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Biomedical subjects

B B Gallagher

Publications and source records attributed to B B Gallagher.

At least 19 recordsLinked to original sources

Comparison of glutamine synthetases from brains of genetically epilepsy prone and genetically epilepsy resistant rats.

Since glutamine synthetase (GS) has been proposed as the primary enzyme in the regulation of glutamate metabolism in the central nervous system and since inhibition of the activity of this enzyme in vivo leads to seizures, it has been proposed that an abnormality in the structure or function of this enzyme could be responsible for the induction of seizures in epilepsy prone rats. To test this hypothesis the glutamine synthetases were purified from the brains of both genetically epilepsy prone rats (GEPR) and their progenitors, genetically epilepsy resistant rats (GERR). The enzymes were compared using both SDS-PAGE and isoelectric focusing. The immunoreactivities of equal amounts of protein were determined using the ELISA technique, and the regulation of the glutamine synthetase activities by Mn2+/Mg2+ ratios were compared. The only difference found between the glutamine synthetases from the two strains was a slightly lower specific activity of the enzyme from the epilepsy prone animals.

Animals

A model for focal magnetic brain stimulation.

In this study, we describe a magnetic coil designed for focal brain stimulation. We determined the distribution of magnetically induced currents using a multi-concentric spherical cranial computer model. The induced currents were primarily linearly oriented and concentrated below the coil's center. In comparison with large coils, small coils were less efficient but produced a more concentrated current distribution. Variations in conductivity among brain, scalp and skull produced secondary currents that reduced the magnetically induced current. This reduction in magnetically induced current was greater for larger coils.

Algorithms

Comparison of CT- versus MRI-guided, computer-assisted depth electrode implantation.

Fourteen candidates for ablative seizure surgery underwent CT-guided, computer-assisted stereotactic depth electrode implantation and 21 underwent MRI-guided, computer-assisted implantation. A hand-held computer with no graphic capability was used for CT-guided procedures. A computer work station which included a high-resolution color graphics terminal with touchscreen interfacing and software capable of simulating targets and trajectories in single or multiple views was used for MRI-guided procedures. Previous phantom studies done with a 1.5-tesla MR scanner suggested acceptable localization error. Localizing information was obtained in 10 (71.4%) of 14 of the CT-guided implants and in 16 (76.2%) of 21 of MRI-guided cases. In the CT group, 7 (70%) were seizure-free and 8 (80%) were greater than 90% improved at 1 year follow-up. In the MRI group, 8 (80%) were seizure-free and 9 (90%) were greater than 90% improved at latest follow-up.

Computer Graphics

Differential effects of left versus right seizure focus on human hippocampal evoked responses.

Hippocampal evoked potentials were recorded using the P3 tonal oddball paradigm in 30 patients with unilateral temporal lobe seizure focus. Spectral power of the evoked potentials was decreased on the side of seizure focus, but this reduction was much greater when the focus was on the left. The effect of left/right focus does not appear to be due to group differences in age, sex, seizure duration, or operative pathology. Remote or finer left/right structural differences or differential left/right hippocampal processing for the sequential tonal task are possible explanations.

Adolescent

Computerized seizure detection of complex partial seizures.

In this study, we describe a computerized method that uses 3 quantified EEG features and discriminant analysis to automatically detect seizure EEG. The quantified EEG features were relative amplitude, dominant frequency and rhythmicity. Using EEGs recorded from intracranial electrodes, the seizure detection method was applied to consecutive non-overlapping 2-channel EEG epochs. A seizure detection sensitivity, ranging from 90% to 100%, was associated with a false positive detection rate of 1.5-2.5/h. The performance of the seizure detection method remained stable for EEG recorded over variable time periods.

Discriminant Analysis

Behavioral state-specific changes in human hippocampal theta activity.

Although there has been extensive examination of the behavioral and physiologic correlates of hippocampal theta activity in animals, the human literature consists of a single case study. We investigated the differential effects of four behavioral states on human hippocampal theta activity in 16 epilepsy surgery patients. Behavioral conditions included resting eyes closed (RC), resting eyes open (RO), eyes open with auditory word activation (AW), and eyes open with visuospatial activation (VS). Hippocampal theta activity decreased during both RO and VS compared to both RC and AW. There were reciprocal changes in delta activity. Comparisons of RO to VS and of RC to AW were nonsignificant. The results demonstrate state-specific changes in human hippocampal theta and are consistent with the animal literature that relates hippocampal theta to sensorimotor integration and forebrain volitional mechanisms.

Adolescent

Adaptive smoothing: an improved method for spectral analysis and its application to seizure EEG.

We describe the data adaptive smoothing method, an improved method for multichannel spectral analysis of seizure EEG. After Fast Fourier Transform of EEG data, spectra were computed by smoothing over adjacent frequency components. Using cross-validatory maximum likelihood criteria, unsmoothed spectral data were used to select the level of smoothing (spectral window effective bandwidth) required to minimize bias and variance errors. The statistical assumptions of this method are consistent with the statistical properties of seizure EEG. On computer simulation of seizure EEG, the smoothing level predicted by this method correlates strongly with the optimum smoothing level. The utility of the method is demonstrated by application to seizure EEG. The consistency of the method's statistical assumptions, the success in selection of the optimum smoothing level, and the variability in optimum smoothing required for seizure EEG suggest that the adaptive smoothing method is a useful method for multichannel spectral analysis.

Electroencephalography

Cerebral language lateralization: evidence from intracarotid amobarbital testing.

Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable.

Amobarbital

An 8-year experience with depth electrodes in the evaluation of ablative seizure surgery candidates.

Stereotactically implanted depth electrodes are one means of localization of seizure foci. Unilateral seizure focus localization was obtained in 72.7% mesial temporal (MT) implants and 50% of focus/extramesial temporal (MT-XMT) implants. Recent increase in localization to over 80% in MT implants was possible because a larger percentage of patients had MT-XMT implants. Increased localization to 60% in MT-XMT implants was related to using more XMT electrodes per patient and to orienting electrodes to monitor larger limbic XMT and neocortical areas. Since MT foci were localized in 25% of MT-XMT cases, MT electrodes should be included with all MT-XMT implants. Depth electrography can also be used to rule out certain patients as surgical candidates. Therefore, a surgical decision can be reached in a very high percentage of patients undergoing depth implantation. Surgical results are comparable to those in our overall series.

Brain Mapping

Comparative cognitive effects of anticonvulsants.

We investigated the neuropsychological effects of carbamazepine, phenobarbital, and phenytoin in 15 partial complex epilepsy patients treated with each drug for 3 months, using a randomized double-blind, triple crossover design. Neuropsychological evaluation at the end of each treatment period included Digit Span, Selective Reminding Test, Digit Symbol, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 evoked potential, and Profile of Mood States. Employing anticonvulsant blood levels and seizure frequencies as covariates, the only significant difference was for Digit Symbol. Performance with phenobarbital was significantly worse than with the other 2 anticonvulsants despite phenobarbital's having had the lowest overall blood levels. Our data show that patients receiving carbamazepine, phenobarbital, and phenytoin have comparable neuropsychological performance on most measures. The results suggest that the differential cognitive effects of anticonvulsants may be subtle.

Adult

Human hippocampal EEG: effects of behavioral activation.

We studied spectral components of human hippocampal EEG in relation to behavioral status in 19 patients with intractable complex partial seizures who had depth electrodes implanted into the anterior hippocampi as a part of their preoperative evaluations. Behavioral conditions included: eyes closed resting, eyes open resting, eyes open with a verbal task, and eyes open with a visuospatial task. Hippocampal EEG spectral power uniformly decreased during behavioral activation. EEG activation was quantitatively different among the 3 activated conditions, with the most prominent change occurring during the visuospatial task. The degree of EEG activation corresponded inversely with the site of epileptic focus during the verbal task. The results demonstrate the response of human hippocampal EEG to behavioral activation. The magnitude of EEG change may reflect the degree of functional activation of the given hippocampus.

Adult

Long-latency evoked potentials during aura of temporal lobe origin.

Long-latency evoked potentials recorded from scalp or scalp/sphenoidal electrodes have been shown to have diminished amplitude and power during interictal recordings on the side ipsilateral to an unilateral mesial temporal lobe (MTL) focus. We now report recordings of long-latency evoked potentials both during a prolonged aura and also on two seizure-free days. P3 amplitude and sphenoidal evoked potential (SpEP) spectral power in the scalp/sphenoidal channels were less, ipsilateral to the MTL focus. During the aura, the SpEPs had reduced power and reduced amplitude. However, the amplitude of the N2 component for the target averages in the CZ-A1A2 channel was markedly enhanced during the aura.

Adolescent

Effect of kainate-induced seizures on tissue trace element concentrations in the rat.

It has been shown that epileptics have lower mean blood concentration of manganese than do controls but the cause of this abnormality has not been determined. In order to investigate the effects of seizures on manganese distribution in the body, rats were treated with kainic acid to produce spontaneous seizures which were quantitated for number and severity. Manganese, zinc, copper and iron concentrations were determined in blood, brain, liver, heart and kidney. Kainate-treated animals ate more food but gained less weight than controls. Liver and kidney manganese concentrations were significantly higher in kainate-treated animals than in controls. Blood manganese concentration showed a significant negative correlation with seizure index while heart manganese concentration showed a significant positive correlation with seizure index. None of the other trace elements showed a significant correlation between trace element concentration and seizure index in any of the tissues, although iron concentration was lower in brain and copper concentration was lower in kidney of kainate-treated animals than in their appropriate controls. These data show that manganese concentrations are generally elevated in tissues of kainate-treated animals. This increased manganese concentration may be related to the increased energy demand of these animals.

Animals

Surgical management of epilepsy.

About 300,000 people in the United States suffer from medically uncontrolled focal epilepsy. It is estimated that about 40,000 of these patients are candidates for surgery. Underuse of surgical treatment of epilepsy is reflected by the fact that only about 1% of these candidates are operated on. Candidates for ablative surgery (ie, removal of seizure focus) must have a focus demonstrated by either extracranial or intracranial electrode recordings. Nearly half of the patients who have ablative surgery become seizure-free, and nearly two thirds have no seizures or only rare ones. Candidates for corpus callosotomy are those patients with multiple seizure types and nonfocal EEG abnormalities. Almost half of these patients have at least a 50% reduction in seizure frequency. Patients with infantile hemiplegia and seizures may have marked improvement in seizure control after physiologic hemispherectomy.

Corpus Callosum

Adult-onset chorea and dementia with propionic acidemia.

Propionic acidemia usually presents in the newborn period with severe metabolic acidosis and lethargy. A 31-year-old man with adult onset chorea and dementia had propionic acidemia due to propionyl CoA carboxylase deficiency. Metabolic investigations may prove useful in patients with movement disorder of unknown etiology.

Adult

Spectral power of human limbic evoked potentials: relationship to seizure onset.

Limbic evoked potentials were recorded from intracerebral electrodes bilaterally implanted in the hippocampi of 16 epileptic patients undergoing evaluation for surgical resection of a seizure focus. Spectral analysis of the limbic evoked potentials revealed consistently lower spectral power of both low-band (1-12.6 Hz) and high-band (13-20 Hz) components recorded form the hippocampus that was associated with the electrographically confirmed seizure focus as compared to the contralateral side. Limbic evoked potential recordings appear to be useful in the determination of a focal functional deficit and thus in identifying the site of epileptogenic pathology. Further, the results support the hypothesis of a local generator for limbic evoked potentials and demonstrate that limbic evoked potentials in humans include not only low-frequency, high-amplitude electric field changes, but also a high-frequency component.

Adolescent

Relationship of limbic evoked potentials to recent memory performance.

The relationship between limbic evoked potentials (LEPs) and memory performance was investigated in eight patients with intractable epilepsy who were candidates for temporal lobectomy. No relationship between the presence or absence of unilateral LEP and memory deficits was present. However, in both patients with bilaterally poorly developed hippocampal LEPs, verbal and visual-spatial memory tasks were impaired. In one patient with well developed LEPs bilaterally, memory function was normal. These data suggest that LEPs may assist in the evaluation of memory function during the preoperative work-up for temporal lobectomy.

Epilepsy