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Gregory G. Heuer, Michelle J. Smith, J. Paul Elliott, H. Richard Winn, and Peter D. Leroux

Object. Increased intracranial pressure (ICP) is well known to affect adversely patients with head injury. In contrast, the variables associated with ICP following aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have been less intensely studied.

Methods. In this retrospective study the authors reviewed a prospective observational database cataloging the treatment details in 433 patients with SAH who had undergone surgical occlusion of an aneurysm as well as ICP monitoring. All 433 patients underwent postoperative ICP monitoring, whereas only 146 (33.7%) underwent both pre- and postoperative ICP monitoring.

The mean maximal ICP was 24.9 ± 17.3 mm Hg (mean ± standard deviation). During their hospital stay, 234 patients (54%) had elevated ICP (> 20 mm Hg), including 136 of those (48.7%) with a good clinical grade (Hunt and Hess Grades I–III) and 98 (63.6%) of the 154 patients with a poor grade (Hunt and Hess Grades IV and V) on admission. An increased mean maximal ICP was associated with several admission variables: worse Hunt and Hess clinical grade (p < 0.0001), a lower Glasgow Coma Scale (GSC) motor score (p < 0.0001); worse SAH grade based on results of computerized tomography studies (p < 0.0001); intracerebral hemorrhage (p = 0.024); severity of intraventricular hemorrhage (p < 0.0001); and rebleeding (p = 0.0048). Both intraoperative cerebral swelling (p = 0.0017) and postoperative GCS score (p < 0.0001) were significantly associated with a raised ICP. Variables such as patient age, aneurysm size, symptomatic vasospasm, intraoperative aneurysm rupture, and secondary cerebral insults such as hypoxia were not associated with raised ICP. Increased ICP adversely affected outcome: 71.9% of patients with normal ICP demonstrated favorable 6-month outcomes postoperatively, whereas 63.5% of patients with ICP between 20 and 50 mm Hg and 33.3% with ICP greater than 50 mm Hg demonstrated favorable outcomes. Among 21 patients whose raised ICP did not respond to mannitol therapy, all experienced a poor outcome and 95.2% died. Among 145 patients whose elevated ICP responded to mannitol, 66.9% had a favorable outcome and only 20.7% were dead 6 months after surgery (p < 0.0001). According to results of multivariate analysis, however, ICP was not an independent outcome predictor (odds ratio 1.26, 95% confidence interval 0.28–5.68).

Conclusions. Increased ICP is common after SAH, even in patients with a good clinical grade. Elevated ICP post-SAH is associated with a worse patient outcome, particularly if ICP does not respond to treatment. This association, however, may depend more on the overall severity of the SAH than on ICP alone.

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Michelle J. Smith, Peter D. Le Roux, J. Paul Elliott, and H. Richard Winn

Object. Nitric oxide (NO) metabolism may influence vasospasm after subarachnoid hemorrhage (SAH). It has been demonstrated in recent studies that erythrocytes carry NO for release in vessels, whereas transfused erythrocytes may lack stored NO. Several converging lines of evidence also indicate that blood transfusion may exacerbate poor outcomes in some critically ill patients. In this study the authors hypothesized that patients with SAH who received red blood cell (RBC) transfusions were at greater risk for vasospasm and poor outcome.

Methods. The authors retrospectively reviewed a prospective observational database, including hospital records, computerized tomography (CT) scans, and pre- and postoperative four-vessel angiograms, in which the management methods used in 441 patients undergoing surgery for ruptured cerebral aneurysms were described. Two hundred seventy patients (61.2%) received an RBC transfusion during their hospital stay. After adjustment for Hunt and Hess grade, SAH grade on CT scans, delay between rupture and surgery, smoking status, and intraoperative aneurysm rupture, a worse outcome was more likely in patients who received intraoperative blood (odds ratio [OR] 2.44, confidence interval [CI] 1.32–4.52; 120 patients). Intraoperative RBC transfusion did not influence subsequent angiographically confirmed vasospasm (OR 0.92, CI 0.6–1.4). Worse outcome was observed in patients who received blood postoperatively (OR 1.81, CI 1.21–2.7), but not after adjustments were made for confounding variables (OR 1.48, CI 0.83–2.63). Angiographic vasospasm was observed in 217 patients and, after adjusting for confounding variables, was more frequent among patients who received postoperative RBC transfusion (OR 1.68, CI 1.02–2.75). Among patients in whom angiographically confirmed vasospasm developed there was a tendency to have received more blood than in those with no vasospasm; however, a clear dose-dependent response was not observed.

Conclusions. Development of angiographically confirmed vasospasm after SAH is associated with postoperative RBC transfusion and worse outcome is associated with intraoperative RBC transfusion. Before blood is transfused, patients with SAH should be carefully assessed to determine if they are symptomatic because of anemia.

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H. Richard Winn

✓ This article details the errors in compliance with federal rules and regulations relating to the healthcare benefits programs at the University of Washington Department of Neurological Surgery from 1996 through 2002. University faculty members, regardless of the organization to which they belong, will be identified by the federal government as the individual responsible in healthcare finance inquiries. A full understanding of all regulations and an active compliance program are necessary to avoid problems, including criminal prosecution.

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Gerald A. Grant, Joseph R. Meno, Thien-Son Nguyen, Kathe A. Stanness, Damir Janigro, and H. Richard Winn

Object. Excitatory amino acid (EAA) uptake by neurons and glia acts synergistically with stereoselective transport across the blood—brain barrier (BBB) to maintain EAA homeostasis in the brain. The endogenous neuroprotectant adenosine counteracts many aspects of excitotoxicity by increasing cerebral blood flow and by producing pre- and postsynaptic actions on neurons. In the present study, the authors explored the effect of adenosine on EAA transport across the BBB.

Methods. The effects of adenosine on the permeability of the BBB and transport of aspartate and glutamate across the BBB were studied in a well-characterized isolated penetrating cerebral arteriole preparation suitable for simultaneous investigations of changes in diameter and permeability. At concentrations within the physiological to low pathophysiological range (10−7–10−6 M), the net vectorial transport of [3H]l-glutamate or [3H]l-aspartate from blood to brain was significantly attenuated, whereas there was no effect of adenosine on paracellular BBB permeability to [14C]sucrose or [3H]d-aspartate. With higher concentrations of adenosine (10−4 M and 10−3 M) the net vectorial transport of [3H]l-glutamate and [3H]l-aspartate returned toward baseline. At 10−3 M, the permeability to [14C]sucrose was significantly altered, indicating a breakdown in the BBB. The effect of adenosine (10−6 M) was blocked by theophylline, a blocker of the A1 and A2 receptors of adenosine.

Conclusions. Adenosine-mediated modulation of glutamate and aspartate transport across the BBB is a novel physiological finding.

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Gerald A. Grant, Robert R. Rostomily, D. Kyle Kim, Marc R. Mayberg, Donald Farrell, Anthony Avellino, Larry G. Duckert, George A. Gates, and H. Richard Winn

Object. In this study the authors investigate delayed facial palsy (DFP), which is an underreported phenomenon after surgery for vestibular schwannoma (VS). The authors identified 15 (4.8%) patients from a consecutive series of 314 who underwent surgery for VS between 1988 and 2000, and in whom DFP developed. Delayed facial palsy was defined as a deterioration of facial nerve function from House—Brackmann Grades 1 or 2 more than 3 days postoperatively.

Methods. All patients underwent intraoperative neurophysiological monitoring of facial nerve function. The average latency of DFP was 10.9 days (range 4–30 days). In six patients (40%) minor deterioration (≤ two House—Brackmann grades) had occurred at a mean of 10.2 days postsurgery, whereas in nine patients (60%) moderate deterioration (≥ three House—Brackmann grades) had occurred at a mean of 11.8 days postoperatively. Five (33%) of 15 patients recovered to Grade 1 of 2 function within 6 weeks of DFP onset. Of the 15 patients with DFP, 14 had completed 1 year of follow up at the time of this study. Twelve (80%) of these 15 patients recovered to Grade 1 or 2 function within 3 months, and 13 (93%) of 14 patients recovered within 1 year. In all cases, stimulation of the seventh cranial nerve on completion of tumor resection revealed the nerve to be intact, both anatomically and functionally, to proximal and distal stimulation at 0.1 mA. A smaller tumor diameter correlated with greater recovery of facial nerve function. There was no correlation between the latency or severity of or recovery from DFP, and the patient's age or sex, the surgical approach, frequency of neurotonic seventh nerve discharges, anatomical relationship of the facial nerve to the tumor, patient's history of tobacco use, or cardiovascular disease.

Conclusions. It appears that DFP is an uncommon consequence of surgery for VS. Although excellent recovery of facial nerve function to its original postoperative status nearly always occurs after DFP, the magnitude and time course of the disorder were not predictors for subsequent recovery of facial nerve function.

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Hisato Higashi, Joseph R. Meno, Amitoj S. Marwaha, and H. Richard Winn

Object. The effects of the adenosine receptor antagonists theophylline (for A1 and A2) and ZM 241385 (for A2A) on hippocampal injury and Morris water maze (MWM) performance in rats were investigated following normoglycemic and hyperglycemic cerebral ischemia (induced by four vessel occlusion for 10 minutes).

Methods. Theophylline (36 mg/kg), ZM 241385 (1 mg/kg), or an equivalent volume of saline was administered to rats intraperitoneally 30 minutes before ischemia was induced. Moderate hyperglycemia was achieved by intraperitoneal administration of D-glucose (3 g/kg, 15 minutes before induction of ischemia). Morris water maze trials were performed on the 6th, 7th, and 8th days after ischemic insult. After the conclusion of the performance tests, the rat brains were cut into 8-xm sections, stained with cresyl violet and acid fuchsin, and evaluated in a blinded fashion to determine the extent of injury. Theophylline worsened injury in the hippocampus following normoglycemic and hyperglycemic ischemia. Moreover, theophylline significantly (p < 0.05, six animals) worsened latency and learning index (LI) scores during the MWM trials in both normoglycemic and hyperglycemic animals. On the other hand, ZM 241385 had no effect on either ischemic injury or MWM performance in normoglycemic animals. In the animals in the hyperglycemic ischemia group, however, ZM 241385 significantly (p < 0.05, five animals) reduced injury in the CA1 (94.6 ± 1.7% compared with 79.2 ± 10.9%), CA3 (26 ± 12.5% compared with 11.2 ± 4.3%), and hilum (22.4 ± 8.1% compared with 11 ± 5.5%) regions. In addition, ZM 241385 significantly improved latency (52 ± 29.7 seconds compared with 24.8 ± 11.2 seconds, p < 0.05) and LI scores (203.2 ± 33.3 compared with 152.1 ± 31.8, p < 0.05) in the MWM trials. A statistically significant correlation was also found between hippocampal injury (CA1, CA3, and hilum) and MWM performance.

Conclusions. The results of this study provide further evidence for a neuromodulatory role of adenosine during normoglycemic and hyperglycemic ischemia.

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H. Richard Winn, John A. Jane, James Taylor, Donald Kaiser, and Gavin W. Britz

Object. The prevalence of unruptured cerebral aneurysms is unknown, but is estimated to be as high as 5%. The goal of this study was to determine the prevalence of asymptomatic incidental aneurysms.

Methods. The authors studied all cerebral arteriography reports produced at a single institution, the University of Virginia, between April 1969 and January 1980. A review of 3684 arteriograms demonstrated 24 cases of asymptomatic aneurysms, yielding a prevalence rate of 0.65%. The majority (67%) of the 24 patients harboring unruptured aneurysms were women. More than 90% of the unruptured aneurysms were located in the anterior circulation and in locations similar to those found in patients with ruptured aneurysms. Nearly 80% of the aneurysms were smaller than 1 cm in their greatest diameter. The frequency of asymmetrical unruptured aneurysms (0.6–1.5%) was constant throughout all relevant age ranges (35–84 years).

Conclusions. While keeping in mind appropriate caveats in extrapolating from these data, the prevalence rate of asymptomatic unruptured aneurysms found in the present study allows an estimation of the yearly rate of rupture of these lesions. The authors suggest that this yearly rate of rupture falls within the range of 1 to 2%.

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H. Richard Winn

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James M. Schuster, Anthony M. Avellino, Frederick A. Mann, Allain A. Girouard, M. Sean Grady, David W. Newell, H. Richard Winn, Jens R. Chapman, and Sohail K. Mirza

Object. The use of structural allografts in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. The authors have identified 47 patients over the last 3.5 years who underwent a surgical decompression and stabilization procedure in which fresh-frozen allografts were used after aggressive removal of infected and devitalized tissue. The patients subsequently underwent 6 weeks of postoperative antibiotic therapy (12 months for those with tuberculosis [TB]).

Methods. Follow-up data included results of serial clinical examinations, radiography, laboratory analysis (erythrocyte sedimentation rate and white blood cell count), and clinical outcome questionnaires. Of the original 47 patients (14 women and 33 men, aged 14–83 years), 39 were available for follow up. The average follow-up period at the time this article was submitted was 17 ± 9 months (median 14 months, range 6–45 months). In the majority of cases (57%), a Staphylococcus species was the infectious organism. Predisposing risk factors included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and concurrent infections. During the follow-up period only two patients suffered recurrent infection at a contiguous level; both had a history of IVDA and one also had a chronic excoriating skin condition. No other recurrent infections have been identified, and no patient has required reoperation for persistent infection or allograft/hardware failure.

Conclusions. It is the authors' opinion that the use of structural allografts in combination with aggressive tissue debridement and adjuvant antibiotic therapy provide a safe and effective therapy in cases of spinal osteomyelitis requiring surgery.