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Background: Following traumatic brain injury (TBI), a disturbed cerebral glucose metabolism contributes to secondary brain damage. To study local cerebral glucose metabolism after TBI, we delivered (13)C-labeled glucose into brain tissue by microdialysis (MD)., Method: MD probes were inserted bilaterally into the parietal cortex of rat brain, one probe in the shear stress zone of the injury and the other at the corresponding contralateral coordinates. A moderately severe controlled cortical contusion was used to model TBI. Dialysate concentrations of glucose, pyruvate, lactate, and glycerol were measured, and following derivatization, (13)C enrichments of the compounds were determined by gas chromatography-mass spectrometry., Findings: We found that (13)C-labeled glucose was rapidly converted into (13)C-lactate and (13)C-glycerol. In the hours following TBI, concentrations and (13)C enrichments of lactate and glycerol increased., Conclusions: The findings confirm the occurrence of anaerobic local glucose metabolism early after TBI. Only a small fraction of the glycerol was newly synthesized, suggesting that the hypothesis that most of the released glycerol after TBI comes from degradation of membrane phospholipids still holds. We conclude that the combination of microdialysis and stable isotope technique is a useful tool for investigating local glucose metabolism following brain injury.

Purpose: Radiation-induced brain injury (RBI) is an insidious side-effect of radiotherapy mediated by vascular alterations, inflammation and ischaemia. In previous studies we had shown potential increases in loco-regional blood flow and glucose metabolism in brain tumours by using electrical cervical spinal cord stimulation (SCS). In this preliminary report we demonstrate the effect of cervical SCS on RBI-tissue metabolism, as assessed using [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET)., Methods: SCS devices were inserted in eight patients with diagnosis of potential RBI in previously irradiated areas. While the SCS device was deactivated, each patient underwent an initial FDG-PET study to evaluate the clinical status. A second FDG-PET study was performed later the same day while the SCS device was activated in order to evaluate the effect of cervical SCS on glucose metabolism., Results: Basal glucose metabolism in RBI areas was 31% lower than peri-RBI areas (p = 0.009) and 32% lower than healthy contra-lateral areas (p = 0.020). There was a significant increase in glucose uptake during SCS in both the RBI (p = 0.005) and the peri-RBI (p = 0.004) areas, with measured increases of 38 and 42%, respectively. The estimated potential maximal residual activity of the first FDG dose's contribution to the activity on the second scan was

A passive oddball experiment was used in which stimuli were emotional exclamations differing in their affective tone. In both electroencephalography (EEG) and magnetoencephalography (MEG), deviants elicited an N300 component, sometimes accompanied by a slow wave. Both components had a symmetrical distribution, but the former was more posterior than the latter. The same responses to prosodic stimuli were significant in 6 of 27 patients with severe disorders of consciousness (persistent vegetative state and minimally conscious state) and in all 3 of the examined locked-in patients, indicating that the procedure can be applied for testing neurological patients. The occurrence of significant responses depended on the presence or absence of a lesion to the right temporal lobe. Obviously, the N300 depends on the activity of the right temporal cortex but does not originate there. We suggest that the component is related not to the recognition of affective prosody as such, but to the following detection of affective mismatch due to violations of emotional context of stimulation.

Objective: The high mortality of acute subdural haematoma (ASDH) is largely explained by its frequent association with primary brain damage consisting of contusion and brain swelling. However, the nature and causes of brain swelling after traumatic brain injury are multifactorial and poorly understood. The purpose of this study was to investigate the pathophysiology of brain swelling associated with ASDH in traumatic brain injury., Methods: We examined whether the thickness of the haematoma, parenchymal injury, or presence of a secondary insult had an effect on traumatic brain swelling. The variables that might affect the pathophysiology of ASDH were examined, including: (1) age and mechanism of injury, (2) neurological findings, (3) secondary insult and extracranial injuries, (4) pre-operative computed tomography (CT) scan results, and (5) outcome., Results: A total of 212 patients were included in this study. On CT scan, 159 patients (75.0%) did not have brain swelling, 29 (13.7%) had hemispheric brain swelling, and 24 (11.3%) had diffuse brain swelling. Brain swelling associated with ASDH is caused by secondary insult in addition to parenchymal injury. In the present study, the outcome of ASDH associated with brain swelling was poor, even when treated with early surgical evacuation; the mortality rate of such patients was over 75%., Conclusions: Given our findings, it is possible that the poor outcome of ASDH patients depends not only on the characteristics of the haematoma itself, but also on the presence of additional cerebral parenchymal injury and secondary insult.

Whether the hippocampus and medial temporal lobe (MTL) play any important role in visual working memory is a relatively new and controversial research question. The primary goal of this study was to assess working memory for faces over very short delays in patients with MTL damage. Patients and matched controls were required to remember one face that was parametrically morphed to be more or less similar to a probe face, over either a 1- or an 8-sec delay. Memory was assessed using both forced choice and old-new recognition tasks. The results show that MTL damage impairs both speed and accuracy of visual working memory across tasks. We speculate that the hippocampus is generally necessary for memory encoding.

Stroke is the world's second leading cause of mortality and long-term disability. Damage to the nondominant right brain has distinct clinical characteristics. The resultant cardiovascular and autonomic dysfunction peculiar to right hemispheric stroke can adversely affect the short- and long-term outcome of stroke victims. Blood flow characteristics to the right hemisphere may also put the right brain at more risk for embolic and silent infarcts.

The effect of retraining a damaged connectionist model of single-word reading was investigated with the aim of establishing whether plasticity-related changes occurring during the recovery process can contribute to our understanding of the pattern of dissociations found in brain-damaged patients. In particular, we sought to reproduce the strong frequency x consistency interactions found in surface dyslexia. A replication of Plaut, McClelland, Seidenberg, and Patterson's (1996) model of word reading was damaged and then retrained, using a standard backpropagation algorithm. Immediately after damage, there was only a small frequency x consistency interaction. Retraining the damaged model crystallized out these small differences into a strong dissociation, very similar to the pattern found in surface dyslexic patients. What is more, the percentage of regularization errors, always high in surface dyslexics, increased greatly over the retraining period, moving from under 10% to over 80% in some simulations. These results suggest that the performance patterns of brain-damaged patients can owe as much to the substantial changes in the pattern of connectivity occurring during recovery as to the original premorbid structure. This finding is discussed in relation to the traditional cognitive neuropsychological assumptions of subtractivity and transparency.

Measurements were made of plasma levels of free (f) thyroxine (fT4), triiodothyronine (fT3), thyrotropic hormone (TSH), adrenocorticotrophic hormone (ACTH), aldosterone, and renin in patients with dyscirculatory encephalopathy (DE). Their influences on the development of chronic circulatory insufficiency were assessed. A total of 39 patients were studied (aged 45-73 years) with DE stages I and II, without acute or chronic (in the exacerbation phase) somatic illness. These observations showed that diffuse lesions of brain tissues of different severities were accompanied by the following changes in thyroid homeostasis: 1) significant combined increases in TSH without alteration to the "fT3-TSH" negative feedback regulatory mechanism in patients with stage I DE; 2) significant combined decreases in TSH levels with marked suppression of the conversion of thyroxine into triiodothyronine and an interaction with impairments in the "fT3-hypophysis" system in patients with stage II DE. In addition, there were changes (increases) in cortisol levels with simultaneous decreases in renin levels in patients with stage II DE as compared with patients with stage I DE. Correlation analysis demonstrated the absence of any relationship between the age of the patients, the state of hormonal homeostasis, and the extent of vascular stenosis. These results suggest a role for hormones of the hypothalamo-hypophyseal-adrenal, thyroid, and renin-angiotensin systems in the mechanism by which DE develops as well as the possibility of using tests for these hormones as additional criteria for assessing the severity of diffuse brain lesions.

Damage to the orbital prefrontal cortex has been implicated in selectively diminishing electrodermal autonomic nervous system responses to anticipated punishing stimuli (e.g., losing money; Bechara, Damasio, & Damasio, 2000), but not to unanticipated punishing stimuli (e.g., loud noises; Damasio, Tranel, & Damasio, 1990). We extended this research by examining the effects of orbitofrontal damage on emotional responses to unanticipated and anticipated acoustic startles and collecting a more extensive set of physiological measures, emotional facial behavior, and self-reported emotional experience. Consistent with previous research, patients showed intact physiology to an unanticipated startle but failed to show appropriate anticipatory cardiovascular responses (patients' heart rates decreased, controls' increased). In addition, patients displayed more surprise facial behavior and reported marginally more fear than did controls in response to the unanticipated startle. Thus, orbitofrontal damage may compromise the ability to anticipate physiologically the onset of aversive stimuli, despite intact or enhanced emotional responses when such stimuli occur unexpectedly.

Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed.

In two recent studies, the hypothesis that recall is more severely impaired than recognition in patients with damage thought to be limited to the hippocampus was tested. Yonelinas et al. (2002) reported findings that appeared to support this hypothesis, whereas Manns, Hopkins, Reed, Kitchener, and Squire (2003) found that recall and recognition were equally impaired. An analysis of the individual subject data from the two studies revealed that the apparent disagreement stemmed from the inclusion of a single outlying recognition score for 1 of the 55 control subjects in Yonelinas et al. (2002). When that outlier was excluded, the studies were in agreement that recognition and recall are substantially and similarly impaired in these patients. Yonelinas et al. (2002) also analyzed remember/know judgments and ROC data in an effort to show that recollection is selectively impaired in patients, but these analyses also raise problems.

In 3 patients with unilateral pulvinar lesions, we tested the pulvinar's role in selective attention processing. Each patient completed four variants of a flanker interference task in which they reported the color of a square of a specified size while ignoring an irrelevant flanker that appeared either contralesionally or ipsilesionally to the target. The main finding was that when target location was not known and target and flanker were associated with competing responses, reaction times to contralesional targets were longer than those to ipsilesional targets. Our findings suggest that pulvinar damage produces a contralesional deficit in response competition.

Background: Cerebral ischemia is considered a key factor in the development of secondary damage after Traumatic Brain Injury (TBI). Studies on Cerebral Blood Flow (CBF) have documented decreased flow in over 50% of patients with TBI, studied in the acute phase. Transcranial Doppler (TCD) sonography is a non-invasive technique, permitting frequent or continuous measurements of blood flow velocity in the basal cerebral arteries., Objectives: To investigate the potential of TCD to detect decreased blood flow velocity in the early phase after TBI;To investigate whether flow velocity differs between hemispheres in patients with focal lesions versus those with more diffuse injuries;To investigate if decreased blood flow velocity is indicative of cerebral ischemia, as evidenced by measurements of brain tissue pO(2)., Methods: TCD examinations were performed in 57 patients with severe TBI (GCS

Background: Regional cerebral blood flow may be compromised during aneurysm surgery. This may occur during vessel occlusion by temporary cliping or result from the malposition of an aneurysm clip. In this report we monitored intra-operatively the brain tissue oxygen concentration (PtiO2) to visualize regional ischaemic events., Method: During surgery of 10 intracranial aneurysms, monitoring of PtiO2 was performed using a polarographic microcatheter (Licox, GMS-Kiel-Germany), which was placed in the vascular territory of the artery harboring the aneurysm., Findings: No complications were observed after implantation of Licox electrodes. In 6 patients PtiO2 decreased during transient clipping. In two patients PtiO2 decreased below 2 mmHg without morphological or clinical signs cerebral ischemia. In four patients, without incidence during surgery, only minor oscillations were observed., Conclusion: Intra-operative monitoring of PtiO2 is a complimentary procedure to monitor cerebral perfusion and detect episodes of ischaemia. Given the rapid detection of these events, therapeutic intervention may be initiated before irreversible neuronal damage occurs.

Neuropsychological studies of patients with acquired semantic impairments have yielded two distinct and contrasting patterns of performance in a spoken-word/picture-matching task (Warrington & Cipolotti, 1996). Patients labeled access/refractory are strongly influenced by presentation rate, semantic relatedness of distractors, and repetition, yet they seem relatively unaffected by lexical frequency. Degraded-store patients, on the other hand, are strongly affected by lexical frequency but are less affected by presentation rate, semantic relatedness, or repetition. Our account of these patterns of performance is based on the distinction between two different types of neurological damage: (1) damage to neuromodulatory systems that function to amplify neural signals while suppressing normal refractory-like effects and (2) damage to connections between groups of neurons that encode semantic information and are sensitive to frequency/familiarity. We present a connectionist model that learns to map spoken-word input to semantic representations and that incorporates a particular form of neural refractoriness referred to as synaptic depression, as well as a simple form of neuromodulation. We show that the model is capable of accounting for the contrasting patterns of semantic impairment under these two different forms of damage and, furthermore, demonstrate how it is capable of handling several documented cases that are exceptions to the basic patterns of impairment. Several predictions and limitations of the present model are discussed.

Posterior parietal cortex lesions have been associated with both hemispatial neglect and spatial-updating deficits. Currently, the relation between these processes remains poorly understood. We tested the ability of parietal patients with neglect to update remembered target locations during passive whole-body rotations. The rotations and manual pointing responses were executed with and without vision. During the rotation, the remembered location stayed on the same side of the body midline or crossed the midline. Parietal patients generally underestimated rotations, as compared with control groups, but updated targets equally well on either side of the body midline, regardless of the amount of updating required. Once parietal patients have localized a target, they can use self-motion information to update its location, even if it passes into the region they typically neglect. This lack of contralesional updating effects contrasts with impairments in eye position updating found in previous work with parietal patients.

Background: The anterior interhemispheric approach offers us an excellent surgical view for suprasellar lesions. Following this approach, we occasionally encounter postoperative brain damage in the frontal lobes. To assess the determinants of such a complication, we undertook a clinical study., Method: Potential causes for such brain damage were evaluated in 28 consecutive patients with suprasellar tumours extirpated using this approach. We focused particularly on the influences of venous involvement during surgery. The draining territory index (DTI) was originally devised for estimating the extent of the draining area of the sacrificed bridging veins., Findings: CT evident brain damage was observed in five of 28 patients (17.8%), but only one patient (3.6%) showed clinically significant postoperative deficits. The patient's age, tumour pathology, tumour character, tumour size, duration of surgery, and radicality of the surgery did not affect the incidence of the brain damage. Of the twelve patients whose bridging veins were sacrificed during surgery, four (33.3%) showed brain damage in the frontal lobes. In contrast, such damage was observed in only one patient out of 16 (6.3%) whose bridging veins were preserved. Among the brain-damaged group, the average DTI of the sacrificed veins was significantly higher than that among the non-brain-damaged group., Interpretation: Venous involvement during surgery significantly aggravated postoperative brain damage following the anterior interhemispheric approach. The DTI was useful in predicting the risk of brain damage, and a large bridging vein with a DTI over 50% should not be sacrificed during surgery.

Objectives: Preservation of brain function while maximizing resection is the main aim of brain tumour surgery. The purpose of this study was to evaluate the efficacy of intra-operative magnetic resonance imaging to preserve brain function in patients with tumours in or near eloquent brain areas., Methods and Material: Between August 1997 and January 1999 fifty-eight craniotomies for intracranial tumours or vascular malformations have been performed at the University of Leipzig using a 0.5 T superconducting MR system "SIGNA SP" (General Electric Medical Systems, USA). In 32 of these patients (15 male/17 female) with intracranial tumours, located in or near eloquent brain areas (sensorimotor cortex/speech center), 34 craniotomies were performed using the image guidance of the interventional MRI., Results: Using intra-operative MRI criteria, complete tumour removal could be achieved in 28 (82%) of 34 procedures. In 3 patients only subtotal tumour removal was possible, because the residual tumour was not visible on the intra-operative MR images, but could be identified on early diagnostic follow-up MR-scans. In 3 patients, incomplete tumour resection was performed in order to avoid neurological impairment. In these patients intra-operative MR-images revealed residual tissue abnormalities involving or encroaching on deep brain structures or motor/language cortex. Pre-operative neurological status was unchanged in 24 patients (70%), worsened in 4 patients (12%) and improved in 6 patients (18%)., Conclusions: Intra-operative MRI is helpful for navigation as well as to demonstrate the tumour margins to achieve a complete and safe resection of intracranial lesions located in or near eloquent brain areas. It enables an image based functional monitoring of the brain which is critical for motor, sensory or language function. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized.

Indications of surgical treatment for lesions in the central nervous system depend on the risk of a definitive neurological deficit, related to the benefit of resection. Detection of eloquent areas is then necessary because of major individual variability. Neuro-imaging functional techniques are in development and are beginning to be efficient for cortical sensorymotor mapping, but still lack sensitivity and specificity for language mapping, and remain unable to give real-time data during surgery and to perform sub-cortical mapping. The more precise and reliable method of functional mapping is represented by the intra-operative direct electrical stimulations (DES), which allow identification and preservation of essential pathways for motricity, sensibility and language, at each level of the central nervous system (cortico-subcortical). We report our experience of DES in the surgery of tumours and vascular malformations located in supra-tentorial brain eloquent areas, with a consecutive series of 60 patients operated on under general or local anaesthesia, from November 1996 until May 1999 in our department at La Salpêtrière Hospital. Presenting symptoms in the 60 subjects (39 males, 21 females, mean age: 45 years) were seizures in 37 cases with normal clinical examination, and mild neurological deficit in 29 cases. MRI showed 60 supra-tentorial brain lesions: 30 precentral, 12 postcentral, 14 perisylvian in the dominant hemisphere, 4 deep-seated. All subjects underwent surgical resection using DES, with supratentorial cortico-subcortical mapping under general anaesthesia for motor areas detection in 43 cases and under local anaesthesia for sensori-motor and/or language tasks in 17 cases. The final histological diagnosis was 44 gliomas (31 low-grade and 13 high-grade), 9 metastasis, 3 cavernomas, 4 arteriovenous malformations (AVM). Resection was total or subtotal in 52 cases (87%) and partial in 8 cases (13%). 29 patients had no post-operative deficit, while the other 31 patients were impaired post-operatively, with in all cases, except 3, a complete recovery delayed for 15 days to 3 months (overall morbidity: 5%). The median follow up was 14 months. Intra-operative direct electrical stimulations of the central nervous system constitute a reliable, precise and safe method, allowing the realization of a functional mapping useful for all operations of lesions located in eloquent areas. This technique allows a minimization of definitive post-operative neurological deficit, and concurrently an improvement in the quality of resection.

An enzyme-histochemical technique was used to examine the changes in cytochrome oxidase activity during acute focal ischaemia in the rat. In the somatosensory cortex, the enzyme activity began to increase significantly (p < 0.01) 1 hour after middle cerebral artery occlusion (MCAO) and continued to increase up to 3 hours, during which ischaemic cell damage was not detected. In the striatum, the enzyme activity increased significantly (p < 0.01) 1 hour after MCAO in the absence of morphological evidence of ischaemic cell damage; a peak activity was reached at 2 hours, and began to decline 3 hours after MCAO when moderate ischaemic change was detected. In both cortical and subcortical areas, the enzyme activity tended to decrease from 4 hours after MCAO, and was reduced to a level similar to or below that of the non-ischaemic hemisphere 5 hours after MCAO, when severe ischaemic damage was demonstrated. The relation of this transient increase of cytochrome oxidase activity in the early stage of acute ischaemia and the hypermetabolism of neuronal cells during ischaemic insult was discussed.

We studied six patients in whom colloid cysts had been removed surgically from the third ventricle. The patients were selected simply by availability for the study, not on grounds of clinically diagnosed amnesia or its absence. The outcomes of operation ranged from one patient who had postoperatively resumed a normal life without complaint of memory disorder at any stage, through four who complained of memory disorder since operation, to one who was so severely amnesic as to require constant supervision. Each patient was given psychometric tests of memory, and was also scanned by magnetic-resonance imaging. One of us examined the six scans and assessed the extent of damage to the fornix, and any other brain damage, in ignorance of the outcomes of the psychometric tests. The fornix in the right hemisphere had been destroyed in all six cases, and all showed evidence of moderate or severe impairment in nonverbal memory. The fornix in the left hemisphere was intact in only one patient; this was the patient who had resumed a normal life without complaint of memory disorder. The left fornix was damaged with some sparing in one further patient, and the remaining four patients showed destruction of the fornix in the left as well as in the right hemisphere. The severity of impairment in verbal memory in these six cases was related to the severity of the damage to the left fornix. No other evidence of brain damage appeared to be systematically related to memory ability. These results add to the evidence that bilateral fornix damage produces amnesia, and that sparing of the left fornix alone is sufficient to ensure a more favourable outcome.

The incidence and clinical significance was studied in 2574 closed head injury patients, each of them having a Glasgow Coma Scale (GCS) 9 to 12 after trauma. All patients underwent computerized tomography (CT) after being admitted to the emergency service. One hundred and six patients (4.1%) experienced seizures within 1 week after head injury; 46 of these (1.8% of the series) had seizures within 24 hours after trauma. There was no statistically significant difference between the early seizure and seizure free group of patients in gender, age and GCS with the exception of cause of injury (p < 0.01). The incidence of intracerebral parenchymal damage was found to be higher with seizures developing between day 2 and day 7 (80%) than those with seizures developing within 24 hours (54.3%). Analysing the data revealed that early posttraumatic seizures were not related to the presence of intracerebral parenchymal damage on CT scan. The occurrence of early seizures did not affect the mortality and outcome of moderate closed head injury patients.

Neonatal encephalopathy, plausibly related to hypoxia and ischaemia, remains one of the main problems in perinatal medicine. Efforts are necessary to find new non-invasive methods for assessing brain oxygenation. Near infrared spectroscopy (NIRS) provides information on the concentrations of the oxygenated and deoxygenated forms of haemoglobin, as well as of the redox state of cytochrome aa3. Different important variables such as cerebral blood volume and flow, and the responses of these to changes in pCO2, can be derived through haemoglobin measurement. Changes in cytochrome aa3 may provide immediate information on intracellular oxygen utilization. Various studies have shown the feasibility of NIRS in preterm infants. Methodological and technical problems of this method are discussed.

To prevent cerebral vasospasm after aneurysmal subarachnoid haemorrhage, cisternal irrigation has been reported to be more effective when combined with continuous head-shaking (head-shaking method). The present study was conducted to evaluate the safety and preventative effect for vasospasm in patients treated with the head-shaking method. Six of 17 patients managed postoperatively by the original head-shaking procedure developed neurological deterioration related to the method: two had intracranial haematoma (one with acute interhemispheric subdural haematoma, and the other with cerebellar haemorrhage), two had acute brain swelling, and two failed to show abnormal findings on computed tomography. These pathological processes may be suitably referred to as "head-shaking syndrome". Delayed ischaemic neurological deficits associated with low-density lesions on computed tomography were demonstrated in five patients (29%). From these observations, the head-shaking method may not be as safe as described in the original articles, and is critically evaluated in terms of its preventative effect for cerebral vasospasm.

In the posttraumatic period, measurement of neural tissue enzymes in serum and cerebrospinal fluid gives quantitative information about the severity of the head injury. In our study, we evaluated the relationship between the serum and cerebrospinal fluid levels of neuron specific enolase and the severity of trauma. Head traumas at different severity were applied experimentally (Mild 0.038 N, Moderate 0.057 N, Severe 0.3 N). Serum and cerebrospinal fluid levels of neuron specific enolase were measured in trauma and control groups of rats. Only in the severe trauma group, the neuron specific enolase levels of cerebrospinal fluid were significantly increased. There was no statistically significant difference between the groups when serum neuron specific enolase levels were evaluated. Our data leads us to conclude that trauma, causing significant neural damage, results in an increase in cerebrospinal fluid neuron specific enolase levels, however the serum neuron specific enolase levels do not seem to run parallel with that increase.

Intraoperative mapping techniques allow a reliable identification or exclusion of eloquent brain areas and are well tolerated by the patients. In dominant opercular tumours radical surgery can only be achieved without lasting deficits with intraoperative histological examination of the resection line and mapping. If an early postoperative MRI shows residual opercular tumour in non-eloquent areas re-operation is recommended. In large dominant insular or opercular-insular tumours only biopsy is recommended, because only an incomplete removal can be accomplished, because the trial of radical removal carries a high risk of postoperative deficits due to possible vascular damage of the lenticulo-striate arteries or internal capsule. Because subtotal removal of low grade gliomas does not increase the progression free interval, we would not recommend surgery in these cases, as they carry a significant risk of a further deficit.

Forty-three patients were operated on for ruptured intracranial aneurysms during a 12-month-period. Intraoperative evaluation of cortical blood flow by means of a thermal diffusion probe was performed in 23 out of the 41 patients who were operated on for aneurysms of the anterior circulation. The autoregulation index was determined at the time of raising the systemic blood pressure after clipping of the aneurysm(s). No statistically significant difference was found between the averages of the autoregulation indexes calculated in the subgroups of patients submitted respectively to early or delayed surgery. There was no correlation of both cortical blood flow and autoregulation with either age of the patients, or preoperative neurological grade. On the contrary, the autoregulation index showed a statistically significant correlation with outcome.

Monitoring cerebral blood flow during focal ischaemia and reperfusion with established techniques such as hydrogen clearance and autoradiography is difficult. Laser Doppler flowmetry is a new technique, it allows one to continuously measure blood flow in small tissue samples. The objective of this study was to compare laser Doppler flowmetry with hydrogen clearance using a new single fiber probe to obtain measurements in deep brain structures and then to show the temporal profile of cerebral blood flow during focal ischaemia and after reperfusion. First, the single fiber laser Doppler method was compared with the hydrogen clearance method in ten Wistar rats. Second, focal cerebral ischaemia was induced in fifteen Wistar rats using a model of middle cerebral artery occlusion based on the intravascular insertion of a nylon suture; reperfusion occurred after withdrawal of the suture. The laser Doppler probe was placed in the lateral caudatoputamen, and local cerebral blood flow was measured continuously before and during occlusion as well as after reperfusion. The relative blood flow values obtained by the laser Doppler method and the hydrogen clearance method showed a good correlation (r = 0.76) and a linear relationship. A rapid decrease in laser Doppler flowmetry to 42 +/- 16% of former baseline values was seen with occlusion of the middle cerebral artery; during occlusion cerebral blood flow remained at this level. Reperfusion resulted in a heterogeneous pattern of cerebral blood flow as laser Doppler flowmetry values ranged from 25% to 134% of baseline values. The effects of middle cerebral artery occlusion and reperfusion on cerebral blood flow can be monitored on-line with laser Doppler flowmetry.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term effect of extra-intracranial arterial bypass on cerebral circulation was examined. Cortical blood flow and cognitive ability were evaluated pre- and up to 3 years post-bypass in a 58-years-old man with severe carotid occlusive lesions, who presented with 3 transient cerebral ischaemic attacks which resulted in mental deterioration over 3 years. Regional cerebral blood flow (rCBF) was evaluated pre- and up to 33 months post-bypass by 123Iodine N-isopropyl-p-iodoamphetamine (IMP) single-photon emission CT (SPECT). Mental abilities were evaluated before and up to 33 months after surgery by the Hasegawa's dementia rating scale (HDRS). Pre-operatively, cerebral angiography showed left carotid siphon occlusion and hypoplastic stenosis of left anterior cerebral artery with collaterals from the anterior communicating artery. CT and MRI showed left temporo-parietal borderzone infarction and an enhanced T 1 lesion by gadolinium-DTPA at left periventriculum. rCBF showed extensive hypoperfusion in left anterior-parieto-temporal-cortex. HDRS scores deteriorated apparently on days 3, 5, which recovered gradually on days 8, 10, 75 after onset of mental deterioration. A bypass was performed 4 months after onset. rCBF showed gradual recovery in the left anterior-parietal cortex up to 33 months after bypass. Semiquantitative rCBF showed gradual decreases of regional asymmetry after the bypass. HDRS scores returned to their maximum up to 37 months after onset. Three-year follow-up shows improved cortical rCBF and cognition after the bypass.

A group of 74 patients with head injury (54 severe, 17 moderate and 3 minor) had continuous monitoring of both arterial and intracranial pressure with computer-based registration of these pressures, cerebral perfusion pressure and other variables. In 60 patients cerebral perfusion pressure CPP fell below 60 mm Hg for periods of 5 minutes or longer. The distribution over time of these reductions in CPP during up to 12 days of monitoring was studied, and each episode of reduced CPP was attributed to a fall in arterial pressure, an increase in intracranial pressure, or both. Two clusters of reduced CPP were found, one during the first 24 hours of monitoring, when reduced CPP was mainly caused by a reduction in arterial pressure, and the other at 5 or 6 days after injury, when reduced CPP was due mainly to an increase in intracranial pressure. There was a significant correlation between low CPP due to reduced arterial pressure and the Injury Severity Score (p < 0.001), suggesting that resuscitative measures may have been less than optimal in these cases. There was also significant correlation between the duration of low CPP and low arterial pressure and an adverse outcome from injury as assessed at 6, 12 and 24 months after injury (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

We will report our accumulated experience in monitoring of brain temperatures in neurosurgical patients. The intraventricular temperature was monitored with a thermocouple designed for the purpose. This thermocouple was introduced through a plastic catheter, which was also used for monitoring intracranial pressure. The rectal and epidural temperature was simultaneously measured, with commercially available thermocouples. Human brain temperature is higher than the central core temperature, and there is also a temperature gradient within the brain, with the central parts being warmer than the surface. The relationship between rectal, epidural and intraventricular temperatures is maintained during anaesthesia. We have also shown that it is possible to lower the temperature of the human brain.

SM-6586 (SM) is a new derivative of dihydropyridine with potent calcium blocking activity and inhibitory activity of the Na+/H+ and Na+/Ca++ exchange transport. The effect of SM on survival rate, brain edema and metabolites was evaluated using two different models in spontaneously hypertensive rat (SHR). Global ischemia was induced by bilateral common carotid artery ligation (BLCL) and focal ischemia was induced by middle cerebral artery occlusion. The survival rate after BLCL was higher in the SM-treated group. The brain water content was lower, the ATP level was higher and lactate level was lower in the SM-treated group compared to the control group. In focal ischemia models, the SM-treated group showed a reduction of T1 relaxation time. The brain water content was significantly decreased in the SM-treated group. These results indicate that SM was effective in ameliorating the ischemic insult in global and focal cerebral ischemia models.

Neurological and neuroelectrophysio-biochemical profiles were evaluated in newborn lambs exposed to severe temporary asphyxia. Isoelectric EEG, marked disturbances of phosphorus magnetic resonance spectrum (31P-MRS), and significant brain intracellular acidosis (pHi) were noted during asphyxia. Following resuscitation, the presence of early postasphyxic blood-brain-barrier (BBB) opening was associated with a marked transient increase in intracranial pressure (ICP), a 50% neonatal mortality and a 67% incidence of severe asphyxic encephalopathy. In contrast, those lambs exposed to the same magnitude of asphyxia, but without early BBB opening experienced neither death nor severe neurological deficits. Further, these lambs showed a rapid progressive normalization of the 31P-MRS and pHi, despite, the lack of EEG recovery in the first hour following resuscitation. Thus, the present study depicts that the early postasphyxic BBB disruption following temporary neonatal asphyxia is associated with poor prognosis.

High-speed MR diffusion/perfusion imaging was performed to assess variable degree stenosis of the MCA and the formation of cytotoxic edema in a cat model of acute ischemia. Sodium transport was estimated in synaptosomes isolated from moderately perfused or non-perfused brain tissue. Complete MCA occlusion for 50-75 min produced a major disruption of brain sodium transport, whereas continued preservation of ion homeostasis and the activation of adaptive cell volume regulatory systems was associated with longer duration of moderate severity of ischemia. Preservation of neuronal ion homeostasis might be one of the main mechanisms contributing to the relative tolerance of the brain to moderate reductions in cerebral blood flow.

Hyponatremia in cats produced brain edema, detectable by both magnetic resonance imaging (MRI) and increased brain water, with a compensatory decrease of brain sodium. Sodium transport was measured in synaptosomes from hyponatremic cat cerebral cortex. The sodium efflux via Na(+)-K(+)-ATPase was significantly higher (144%) than control, while sodium influx via the Na+/H+ antiporter was significantly decreased (74%). Both responses tend to decrease brain intracellular sodium and thus, brain cell osmolality. Ischemia following unilateral middle cerebral artery occlusion also resulted in brain edema. However, the efflux of sodium via both Na(+)-K(+)-ATPase and sodium channels actually decreased, both maladaptive responses. Furthermore, when ischemia was superimposed upon hyponatremia, all of the cerebral adaptive changes which had been induced by hyponatremia alone were rendered ineffective. This resulted in further elevations of brain water and sodium. Hyponatremia superimposed upon ischemia thus worsens the brain edema associated with ischemia alone. Thus, ischemia impairs the ability of the brain to adapt to hyponatremia, probably by eliminating the compensatory mechanisms of brain sodium transport initiated by hyponatremia.

The present study was aimed at determining chronological alterations of Ca2+/calmodulin (CaM)-dependent and -independent nitric oxide synthase (NOS) activities in brain microvessels (MV) isolated from the affected hemisphere following an occlusion of the middle cerebral artery (MCAo) in rats. It was shown that significant enhancements of Ca2+/CaM-independent NOS activity to 922% and 920% of control level were manifested at 4 h and 24 h, respectively, which returned to the control level at 48 h after MCAo. Regarding Ca2+/CaM-dependent NOS, on the other hand, it was shown that the activity was invariably increased to 374% and 743% of control level at 48 h and 1 week following MCAo, respectively. Thus, the present study provided the first evidence that two distinct types of NOS activities were increased with different temporal patterns after MCAo. These heterogeneous alterations of NOS activities may be of critical importance for the induction of brain damage following cerebral ischemia.

Out of a series of 43 cases operated on for ruptured intracranial aneurysms over a 12-month-period, 32 patients were followed up to 12 months postoperatively with repeated evaluations of cerebral blood flow, using the Xenon133 inhalation technique. No statistically significant differences in cerebral perfusion were detected between the subgroups of good-grade patients, who were submitted respectively to early, or delayed surgery. Depression of flow in the affected hemisphere of poor-grade patients was principally related to the preoperative occurrence of an intracerebral haematoma. The overall results were not consistent with the hypothesis that early surgical intervention results in long-lasting effects on the cerebral circulation.

This report summarizes the results of our studies on the effects of prostacyclin (PGI2) on the outcome of global cerebral ischemia (GCI). GCI was produced for 15 and 20 min. In vivo dialysis of the hippocampus was used to determine the changes in extracellular concentrations of calcium (Ca/2e) and blood-brain barrier (BBB) permeability. Moreover, EEG and general physiological parameters were recorded. This was combined with morphological observations. PGI2 was infused continuously i.v. at a rate of 2 micrograms/kg/min. Rabbits with untreated GCI served as reference. Treatment with PGI2 significantly enhanced EEG recovery and normalization during recirculation, and reduced both the decrease in Ca+2e, and the BBB leakage. The number of ischemic neurons in the PGI2-treated rabbits was significantly lower than in the non-treated ones. PGI2 reduced brain edema. These data suggest that PGI2 may protect against postischemic brain damage, in part by inhibiting excessive calcium influx to neurons and in part by tightening of BBB.

We studied acoustic startle response and its modulation by prestimulation and by short-term and long-term habituation in 54 autistic patients and 72 normal age-matched controls. The startle response was measured as the amplitude and onset latency of the integrated orbicularis oculi EMG. There were no consistent significant differences between the autistic and control subjects in startle modulation by inhibitory or facilitatory prestimulation, short-term habituation of startle amplitude, long-term habituation of either startle amplitude or latency, or unmodulated startle amplitude. Differences between autistic and control subjects were limited to prolongation of unmodulated startle onset latencies in the autistics in all of the experimental paradigms (significant p = .005 only in the context of short-term habituation) and a statistically significant (p < .05) slower rate of short-term habituation of startle onset latency in the autistic patients, relative to the controls. Results provide only limited support for hypotheses of brainstem pathophysiology and no support for hypotheses of cerebellar pathophysiology in autism.

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of jugular venous desaturation and neurological outcome was examined in 116 patients with severe head injury. Seventy-six episodes of jugular venous desaturation were prospectively identified in 46 (40%) of the patients. The etiology of the desaturations varied, including both systemic and cerebral causes. A poor neurological outcome was strongly associated with the occurrence of jugular venous desaturation.

The outcome from severe head injury (GCS < or = 8 mmHg) was prospectively studied in patients from the Traumatic Coma Data Bank. We investigated the impact on outcome of hypotension (SBP < 90 mmHg) occurring from injury through resuscitation (early hypotension; N = 717) or in the Intensive Care Unit [ICU] (late hypotension; N = 493). Early hypotension occurred in 248 patients (34.6%) and was associated with a doubling of mortality (55% vs. 27%). If shock was present on admission, the mortality was 65%. These effects were independent of age, admission GCS motor score, presence of hypoxia, or associated severe extracranial trauma, suggesting that the influence of multiple system trauma in head injured patients is primarily due to associated hypotension. Late hypotension occurred in 156 of 493 patients (32%) and was the only hypotensive episode in 117 (24%). For 117 patients whose only hypotensive episode occurred in the ICU, 66% either died or were vegetative survivors, compared to 17% of patients who never suffered an hypotensive episode. Logistic regression modelling suggested that early and late shock were the most powerful independent predictors of mortality in this group of patients. These data demonstrate that hypotension is a common and devastating secondary brain insult in severe head injury patients, occurring not only during transport and resuscitation but also "right under our noses" in the ICU. We suggest that vigorous attention to eliminate or minimize such insults has the potential of markedly improving outcome from severe head injury.

Nuclear magnetic resonance (NMR) spectroscopy is now established as a non-invasive method of studying metabolism in living systems, ranging from cellular suspensions to man. With respect to clinical applications, recent developments include the successful implementation of new techniques for spatial localisation, and in particular the acquisition of excellent 1H spectra from selected regions of the human brain. Localised 1H spectroscopy opens the way to monitoring a wide range of compounds that are inaccessible to 31P NMR, and should add considerably to the information that is available from 31P studies. NMR spectroscopy does, however, have its limitations, which arise primarily from the fact that it is an insensitive technique. This lack of sensitivity limits the spatial resolution for metabolic studies, and means that metabolites must be present at fairly high concentrations in order to produce detectable signals. In this article, we illustrate the scope and limitations of NMR spectroscopy by describing a few examples of studies undertaken on animals and humans.

Several putative mediators of vasogenic brain edema will be considered with respect to the following criteria: 1) their effect on blood-brain barrier (BBB) permeability, 2) their vasomotor actions which may increase driving forces for transmural bulk flow, 3) their influence on edema formation, 4) their actual tissue concentration in pathological states, and 5) the therapeutic results after specific treatment. Bradykinin (BK) can induce brain edema by increasing BBB permeability to small solutes and enhancing blood pressure in the microcirculation due to arterial dilatation and venous constriction. Its interstitial concentration is enhanced after experimental trauma. Since kallikrein inhibitors reduce brain swelling all criteria favour BK as a mediator of vasogenic edema. Arachidonic acid (AA) opens BBB also for large tracers but exerts only small vasomotor effects. The edema formation is associated with an increase of the AA concentration in the interstitial space. However, convincing therapeutic results on inhibition of AA are still lacking. In addition to the formation of vasogenic edema AA has been found to induce cytotoxic edema. From experiments dealing with the vasomotor effects Ellis et al. (Am J Physiol 255: H397-H400, 1988) concluded an interaction of BK and AA in brain injury. However, our own results do not favour this hypothesis since we found divergent vasomotor and permeability effects of BK and AA. Histamine (HA) opens BBB unspecifically and dilates cerebral vessels, mechanisms by which edema formation can be explained.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevation of the head as a common practice to reduce raised intracranial pressure (ICP) has been discussed controversially of late. Some investigators were able to show that besides lowering ICP head elevation may also reduce cerebral perfusion pressure (CPP). For a new evaluation of optimal head position in neurosurgical care it would be of importance to know the influence of body position on cerebral perfusion. We therefore employed continuous jugular venous oximetry, monitoring cerebral oxygenation, to study the effect of 0 degrees, 15 degrees, 30 degrees, and 45 degrees head elevation on ICP, CPP and jugular venous oxygen saturation (SJVO2) in 25 comatose patients with reduced intracranial compliance. As expected, head elevation significantly reduced ICP from 19.8 +/- 1.3 mmHg at 0 degrees to 10.2 +/- 1.2 mmHg at 45 degrees. Already at 30 degrees 92% of the possible effect on ICP was detected. There was no statistically significant change in CPP and SJVO2 associated with varying head position. Individual reactions of CPP to changes in head position, however, were quite unpredictable. The data suggest that an individual approach to head elevation is to be preferred. A moderate head elevation between 15 degrees and 30 degrees significantly reduces ICP and, in general, does not impair cerebral perfusion. Jugular venous oximetry may be used to optimize ICP, CPP and cerebral oxygenation.

Experimental evidence conveys clear suggestions that early reperfusion following at least focal cerebral ischemia in the primate is accompanied by a return of function demonstrably suspended during the ischemic period. Complete and permanent arrest of the cerebral circulation has been known within seconds to lead to depression of brain electrical activity, and within minutes to gross disruption of the normal energy metabolism with failure of ionic homeostatic mechanisms. There is irreversible cell change and death within 5 to 10 minutes. Very much more protracted periods of ischemia have been shown more recently to be associated with potential viability of neuronal function, and in clinical neurosurgery we have known for years that patients with established cerebral vascular occlusion and a dense neurological deficit may show quite evident improvement over months or years. In these protracted recoveries, the potential for re-learning in nervous circuits may play a part, but in more acute circumstances, for example in the progressive recovery from vasospasm, re-learning is clearly not a factor, and this demonstrates quite evidently that neurons at one moment apparently non-functioning, can again within a few minutes recover function even after hours of apparent suppression. The experimental evidence is fairly well known. In this symposium and elsewhere we have presented a model of experimental occlusion of the middle cerebral artery in primates demonstrating irreversible recovery of electrical function after some 20 minutes of middle cerebral artery occlusion, and reversible recovery of ionic homeostasis after periods of up to an hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of regional cerebral blood flow (rCBF) in head-injured patients is considered useful for understanding the cerebral hemodynamics of brain trauma and for determining the optimal therapy. Most data thus far obtained with 133Xe clearance techniques have made only relative contribution, due to limitations of the 133Xe method. More recently, is has become possible to measure rCBF by xenon-enhanced computerized tomography (Xe-CT), which obviates most problems inherent to the 133Xe method. On the other hand, computational errors and concerns regarding the safety of xenon inhalation have thwarted the clinical use of Xe-CT. Recent advances in CT technology, however, have largely eliminated these problems. Xe-CT CBF measurements in severe head injury demonstrate a good correlation between CBF values obtained with 133Xe and Xe-CT. By consistently applying these studies in conjunction with conventional CT, information on very early flow derangements (within 1 to 2 hours after injury) can be obtained, in relation to anatomical lesions. Preliminary data reveal higher incidences of global and focal ischaemia than found previously. Local ischaemia tends to evolve to hyperemia in the ensuing days.