Measurement of cardiac troponin T is an effective method for predicting complications among emergency department patients with chest pain.

STUDY OBJECTIVES: To determine the test performance characteristics of serum cardiac troponin T (cTnT) measurement for diagnosis of acute myocardial infarction (AMI), and to determine the ability of cTnT to stratify emergency department patients with chest pain into high- and low-risk groups for cardiac complications. METHODS: We conducted a prospective observational cohort study with convenience sampling in a tertiary care, urban ED. The study sample comprised 667 patients presenting to the ED with a complaint of chest pain or other symptoms suggesting acute ischemic coronary syndrome (AICS). Patients were assigned to different blood sampling protocols for cTnT therapy on the basis of their ECG at presentation: nondiagnostic for AMI at 0, 3, 6, 9, 12, and 24 hours after ED presentation; or ECG diagnostic for AMI at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 18, and 24 hours after ED presentation. RESULTS: Of 667 patients, 34 had AMI diagnosed within 24 hours of ED arrival. Using a .2 microgram/L discrimination level for cTnT, sensitivity for AMI within 24 hours of ED arrival was 97% (95% confidence interval, 91.4% to 99.9%), and specificity was 92% (89.8%-94.1%). When the effects of age, race, sex, and creatine kinase-MB isoenzyme subunit test results were controlled, a patient with cTnT of .2 microgram/L or greater was 3.5 (1.4 to 9.1) times more likely to have a cardiac complication within 60 days of ED arrival than a patient with a cTnT value below .2 microgram/L. CONCLUSION: Measurement of cTnT will accurately identify myocardial necrosis in patients presenting to the ED with possible AICS. Elevated cTnT values identify patients at increased risk of cardiac complications.

The effect of reference-electrode choice on the spatial resolution of topographical potential maps in the discrimination of deep cerebral sources.

Although scalp potential distributions do not uniquely determine the location and configuration of neural generators, they are important because they provide the necessary conditions that any hypothesized sources must satisfy and suggest a basis for testing alternate source hypotheses. One problem that could confound the correct interpretation of scalp potentials is the choice of reference electrode. Changing the reference may make activity patterns and waveform components appear and disappear (Pascual-Marqui et al. (1988) Int. J. Neurosci., 43: 237-249). The cortical imaging technique (CIT), a method for approximating potential fields on the cortical surface, was used to test the effects of the choice of reference electrode on these fields. Simulated and empirical evoked potential scalp-recorded referential data were mathematically analyzed for the case in which the reference (linked-ears) was arbitrarily assumed to be at zero potential, and the case in which the reference was the 'average' electrode, the arithmetic mean of all of the scalp-recorded voltages in the referential montage. The results for the two references were similar. This is encouraging because potential measurements relative to a point at infinity (zero potential) are never available and the assumption that any actual reference used for a recording is at zero potential is therefore suspect.

Source localization and bioelectric imaging as it relates to continuous waveform analysis.

One of the goals of the mathematical analysis of scalp-recorded continuous EEG waveforms is to elucidate non-invasively the neural generators of these voltages. One way of accomplishing this is to simulate these generators by equivalent current sources and follow the apparent motion of these theoretical generators during the temporal evolution of the EEG. Another way of accomplishing this is to follow the changes in scalp or simulated cortical surface potential or Laplacian maps during the temporal evolution of the EEG. We first discuss the possible theoretical pitfalls of using linear techniques on an essentially nonlinear problem (the localization of the sources of the EEG), as well as possible computational pitfalls associated with realistic, but complex, conductive medium models simulating the head. Various mathematical source localization methods and bioelectric imaging techniques are then outlined. Later in this paper a collaborative project involving mathematicians, computer scientists, and clinical neuroscientists is described. In this project EEG waveform data will be analyzed, millisecond-to-millisecond, using the various mathematical techniques for localizing equivalent current sources and simulating cortical surface potential and Laplacian topographical maps mentioned above. One of the clinical aims of this research project is to localize epileptic foci without employing invasive recording procedures. Since the EEG datasets that will be analyzed are large (22 Mb, in some cases), data compression and parallel processing strategies will be important parts of this research project. Such strategies, as they may apply to continuous waveform analysis, are discussed in the two appendices at the end of this paper. Many of the presentations at the Symposium and the corresponding papers in this Supplement are related to the ideas and goals of this research project and the implementation of the mathematical/computational techniques for realizing these goals.

Exertional heat stroke in a young woman: gender differences in response to thermal stress.

Exertional heat stroke (EHS) is an acute life-threatening emergency that necessitates the immediate institution of cooling measures. Reported here is a case of EHS in a nonacclimatized young woman who was undergoing strenuous exercise. The patient developed many of the characteristic features of EHS, including central nervous system disturbances, lactic acidosis, rhabdomyolysis, coagulopathy, and abnormal myocardial conduction. While EHS is relatively common in young men, the condition is rare in women. This case presentation addresses gender differences in the response to the thermal stress of intense physical activity.

Optimal electrode placements for adequate spatial sampling of auditory evoked potentials.

When evoked responses are used in clinical practice and research the measures that are most commonly considered are the latencies and amplitudes of EP components as measured at a single electrode site. Our recent studies have shown that multichannel recordings yield measures such as potential field asymmetry that may be as important as component latency and amplitude. The purpose of this short technical note is to suggest that electrode placement is critical for demonstrating interesting features of the potential field topography, specifically, bilateral, homologous generator sites. The cortical imaging technique (CIT) was used to analyze the averaged responses for a group of thirty normal young adults to a repeated tone and a random oddball tone. Recordings were obtained at 28 scalp recording sites which included 20 placements from the 10-20 system and eight additional sites. Simulated cortical maps were derived for four components, the N1 frequent response and the N2a, P3, and N3, rare minus frequent responses for three different electrode arrays. These arrangements included the full 28-channel array, a 20-channel array that excluded eight additional central sites, and a 20-channel array that included the eight additional sites and excluded peripheral sites. This study demonstrates that for these auditory paradigms, the placement of the electrodes is critically important for discriminating important features of the potential fields.

Spatio-temporal progression of the AEP P300 component using the cortical imaging technique.

The cortical imaging technique (CIT), a mathematical method for simulating the potential fields on the surface of the brain, was used to analyze the spatio-temporal progression of the AEP P300 component (as well as the preceding and subsequent N2a and N3 components) from thirty normal adult subjects recorded in a standard "oddball" paradigm. Comparisons were made between the progressions of the endogenous event-related cognitive potentials and the exogenous stimulus-dependent potentials (N1 component). Cortical imaging results suggest that different and multiple generator sites are involved in the production of exogenous and endogenous evoked responses. We particularly note the asymmetric development of the P300 component and the apparent anterior generator sites for the N2a component. This last result is interesting because the N2a precedes the P300 component and supports an earlier frontal contribution.

Experimental tests of the cortical imaging technique--applications to the response to median nerve stimulation and the localization of epileptiform discharges.

In a previous paper a method for simulating the electric potentials on the surface of the brain was introduced. This method consisted of the construction of a layer of radially oriented current dipoles in a conducting sphere that simulated the head so that the voltages generated by the layer would take the values measured on the surface of the medium (the scalp). The harmonic potential function for this layer was then evaluated in the interior of the medium in an attempt to approximate the potentials that would be generated by the actual neural sources but which could not be observed without recourse to invasive recording techniques. This method, the cortical imaging technique (CIT), has been previously tested by applying it to artificially generated data where the "cortical surface" potentials were known and could be compared with CIT-generated potentials. In this paper the method is tested by applying it to the scalp-recorded potentials evoked by right median nerve stimulation, where direct cortical recordings are available for comparison, and to the scalp-recorded epileptiform discharges from two patients where the spike foci were well defined. The effects of varying the "noise ratio," an input parameter in CIT which allows one to account for noise in scalp-recorded data, is discussed.

A method for simulating intracerebral potential fields: the cortical imaging technique.

Source localization techniques such as the dipole localization method (DLM) have been used to elucidate the neural origins of scalp-recorded potentials. The type of source assumed in such techniques is usually suggested by the distribution of voltage maximums and minimums in scalp topographical contour maps. Unfortunately, the physical layers between the neural generators and scalp recording sites tend to smear and attenuate the potential fields, making it impossible, in some cases, to distinguish between single and multiple sources or extended layers. In this report, a mathematical (noninvasive) technique is described for simulating the potential fields that could be recorded directly on the surface of the brain. Such "cortical" potential fields exhibit details that are not apparent in the scalp topography. In several recent publications, this cortical imaging technique (CIT) has been tested on artificial and experimental data. After describing these results, some possible applications of CIT to clinical data will be presented.

Numerical tests of a method for simulating electrical potentials on the cortical surface.

A mathematical imaging method for simulating cortical surface potentials was introduced at recent neurosciences meetings [1a], [1b], [2] and was applied to elucidate the neural origins of evoked responses in normal volunteers and certain patient populations. This method consists of the solution of an inward harmonic continuation problem and its effect is to simulate data that has not been attenuated and smeared by the skull. This cortical imaging technique (CIT) is validated by applying it to artificially derived data. Pairs of dipolar sources with different depths and separations are introduced into a spherical conducting medium simulating the head. Scalp potential maps are constructed by interpolating the simulated data between 28 "scalp" electrode positions. Noise is added to the data to approximate the variability in measured potentials that would be observed in practice. CIT is used in each case to construct potential maps on layers concentric to and within the layer representing the scalp. In several instances when the dipole pair is deep and closely spaced, the sources cannot be separated by the scalp topographical maps but are easily separated by the "cortical" topographical maps. CIT is also applied to scalp-recorded potentials evoked by bilateral median nerve stimulation and pattern-reversal visual stimulation.

Age-related features of the resting pattern-reversal visual evoked response using the dipole localization method and cortical imaging technique.

Two mathematical techniques, the dipole localization method (DLM) and the cortical imaging technique (CIT), are used to analyze the resting visual response to pattern-reversal stimulation. These methods identify certain age-related features of this evoked response that are not found by using standard topographic maps. These features include the symmetry of the N1 and P1 responses. The amplitudes of the N1 and P2 responses and the latency of N2 are also significantly different between old and young groups of test subjects, findings consistent with differences seen in conventional topographical analyses. Theoretical dipole sources and simulated cortical surface maps are also constructed for the "average" normal older subject and one patient with documented progressive frontal lobe degenerative disease. Standard topographical imaging studies of this patient were unremarkable, except for the P300 auditory response. DLM and CIT analyses of the VER components were exceptional and consistent with the clinical diagnosis. These mathematical methods appear to enhance the discriminating power of traditional electrophysiological measures.

Age-related features of the resting and P300 auditory evoked responses using the dipole localization method and cortical imaging technique.

Two mathematical techniques, the dipole localization method (DLM) and the cortical imaging technique (CIT), are used to analyze the resting and P300 auditory responses in young and old normal volunteers. These methods identify certain age-related features of these evoked responses that are not found by standard topographic methods. These features include the orientation of the P200 resting response, and the laterality of the N120 response, and the eccentricity of the P300 response in the P300 stimulus condition. Theoretical dipole sources and simulated cortical surface maps are also constructed for one normal subject and one psychiatric inpatient and compared. These mathematical methods appear to enhance the discriminating power of traditional electrophysiological measures.

A reliable method for localizing deep intracranial sources of the EEG.

We have demonstrated the reliability of a noninvasive method for successfully localizing the intracranial origin of the EEG. The dipole localization method (DLM) is a computer-assisted, mathematical method based on electrical field theory and is similar to localization methods currently used by electrocardiologists. In 12 patients with intractable epilepsy who were being evaluated for surgery, a known current source was introduced between two adjacent depth electrodes. Using scalp-recorded EEG only, DLM accurately and reliably localized the source to within 2 cm of the known origin in all instances where a discrete source was present. We conclude that DLM is a valid and reliable noninvasive method for localizing the intracranial source of some scalp-recorded EEG potentials, and that in some patients, use of this method may obviate the need for depth electrode implantation.

Scalp and depth recordings of induced deep cerebral potentials.

A balanced square wave was introduced between two adjacent depth electrodes implanted in the course of studying patients with intractable epilepsy and who were being considered for surgery. The stimulus current was designed so that charge density loading was well within limits of safety to avoid tissue damage. No neuronal activation was seen, and the stimulus intensity was significantly less than that used in subsequent stimulation session for the purpose of eliciting a clinical response and after-discharges. Averaging techniques were used to record the stimulus at distant electrodes both within the cerebrum and on the scalp. The recorded voltage decrement from the source was nearly identical with the theoretical voltage decrement predicted using principles of electric field theory in which the brain was assumed to be a homogeneous conductive medium. When the voltage recorded on the scalp was compared with the voltages recorded from depth electrodes, it was found that the effect of the highly resistive skull on voltage decrement was relatively less the more centric the source. This result also confirmed predictions based on electric field theory. Most significantly, voltages well within the physiologic range introduced in deep mesial temporal lobe structures were recorded from the scalp.

A method for localization of sources of human cerebral potentials evoked by sensory stimuli.

A method based on potential field theory is described for assessing the location and orientation of dipole generators of the human scalp-recorded sensory evoked potential (EP). The method assumes that the EP at a given moment is due to a single dipole source and that the head can be modeled by a homogeneous conductive sphere (brain) surrounded by inner (skull) and outer (scalp) shells of differing conductivity (three-sphere model). Solution for source location and orientation from the surface potential field is given for the case of a single homogeneous sphere (one-sphere model). It is then shown that a unique solution for the three-sphere model can be derived from the one-sphere solution. Solutions are obtained by application of an iterative procedure which minimizes the error between calculated and empirical potential fields. A test of the method is described in which the calculated location and orientation of a dipole was in good agreement with the known source of an early component of the human somatosensory EP.