Three-year outcome of shunted idiopathic NPH patients.

The incidence of idiopathic normal pressure hydrocephalus (iNPH) has increased as a result of improved longevity. This report describes the 3-year outcome of shunted iNPH patients compared to three-month outcome after shunting. Patients (n = 50) (Age 70.4 +/- 8.9) admitted to our service were diagnosed and treated according to a fixed protocol for management of iNPH and after shunting were followed at least three times per year in clinic. The outcome of 50 patients was graded according to the level of improvement in symptoms as Excellent/Good, Partial or None in each category of Gait, Incontinence and Dementia. If we lump favorable (excellent, good, partial recovery) vs poor recovery (none), we found from 3 months to 3 years, a moderate decline in gait performance (91% to 75%), a retention of memory improvement (80%-80%) and an improvement in incontinence occurred over time (70%-82.5%). With proper diagnosis and management of iNPH, shunting of patients is associated with a favorable risk/benefit ratio that is reasonably long lasting.

Acute and late changes in N-acetyl-aspartate following diffuse axonal injury in rats: an MRI spectroscopy and microdialysis study.

N-acetyl-aspartate (NAA) measured by proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used as a marker of neuronal injury in many cerebral pathologies. Therefore, we evaluate the roles of microdialysis vs. 1H-NMR as techniques to assess NAA (NAAd; NAA/Creatine ratio) in the living brain, and compare the results with whole brain NAA (NAAw), analyzed by HPLC after diffuse traumatic brain injury (TBI). Acute (4 h post-injury survival) and late (48 h survival) changes were studied in a sham-operated group (Sham, n = 4), and two injured groups (TBI/4 h, n = 8; TBI/48 h, n = 7). Baseline NAAd was 8.17 +/- 1 microM, and there was no significant difference between groups. There was only a small (twice of control), but transient increase in NAAd in the TBI/4 h group after trauma. Baseline NAA/Cr ratio was 1.35 +/- 0.2, which did not change significantly between baseline, 1, 2, 3, 4 and 48 h or between groups after TBI. Whole brain NAAw (baseline 8.5 +/- 0.5 mmol kg-1 wet weight) did not differ significantly between groups before and after TBI. Diffuse TBI did not produce long-term changes in NAA, assessed by three different methods. These results may indicate that NAA is not a sensitive marker of the severity of diffuse axonal damage. However, further studies are needed to evaluate whether confounding factors such as microdialysis probe, voxel position and non-regional tissue homogenization might have influenced our data.

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

Low extracellular (ECF) glucose affects the neurochemical profile in severe head-injured patients.

Glucose (Gluc) is the main energy source for the brain. After severe head-injury energy demand is massively increased and supply is often decreased. In pilot microdialysis studies, many patients with severe head-injury had undetectable glucose concentrations, probably reflecting changes in metabolism and/or reduced supply. We therefore investigated whether patients with low ECF glucose (criterion: < 50 microM for > or = 5 hrs), LOWgluc, differ from patients with higher glucose levels (NORMALgluc) We also tested the interrelationships between other parameters such as lactate, glutamate, K+, brain O2 and CO2, ICP, CPP, and CBF in these two groups. We found that patients with low ECF glucose, LOWgluc, have significantly lower lactate concentrations than patients with "normal" glucose, NORMALgluc, levels do. Spearman correlations between glucose and most other parameters were similar in both patient groups. However, glutamate correlated positively with glucose, lactate, brain CO2 and negatively with brain O2 in the NORMALgluc patient group, whereas glutamate did not significantly correlate with any of these parameters in the LOWgluc group. There was also no correlation between outcome and the dialysate glucose. The results indicate that low ECF glucose is almost always present in severe head-injury. Moreover, the lack of correlation between low glucose and outcome, however, suggests that other energy substrates, such as lactate, are important after TBI.

Intracranial extension of an eccrine porocarcinoma. Case report and review of the literature.

Eccrine porocarcinoma is a rare malignant tumor of the true sweat gland. It commonly presents in the lower extremities with lymphatic metastasis. The authors describe the clinical presentation, radiographic evidence, operative discoveries, and pathological findings in a patient with an eccrine porocarcinoma involving the soft tissue of the occiput, which had eroded through the cranium. A review of the literature failed to reveal any other such case. The discussion includes the epidemiology, pathogenesis, treatment, and outcome of eccrine porocarcinomas. The six reported cases of scalp eccrine tumors are reviewed.

Glucose and lactate metabolism after severe human head injury: influence of excitatory neurotransmitters and injury type.

The survival of traumatized brain tissue depends on energy substrate delivery and consumption. Excitatory amino acids produce a disturbance of ion homeostasis and thus, increase energy demand. In head-injured patients, massive release of glutamate has been reported, especially in patients with focal contusions. Therefore, we studied the interrelationship between glutamate, glucose and lactate in relation to the type of injury. We investigated 37 severely head-injured patients in which a microdialysis probe was placed next to a focal contusion (n = 14) or together with a ventricular catheter in diffusely injured tissue (n = 23). Within-subject Spearman-rank correlation revealed an overall strong relationship between glutamate and lactate (p < 0.001) and glutamate and glucose (p < 0.01), but not between glucose and lactate (n.s.). The interrelationship was more pronounced in diffusely injured brain (normal CT appearance) compared to the contused tissue. The results demonstrate that glutamate clearly influences the release of lactate following injury, supporting the hypothesis that glutamate "drives" glycolysis in astrocytes. The strong positive correlation between glutamate and glucose might indicate an effect of glutamate upon glucose uptake by cells which differs according to the type of injury.

Factors affecting excitatory amino acid release following severe human head injury.

OBJECT: Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. METHODS: In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27+/-22 micromol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 micromol/L; p < 0.01). CONCLUSIONS: The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Cortical extracellular sodium transients after human head injury: an indicator of secondary brain damage?

Animal studies indicate that elevated extracellular sodium can increase glutamate-induced excitotoxicity. Therefore, we investigated the relationship between sodium and glutamate and the effect of changes in sodium concentrations on the outcome of head-injured patients. Thirty-four (34) patients were selected for this study and divided into a group of patients having episodes (> or = 30-min) of high sodium in dialysates (> or = 200 mM; HIGH, n = 11) and a group of patients having no such episodes (NORMAL, n = 23). Levels for sodium (226 +/- 5.7 mM), glutamate (12.53 +/- 2.2 microM) and ICP (32.2 +/- 4.0 mm Hg,) were relatively high during the high sodium episodes. Overall, mean values for glutamate, ICP and outcome did not differ amono both groups. The mean dialysate sodium concentration, however, was significantly higher in the HIGH (178 +/- 6 mM) compared to the NORMAL group (158 +/- 3 mM; p < 0.01). Spearman rank correlation between sodium and glutamate or ICP were not significant. The HIGH sodium group did not have significantly more patients with poor outcome than the NORMAL group. The results indicated sodium concentrations did not affect the outcome of head-injured patients. However, other sodium monitoring techniques are desirable to elucidate these apparent potentially major sodium transients, which we have observed in the human cortex, after severe head injury.

Relationship between excitatory amino acid release and outcome after severe human head injury.

In previous studies, Katayama and our group have documented a massive increase in excitatory amino acid release following traumatic brain injury, in both rat fluid percussion, and humans [2,5]. To test the hypothesis that the magnitude of this "Excitotoxic Surge" plays a significant role in determining 6-month patient outcome. We have studied 83 consecutive severely head injured patients at the Medical College of Virginia for inclusion into this study. A microdialysis probe was placed within the cortex to continuously measure dialysate excitatory amino acids (Glutamate and Aspartate), along with several other analytes for approximately 5 days after injury. ICP, CPP, and MABP measurements were also time linked with each analyte measurement to create a neurochemical, clinical, and physiological "profile" for each patient. Outcome was determined by follow up using the Glasgow 6-Month outcome scale. A very strong correlation existed between the release of the EAA's glutamate and aspartate after TBI (p < 0.0001). Patients with significantly elevated mean glutamate values for the entire monitoring period were most likely to exhibit elevated levels of ICP. The magnitude of glutamate released significantly correlates with 6-month patient outcome (p = 0.0234). When patients were subdivided by the CT diagnosis of lesion type, we found that those patients with contusions displayed the highest overall of EAA's.

Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow--a better way of monitoring the severely injured brain?

BACKGROUND: The ideal method for monitoring the acutely injured brain would measure substrate delivery and brain function continuously, quantitatively, and sensitively. We have tested the hypothesis that brain PO2, pCO2, and pH, which can now be measured continuously using a single sensor, are valid indicators of regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its product, brain pCO2. METHODS: Twenty-five patients (Glasgow Coma Score < or = 8) were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7, Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain PO2, pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies. Regional CBF was measured around the probe, using stable xenon computed tomography. Regression analyses and Spearman Rank tests were used for data analysis. RESULTS: Regional CBF and mean brain PO2 were strongly correlated (r=0.74, p=0.0001). CBF values < 18 mL/100 g/min were all accompanied by brain PO2 < or = 26 mm Hg. The four patients with a brain PO2 < 18 mm Hg died. Brain pCO2 and pH, however, were not correlated with CBF (r=0.36, p=0.24 and r=0.30, p=0.43, respectively). CONCLUSIONS: Until recently, substrate supply to the severely injured brain could only be intermittently estimated by measuring CBF. The excellent intra-regional correlation between CBF and brain pO2, suggests that this method does allow continuous monitoring of true substrate delivery, and offers the prospect that measures to increase O2 delivery (e.g., increasing CBF, CPP, perfluorocarbons etc.) can be reliably tested by brain PO2 monitoring.

Increased free radical production due to subdural hematoma in the rat: effect of increased inspired oxygen fraction.

Acute subdural hematoma (ASDH) complicates about 15%-20% of severe head injury patients and is one of the major causes for bad outcome, yet the pathomechanisms involved are not well understood. This study has employed a recently developed technique to determine whether ASDH induces free radicals in the underlying brain. We also studied the effect of increased inspired oxygen fraction (FiO2) on free radical production, both in the normal rat brain and after ASDH induction. Twelve male Sprague Dawley rats were studied over 5 h (2 h of FiO2 = 30%, 3 h of FiO2 = 100%). Hydroxyl radical production was measured with microdialysis using the salicylate trapping technique by quantitating the 2,3 dihydroxy benzoic acid (2,3 DHBA) and 2,5 dihydroxy benzoic acid (2,5 DHBA), degradation products, in either noninjured brain (n = 6) or after ASDH (n = 6). Both 2,3 DHBA and 2,5 DHBA increased significantly by 39% and 108%, respectively, after the induction of the SDH (p < 0.05). By increasing the FiO2 to 100%, 2 h after ASDH induction, the 2,3 DHBA and 2,5 DHBA further increased only slightly (ns). After increasing the FiO2 to 100% in the noninjured group, the mean level of 2,3 DHBA increased by 56% (p = 0.06, ns). The level of 2,5 DHBA in the dialysate increased significantly by 56% (p < 0.05), when the FiO2 was increased to 100% ASDH results in a significant increase in free radical production. At the same time, prolonged increase in FiO2 does not lead to further increase in free radical production in the injured brain.

Extended neuromonitoring: new therapeutic opportunities?

In order to optimize therapy for the injured brain it is desirable to continuously monitor substrate delivery in the critically ill patient. Interruption of substrate delivery is a major factor of the great vulnerability to ischemic damage, which affects a majority of patients after severe head injury, stroke or subarachnoid hemorrhage. An approach to protecting the brain during ischemia is to increase the delivery of oxygen via residual blood flow through ischemic tissue. Hypothermia is also an important means of protecting brain cells from the deleterious effects of ischemia, after severe head injury, because it reduces metabolic demands. In this study we continuously measured brain oxygen, brain CO2, brain pH and brain temperature, as well as hourly brain glucose and lactate. A multiparameter sensor was inserted into brain tissue, via a three lumen bolt, along with a ventriculostomy catheter and a microdialysis probe in 60 severely head injured patients. Brain oxygen delivery was increased by stepwise increase of inspired oxygen (FiO2) from 30% to 60% to 100% over a period of 6 h, in order to test the effect of enhanced oxygen tension, on tissue oxygen. In most patients brain oxygen was initially low, and progressively increased, over the monitoring period, to a steady state level, around 30-40 mmHg. In those who died or remained vegetative, brain oxygen fell to anerobic levels. Episodes of increased ICP (n = 25), hypotension (n = 15), and respiratory difficulties (n = 9) caused an immediate increase in brain CO2. Multiple logistic regression analysis showed brain oxygen to be the strongest predictor for outcome in these patients. By increasing FiO2, an increase in oxygen delivery of more than 100%, and a simultaneous decline in lactate production was seen (p < 0.01). Brain temperature was closely related to rectal temperature, brain oxygen, and cerebral blood flow. Patients who were spontaneously hypothermic had a poor outcome (p < 0.01). A fuller understanding of dynamic factors affecting brain metabolism and substrate delivery may be obtained with extended neuromonitoring.

Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion.

OBJECT: High-flow microinfusion is a novel technique for delivery of compounds directly into brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into brain parenchyma represents an additional potential application of this technique not previously described. In this report the authors sought to examine the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) for this reason. METHODS: An 18-mer 35S-PS-ODN (Mr approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was analyzed to determine the radioactivity and stability of the 35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The 35S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 1% (50 +/- 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, but stabilized at a lower CSF content of 0.2% (1 +/- 0.1 nCi) thereafter. The volume of distribution was 105 +/- 7.9 mm3 at 1 hour, representing a volume of distribution/volume of infusion ratio of 5.2. The volume of distribution increased to 443 +/- 62.3 mm3 at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 microM to 3.2 microM. Undegraded 18-mer was observed throughout the 48-hour period by means of 20% polyacrylamide/7 M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity and minimal structural changes in tissue were observed on histological investigation. CONCLUSIONS: The authors found that PS-ODNs can be safely delivered in high concentrations to wide areas of rat brain by using high-flow microinfusion and are stable even after 48 hours in situ.

Social reasoning in individuals with persecutory delusions: the effects of additional information on attributions for the observed behaviour of others.

The extent to which individuals suffering from persecutory delusions, as compared to matched controls, were prepared to change their attributional judgments following additional information, was investigated. Participants were required to decide whether the actor or target individual had caused an action before and after information, which was either high or low in terms of distinctiveness, consistency and consensus. There were no differences between the three participant groups which all made decisions, and changed their decisions, in the directions predicted by attribution theory.

Intraoperative monitoring of substrate delivery during aneurysm and hematoma surgery: initial experience in 16 patients.

The effects of proximal occlusion of the parent artery during aneurysm surgery in humans are not fully understood, although this method is widely used. The reduction in substrate that can be tolerated by normal and subarachnoid hemorrhage (SAH)-affected brain is unknown. Therefore, the authors measured brain oxygen tension (brain PO2), carbon dioxide tension (brain PCO2), pH, and hemoglobin oxygen (HbO2) saturation before and after temporary occlusion in 12 patients with aneurysms. The effect of removal of a traumatic intracranial hematoma on cerebral oxygenation was also studied in four severely head injured patients. A multiparameter sensor was placed in the cortex of interest and locked by means of a specially designed skull bolt. The mean arterial blood pressure, inspired O2 fraction, and end-tidal PCO2 were analyzed. Brain PO2 and HbO2 saturation data were collected every 10 seconds. Descriptive and nonparametric analyses were used to analyze the data. A wide range in baseline PO2 was seen, although a decrease from baseline in brain PO2 was found in all patients. During temporary occlusion, brain PO2 in patients with unruptured aneurysm (seven patients) dropped significantly, from 60 +/- 31 to 27 +/- 17 mm Hg (p < 0.05). In the SAH group (five patients), the brain PO2 dropped from 106 +/- 74 to 87 +/- 73 mm Hg (not significant). Removal of intracranial hematomas in four severely head injured patients resulted in a significant increase in brain PO2, from 13 +/- 9 to 34 +/- 13 mm Hg (p < 0.05). The duration of safe temporary occlusion could not be determined from this group of patients, because none developed postoperative deterioration in their neurological status. However, the data indicate that this technique is useful to detect changes in substrate delivery during intraoperative maneuvers. This study also reemphasizes the need for emergency removal of intracranial hematomas to improve substrate delivery in severely head injured patients.

Continuous monitoring of cerebral substrate delivery and clearance: initial experience in 24 patients with severe acute brain injuries.

OBJECTIVE: Current neuromonitoring techniques in severe human head injury often fail to detect the causes of clinical deterioration. A sensor is now available for continuous monitoring of brain oxygen tension, carbon dioxide tension, and pH values. In this study, brain tissue oxygen tension was used to differentiate patients at risk for brain ischemia and to predict outcome. METHODS: The multiparameter sensor was inserted into brain tissue, along with a standard ventriculostomy catheter and a microdialysis probe, in 24 patients. Lactate and glucose were measured by high-pressure liquid chromatography in hourly dialysate samples. RESULTS: Patients who experienced a good recovery (n = 8) sustained a mean brain partial oxygen pressure of 39 +/- 4 mm Hg, brain partial carbon dioxide pressure (PCO2) of 50 +/- 8 mm Hg, and a brain pH of 7.14 +/- 0.12. Patients with moderate to severe disability (n = 6) sustained a mean brain partial oxygen pressure of 31 +/- 5 mm Hg, brain PCO2 of 47 +/- 2 mm Hg, and a brain pH of 7.11 +/- 0.12. Ten patients who died or remained vegetative sustained a mean brain partial oxygen pressure of 19 +/- 8 mm Hg, a brain PCO2 of 64 +/- 21 mm Hg, and a brain pH of 6.85 +/- 0.41. Mean brain PCO2 levels of 90 to 150 mm Hg were consistently observed after cerebral circulatory arrest or brain death. Dialysate lactate and glucose were less clearly correlated to outcome than brain oxygen tension. Dialysate glucose was extremely low in all patients and zero in most patients who died. CONCLUSION: Brain oxygen pressure, brain carbon dioxide pressure, and brain pH measurements, as well as a microdialysis probe for glucose and lactate analysis, may optimize the management of comatose neurosurgical patients by allowing a fuller understanding of the dynamic factors affecting brain metabolism.

Effects of the allosteric modification of hemoglobin on brain oxygen and infarct size in a feline model of stroke.

BACKGROUND AND PURPOSE: Cerebral ischemia and stroke are leading causes of morbidity and mortality. An approach to protecting the brain during ischemia is to try to increase the delivery of oxygen via the residual blood flow through and around ischemic tissue. To test this hypothesis, we used a novel oxygen delivery agent, RSR-13 (2-[4-[[(3,5-dimethylanilino)-carbonyl]-methyl]phenoxy]-2-methylpr opionic acid). Intravenous administration of RSR-13 increases oxygen delivery through allosteric modification of the hemoglobin molecule, resulting in a shift in the hemoglobin/oxygen dissociation curve in favour of oxygen delivery. METHODS: We studied RSR-13 in a feline model of permanent middle cerebral artery occlusion to assess its effects on cerebral oxygenation and infarct size. A randomized, blinded study of RSR-13 (n = 6) versus 0.45% saline (n = 12) was conducted, after an RSR-13 dose-escalation study (n = 4). Drug was administered as a preocclusion bolus followed by a continuous infusion for the duration of the experiment (5 hours). Brain oxygen was measured continuously with the use of a Clark oxygen electrode. Infarct size was measured at 5 hours after occlusion with computer-assisted volumetric analysis. RESULTS: The drug treatment group had consistently higher mean brain oxygen tension than controls (33 +/- 5 and 27 +/- 6 mm Hg, respectively) and significantly smaller infarcts (21 +/- 9% versus 33 +/- 9%, respectively, P < .008). We observed an inverse relationship between the dose response of RSR-13 (the shift in the hemoglobin/oxygen dissociation curve) and infarct size. CONCLUSIONS: These results are evidence that allosteric hemoglobin modification is protective to the brain after acute focal ischemia, providing a new opportunity for neuroprotection and raising the possibility of enhancing the protective effect of thrombolysis and ion channel blockade.

Multiparametric continuous monitoring of brain metabolism and substrate delivery in neurosurgical patients.

Brain function and tissue integrity are highly dependent on continuous oxygen supply and clearance of CO2. Aerobic metabolism is the major energy source to normal brain, however, during hypoxia and ischemia, lactate accumulation may sometimes be seen, indicating anaerobic glycolysis after severe head injury. Current monitoring techniques often fail to detect such events which can affect substrate delivery to the injured brain. We have recently adapted a method for continuous monitoring of brain tissue pO2, pCO2, pH and temperature, using a single sensor. The multiparameter sensor is inserted into brain tissue, via a new three lumen bolt, together with a standard ventriculostomy catheter and a microdialysis probe. The system has been left in place as long as needed, but never more than 7 days. All readings were compared to clinical parameters, and outcome. Stable measurements could be obtained in the first group of 20 patients, after calibration and rigid fixation, using the new bolt. Severely head injured patients had brain oxygen levels of less than 25-30 mmHg for the first hours after injury. Thereafter two patterns could be seen. Patients with favorable outcome had a slow increase in brain oxygen, and brain CO2 decreased to normal values, as long as the cerebral perfusion pressure (CPP) was kept above 70 mmHg. However, in those patients with secondary ischemic events, and bad outcome, a further decline in brain oxygen to anaerobic levels (< 20 mmHg) was seen. For these patients, both decreased and increased brain CO2 levels could be seen. Brain CO2 levels of 90-150 mmHg were consistently seen after brain death. Brain pH was inversely related to brain CO2 for all patients. Brain glucose and lactate in patients with poor outcome were 639 microM l-1 +/- 330, and 1642 microM l-1 +/- 788, whereas patients with good outcome had brain glucose levels of 808 microM l-1 +/- 321 and lactate levels of 1001 microM l-1 +/- 417. Extended neuromonitoring using a combined sensor for brain oxygen, CO2, pH and temperature measurements, as well as a microdialysis probe for glucose and lactate analysis may optimize the management of comatose neurosurgical patients in the future, by allowing a fuller understanding of dynamic factors affecting brain metabolism.