Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO 2 ) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR)440) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO 2 ). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO 2 (Po0.001), but not with OEF or CvO 2 . Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

To evaluate the variability in the reported diagnostic accuracy of the exercise electrocardiogram, we applied meta-analysis to 147 consecutively published reports comparing exerciseinduced ST depression with coronary angiography. These reports involved 24,074 patients who underwent both tests. Population characteristics and technical and methodologic factors, including publication year, number of electrocardiographic leads, exercise protocol, use of hyperventilation, definition of an abnormal ST response, exclusion of certain subgroups, and blinding of test interpretation were analyzed. Wide variability in sensitivity and specificity was found (mean sensitivity, 68%; range, 23-100%; SD, 16%; and mean specificity, 77%; range, 17-100%; SD, 17%). The four study characteristics found to be significantly and independently related to sensitivity were the treatment of equivocal test results, comparison with a "better" test such as thallium scintigraphy, exclusion of patients on digitalis, and publication year. The four variables found to be significantly and independently related to specificity were the treatment of upsloping ST depressions, the exclusion of subjects with prior infarction or left bundle branch block, and the use of preexercise hyperventilation. Stepwise linear regression explained less than 35% of the variance in sensitivities and specificities reported in the 147 publications. There is wide variability in the reported accuracy of the exercise electrocardiogram. This variability is not explained by information reported in the medical literature. (Circulation 1989;80:87-98) T he diagnosis of coronary artery disease in patients with chest pain syndromes is a major application of the exercise electrocardiogram (ECG) sion to determine the expected value and variability in this test's accuracy and determine which technical and methodologic factors independently affect the reported accuracy and its variability. Methods Literature ReviewThe Bibliography Retrieval Service and Medlars were used to search the National Library of Medicine data base for reports published after 1967 on the diagnostic accuracy of the exercise ECG when compared with coronary angiography. Though both exercise testing and angiography were used before 1967, few reports of their use in the same patients had appeared before that date. The search terms used were "exercise electrocardiogram" and "coronary artery disease." The bibliographies of three major textbooks on the subject were also searched.1-3 The bibliographies of review articles published between 1984 and 1987 and retrieved from the computer search were also scanned to complete the meta-analytic data base.The 325 publications resulting from these searches were screened for studies involving groups of 50 patients or more undergoing exercise electrocardiography with ST segment measurement and coronary angiography; for the latest report when more than one report from the same institution and same time period (within 3 years) was found, unless it could be verified that duplicatio...

Experimental traumatic brain injury studies have shown that cerebral hyperglycolysis is a pathophysiological response to injury-induced ionic and neurochemical cascades. This finding has important implications regarding cellular viability, vulnerability to secondary insults, and the functional capability of affected regions. Prior to this study, posttraumatic hyperglycolysis had not been detected in humans. The characteristics and incidence of cerebral hyperglycolysis were determined in 28 severely head injured patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). The local cerebral metabolic rate of glucose (CMRG) was calculated using a standard compartmental model. In six of the 28 patients, the global cerebral metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements of arteriovenous differences of oxygen and cerebral blood flow (xenon-133). Hyperglycolysis, defined as an increase in glucose utilization that measures two standard deviations above expected levels, was documented in all six patients in whom both FDG-PET and CMRO2 determinations were made within 8 days of injury. Five additional patients were found to have localized areas of hyperglycolysis adjacent to focal mass lesions. Within the 1st week following the injury, 56% of patients studied had presumptive evidence of hyperglycolysis. The results of this study indicate that the metabolic state of the traumatically injured brain should be defined differentially in terms of glucose and oxygen metabolism. The use of FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally following severe head injury in humans. The results of this clinical study directly complement those previously reported in experimental brain-injury studies, indicating the capability of imaging a fundamental component of cellular pathophysiology characteristic of head injury.

During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.

Intensive insulin therapy results in a net reduction in microdialysis glucose and an increase in microdialysis glutamate and lactate/pyruvate without conveying a functional outcome advantage.

Approximately 50% of patients with moderate or severe TBI have at least transient AI. Younger age, greater injury severity, early ischemic insults, and the use of etomidate and metabolic suppressive agents are associated with AI. Because lower cortisol levels were associated with lower blood pressure and higher vasopressor use, consideration should be given to monitoring cortisol levels in intubated TBI patients, particularly those receiving high-dose pentobarbital or propofol. A randomized trial of stress-dose hydrocortisone in TBI patients with AI is underway.

Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.

Objective: To determine if posttraumatic nonconvulsive electrographic seizures result in longterm brain atrophy. Methods:Prospective continuous EEG (cEEG) monitoring was done in 140 patients with moderate to severe traumatic brain injury (TBI) and in-depth study of 16 selected patients was done using serial volumetric MRI acutely and at 6 months after TBI. Fluorodeoxyglucose PET was done in the acute stage in 14/16 patients. These data were retrospectively analyzed after collection of data for 7 years.Results: cEEG detected seizures in 32/140 (23%) of the entire cohort. In the selected imaging subgroup, 6 patients with seizures were compared with a cohort of 10 age-and GCS-matched patients with TBI without seizures. In this subgroup, the seizures were repetitive and constituted status epilepticus in 4/6 patients. Patients with seizures had greater hippocampal atrophy as compared to those without seizures (21 Ϯ 9 vs 12 Ϯ 6%, p ϭ 0.017). Hippocampi ipsilateral to the electrographic seizure focus demonstrated a greater degree of volumetric atrophy as compared with nonseizure hippocampi (28 Ϯ 5 vs 13 Ϯ 9%, p ϭ 0.007). A single patient had an ictal PET scan which demonstrated increased hippocampal glucose uptake. Conclusion:Acute posttraumatic nonconvulsive seizures occur frequently after TBI and, in a selected subgroup, appear to be associated with disproportionate long-term hippocampal atrophy. These data suggest anatomic damage is potentially elicited by nonconvulsive seizures in the acute postinjury setting. Neurology ® 2010;75:792-798 GLOSSARY cEEG ϭ continuous EEG; FLAIR ϭ fluid-attenuated inversion recovery; GCS ϭ Glasgow Coma Scale score; GRE ϭ gradient recalled echo; ICU ϭ intensive care unit; TBI ϭ traumatic brain injury.Neurologic critical care of traumatic brain injury (TBI) focuses on avoiding secondary insults.