Sung C. Choi

Improved confidence of outcome prediction in severe head injury A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEPs), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEPs represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

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.

Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference.

A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing.

Statistical Methods for Determining Prognosis in Severe Head Injury

Determining the prognostic significance of clinical factors for patients with severe head injury can lead to an improved understanding of the pathophysiology of head injury and to improvement in therapy. A technique known as the sequential Bayes method has been used previously for the purpose of prognosis. The application of this method assumes that prognostic factors are statistically independent. It is now known that they are not. Violation of the assumption of independence may produce errors in determining prognosis. As an alternative technique for predicting the outcome of patients with severe head injury, a logistic regression model is proposed. A preliminary evaluation of the method using data from 115 patients with head injury shows the feasibility of using early data to predict outcome accurately and of being able to rank input variables in order of their prognostc significance.

Outcome Measures for Clinical Trials Involving Traumatically Brain-Injured Patients

A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing.

Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.

The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse.

CHOICE OF THE SMOOTHING PARAMETER AND EFFICIENCY OF k-NEAREST NEIGHBOR CLASSIFICATION

Abstract A simulation study was performed to investigate the sensitivity of the k -nearest neighbor (NN k ) rule of classification to the choice of k . The optimal choice of k was found to be a function of the dimension of the sample space, the size of the space, the covariance structure and the sample proportions. The nearest neighbor rules chosen using the k suggested by the simulations had correct classification rates at least as high as those rates for the linear discriminant function and the logistic regression method. In particular, the rule became more efficient as the difference in the covariance matrices increased, and also when the difference in sample proportion was large. An adaptive rule which selects k by iteratively maximizing the local Mahalanobis distance is shown to be efficient, thus abrogating the need to know the underlying population variance-covariance structure.

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia.

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15 ± 4.3 versus 34 ± 11 g/min, P < 0.002) and CBV (2.5 ± 1.0 versus 4.9 ± 1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means ± standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.

Traumatic Brain Tissue Acidosis: Experimental and Clinical Studies

We have been focusing on potential metabolic derangement associated with severe head injury and a clinical trail directed toward treating brain tissue acidosis is currently underway. More specifically, we based this study on the hypothesis that following brain trauma brain tissue acidosis develops which may contribute to the prolongation of coma and neurologic deficit. Tromethamine (THAM), a safe and low toxicity agent which buffers in major part by causing a hypocapnic alkalosis, was selected for trial. Patients admitted with GCS < 8 were randomized into one of three arms: control: THAM plus hyperventilation; hyperventilation alone. Each regimen was maintained for 5 days post injury. Our analysis of 3 and 6 months Glasgow outcome score showed that prophylactic hyperventilation retards recovery, and the use of THAM overcomes the apparent deleterious effects of hyperventilation. One explanation is that the reduced ICP instability observed in THAM treated patients may account for this improvement. Is THAM effective in buffering traumatized brain tissue? What factors account for improvement in ICP stability? We addressed these questions in experimental studies utilizing MR spectroscopy to measure brain lactate production and tissue pH in fluid percussed anaesthetized cats. The protocol was designed to match our clinical trial, and brain injured animals were randomized into control, THAM, and hyperventilated groups. We observed that brain lactate production increased with trauma and remained above control at 8 hrs post injury. Lactate production in THAM treated animals was not elevated. Highest lactate production was associated with injured animals treated with sustained hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Design and statistical issues in multicenter trials of severe head injury.

Abstract Multicenter clinical trials are the most powerful agent to evaluate new therapies in medicine, but have failed to impact traumatic brain injury, in which at least 20 such trials have been performed, without a positive result. Such trials need to be carefully planned, with a run-in period to ensure center compliance. Stratification, careful monitoring, adequate sample size, interim analysis and adequate numbers of patients per center are all vital requirements for a useful outcome in such trials. [Neurol Res 2001; 23: 190-192]