Intraoperative magnesium infusion during carotid endarterectomy: a double-blind placebo-controlled trial.

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.

The impact of microsurgical fenestration of the lamina terminalis on shunt-dependent hydrocephalus and vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Chronic hydrocephalus requiring shunt placement and cerebral vasospasm are common complications after aneurysmal subarachnoid hemorrhage. Recent publications have investigated the possibility that microsurgical fenestration of the lamina terminalis during aneurysm surgery may reduce the incidence of shunt-dependent hydrocephalus and cerebral vasospasm. We reviewed a single-surgeon series to compare postsurgical outcomes of patients who underwent fenestration of the lamina terminalis against those who did not. METHODS: This study is a retrospective review of the medical records of 369 consecutive patients with aneurysmal subarachnoid hemorrhage admitted to Columbia University Medical Center between January 2000 and July 2006. All patients underwent craniotomy and clipping of at least one ruptured cerebral aneurysm by a single neurosurgeon (ESC). The incidences of shunt-dependent hydrocephalus, conversion from acute hydrocephalus on admission to chronic hydrocephalus, and clinical cerebral vasospasm were compared in patients who underwent fenestration of the lamina terminalis with those who did not. The patient cohort was thus divided into three subgroups: 1) patients whose operative records clearly indicated that they underwent fenestration of the lamina terminalis, 2) patients whose operative records clearly indicated that they did not undergo fenestration of the lamina terminalis, and 3) patients whose operative records did not indicate one way or another whether they received fenestration of the lamina terminalis. We performed two separate analyses by comparing the postsurgical outcomes in those patients who were fenestrated versus those who were definitively not fenestrated and comparing the postsurgical outcomes in those patients who were fenestrated versus those who were not plus those whose records did not document fenestration. To further control for any cohort differences, we performed a comparison between patients who were fenestrated and those who were not after matching 1:1 for presenting radiographic and clinical characteristics predictive of hydrocephalus and vasospasm. Outcomes were compared using logistic regression and multivariable analysis. RESULTS: In the first model, fenestrated patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 25, 50, and 23%, respectively, versus 20, 27, and 27% in nonfenestrated patients, respectively (P = 0.28, 0.21, and 0.32, respectively). In the second model, the nonfenestrated patients plus nondocumented patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 16, 40, and 20%, respectively (P = 0.19, 0.33, and 0.60, respectively). In the matched cohort, fenestrated patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 29, 67, and 20%, respectively, versus 20, 25, and 25% in nonfenestrated patients, respectively (P = 0.30, 0.24, and 0.20, respectively). CONCLUSION: In contrast to other retrospective multisurgeon series, our retrospective single-surgeon series suggests that microsurgical fenestration of the lamina terminalis may not reduce the incidence of shunt-dependent hydrocephalus or cerebral vasospasm after aneurysmal subarachnoid hemorrhage. A prospective multicenter trial is needed to definitively address the use of this maneuver.

A mouse model of intracerebral hemorrhage using autologous blood infusion.

The development of controllable and reproducible animal models of intracerebral hemorrhage (ICH) is essential for the systematic study of the pathophysiology and treatment of hemorrhagic stroke. In recent years, we have used a modified version of a murine ICH model to inject blood into mouse basal ganglia. According to our protocol, autologous blood is stereotactically infused in two stages into the right striatum to mimic the natural events of hemorrhagic stroke. Following ICH induction, animals demonstrate reproducible hematomas, brain edema formation and marked neurological deficits. Our technique has proven to be a reliable and reproducible means of creating ICH in mice in a number of acute and chronic studies. We believe that our model will serve as an ideal paradigm for investigating the complex pathophysiology of hemorrhagic stroke. The protocol for establishing this model takes about 2 h.

Pre-clinical evaluation of an sLe x-glycosylated complement inhibitory protein in a non-human primate model of reperfused stroke.

BACKGROUND: Soluble complement receptor-1 (sCR1), a potent complement inhibitor, confers neuroprotection in a murine stroke model. Additional neuroprotective benefit is achieved by sLe x-glycosylation of sCR1. In an effort to translate sCR1-sLe x to clinical trials, we evaluated this agent in a primate stroke model. METHODS: Adult male baboons randomly received either sCR1-sLe x or vehicle. Stroke volume was assessed on day 3, and neurological examinations were conducted daily. Complement activity (CH50) was measured at 30 minute, 2, 6, 12 hour, 3, and 10 days post-ischemia. RESULTS: The experiment was terminated prematurely following an interim analysis. In a preliminary cohort (n = 3 per arm), infarct volume was greater in the treated animals. No difference in neurological score was found between groups. CH50 levels were significantly reduced in the sCR1sLe x-treated groups. A hypotensive response was also observed in animals treated with sCR1-sLe x. Conclusions Further work is necessary to explain the hypotensive response observed in primates prior to further clinical development of sCR1-sLe x.