BACKGROUND:Epilepsy is a prominent sign of neurologic dysfunction in some children with fetal alcohol syndrome (FAS). However, it is unknown whether the epileptic disorders in these children are directly due to the neuroteratogenic effects of alcohol or to some other factor accompanying maternal alcoholism. The hippocampus is vulnerable to alcohol-induced pathologic changes, and dysfunction of the hippocampus often manifests as epilepsy. We examined the effect of alcohol exposure during development on the seizure threshold and examined the relationship between alteration of seizure threshold and alcohol-induced neuronal loss from the hippocampus.METHODS:Rat pups received 0.85, 2.5, or 3.75 g/kg of alcohol via intragastric intubation daily over postnatal days (PD) 4-9. An intubated control and a suckle control group were also included. To assess the effect of a single day of alcohol exposure, an additional group received 3.75 g/kg of alcohol on PD 4 alone. Behavioral seizure thresholds were determined by intravenous infusion of the proconvulsant, pentylenetetrazol (PTZ), on PD 31 or on PD 90. In addition, electrographic seizure thresholds were determined by recording extracellular field potentials from the dentate gyrus. The number of hippocampal CA1 pyramidal cells, CA3 pyramidal cells, and granule cells of the dentate gyrus were determined by stereology.RESULTS:Daily exposure to alcohol resulted in a dose-dependent decrease in the seizure threshold and in the selective loss of CA1 pyramidal cells. Reduction in the seizure threshold was significantly correlated with loss of CA1 pyramidal cells. Recordings of extracellular field potentials confirmed the alcohol-induced reduction in seizure threshold, demonstrated that PTZ-induced seizures involve hippocampal-parahippocampal circuitry, and provided evidence that the hippocampal formation is the generator of the PTZ-induced seizures in alcohol-exposed animals.CONCLUSIONS:These findings demonstrate that exposure of the developing brain to alcohol can permanently reduce the threshold for both behavioral and electrographic seizures and can selectively kill hippocampal CA1 pyramidal cells. Both the pathologic findings and the physiologic recordings support the concept that the reduced seizure threshold in alcohol-exposed animals is due to hippocampal pathology.

Studies have suggested that in the immature brain an unusually high ceiling level for potassium may lead to an increased propensity for seizures. In these experiments, the peak levels of extracellular potassium in the hippocampus in vivo were recorded in immature rats 10-27 days old and compared to levels reached in adults. There was no difference in the peak level of potassium attained during an afterdischarge in any of the age groups tested.

The cellular and molecular pathophysiology of status epilepticus (SE) provides a conceptual framework for understanding clinical scenarios and prospectively designing logical therapies. SE is a dynamic process that evolves over time in a predictable manner with an established sequence of EEG, motor, physiologic, and cellular changes. Neuronal injury and death are the result of processes intrinsic to the brain, mediated by a complex neurotoxic cascade consisting of multiple serial and parallel processes. The risk of cell injury depends also on the overall pathophysiologic profile, including the presence of alterations resulting from SE and occurring independent of SE. On neurophysiologic grounds, we divide SE into "spike-wave" and "nonspike-wave" forms. Spike-wave "absence" status epilepticus carries a low risk of epileptic brain damage, and therapy should be adjusted accordingly. All nonspike-wave SE has a theoretical basis for epileptic brain damage, but the actual risk is variable. There is a significant known risk of cell injury during generalized convulsive SE, a variety of nonspike-wave SE, so aggressive treatment is warranted to prevent sequelae. There is also a theoretical basis for epileptic brain damage in nonspike-wave nonconvulsive SE, but prospective studies are needed to determine which of these patients warrant aggressive therapy. Based on pathophysiologic principles, future treatment of nonspike-wave SE may use a combination of anti-ictal agents, including gamma-aminobutyric acid agonists and N-methyl-D-aspartate antagonists, as well as various neuroprotectants.

HippocampusVolume 4, Issue 3 p. 286-290 Article Seizure circuits in the hippocampus and associated structures Eric W. Lothman M. D., PhD., Corresponding Author Eric W. Lothman M. D., PhD. Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, VirginiaDepartment of Neurology—Box 394, University of Virginia Health Science Center, Charlottesville, VA 22908Search for more papers by this author Eric W. Lothman M. D., PhD., Corresponding Author Eric W. Lothman M. D., PhD. Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, VirginiaDepartment of Neurology—Box 394, University of Virginia Health Science Center, Charlottesville, VA 22908Search for more papers by this author First published: June 1994 https://doi.org/10.1002/hipo.450040311Citations: 34AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Amaral DG, Witter MD (1989) The three-dimensional arrangement of the hippocampal formation: a review of anatomical data. 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We have studied outward currents of neurons acutely dissociated from the dentate gyrus region of hippocampus using whole-cell and perforated patch recordings. Depolarizing voltage commands activated sustained outward currents at all ages tested (P5–P30). Outward currents were blocked by tetrathylammonium (10 mM) but not 4-aminopyridine (25 mM). Comparison of sustained potassium current during postnatal development showed a significant increase in current amplitude with age reaching a peak between P20 and P30. These results suggest an overall increase in the number of voltage-dependent ionic channels during development, specifically those underlying TEA-sensitive potassium currents.

There is a critical role for loss of GABA-mediated inhibition in the CA1 region of the hippocampus in the emergence of partial status epilepticus (SE) in experimental animals.' We demonstrated loss of GABA-mediated inhibition in the CA1 region of the hippocampus by the paired-pulse method in several different experimental models of partial SE.' The cellular mechanism underlying loss of GABA-mediated inhibition during SE remains unclear. This study investigates the effect of experimental SE on rat forebrain GABA receptor. We studied the effect of a combination of lithium and pilocarpine and lithium alone on GABA-mediated inhibition in the CA1 region of the hippocampus by paired-pulse inhibition technique.2 Methods. SE was induced by a method described by Honchar et aL3 Briefly, adult male Sprague-Dawley rats weighing 175 to 250 grams were each given 3 mEqlkg lithium chloride as a single intraperitoneal injection followed 20 hours later by 50 mglkg pilocarpine. Animals started having seizures 13 to 46 minutes after pilocarpine injection, and these seizures continued for 30 to 47 minutes before termination. The seizures were terminated by ether anesthesia and the forebrains were rapidly removed from the skulls, placed in a chilled sucrose buffer, and homogenized. The sucrose buffer contained 0.32 M sucrose, 100 mM PIPES, 10 mM EGTA, and 20 mM EDTA. The homogenate was spun at 5,000 g for 10 minutes in a Beckman 52-21 centrifuge. The supernatant was then spun at 18,000 g for 20 minutes. The resultant pellet (P2 fraction) was osmotically shocked in a lox volume of distilled water. The synaptic plasma membrane fractions derived by this procedure were suspended in 50 mM Tris citrate buffer (pH 7.4) and washed three times in Tris buffer. After three washes, the membranes were stored at -70 "C. Fifty p1 of 3H-muscimol was added to 100 pl membranes and 850 p1 50 mM Tris citrate to reach final muscimol concentrations varying from 3 nM to 100 nM. Based on preliminary experiments, nonspecific binding was obtained in the presence of 100 mM GABA. The membranes were incubated with radioligand for 20 minutes and then reaction was terminated by rapid filtration under vacuum on Whatman GF/B filters. Filters were washed three times, then digested in 3 ml of Insta-Gel Packard scintillation fluid. Radioactivity was measured by conventional scintillation counting. Binding data is presented as specific binding, calculated by subtracting binding in presence of GABA from total binding. Paired-pulse inhibition technique was utilized to measure GABA-mediated inhibition in the CA1 region of the hippocampus of urethane (1.3 to 1.5 gkgbanesthetized animals. We have previously described* this procedure for studying paired-pulse inhibition in detail. In one set of experiments, naive animals were studied; in the second set of experiments, rats were given 3 mEqlkg lithium chloride intraperitoneally 20 hours prior to urethane anesthesia. In the lithium-pretreated animals, inhibition was measured, 50 m g k g pilocarpine was administered, and 15 minutes later paired-pulse inhibition was measured again. Results. All animals injected with lithium and pilocarpine experienced seizures for at least 30 minutes. No seizures were observed in animals treated with lithium alone or in naive animals. A specific high-affinity saturable binding site for 3H-muscimol was defined in rat forebrain synaptic plasma membranes. In three separate experiments, a saturation curve for specific 3H-muscimol binding was generated by measuring total and nonspecific binding for free 3H-muscimol concentration ranging from 6 nM to 100 nM. Specific binding was approximately 50% of total binding. For each experiment, synaptic plasma membranes from five naive rats and from five animals undergoing SE were pooled; for each 3H-muscimol concentration, three separate measurements of total and nonspecific binding were made. Each measurement was repeated once. Synaptic plasma membranes from naive rats and from those undergoing SE were 0 8 -

The effect of recurrent seizures on the hippocampus has been controversial for many years. To determine the effect different seizure paradigms had on the structure of the dentate gyrus, we conducted histological studies on the dentate gyrus (DG) from three groups of rats: (1) those that had experienced 1500 intermittent kindled seizures; (2) those that had experienced a single episode of limbic status epilepticus (SE); and (3) control rats that had been implanted with electrodes. When compared to controls the DG of SE rats was overall slightly, but non-significantly, smaller, but the DG of rats with 1500 kindled seizures was significantly larger. The decrease of size following SE was attributable to a significant atrophy of the molecular layer. The increase in area associated with kindling was the result of an enlargement of the molecular layer and the hilus. Absolute neuronal counts showed a decrease in the hilus after SE but no change following kindling, but both groups had decreased neuronal densities in the hilus when compared to controls. The decreased density after SE was secondary to neuronal loss, but the decrease in neuronal density following kindling was the result of the expansion of the hilar neuropil without change in the number of neurons. This study extends our previous findings in Ammon's horn and indicates that SE induces significant neuronal loss, but numerous intermittent kindled seizures have no effect on neuronal numbers in the DG.

We have recently demonstrated that electrically induced seizures lead to dramatic increases in mRNA for GFAP in areas in which seizures occur. The present study evaluates the time course of the changes in the GFAP-mRNA levels after seizures and the relationship between these changes and GFAP protein levels to understand the role of neuronal activity in regulating glial gene expression. GFA protein and mRNA levels were measured in hippocampi from rats in which seizures were induced by: (1) 50-Hz stimulus trains delivered 12 times over the course of 1 day via indwelling electrodes implanted chronically in the CA3 region of the hippocampus; and (2) intraperitoneal injections of pentylenetetrazol. In the case of the electrically induced seizures, we also compared the glial response in animals that had never experienced a seizure with the response in animals that previously had been kindled but had not experienced a seizure for 30 days. Electrically induced seizures led to rapid transient increases in GFAP-mRNA levels in the hippocampus ipsi- and contralateral to the stimulation. GFAP-mRNA increased about five-fold 1 day after the end of seizure activity and returned to near-control levels by 4 days. There were no detectable increases in GFA protein at 1 day but by 2 days GFA protein levels had increased about two-fold. GFA protein levels remained elevated until 4 days poststimulation and then began to decrease. The responses were similar when seizures were induced in kindled animals, except that the GFAP protein levels remained elevated for somewhat longer. Pentylenetetrazol-induced seizures also led to increases in GFAP-mRNA and GFA protein levels but the extent of the increases was not as great as after kindled seizures. These results suggest that gene expression in astrocytes in likely to be upregulated in any situation in which seizures occur. These changes may fundamentally alter the homeostatic activities of the affected astrocytes which, in turn, could have important consequences on the development of the epileptic state.

Determining whether and under what conditions status epilepticus (SE) leads to undesirable long-term sequelae has major clinical ramifications. In addition to structural brain damage and enduring neurological deficits following SE, it has been suggested that SE can establish a chronic condition of active epilepsy. These three residua (epileptic brain damage, neurological deficits, and epilepsy) have been especially linked to protracted SE. The older clinical literature indicates that these sequelae are especially likely if SE occurs in an immature brain, but this point has been challenged in recent studies. Clinical and animal model work that examines the issue of chronic nervous system deficits arising as a consequence of SE is reviewed, with particular attention to the question of the epileptogenic effect of SE. Because of the inherent problem of not being able to exclude occult neurological disease antecedent to SE in brain, animal model work promises to be especially relevant to the issues at hand. Work done on adult rats has shown that a previously normal brain can be "converted" after a bout of SE to an epileptic brain, as manifest both by epileptic brain damage resembling that found in the hippocampus of patients with intractable temporal lobe epilepsy and by spontaneous recurrent seizures registered in the hippocampus. A two-step model is proposed: morphological brain injury takes place first and this change, in turn, promotes seizures. This model is offered as one way in which chronic active epilepsy can be established by a transient episode of SE. Although some findings from work with animal models have been interpreted as not supporting the idea that the immature brain is sensitive to a chronic epileptogenic influence initiated by SE, the majority of such work is consistent with this idea. On the other hand, a considerable amount of animal work indicates that the brains of immature animals are quite resistant to SE-induced brain damage, in contrast to those of adults. Thus, under these circumstances, a different process of epileptogenesis than the two-step model may be operational. It is concluded that, under appropriate conditions, SE does exert an epileptogenic effect that persists.

.Properly classifying epileptic seizures and epileptic syndromes is important for developing treatment strategies and determining prognoses for individual patients. Among the many factors important in such classification are the electrographic features of paroxysmal discharges. While many forms of paroxysmal discharges are described in the clinical and EEG literature, current understanding of the basic neurobiological events behind these discharges is limited to a few of them. In the review given below, three "prototypical" epileptiform events–interictal events, tonic-clonic electrographic seizures, and spike-wave seizures–are identified and the basic mechanisms by which they arise are discussed. The information provided considers functional anatomy in terms of major networks within the brain, a "fundamental local circuit" consisting of an excitatory neuron and the inhibitory neuron it is coupled to in a feedback circuit, and cellular processes of inhibition and excitation. The ways in which amino acid neurotransmitters exert excitatory synaptic events, via glutamate receptors, and inhibitory synaptic events, via gamma-aminobutyric acid (GABA) receptors are presented. In addition, key types of membrane potential-regulated ion channels in neurons are introduced. Details are then given as to how these basic neurobiological processes interact to produce the prototypical paroxysmal discharges. A distinct set of mechanisms is responsible for each of the discharges. Depending on the type of discharge, certain mechanisms are shared between types of discharges while others are not. With the information covered, one can gain an understanding of how common and important EEG paroxysms originate at the cellular and synaptic level.

In vivo experiments were carried out to examine whether the period during which gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus matures is associated with a decrease in epileptogenesis. Seizures were elicited with bipolar electrodes stereotactically positioned in the hippocampus of urethane-anesthetized rat pups from postnatal (PN) 7 through 28 days of age. No clinical seizure activity was detected but electrographic seizures (afterdischarges) were induced at all ages. Afterdischarge thresholds (ADT) varied inversely with age. However, the durations of initial afterdischarges and the degree of lengthening of afterdischarges with the rapidly recurring hippocampal seizure (RRHS) protocol were not different for the various age animals studied. Paired pulse inhibition was assessed with a twin pulse paradigm that has been shown to monitor GABAergic inhibition. Measurements were made before and 60 min after a single seizure and again 60 min after the RRHS protocol. At no age was there a significant change in paired pulse inhibition after a single seizure. After RRHS there was a significant reduction of paired pulse inhibition only in the groups that had manifested adult levels of paired pulse inhibition in preseizure measurements (greater-than-or-equal-to PN 21). These studies indicate that heightened epileptogenesis in the young hippocampus cannot simply be explained on the basis of an immaturity of GABA-mediated inhibition.

The influence of electrical stimulus parameters on focal seizure production was studied. Stimulations and recordings were carried out with bipolar electrodes stereotactically positioned in the ventral hippocampus of kindled rats. Afterdischarge thresholds were determined for stimulus trains with different combinations of train durations (0.5, 1, 2, 5, 10 s), intratrain frequencies (10, 20, 50, 60, 100 Hz), and pulse widths (0.5 and 1.0 ms). For a given combination of pulse width and intratrain frequency, thresholds decreased as train duration increased; the effect was profound with shorter durations but markedly attenuated with train durations ⩾ 5 s. For a particular train duration and pulse width, thresholds varied inversely with intratrain frequency; the degree of variation in the thresholds with frequency was greater the shorter the train. For the train durations studied, thresholds were lower with 1.0-ms pulses for intratrain frequencies ⩾ 20 Hz. However, for 10 Hz, the 0.5-ms pulses were more effective for 2-, 5- and 10-s trains. Afterdischarge thresholds were found to also vary with the number of pulses in the stimulus trains. For stimuli with fewer pulses, thresholds were higher and showed marked variation with train duration, intratrain frequency, and pulse width. For stimuli with more pulses, thresholds fell to a lower limit and the influence of train duration was substantially lessened. This study provides a systematic examination of the influence of stimulus parameters on generation of focal seizures and should prove useful in designing and interpreting future experiments studying the neurobiology of seizures in the hippocampus and related structures and helpful in antiepileptic drug testing.

Previously, a unique type of epileptiform discharge, recorded in the dentate gyrus, has been identified and termed maximal dentate activation. Maximal dentate activation is defined by the presence of bursts of large amplitude population spikes, associated with a secondary rise in the extracellular potassium and a negative shift of the dc potential. Prior work has linked maximal dentate activation to lengthening of afterdischarges when they are elicited in the hippocampus or outside of the hippocampus in the amygdala. The current study used two approaches to further examine the relationship of maximal dentate activation to seizures in limbic circuits in urethane-anesthetized rats. First, simultaneous recordings were employed to document that during maximal dentate activation, synchronous discharges occurred in the dentate gyrus, cornu Ammonis, subiculum, and entorhinal cortex. From anatomical work, these structures are known to be connected in a hippocampal-parahippocampal loop. The second approach used lesions of the entorhinal cortex to document the importance of this loop in the initiation and maintenance of maximal dentate activation. Both electrolytic and chemical (focal injections of tetrodotoxin) lesions of the entorhinal cortex blocked maximal dentate activation on the side of the lesion. However, maximal dentate activation was maintained on the opposite side, where the hippocampal-parahippocampal loop was intact. Altogether, these data support the hypothesis that maximal dentate activation is a marker for the presence of reverberatory, synchronized paroxysmal activity throughout the hippocampal-parahippocampal loop and that this loop behaves as a unit in epileptogenesis.

Understanding the molecular basis of altered neuronal excitability in epilepsy is a major challenge in neuroscience research. The present study suggests an inverse correlation between changes in neuronal excitability in status epilepticus and the activity of type II multifunctional calcium/calmodulin-dependent kinase II (CaM kinase II), a major Ca2+-signal transducing system in brain. ‘Continuous’ hippocampal stimulation (CHS), a new model of non-convulsive limbic status epilepticus (SE), mimics the progression of electrographic changes characteristic in human SE and allows for quantitation of post-stimulus seizure severity. In the present study, hippocampus and anterior neocortex from CHS-stimulated rats and paired surgical controls were assayed for CaM kinase II activity by incorporation of radiolabeled phosphate from [γ-32P]ATP into the 50-kDa subunit of the kinase itself (autophosphorylation). In all instances, CHS induced sustained interictal bursting and/or electrographic seizures. Decreased CaM kinase II activity was seen in all preparations from electrically stimulated hippocampus. CaM kinase II activity in CHS animals was diminished by 37% relative to controls (P < 0.01; Student's paired t-test). The progressive intensity of the EEG discharges correlated directly with the decrement of CaM kinase II activity (P < 0.05; Spearman's rank correlation test, n = 5). This is the first report of a dynamic modulation of a biochemical system that has been implicated in neuronal excitability in coordination with the characterized developmental stages of SE.

The functional topography and parameters of excitation and inhibition were determined in the in situ associational pathway of the rat dentate gyrus. The functional topography was found to be consistent with previous anatomical studies. The greatest amplitude population spikes and the strongest paired-pulse inhibition were generated with the stimulating electrode placed in the hilus at least 1.5 mm caudal to the ipsilateral dentate gyrus recording electrode. With this standard electrode configuration, neither long-term potentiation of the population spike nor of the population excitatory postsynaptic potential occurred. Hilar associational pathway activation of dentate gyrus granule cells elicited paired-pulse responses similar to those produced in granule cells by perforant path stimulation. Thus, the associational pathway provides another way to assess dentate granule cell function electrophysiologically.

Changes in electrophysiological function in the hilar associational pathway terminating on dentate granule cells in the rat hippocampal formation were studied following unilateral entorhinal cortex lesions. In rats lesioned as pups (postnatal day 4 [PN 4]) or as adults (PN 60) there was a profound loss of paired‐pulse inhibition at 30 days postlesion. Inhibition was unaffected at 10 days postlesion. Entorhinal cortex lesions did not affect population spike amplitude, population excitatory postsynaptic potentials slopes, or long‐term potentiation compared to the unlesioned hemisphere. The presence of a complete hippocampal commissurotomy had no effect on excitatory or inhibitory parameters. Laminar analyses of extracellular field potentials from animals lesioned as adults revealed an expansion of functional synapses outward into the dentate molecular layer. This expansion was complete by 10 postlesion days. The changes observed with laminar analyses were not contemporaneous with the changes in paired‐pulse inhibition. The loss of inhibition in the hilar associational pathway of entorhinal cortex‐lesioned animals thus implies a change in local circuit function rather than an effect from sprouted associational fibers directly onto granule cells. The lack of inhibition in the associational pathway in lesioned animals was not due to a failure of local circuit inhibitory function to develop, since the same findings were obtained when lesions were made neonatally or as adults. Rather, the authors suggest that the present findings arise because of the formation of functional, recurrent, excitatory mossy fiber collateral synapses following entorhinal cortex lesions.

El kindling es un modelo que consiste en la repetición de estímulos para producir crisis epilépticas espontáneas (CEE).Distinguir efecto convulsivo y subconvulsivo en ratones viejos y jóvenes, para evaluar las diferencias entre la ictogénesis y epileptogénesis.Se realizó kindling rápido utilizando pentilentetrazol (PTZ) en ratones C57BL/6. Utilizando dosis convulsivas (C) (75 mg/kg en una inyección) y subconvulsiva (SC) (10 mg/kg cada cinco minutos por 30 minutos, siendo un total de cinco inyecciones). Se conformaron cuatro grupos, sujetos de experimentación (SE) jóvenes (<32 semanas; C = 8; SC = 9) y 16 SE viejos (>32 semanas; C = 8; SC = 8). Utilizando Score de Racine (SR). Estadística descriptiva.Realizamos 16 protocolos C y 17 protocolos SC. El tiempo de latencia a fase 1 en segundo es menor en C viejos (50,5 seg) que en C jóvenes (170,3). En SC, fue mayor en el grupo de viejos 170,3 vs. jóvenes 105,5 (p = 0,001). El grupo C jóvenes presentaron mayor tiempo durante fase 1 a 3, y C viejos durante fase 4 y 5. Los SC jóvenes presentan mayor duración en fase 2, a diferencia de SC viejos con duración lineal en diferentes fases SR (p = 0,001). No hubo diferencias en muerte espontánea.El tiempo de latencia a fase 1 fue menor en SE viejos convulsivos y mayor que los SE jóvenes SC, sugiriendo mayor ictogénesis y menos epileptogénesis en la población vieja. La tendencia en SE viejos a permanecer más tiempo en fases 4 y 5 en dosis convulsivas sugiere mayor tendencia a ictogénesis y mayor severidad de las CE.Kindling Model consist sequential injections of a dose Pentylenetetrazole causing spontaneous seizures. (ES)Compare convulsive and subconvulsive effect in old and young mice, to evaluate the differences between ichthyogenesis and epileptogenesis.Rapid kindling model was performed using pentylenetetrazole in C57BL/6 mice. Using convulsive doses (C) (75 mg/kg in one injection) and sub-convulsive (SC) (10 mg/kg every 5 minutes for 30 minutes, for a total of 5 injections). Four groups were formed, young mouse (<32 weeks; C = 8; SC = 9) and 16 Old mouse (>32 weeks; C = 8; SC = 8). Using Racine Score. Descriptive statistics.Has been made 16 C protocols and 17 SC protocols. The latency time to phase 1 in sec. it is lower in old C (50.5 sec) than in young C (170.3). In SC, it was higher in the old group 170.3 vs young 105.5 (P = 0.001). Young C group presented longer time during Phase 1 to 3, and old C group during phase 4 and 5. Young SC presented longer duration in phase 2, unlike old SC with linear duration in different SR phases (P = 0.001). There were no differences in spontaneous death in all groups.Latency time to Phase 1 was shorter in old convulsives and longer than young SC, indicative greater ichthyogenesis and less epileptogenesis in the old population. Tendency in the elderly to stay longer in phases 4 and 5 in convulsive doses suggests a greater tendency to ichthyogenesis and greater severity of spontaneous seizures.