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Jerome Engel

Publications and source records attributed to Jerome Engel.

40 records · Page 3Linked to original sources

Rate of interictal events and spontaneous seizures in epileptic rats after electrical stimulation of hippocampus and its afferents.

PURPOSE: Deep brain stimulation has been used by several investigators to prevent the occurrence of spontaneous seizures in patients with intractable epilepsy. With the kainic acid rat model of spontaneous recurrent seizures, we examined the consequences of subthreshold electrical stimulation of commissural pathways and perforant path on the synaptic plasticity, rate of interictal epileptiform events (IIEs), and spontaneous seizures in kainic acid (KA)-treated rats epileptic rats. METHODS: Recording microelectrodes were implanted bilaterally in the dentate gyrus and entorhinal cortex. Stimulating electrodes were implanted into the rostral part of the right hippocampus and right perforant path. Stimulation was performed daily with 200 Hz/0.5-s duration trains, 10-min duration 1-Hz train, or 2-h, 1-Hz train and 2-h duration, 50-Hz trains. Integrated amplitude of evoked potentials, rate of IIE, and spontaneous seizures was analyzed before and after stimulation. RESULTS: High-frequency tetani evoked long-term potentiation in 50% of epileptic rats compared with 100% of control rats. No long-term depression was observed after 1-Hz train. Decrease rate of IIE was found during 1-Hz and 50-Hz stimulation and returned to the basal level within 30-60 min. No significant change of the spontaneous seizure rate was found. CONCLUSIONS: Epileptic brain is less prone to plastic changes compared with the normal brain. Daily 2-h electrical stimulation with either low or high frequency does not have a long-term effect on the rate of interictal events and spontaneous seizures.

Afferent Pathways↗

Epileptogenesis after self-sustaining status epilepticus.

PURPOSE: To describe the natural history of chronic epilepsy after experimental self-sustaining status epilepticus (SSSE) and to correlate patterns of SSSE with ictal, interictal, and plastic changes that characterize chronic epilepsy. METHODS: SSSE was induced in adult Wistar rats by 30-min intermittent electrical stimulation of the perforant path. In some animals, SSSE was treated by short-term administration of antiepileptic drugs (AEDs). After SSSE, EEG and animal behavior were monitored for </=1 year. Some animals were killed to study mossy fiber sprouting in the dentate gyrus. RESULTS: Despite the high reproducibility of the electrographic and behavioral manifestations of SSSE, patterns of chronic epilepsy varied considerably among animals in terms of seizure frequency, initial seizure pattern at the onset of chronic epilepsy, and frequency of interictal spikes. Statistically significant correlations were found between spike frequency during SSSE and interictal spike frequency, as well as between the frequency of spontaneous seizures and degree of mossy fiber sprouting. Early treatment of SSSE prevented the occurrence of spontaneous seizures and significantly decreased frequency of interictal spikes. Late treatment of SSSE did not prevent spontaneous seizures, but significantly decreased their frequency, and eventually may lead to remission of epilepsy. CONCLUSIONS: SSSE leads after a "silent" period to chronic epilepsy, which is maintained for > or =1 year in the rat. The silence is only behavioral, because EEG paroxysmal activity is seen in every animal. In this model of SSSE, the timing of treatment is a major determinant of outcome. Early treatment reduces the incidence of chronic epilepsy, whereas late treatment only reduces its severity. The possibility that this reduction of the severity of epilepsy may led to spontaneous remissions merits further study.

Animals↗

Quantitative analysis of high-frequency oscillations (80-500 Hz) recorded in human epileptic hippocampus and entorhinal cortex.

High-frequency oscillations (100-200 Hz), termed ripples, have been identified in hippocampal (Hip) and entorhinal cortical (EC) areas of rodents and humans. In contrast, higher-frequency oscillations (250-500 Hz), termed fast ripples (FR), have been described in seizure-generating limbic areas of rodents made epileptic by intrahippocampal injection of kainic acid and observed in humans ipsilateral to areas of seizure initiation. However, quantitative studies supporting the existence of two spectrally distinct oscillatory events have not been carried out in humans nor has the preferential appearance of FR within seizure generating areas received statistical evaluation based on analysis of a large sample of oscillatory events. Interictal oscillations within the bandwidth of 80-500 Hz were detected in Hip and EC areas of patients with mesial temporal lobe epilepsy using wideband EEG recorded during non-rapid eye-movement sleep from chronically implanted depth electrodes. Power spectral analysis showed that oscillations detected from Hip and EC areas were composed of two spectrally distinct groups. The lower-frequency ripple group was defined by a frequency of 96 +/- 14 Hz (median +/- width), while the higher-frequency FR group had a frequency of 262 +/- 59 Hz. FR oscillations were significantly shorter in duration compared with ripple oscillations (P < 0.0001). In regard to the occurrence of FR and ripples in epileptic Hip and EC, the mean ratio of the number of FR to ripples generated in areas ipsilateral to seizure onset was significantly higher compared with the mean ratio of FR to ripple generation from contralateral areas (P = 0.008). Furthermore, sites ipsilateral to seizure onset with hippocampal atrophy had significantly higher ratios compared with sites contralateral to both seizure onset and hippocampal atrophy (P = 0.001). These data provide compelling quantitative and statistical evidence for the existence of two spectrally distinct groups of limbic oscillations that have frequency and duration characteristics similar to those previously described in epileptic rat and human Hip and EC. The strong association between FR and regions of seizure initiation supports the view that FR reflects pathological hypersynchronous events crucially associated with seizure genesis.

Electrodes, Implanted↗