✓ A new model for establishing a successful and consistent arterial recirculation has been devised following middle cerebral artery (MCA) occlusion in the rat. A snare ligature was introduced at the stem of the MCA just distal to the lenticulostriate branches, and occlusion and recirculation were performed by pulling and releasing the thread. This method had an advantage over the use of a small clip which caused damage to the artery without good recirculation. Study of local cerebral blood flow using carbon-14 (14C)-iodoantipyrine, of cerebrovascular permeability using 14C-aminoisobutyric acid, and of brain-water content using the microgravimetric technique was performed upon recirculation following various periods of occlusion and compared with the results in permanent ischemia. A reactive hyperemia was noted within the previously ischemic area immediately upon recirculation following either a 30-minute or a 2-hour ischemic period. One or 2 hours later, delayed hypoperfusion developed in this region, but the circulation over the periphery of the ischemic area recovered well. Cerebrovascular permeability was not, however, altered during the time courses studied. Topographic changes in tissue specific gravity were compared between permanent and transient ischemia in the corresponding time-courses. Although there was a greater decrease in tissue specific gravity following recirculation when the ischemic period was maintained longer, edema formation was resolved by recirculation. Further study is required to determine thresholds of ischemic brain damage and edema formation at recirculation following focal cerebral ischemia.
Cerebral blood flow, cerebrovascular permeability, and brain edema
Taku Shigeno, Graham M. Teasdale, James McCulloch and David I. Graham
Damianos E. Sakas, M. Ross Bullock and Graham M. Teasdale
✓ Forty consecutive patients who underwent craniotomy for traumatic hematoma after developing bilateral fixed dilated pupils were studied to determine the factors influencing quality of survival and to seek criteria for management. Clinical and computerized tomography (CT) data were correlated with outcome 1 year after craniotomy. The functional recovery (good outcome or moderate disability) rate was 25%, with a mortality rate of 43%. Patients with subdural hematoma had a higher mortality rate (64%) compared to patients with extradural hematoma (18%) (chi-square test, p > 0.05). Other factors associated with markedly increased morbidity and mortality were increasing age (> 20 years), a prolonged interval (> 3 hours) between loss of pupillary reactivity and craniotomy, compression of basal cisterns, and presence of subarachnoid hemorrhage on CT. There were no survivors among patients exhibiting any of the following features: surgery 6 hours or more after bilateral loss of pupillary reactivity; age greater than 65 years; or absent motor response. Apart from the latter group, the nature of motor response (before pharmacological paralysis and intubation) was not a reliable predictor of mortality. The results suggest that the presence of an acute subdural hematoma is the single most important predictor of negative outcome in patients with bilateral unresponsive pupils.
Paul M. Brennan, Gordon D. Murray and Graham M. Teasdale
Glasgow Coma Scale (GCS) scores and pupil responses are key indicators of the severity of traumatic brain damage. The aim of this study was to determine what information would be gained by combining these indicators into a single index and to explore the merits of different ways of achieving this.
Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis.
Methods of combining the Glasgow Coma Scale and pupil response data varied in complexity from using a simple arithmetic score (GCS score [range 3–15] minus the number of nonreacting pupils [0, 1, or 2]), which we call the GCS-Pupils score (GCS-P; range 1–15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke’s R2.
Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P.
A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice.
Gordon D. Murray, Paul M. Brennan and Graham M. Teasdale
Clinical features such as those included in the Glasgow Coma Scale (GCS) score, pupil reactivity, and patient age, as well as CT findings, have clear established relationships with patient outcomes due to neurotrauma. Nevertheless, predictions made from combining these features in probabilistic models have not found a role in clinical practice. In this study, the authors aimed to develop a method of displaying probabilities graphically that would be simple and easy to use, thus improving the usefulness of prognostic information in neurotrauma. This work builds on a companion paper describing the GCS-Pupils score (GCS-P) as a tool for assessing the clinical severity of neurotrauma.
Information about early GCS score, pupil response, patient age, CT findings, late outcome according to the Glasgow Outcome Scale, and mortality were obtained at the individual adult patient level from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9045) and IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) databases. These data were combined into a pooled data set for the main analysis. Logistic regression was first used to model the combined association between the GCS-P and patient age and outcome, following which CT findings were added to the models. The proportion of variability in outcomes “explained” by each model was assessed using Nagelkerke’s R2.
The authors observed that patient age and GCS-P have an additive effect on outcome. The probability of mortality 6 months after neurotrauma is greater with increasing age, and for all age groups the probability of death is greater with decreasing GCS-P. Conversely, the probability of favorable recovery becomes lower with increasing age and lessens with decreasing GCS-P. The effect of combining the GCS-P with patient age was substantially more informative than the GCS-P, age, GCS score, or pupil reactivity alone. Two-dimensional charts were produced displaying outcome probabilities, as percentages, for 5-year increments in age between 15 and 85 years, and for GCS-Ps ranging from 1 to 15; it is readily seen that the movement toward combinations at the top right of the charts reflects a decreasing likelihood of mortality and an increasing likelihood of favorable outcome.
Analysis of CT findings showed that differences in outcome are very similar between patients with or without a hematoma, absent cisterns, or subarachnoid hemorrhage. Taken in combination, there is a gradation in risk that aligns with increasing numbers of any of these abnormalities. This information provides added value over age and GCS-P alone, supporting a simple extension of the earlier prognostic charts by stratifying the original charts in the following 3 CT groupings: none, only 1, and 2 or more CT abnormalities.
The important prognostic features in neurotrauma can be brought together to display graphically their combined effects on risks of death or on prospects for independent recovery. This approach can support decision making and improve communication of risk among health care professionals, patients, and their relatives. These charts will not replace clinical judgment, but they will reduce the risk of influences from biases.
Joanna M. Wardlaw, Ruth Offin, Graham M. Teasdale and Evelyn M. Teasdale
In this prospective observational study, the authors assess the impact of routine transcranial Doppler (TCD) ultrasound monitoring on the diagnosis, management, and outcome of delayed ischemic neurological deficit complicating subarachnoid hemorrhage (SAH). Over a 10-month period 186 patients admitted to a regional neurosciences center were included in the study. Three times a week, routine TCD examinations performed by neuroradiographers made an important positive contribution to the diagnosis of delayed ischemic neurological deficit in 72% of patients with this complication and altered management for the benefit of the patient in 43%. In 9% of patients with recent SAH, it was believed that the outcome might have been better if the TCD result had been acted upon appropriately. The TCD results did not adversely influence management or outcome and were accurate when compared with those obtained on angiography. The authors conclude that a routine TCD service provided by neuroradiographers is accurate and useful in diagnosing and managing elevated blood velocities and ischemic neurological deficit following SAH. In addition, it is possible that if the information gleened from TCD findings was used more often in patient management, outcome might be improved; however, a randomized controlled trial is necessary to assess this definitively.
Joanna M. Wardlaw, Ruth Offin, Graham M. Teasdale and Evelyn M. Teasdale
Object. In this prospective observational study, the authors assess the impact of routine transcranial Doppler (TCD) ultrasound monitoring on the diagnosis, management, and outcome of delayed ischemic neurological deficit complicating subarachnoid hemorrhage (SAH).
Methods. Over a 10-month period 186 patients admitted to a regional neurosciences center were included in the study. Three times a week, routine TCD examinations performed by neuroradiographers made an important positive contribution to the diagnosis of delayed ischemic neurological deficit in 72% of patients with this complication and led to altered management for the benefit of the patient in 43%. In 9% of patients with recent SAH, it was believed that the outcome might have been better if the TCD result had been acted upon appropriately. The TCD results did not adversely influence management or outcome and were generally accurate when compared with those obtained on angiography.
Conclusions. A routine TCD service provided by neuroradiographers is accurate and useful in diagnosing and managing elevated blood velocities and ischemic neurological deficit following SAH. In addition, it is possible that if the information gleaned from TCD findings was used more often in patient management, outcome might be improved; however, a randomized controlled trial is necessary to assess both these points definitively.
Dorothy A. Lang, Graham M. Teasdale, Peter Macpherson and Audrey Lawrence
✓ A series of 118 patients with diffuse traumatic brain swelling was studied retrospectively in order to compare the clinical findings in children with those in adults, and to determine the occurrence of neurological deterioration and outcome. The computerized tomography (CT) picture of absent third ventricle and basal cisterns was used to identify the cases. Although this condition has been associated with children, we found the same number of children and adults (59 cases each). Secondary deterioration (decline in consciousness, the development of new focal neurological signs, or an increase in intracranial pressure) occurred in 40% of cases and was more common in adults than children. Features that were significantly associated with deterioration were the presence of prolonged coma (> 1 hour) after the injury, CT signs of diffuse axonal injury or subarachnoid hemorrhage, or a recorded episode of hypotension. A moderate or good recovery at 6 months was achieved by 70 patients (59%), but 45 patients had a poor outcome (severe disability in nine, vegetative state in three, and death in 33) and this was often a consequence of secondary deterioration. In three patients, the outcome was not known. The combination of a severe initial injury, secondary insult, and diffuse swelling is associated with a poor outlook, particularly in adults. The CT appearance of diffuse swelling may develop more readily in children because of the lack of cerebrospinal fluid available for displacement. In children, diffuse swelling may have a relatively benign course unless there is a severe primary injury or a secondary hypotensive insult.
Michael C. Wallace, Graham M. Teasdale and James McCulloch
✓ The clinical utility of N-methyl-D-aspartate (NMDA) receptor antagonists is now being assessed in ischemic brain injury in humans. The uptake and retention of NMDA receptor antagonists in ischemic tissue will influence the design of clinical trials. The effects of permanent occlusion of the middle cerebral artery, induced 15 minutes prior to isotope administration, on the uptake of 3H-MK-801 (dizocilpine) have been assessed in the rat with quantitative autoradiography. In a group of three rats at 15 minutes after the intravenous administration of 3H-MK-801, the level (mean ± standard error of the mean) of isotopic tracer in the ischemic cortex and striatum was markedly less than that in the contralateral hemisphere (ipsilateral vs. contralateral caudate nucleus: 22 ± 4 vs. 84 ± 11 pmol/gm, p < 0.01). In contrast, in a group of five rats at 60 minutes after the intravenous administration of 3H-MK-801, the level of isotopic tracer in the ischemic cortex and striatum was greater than that in the contralateral hemisphere (ipsilateral vs. contralateral caudate nucleus: 52 ± 8 vs. 32 ± 4 pmol/gm, p < 0.05). There were no significant alterations in the specific binding of 3H-MK-801 in vitro in ischemic tissue at equivalent times. The early uptake of 3H-MK-801 into the central nervous system is dominated by the level of cerebral blood flow, whereas at later times after administration enhancement of MK-801 binding by elevated extracellular glutamate concentrations appears to be more important in determining the level of the drug in ischemic tissue.