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William J. Mack, J Mocco, Daniel J. Hoh, Judy Huang, Tanvir F. Choudhri, Kurt T. Kreiter, Alan Lozier, Marcello Opperman, Alexander Poisik, Joshua Yorgason, Robert A. Solomon, Stephan A. Mayer and E. Sander Connolly Jr.

Object. Although upregulated adhesion molecule expression has been demonstrated in experimental models of subarachnoid hemorrhage (SAH) and in the cerebrospinal fluid of patients with aneurysmal SAH, the clinical significance of these proinflammatory findings remains unclear. The authors hypothesize that 1) serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) are increased in all patients with aneurysmal SAH shortly after the hemorrhagic event, and 2) elevated soluble ICAM-1 values are associated with poor patient outcome, even when controlling for the severity of the initial hemorrhagic insult.

Methods. One hundred one patients were prospectively enrolled and stratified according to their admission Hunt and Hess grade and functional status at discharge (modified Rankin Scale [mRS] score). Soluble ICAM-1 levels were determined every other day for 12 days post-SAH by using the enzyme-linked immunosorbent assay. Early soluble ICAM-1 levels (post-SAH Days 2–4) were increased compared with levels in control patients without SAH (p < 0.05). Patients with aneurysmal SAH who had a poor outcome (mRS Grades 4–6) had significantly higher soluble ICAM-1 levels over the first 2 weeks post-SAH compared with patients who had a good outcome (mRS Grades 0–3, p < 0.01). This association with outcome was predicted by late increases (Day 6, p = 0.07; Days 8–12, p < 0.05) rather than early increases (p = not significant) and was best seen in patients with Hunt and Hess Grades I and II, in whom only those with poor outcomes demonstrated delayed ICAM-1 elevations (p < 0.05).

Conclusions. These data demonstrate a correlation between soluble ICAM-1 levels and functional outcome following aneurysmal SAH that appears to be, at least in part, independent of the initial hemorrhage.

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J Mocco, William J. Mack, Grace H. Kim, Alan P. Lozier, Ilya Laufer, Kurt T. Kreiter, Robert R. Sciacca, Robert A. Solomon, Stephan A. Mayer and E. Sander Connolly Jr.

Object. Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule—1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1–2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm.

Methods. Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, ≤ 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade—matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade—matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001).

Conclusions. These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.

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William J. Mack, Ryan G. King, Andrew F. Ducruet, Kurt Kreiter, J Mocco, Ahmed Maghoub, Stephan Mayer and E. Sander Connolly Jr.

Object

Elevated intracranial pressure (ICP) is an important consequence of aneurysmal subarachnoid hemorrhage (SAH) that often results in decreased cerebral perfusion and secondary clinical decline. No definitive guidelines exist regarding methods and techniques for ICP management following aneurysm rupture. The authors describe monitoring practices and outcome data in 621 patients with aneurysmal SAH admitted to their neurological intensive care unit during an 8-year period (1996–2003).

Methods

A fiberoptic catheter tip probe or external ventricular drain (EVD) was used to record ICP values. The percentage of monitored patients varied, as expected, according to admission Hunt and Hess grade (p < 0.0001). Intracranial pressure monitoring devices were used in 27 (10%) of 264 Grade I to II patients, 72 (38%) of 189 Grade III patients, and 134 (80%) of 168 Grade IV to V patients. There was a strong propensity to favor transduced ventricular drains over parenchymal fiberoptic bolts, with the former used in 221 (95%) of 233 cases. This tendency was particularly strong in the poor-grade cohort, in which EVDs were placed in 99% of monitored individuals. The rates of cerebrospinal fluid infection in patients in whom ICP probes (0%) and ventricular drains (12%) were placed accorded with those in the literature.

Conclusions

Following aneurysmal SAH, ICP monitoring prevalence and techniques differ with respect to admission Hunt and Hess grade and are associated with the patient's functional status at discharge.

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J Mocco, William J. Mack, Andrew F. Ducruet, Ryan G. King, Michael E. Sughrue, Alexander L. Coon, Sergei A. Sosunov, Robert R. Sciacca, Yuan Zhang, Henry C. Marsh Jr., David J. Pinsky and E. Sander Connolly Jr.

Object

Postischemic cerebral inflammatory injury has been extensively investigated in an effort to develop effective neuroprotective agents. The complement cascade has emerged as an important contributor to postischemic neuronal injury. Soluble complement receptor Type 1 (sCR1), a potent inhibitor of complement activation, has been shown to reduce infarct volume and improve functional outcome after murine stroke. Given numerous high-profile failures to translate promising antiinflammatory strategies from the laboratory to the clinic and given the known species-specificity of the complement cascade, the authors sought to evaluate the neuroprotective effect of sCR1 in a nonhuman primate model of stroke.

Methods

A total of 48 adult male baboons (Papio anubis) were randomly assigned to receive 15 mg/kg of sCR1 or vehicle. The animals were subjected to 75 minutes of middle cerebral artery occlusion/reperfusion. Perioperative blood samples were analyzed for total complement activity by using a CH50 assay. Infarct volume and neurological scores were assessed at the time the animals were killed, and immunohistochemistry was used to determine cerebral drug penetration and C1q deposition. An interim futility analysis led to termination of the trial after study of 12 animals. Total serum complement activity was significantly depressed in the sCR1-treated animals compared with the controls. Immunostaining also demonstrated sCR1 deposition in the ischemic hemispheres of treated animals. Despite these findings, there were no significant differences in infarct volume or neurological score between the sCR1- and vehicle-treated cohorts.

Conclusions

A preischemic bolus infusion of sCR1, the most effective means of administration in mice, was not neuroprotective in a primate model. This study illustrates the utility of a translational primate model of stroke in the assessment of promising antiischemic agents prior to implementation of large-scale clinical trials.

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Omar N. Syed, Todd C. Hankinson, William J. Mack, Neil A. Feldstein and Richard C. E. Anderson

Pediatric neurosurgeons frequently care for children with traumatic scalp and skull injury. Foreign objects are often observed on imaging and may influence the clinician's decision-making process. The authors report on 2 cases of poorly visualized hair beads that had become embedded into the skull during blunt trauma. In both cases, skull radiography and CT scanning demonstrated depressed, comminuted fractures with poorly demonstrated spherical radiolucencies in the overlying scalp. The nature of these objects was initially unclear, and they could have represented air that entered the scalp during trauma. In one case, scalp inspection demonstrated no evidence of the bead. In the other case, a second bead was observed at the site of scalp laceration. In both cases, the beads were surgically removed, the fractures were elevated, and the patients recovered uneventfully. Radiolucent fashion accessories, such as hair beads, may be difficult to appreciate on clinical examination and may masquerade as clinically insignificant air following cranial trauma. If they are not removed, these foreign bodies may pose the risk of an infection. Pediatric neurosurgeons should consider hair accessories in the differential diagnosis of foreign bodies that may produce skull fracture following blunt trauma.

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William J. Mack, Christopher P. Kellner, Daniel H. Sahlein, Andrew F. Ducruet, Grace H. Kim, J Mocco, Joseph Zurica, Ricardo J. Komotar, Raqeeb Haque, Robert Sciacca, Donald O. Quest, Robert A. Solomon, E. Sander Connolly Jr. and Eric J. Heyer

Object

Recent data from both experimental and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. This study assessed whether intraoperative magnesium therapy improves neuropsychometric testing (NPT) following carotid endarterectomy (CEA).

Methods

One hundred eight patients undergoing CEA were randomly assigned to receive placebo infusion or 1 of 3 magnesium-dosing protocols. Neuropsychometric testing was performed 1 day after surgery and compared with baseline performance. Assessment was also performed on a set of 35 patients concurrently undergoing lumbar laminectomy to serve as a control group for NPT. A forward stepwise logistic regression analysis was performed to evaluate the impact of magnesium therapy on NPT. A subgroup analysis was then performed, analyzing the impact of each intraoperative dose on NPT.

Results

Patients treated with intravenous magnesium infusion demonstrated less postoperative neurocognitive impairment than those treated with placebo (OR 0.27, 95% CI 0.10–0.74, p = 0.01). When stratified according to dosing bolus and intraoperative magnesium level, those who were treated with low-dose magnesium had less cognitive decline than those treated with placebo (OR 0.09, 95% CI 0.02–0.50, p < 0.01). Those in the high-dose magnesium group demonstrated no difference from the placebo-treated group.

Conclusions

Low-dose intraoperative magnesium therapy protects against neurocognitive decline following CEA.

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Martin H. Pham, Gabriel Zada, Gina M. Mosich, Thomas C. Chen, Steven L. Giannotta, Kai Wang and William J. Mack

Although a majority of meningiomas are benign neoplasms, those occurring at the cranial base may be challenging tumors to treat because of extensive tissue invasion, an inability to achieve gross-total microscopic resection, and local tumor recurrence and/or progression. A more comprehensive understanding of the genetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide novel targets for grading assessments and individualizing molecular therapies for skull base meningiomas. The authors performed a review of the current literature to identify genes that have been associated with the formation and/or progression of meningiomas. Mutations in the NF2 gene have been most commonly implicated in the formation of the majority of meningiomas. Inactivation of other tumor suppressor genes, including DAL-1 and various tissue inhibitors of matrix metalloproteinases, upregulation of several oncogenes including c-sis and STAT3, and signaling dysregulation of pathways such as the Wnt pathway, have each been found to play important, and perhaps, complementary roles in meningioma development, progression, and recurrence. Identification of these genetic factors using genome-wide association studies and high-throughput genomics may provide data for future individualized treatment strategies.

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Leonid I. Groysman, Benjamin A. Emanuel, May A. Kim-Tenser, Gene Y. Sung and William J. Mack

Induced hypothermia has been used for neuroprotection in cardiac and neurovascular procedures. Experimental and translational studies provide evidence for its utility in the treatment of ischemic cerebrovascular disease. Over the past decade, these principles have been applied to the clinical management of acute stroke. Varying induction methods, time windows, clinical indications, and adjuvant therapies have been studied. In this article the authors review the mechanisms and techniques for achieving therapeutic hypothermia in the setting of acute stroke, and they outline pertinent side effects and complications. The manuscript summarizes and examines the relevant clinical trials to date. Despite a reasonable amount of existing data, this review suggests that additional trials are warranted to define the optimal time window, temperature regimen, and precise clinical indications for induction of therapeutic hypothermia in the setting of acute stroke.

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Peter Adamczyk, Arun Paul Amar, William J. Mack and Donald W. Larsen

Endovascular embolization with Onyx has been increasingly used to treat intracranial and spinal dural arteriovenous fistulas (DAVFs). Several case series have been published in recent years reporting high DAVF cure rates with this technique. Although it is seldom reported, DAVF recurrence may occur despite initial “cure.” The authors present 3 separate cases of a recurrent DAVF after successful transarterial Onyx embolization. Despite adequate Onyx penetration into the fistula and draining vein, these cases demonstrate that DAVF recanalization may reappear with filling from previous or newly recruited arterial feeders. Other published reports of DAVF recurrence are examined, and potential contributory factors are discussed. These cases highlight the need for awareness of this possible phenomenon and suggest that follow-up angiography should be considered in patients treated with catheter embolization.