aaron S. Dumont

Intracerebral hemorrhage (ICH) is a lingering cause of significant mortality and morbidity rates in contemporary society. Despite its established burden, considerably less investigative attention has been devoted to the study of ICH than other forms of stroke. Only a limited number of clinical studies have been performed to examine the surgical (both craniotomy and minimally invasive) and medical management of patients with ICH. No consistently efficacious strategies have been identified through such investigations. Limitations in study design and execution have universally impaired the interpretation and impact of available data. Management of ICH unfortunately remains heterogeneous across institutions, and it continues to suffer from the lack of proven medical and surgical effectiveness. Urgently needed are further prospective randomized controlled trials in which investigators consider the shortcomings of previous endeavors in the management of ICH. In the present article the authors review the current management practices of ICH, discuss the controlled trials, and highlight recent trials and future avenues of further study.