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Biomedical subjects

Jerome Engel

Publications and source records attributed to Jerome Engel.

At least 19 recordsLinked to original sources
PubMed2006

Reduced neocortical thickness and complexity mapped in mesial temporal lobe epilepsy with hippocampal sclerosis.

We mapped the profile of neocortical thickness and complexity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Thirty preoperative high-resolution magnetic resonance imaging scans were acquired from 15 right (mean age: 31.9 +/- 9.7 standard deviation [SD] years) and 15 left (mean age: 30.8 +/- 8.4 SD years) MTLE patients who were seizure-free for 2 years after anteriomesial temporal resection. Nineteen healthy controls were also scanned (mean age: 24.8 +/- 3.9 SD years). A cortical pattern matching technique mapped thickness across the entire neocortex. Mesial temporal structures were not included in this analysis. Cortical models were remeshed in frequency space to compute their fractal dimension (surface complexity). Both MTLE groups showed up to 30% bilateral decrease in cortical thickness, in the frontal poles, frontal operculum, orbitofrontal, lateral temporal, and occipital regions. In both groups, cortical complexity was decreased in multiple lobar regions. Significant linkages were found relating longer duration of epilepsy to greater cortical thickness reduction in the superior frontal and parahippocampal gyrus ipsilateral to the side of seizure onset. The pervasive extrahippocampal structural deficits may result from chronic seizure propagation or may reflect other causes such as initial precipitating factors leading to MTLE.

Adult↗
PubMed2006

ILAE classification of epilepsy syndromes.

The efforts of the International League against Epilepsy (ILAE) to devise classifications of the epilepsies has greatly improved communication among epileptologists and influenced both basic and clinical research. Several classifications have been proposed since 1970; the most recent classification of epilepsy syndromes and epilepsies was published in 1989. Since 1997, the ILAE Task Force on Classification and Terminology has been evaluating this classification and some modifications have been recommended. Although the 1989 classification can be criticized and needs to be updated, it has been widely accepted and is universally employed. Consequently, the Task Force has agreed not to propose a replacement until a clearly better classification can be created.

Epilepsy↗
PubMed2006

Extracellular adenosine in the human brain during sleep and sleep deprivation: an in vivo microdialysis study.

STUDY OBJECTIVES: To examine the pattern of extracellular adenosine in the human brain during sleep deprivation, sleep, and normal wake. DESIGN: Following recovery from implantation of clinical depth electrodes, epilepsy patients remained awake for 40 continuous hours, followed by a recovery sleep episode. SETTING: Neurology ward at UCLA Medical Center. PATIENTS OR PARTICIPANTS: Seven male epilepsy patients undergoing depth electrode localization of pharmacologically refractory seizures. INTERVENTIONS: All subjects were implanted with depth electrodes, a subset of which were customized to contain microdialysis probes. Microdialysis samples were collected during normal sleep, sleep deprivation, and recovery sleep from human amygdalae (n = 8), hippocampus (n = 1), and cortex (n = 1). MEASUREMENTS AND RESULTS: In none of the probes did we observe an increase in extracellular adenosine during the sleep deprivation. There was a significant, though very small, diurnal oscillation (2.5%) in 5 of the 8 amygdalae. There was no effect of epileptogenicity on the pattern of extracellular adenosine. CONCLUSIONS: Our observations, along with those in animal studies, indicate that the role of extracellular adenosine in regulating sleep pressure is not a global brain phenomenon but is likely limited to specific basal forebrain areas. Thus, if energy homeostasis is a function of sleep, an increased rate of adenosine release into the extracellular milieu of the amygdala, cortex, or hippocampus is unlikely to be a marker of such a process.

Adenosine↗
PubMed2006

Report of the ILAE classification core group.

A Core Group of the Task Force on Classification and Terminology has evaluated the lists of epileptic seizure types and epilepsy syndromes approved by the General Assembly in Buenos Aires in 2001, and considered possible alternative systems of classification. No new classification has as yet been proposed. Because the 1981 classification of epileptic seizure types, and the 1989 classification of epilepsy syndromes and epilepsies are generally accepted and workable, they will not be discarded unless, and until, clearly better classifications have been devised, although periodic modifications to the current classifications may be suggested. At this time, however, the Core Group has focused on establishing scientifically rigorous criteria for identification of specific epileptic seizure types and specific epilepsy syndromes as unique diagnostic entities, and is considering an evidence-based approach. The short-term goal is to present a list of seizure types and syndromes to the ILAE Executive Committee for approval as testable working hypotheses, subject to verification, falsification, and revision. This report represents completion of this work. If sufficient evidence subsequently becomes available to disprove any hypothesis, the seizure type or syndrome will be reevaluated and revised or discarded, with Executive Committee approval. The recognition of specific seizure types and syndromes, as well as any change in classification of seizure types and syndromes, therefore, will continue to be an ongoing dynamic process. A major purpose of this approach is to identify research necessary to clarify remaining issues of uncertainty, and to pave the way for new classifications.

Adolescent↗
PubMed2005

Reduced anesthetization during the intracarotid amobarbital (Wada) test in patients taking carbonic anhydrase-inhibiting medications.

PURPOSE: Failure to show adequate anesthetization during the intracarotid amobarbital procedure (IAP or "Wada test") is a rare complication. After an unusually high rate of recent anesthetization failures, we sought to determine the frequency of reduced anesthetization and any common factors underlying these failures. METHODS: We reviewed the records of all patients who underwent IAP tests through the UCLA Seizure Disorder Center between September 1999 and May 2002. Age, date, epileptogenic focus, radiologist, and current medications were all considered. RESULTS: Of a total of 56 patients who underwent our intracarotid amobarbital examination, 11 (19.6%) showed either very rapid recovery ( /=8 weeks after discontinuation of such medications.

Amobarbital↗
PubMed2005

Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Brain↗
PubMed2005

Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats.

PURPOSE: The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection. METHODS: Pairs of tungsten electrodes (50 microm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days. RESULTS: Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low-voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta-gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta-gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG-evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30-ms interval increased. CONCLUSIONS: If ripple and FR oscillations indicate the seizure-generating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired-pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.

Animals↗
PubMed2005

Analysis of seizure onset on the basis of wideband EEG recordings.

Seventy-five seizure onsets recorded with depth electrodes in the frequency band from 0.1 to 70 Hz were analyzed in 19 patients with intractable temporal lobe epilepsy. It was shown that 89% of low-voltage fast-type seizures contained an initial slow wave, whereas hypersynchronous-type seizures did not show an initial slow wave. Voltage depth profile analysis illustrated that the peak amplitude of the initial slow-wave onset was in white matter, whereas the peak amplitude of hypersynchronous onset was in deep temporal areas (hippocampus, entorhinal cortex, or amygdala). The difference in voltage depth profiles suggests that these two types of seizure onsets have different mechanisms of generation. The absence of phase reversal of the initial slow wave in white matter or at the border of deep temporal areas indicates a possible nonneuronal mechanism of generation.

Amygdala↗
PubMed2004

Large-scale microarray gene expression analysis in discrete electrophysiologically identified neuronal clusters.

The normal processes of learning and memory as well as the pathological progress of various neurological diseases may result in changes in gene expression in small, local populations of neurons in any given brain area, leading to the occurrence of specific patterns of electrical activity without easily detectable changes in the morphology of this brain area. One way of identifying these changes might be the comparison of gene expression of areas which generate and areas which do not generate specific patterns of electrical activity. A method for microbiopsy of limited (0.5-1.0 mm3) tissue samples from electrophysiologically identified areas of neurons generating epileptiform activity in the rat brain is described. Here we demonstrate that total RNA isolated from individual microbiopsy samples might be successfully used for microarray based gene expression analysis of any discretely localized neuronal group which can be identified electrophysiologically, including neurons in cortical columns, cell assemblies or other functional units.

Animals↗
PubMed2004

High-frequency oscillations recorded in human medial temporal lobe during sleep.

The presence of fast ripple oscillations (FRs, 200-500 Hz) has been confirmed in rodent epilepsy models but has not been observed in nonepileptic rodents, suggesting that FRs are associated with epileptogenesis. Although studies in human epileptic patients have reported that both FRs and ripples (80-200 Hz) chiefly occur during non-rapid eye movement sleep (NREM), and that ripple oscillations in human hippocampus resemble those found in nonprimate slow wave sleep, quantitative studies of these oscillations previously have not been conducted during polysomnographically defined sleep and waking states. Spontaneous FRs and ripples were detected using automated computer techniques in patients with medial temporal lobe epilepsy during sleep and waking, and results showed that the incidence of ripples, which are thought to represent normal activity in animal and human hippocampus, was similar between epileptogenic and nonepileptogenic temporal lobe, whereas rates of FR occurrence were significantly associated with epileptogenic areas. The generation of both FRs and ripples showed the highest rates of occurrence during NREM sleep. During REM sleep, ripple rates were lowest, whereas FR rates remained elevated and were equivalent to rates observed during waking. The predominance of FRs within the epileptogenic zone not only during NREM sleep, but also during epileptiform-suppressing desynchronized episodes of waking and REM sleep supports the view that FRs are the product of pathological neuronal hypersynchronization associated with seizure-generating areas.

Animals↗
PubMed2004

Seizure incidence during single- and paired-pulse transcranial magnetic stimulation (TMS) in individuals with epilepsy.

OBJECTIVE: We reviewed published data and our own data to determine a quantitative incidence of seizure in subjects with epilepsy undergoing single- and paired-pulse transcranial magnetic stimulation (spTMS and ppTMS) and to explore conditions that may increase this risk. METHODS: A PubMed literature search was performed, and articles from this search were reviewed. Subjects from our institution also were included. RESULTS: The crude risk of a TMS-associated seizure ranges from 0.0 to 2.8% for spTMS and 0.0-3.6% for ppTMS. Medically intractable epilepsy and lowering antiepileptic drugs were associated with increased incidence. There was significant center-to-center variability that could not be explained by differences in patient population or by differences in reported stimulation parameters. In all cases, seizures were similar to each subject's typical seizure and without long-term adverse outcome. In most cases, doubt was expressed in the original reports as to whether the seizures were induced by TMS or merely coincidental. CONCLUSIONS: The incidence of seizure in a subject with epilepsy during spTMS and ppTMS appears to be small and not associated with long-term adverse outcome. The incidence is higher under the specific conditions mentioned above. SIGNIFICANCE: These findings may enable researchers to more accurately inform subjects of seizure risk during TMS.

Electric Stimulation↗
PubMed2004

Models of focal epilepsy.

Focal symptomatic epilepsy is the most common and most refractory form of human epilepsy and is an important subject of basic research. Although advanced diagnostic technologies and epilepsy surgery facilities are providing increasing opportunities to carry out investigations directly on patients with focal epilepsy, inherent limitations make research with animal models essential to elucidate basic mechanisms, improve diagnosis, and test potential therapies. Numerous animal models are available, but proper use requires that they be validated for specific investigative purposes and, preferably, studied along with patients, employing reiterative parellel experimental paradigms. Clinical research establishes the critical questions that cannot be completely answered with human investigation, while results of animal research carried out to resolve these questions must be reexamined clinically to confirm their relevance to the human condition. Better and cheaper animal models are necessary for optimum cost-effective parallel research activities, which includes not only models of specific types of acute epileptic seizures, and chronic epilepsy, but models of component parts of seizures and epilepsy that can be used as surrogate, or biological, markers of epileptogenesis and epileptogenicity. Appropriate use of markers such as FR could greatly reduce the expense, and time required, to produce the necessary research results.

Animals↗