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Object: In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy., Methods: The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-beta or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or > or = 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements., Results: Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 x 10(9)/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO., Conclusions: Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.

Object: Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH., Methods: Within 72 hours of aSAH, 80 patients (age range 24-82 years) were randomized to receive intravenous EPO (30,000 U) or placebo every 48 hours for a total of 90,000 U. Primary end points were the incidence, duration, and severity of vasospasm and impaired autoregulation on transcranial Doppler ultrasonography. Secondary end points were incidence of DIDs and outcome at discharge and at 6 months., Results: Randomization characteristics were balanced except for age, with the EPO group being older (mean age 59.6 vs 53.3 years, p=0.034). No differences were demonstrated in the incidence of vasospasm and adverse events; however, patients receiving EPO had a decreased incidence of severe vasospasm from 27.5 to 7.5% (p=0.037), reduced DIDs with new cerebral infarcts from 40.0 to 7.5% (p=0.001), a shortened duration of impaired autoregulation (ipsilateral side, p<0.001), and more favorable outcome at discharge (favorable Glasgow Outcome Scale score, p=0.039). Among the 71 survivors, the EPO group had fewer deficits measured with National Institutes of Health Stroke Scale (median Score 2 vs 6, p=0.008)., Conclusions: This preliminary study showed that EPO seemed to reduce delayed cerebral ischemia following aSAH via decreasing severity of vasospasm and shortening impaired autoregulation.

Object: Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between mean intracranial pressure (ICP) and mean arterial blood pressure., Methods: The authors analyzed a database consisting of 398 patients with head injuries who underwent continuous monitoring of cerebrovascular pressure reactivity. In 298 patients, the PRx was compared with a transcranial Doppler ultrasonography assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17 patients with the PET-assessed static rate of autoregulation, and in 22 patients with the cerebral metabolic rate for O(2). Patient outcome was assessed 6 months after injury., Results: There was a positive and significant association between the PRx and Mx (R(2) = 0.36, p < 0.001) and with the static rate of autoregulation (R(2) = 0.31, p = 0.02). A PRx > 0.35 was associated with a high mortality rate (> 50%). The PRx showed significant deterioration in refractory intracranial hypertension, was correlated with outcome, and was able to differentiate patients with good outcome, moderate disability, severe disability, and death. The graph of PRx compared with cerebral perfusion pressure (CPP) indicated a U-shaped curve, suggesting that too low and too high CPP was associated with a disturbance in pressure reactivity. Such an optimal CPP was confirmed in individual cases and a greater difference between current and optimal CPP was associated with worse outcome (for patients who, on average, were treated below optimal CPP [R(2) = 0.53, p < 0.001] and for patients whose mean CPP was above optimal CPP [R(2) = -0.40, p < 0.05]). Following decompressive craniectomy, pressure reactivity initially worsened (median -0.03 [interquartile range -0.13 to 0.06] to 0.14 [interquartile range 0.12-0.22]; p < 0.01) and improved in the later postoperative course. After therapeutic hypothermia, in 17 (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold of 37 degrees C, ICP remained stable, but the average PRx increased to 0.32 (p < 0.0001), indicating significant derangement in cerebrovascular reactivity., Conclusions: The PRx is a secondary index derived from changes in ICP and arterial blood pressure and can be used as a surrogate marker of cerebrovascular impairment. In view of an autoregulation-guided CPP therapy, a continuous determination of a PRx is feasible, but its value has to be evaluated in a prospective controlled trial.

Object: The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects., Methods: Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period., Results: No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002)., Conclusions: In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.

Object: Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses., Methods: Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted., Results: There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition., Conclusion: Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

Object: Systemic administration of 23.5% hypertonic saline enhances cerebral blood flow (CBF) in patients with poor-grade spontaneous subarachnoid hemorrhage (SAH). Whether the increment of change in CBF correlates with changes in autoregulation of CBF or outcome at discharge remains unknown., Methods: Thirty-five patients with poor-grade spontaneous SAH received 2 ml/kg 23.5% hypertonic saline intravenously, and they underwent bedside transcranial Doppler (TCD) ultrasonography and intracranial pressure (ICP) monitoring. Seventeen of them underwent Xe-enhanced computed tomography (CT) scanning for measuring CBF. Outcome was assessed using the modified Rankin Scale (mRS) at discharge from the hospital. The data were analyzed using repeated-measurement analysis of variance and Dunnett correction. A comparison was made between patients with favorable and unfavorable outcomes using multivariate logistic regression., Results: The authors observed a maximum increase in blood pressure by 10.3% (p < 0.05) and cerebral perfusion pressure (CPP) by 21.2% (p < 0.01) at 30 minutes, followed by a maximum decrease in ICP by 93.1% (p < 0.01) at 60 minutes. Changes in ICP and CPP persisted for longer than 180 and 90 minutes, respectively. The results of TCD ultrasonography showed that the baseline autoregulation was impaired on the ipsilateral side of ruptured aneurysm, and increments in flow velocities were higher and lasted longer on the contralateral side (48.75% compared with 31.96% [p = 0.045] and 180 minutes compared with 90 minutes [p < 0.05], respectively). The autoregulation was briefly impaired on the contralateral side during the infusion. A dose-dependent effect of CBF increments on favorable outcome was seen on Xe-CT scans (mRS Score 1-3, odds ratio 1.27 per 1 ml/100 g tissue x min, p = 0.045)., Conclusions: Bolus systemic hypertonic saline therapy may be used for reversal of cerebral ischemia to normal perfusion in patients with poor-grade SAH.

Object: The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow., Methods: In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation., Conclusions: The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.

Object: Patients with intracranial aneurysms tend toward raised blood pressure and abnormal pulse pressure profiles. The authors have investigated the influence of three antihypertension agents on blood pressure and pulse pressure waveforms in patients with known intracranial aneurysms, with a view to assessing the potential benefits of longterm antihypertension therapy on the progression of unruptured intracranial aneurysms., Methods: Nineteen patients with a mean age of 56 years (range 38-76 years) were recruited for this study. All patients had confirmed intracranial aneurysms. A double-blind, randomized, crossover study was performed using perindopril, irbesartan, isosorbide mononitrate, and a placebo. Blood pressure and pulse pressure waveforms were assessed at the end of each 4-week treatment period. Perindopril and irbesartan were well tolerated. For all measured parameters except heart rate (p = 0.03), no significant difference between baseline and placebo was identified. Each drug when compared with placebo reduced peripheral arterial blood pressure. Perindopril significantly decreased mean blood pressure by 10 mm Hg (p = 0.004), irbesartan by 9 mm Hg (p = 0.004), and isosorbide mononitrate by 13 mm Hg (p = 0.005). The administration of each drug effected a significant reduction in the carotid artery augmentation index (AIX) compared with baseline values (perindopril p = 0.01, irbesartan p = 0.0002, and isosorbide mononitrate p = 0.03). There was also a significant difference in the AIX between irbesartan and the placebo (p = 0.05). Compared with the placebo, there was a significant difference in AIX (adjusted for heart rate) following the administration of irbesartan (p = 0.003) and isosorbide mononitrate (p = 0.01), but not with perindopril (p = 0.17)., Conclusions: Irbesartan appears to be the most effective treatment for the combined suppression of blood pressure and AIX in patients with intracranial aneurysms and has a high degree of patient tolerance.

Object: The aim of this study was to investigate potential episodes of cerebral ischemia during surgery for large and complicated aneurysms, by examining the effects of arterial temporary clipping and the impact of confounding variables such as blood pressure and cerebrospinal fluid (CSF) drainage., Methods: Brain tissue PO2, PCO2, and pH, as well as temperature and extracellular glucose, lactate, pyruvate, and glutamate were monitored in 46 patients by using multiparameter sensors and microdialysis. Baseline data showed that brain tissue PO2 decreased significantly, below a mean arterial pressure (MAP) threshold of 70 mm Hg. Further evidence of its relationship with cerebral perfusion pressure was shown by an increase in mean brain tissue PO2 after drainage of CSF from the basal cisterns (Wilcoxon test, p < 0.01). Temporary clipping was required in 31 patients, with a mean total duration of 14 minutes (range 3-52 minutes), causing brain tissue PO2 to decrease and brain tissue PCO2 to increase (Wilcoxon test, p < 0.01). In patients in whom no subsequent infarction developed in the monitored region, brain tissue PO2 fell to 11 mm Hg (95% confidence interval 8-14 mm Hg). A brain tissue PO2 level below 8 mm Hg for 30 minutes was associated with infarction in any region (p < 0.05 according to the Fisher exact test); other parameters were not predictive of infarction. Intermittent occlusions of less than 30 minutes in total had little effect on extracellular chemistry. Large glutamate increases were only seen in two patients, in both of whom brain tissue PO2 during occlusion was continuously lower than 8 mm Hg for longer than 38 minutes., Conclusions: The brain tissue PO2 decreases with hypotension, and, when it is below 8 mm Hg for longer than 30 minutes during temporary clipping, it is associated with increasing extracellular glutamate levels and cerebral infarction.

Object: The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning., Methods: A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H2(15)O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (deltaPbO2) and the change in PvO2 (deltaPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (p = 0.78, p = 0.0035)., Conclusions: The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between deltaPbO2 and deltaPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.

Object: Applanation tonometry is a noninvasive method of assessing both peripheral and central arterial blood pressure (BP) profiles. In this study the authors examine whether there are differences in these profiles in patients with intracranial aneurysms when compared with age-matched controls., Methods: Carotid artery (CA) and derived aortic BP waveforms were obtained using a pulse wave analysis system. The ratio of the pressure wave amplitude above the systolic shoulder to the total systolic BP (augmentation index [AI]) was recorded. One hundred seventy-three patients with intracranial aneurysms (23 unruptured lesions) and 173 healthy control volunteers were examined. For the patients with aneurysms the right and left CA AIs (mean +/- standard deviation) were 125.6 +/- 23.1% and 128.3 +/- 22.1%, respectively. Corresponding values for the control group were 118.4 +/- 22.6% and 119.4 +/- 21.8%. The calculated AI for the ascending aorta was 29.8 +/- 10.5% and 25.6 +/- 12.2% for patients with aneurysms and control volunteers, respectively. Significant asymmetry in CA AI was seen in patients with aneurysms, the left being greater (p = 0.002). No significant differences were seen in mean BP (108 +/- 14 mm Hg in patients with aneurysms compared with 106 +/- 16 mm Hg in controls; p = 0.2). Multivariate analysis excluded the influence of BP and other potential confounding vascular risk factors for increased AI., Conclusions: Significant differences in AI, both in magnitude and symmetry, were identified in patients with intracranial aneurysms when compared with matched controls.

Object: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC)., Methods: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations., Conclusions: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

Object: This study was conducted to define neuropsychological changes following operation for subarachnoid hemorrhage (SAH) caused by rupture of an anterior communicating artery (ACoA) aneurysm and to assess the influence of the timing of surgery to clip the aneurysm., Methods: Cognitive outcome was evaluated using the Cambridge Neuropsychological Test Automated Battery in patients with an ACoA aneurysm that had caused an SAH. Adult patients younger than 70 years of age who had achieved a favorable neurological outcome (Glasgow Outcome Scale scores of 4 or 5) were studied 6 to 24 months postsurgery. Patients were divided into early (Days 0-3) and late surgery groups (after Day 3) according to the timing of surgery after the ictus. Neuropsychological analysis was performed by reviewers who were blinded to the timing of surgery. Forty-seven patients whose mean age was 51.5 years were tested. They were compared with age- and intelligence quotient (IQ)matched controls by using premorbid IQ as estimated on the National Adult Reading Test. Patients showed deficiencies in several tasks of verbal fluency, pattern recognition, and spatial working memory; this profile of deficits was similar to that seen in patients who underwent temporal lobe excisions. However, there was no significant difference in cognitive performance between the early and late surgery groups., Conclusions: After open surgery for ruptured ACoA aneurysms, patients who have achieved a favorable neurological outcome still exhibit significant cognitive deficits, primarily in tests sensitive to temporal lobe dysfunction. However, early surgery does not carry a higher risk of neuropsychological disability.

Object: Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves., Methods: One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed. The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p < 0.05) and TCD pulsatility increased (p < 0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury., Conclusions: The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.

Object: Signal changes in adult extracranial tissues may have a profound effect on cerebral near-infrared spectroscopy (NIRS) measurements. During carotid surgery NIRS signals provide the opportunity to determine the relative contributions from the intra- and extracranial vascular territories, allowing for a more accurate quantification. In this study the authors applied multimodal monitoring methods to patients undergoing carotid endarterectomy and explored the hypothesis that NIRS can define thresholds for cerebral ischemia, provided extracranial NIRS signal changes are identified and removed. Relative criteria for intraoperative severe cerebral ischemia (SCI) were applied to 103 patients undergoing carotid endarterectomy., Methods: One hundred three patients underwent carotid endarterectomy. An intraoperative fall in transcranial Doppler-detected middle cerebral artery flow velocity (%deltaFV) of greater than 60% accompanied by a sustained fall in cortical electrical activity were adopted as criteria for SCI. Ipsilateral frontal NIRS recorded the total difference in concentrations of oxyhemoglobin and deoxyhemoglobin (Total deltaHb(diff)). Interrupted time series analysis following clamping of the external carotid artery (ECA) and the internal carotid artery (ICA) allowed the different vascular components of Total deltaHb(diff) (ECA deltaHb(diff) and ICA deltaHb(diff)) to be identified. Data obtained in 76 patients were deemed suitable. A good correlation between %deltaFV and ICA deltaHb(diff) (r = 0.73, p < 0.0001) was evident. Sixteen patients (21%) fulfilled the criteria for SCI. All patients who demonstrated an ICA deltaHb(diff) of greater than 6.8 micromol/L showed SCI, and in two patients within this group nondisabling watershed infarction developed, as seen on postoperative computerized tomography scans. No patient with an ICA deltaHb(diff) less than 5 micromol/L exhibited SCI or suffered a stroke. Within the resolution of the criteria used an ICA deltaHb(diff) threshold of 6.8 micromol/L provided 100% specificity for SCI, whereas an ICA deltaHb(diff) less than 5 micromol/L was 100% sensitive for excluding SCI. When Total deltaHb(diff) was used without removing the ECA component, no thresholds for SCI were apparent., Conclusions: Carotid endarterectomy provides a stable environment for exploring NIRS-quantified thresholds for SCI in the adult head.

Object: The authors studied the reliability of a new method for noninvasive assessment of cerebral perfusion pressure (CPP) in head-injured patients in which mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral artery mean and diastolic flow velocities are measured., Methods: Cerebral perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20 minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow Coma Scale score < 13) who were admitted to the intensive care unit. All patients were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus intracranial pressure, measured using an intraparenchymal microsensor) were compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6). In 71% of the examinations, the estimation error was less than 10 mm Hg and in 84% of the examinations, the error was less than 15 mm Hg. The method had a high positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in situations such as plateau and B waves of intracranial pressure, arterial hypotension, and refractory intracranial hypertension. A good correlation was found between the average measured CPP and eCPP when day-by-day variability was assessed in a group of 41 patients (r=0.71)., Conclusions: Noninvasive estimation of CPP by using transcranial Doppler ultrasonography may be of value in situations in which monitoring relative changes in CPP is required without invasive measurement of intracranial pressure.

A multimodality recording system was used in 14 ventilated patients with closed head injury to assess the potential use of near-infrared spectroscopy (NIRS) in the neurointensive care unit. Signals of intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, jugular venous saturation, and NIRS-derived changes in the chromophores of oxy- and deoxyhemoglobin were digitized and recorded. After a review of 886 hours of continuous monitoring, 376 hours were considered free from artifact and were entered for final analysis. In nine of the patients 38 events were recorded that demonstrated clear changes in cerebral perfusion pressure accompanied by hemodynamic changes in middle cerebral artery flow velocity (transcranial Doppler) and cortical perfusion (laser Doppler flowmetry). Near-infrared spectroscopy showed correlated changes in 37 events (97%) whereas jugular venous saturation monitoring registered only 20 (53%). There was associated peripheral oxygen desaturation in eight cases (21%), intracranial hypertension in 10 (26%), and cerebral hyperemia in eight (21%). The remaining 12 events (32%) appeared to be complex changes of uncertain origin. Iatrogenic factors were identified as causative in 14 cases (37%). The potential application of NIRS in adults and the importance of using multiple parameter recording systems in the interpretation of cerebral events are discussed.

Near-infrared spectroscopy was used to monitor changes in the cerebral oxygenation state in 13 patients during carotid endarterectomy. Variations in the levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb) were compared with changes in middle cerebral artery flow velocity measured using transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow velocity on application of the internal carotid artery cross-clamp, seven demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy, recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in three of these patients. Intraoperative shunts accelerated recovery of HbO2 and Hb signals in two of three individuals. Release of the internal carotid cross-clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those patients in whom spontaneous recovery had not occurred; in five instances, a hyperemia evolved with raised flow velocity and HbO2 to above baseline values. Cross-clamping and subsequent reperfusion of the external carotid artery had no effect on any parameter measured. The authors conclude that near-infrared spectroscopy can register changes in cerebral oxygenation during carotid endarterectomy without significant contamination from extracranial tissues.

Thirty-one patients with a mean age of 18.9 years (range 3 to 53 years) who underwent temporal lobe surgery for tumor-related epilepsy over a 14-year period are presented. All had suffered chronic drug-resistant temporal lobe seizures (mean age at onset 6.9 years, range 0 to 30 years; mean duration of condition 11.9 years, range 3 to 39 years). Preoperative interictal scalp electroencephalography tracings indicated unilateral localized epileptic foci in 90% of patients, and computerized tomography scans showed abnormalities within the temporal lobe in 87%. All patients underwent en bloc temporal lobectomy. No patient received adjuvant radiotherapy or chemotherapy. Review of the histological material showed dysembryoplastic neuroepithelial tumor in 27 (87%) of the specimens and microscopic evidence of incomplete removal of tumor in 22 (71%). At long-term follow-up evaluation (mean duration 5.8 years, range 1 to 14 years), 81% of patients were completely free of seizures (Engel grade I) and 10% were almost seizure free (Engel grade II) with no deaths reported in either early or late follow-up review. Only one patient in the series failed to benefit from the surgery. Four patients suffered permanent neurological deficit causing a mild disability. Psychological assessment showed no significant fall in verbal or performance intelligent quotient for the group, but a mild memory impairment was evident in 32%. Behavioral and social aspects improved in nearly all (94%) cases. Relief of seizures could not be predicted by intraoperative electrocorticography, and outcome was independent of the completeness of tumor resection. Postoperative electroencephalographic findings identified epileptiform potentials in 65% of patients, which were associated with a worse seizure-control outcome grade.