[Prevention of post-traumatic epilepsy].
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Biomedical subjects
Publications and source records attributed to J Majkowski.
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Changes in EEG and susceptibility to electrically induced seizures were examined in the ferret with lissencephaly produced by exposure to a single injection of methylazoxymethanol acetate (MAM Ac) given to the pregnant jill on gestation day 32. Ten lissencephalic and 11 normal ferrets were chronically implanted with 14 cortical stainless steel electrodes. EEG records were sampled from various stages of the sleep/awake cycle. Six of each group were subjected to electrical stimulation for seizure threshold. Although the number of stimulations and the current intensity required to produce epileptiform afterdischarges (AD) and seizures were not different between the two groups, the lissencephalic ferrets had significantly longer AD and seizures, and a greater number of generalized seizures, indicating an enhanced seizure susceptibility. The EEG of the lissencephalic ferrets was characterized by increased slow wave activity within the low theta band range, extreme spindle activity, focal or multifocal slow and sharp waves, spikes, or spike and slow wave complexes. The differences in the EEG were more pronounced during drowsiness and sleep stages. The brains of all of the treated animals were lissencephalic and hydrocephalic, and weighed significantly less than those of the normals. The cerebral cortex was thin and flattened, with the parieto-occipital region most severely affected. Heterotopic foci were found in the cerebellum as well as in the cerebral cortex. Abnormalities in the configuration of the cerebellar folia were also seen. Comparison between the electrophysiological and neuropathological data suggests that the extent of the extreme spindle activity, and longer AD and seizure duration depended on the degree of cerebellar dysplasia, whereas the EEG focal abnormalities were related to lesions in the cerebral hemispheres.
In 26 seizure-prone gerbils, with chronically implanted electrodes, the electro-clinical relationship of seizures was studied. The results are based on 70 EEG recordings of fully developed seizures resulting from: (1) moving the animal from its home cage to the testing area, i.e., the naturally occurring environmentally precipitated seizures (EPS); (2) electrically induced by stimulation of cortical electrodes (ICS); and (3) electrically induced by stimulation of hippocampal electrodes (IHS). The EPS were categorized into 4 electro-clinical phases: myoclonic, clonic-tonic, tonic, and clonic movements; usually preceded by an incipient period and followed by a post-seizure period. Usually the EPS were preceded by focal single spiking in the posterior part of the hemisphere, during which the animal's behavior was normal. This spiking turned to generalized epileptic discharges (incipient period without epileptic behavior) which were followed by the 4 phases of generalized myoclonic and clonic-tonic seizures. Post-seizure coma-like behavior was associated with EEG depression. The ICS were very similar to the EPS, but of course lacking the incipient phase. In contrast to the EPS and ICS, the IHS were very different both in terms of EEG and clinical manifestations. Moreover, the post-seizure depression was absent or negligible. We concluded that in the EPS in gerbils, the cortex is of primary importance as to the site of origin of the seizure, while the hippocampal involvement is secondary to it.
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BAERs from 16 subjects during 3 sessions varied in the latency or amplitude of some components depending upon level of arousal as indicated by EEG patterns. There was a general tendency for activation to produce the fastest responses with the largest amplitudes and for drowsiness to produce the slowest responses with the smallest amplitudes. The latency of P2 was significantly prolonged during drowsiness, relative to those during relaxation or activation. For right-ear stimulation, P5 latency was longest during drowsiness, and shortest during activation while for left-ear stimulation the shortest latency occurred during relaxation. The amplitudes of Wave II and Wave VII were significantly smaller during drowsiness than during activation. Although the differences were below the level of clinical significance, the data indicate a modification in the characteristics of brainstem transmission as a function of concurrent activity in other brain areas.
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In normal and lissencephalic ferrets with chronically implanted electrodes, two antiepileptic drugs, (E)-2-[(amino)phenylmethylen]-benzo [b] thiophen-3(2H)-on (AF-CX 921 XX) and carbamazepine (CBZ), were compared. The variables included afterdischarges (AD) and seizures induced by cortical electrical stimulations (ES). Both drugs were given orally, 100 mg/kg of pure substance. ES was applied before and 1, 2, 3, 4, 5, and 24 h after drug administration. Lissencephaly was produced by a single intraperitoneal injection of 15 mg methylazoxymethanol acetate to pregnant animals. The administration of both drugs resulted in increases of the AD threshold current to 240% in the normal and to 170% in the lissencephalic ferrets, in comparison with control stimulations (the difference significant at p less than 0.001). Moreover, duration of the AD was shorter (p less than 0.01) than before the drugs. Seizure threshold also increased 170% after AF-CX 921 XX and 175% after CBZ in normal and 153% and 138% in lissencephalic ferrets, respectively. The difference between the two drugs was significant. However, in contrast to the threshold, duration of seizures during AF-CX 921 XX administration was significantly shorter (p less than 0.05) than during CBZ. In general, lissencephalic ferrets responded less than normal ferrets to both drugs, but AF-CX 921 XX had a greater inhibitory effect on the duration of seizures. The lissencephalic ferret is proposed as an animal model of epilepsy with diffuse developmental defects.
The relationship between seizure propensity and the vascular anatomy of the anterior cerebral arteries, or stroke induced by unilateral ligation of the common carotid artery, was investigated utilizing well differentiated colonies of seizure-prone (SP) and non-seizure-prone (NSP) gerbils. Twenty SP and 20 NSP gerbils were perfused with a latex dye and the vascular patterns of the anterior cerebral arteries (ACA) were analyzed. In addition, 30 SP and 30 NSP gerbils were subjected to unilateral ligation of the common carotid artery and the number developing stroke (determined by clinical observation as well as by microscopic examination of the brain) was recorded. We found that in all animals the ACAs formed a fused-central vessel which vascularized the olfactory bulbs, as well as two lateral vessels (rostral arteries) that vascularized a previously undescribed nasal plexus. Neither the vascular pattern of the ACA, nor the frequency of occurrence of stroke following unilateral ligation was related to seizure propensity.
Cortical somatosensory evoked potential (SSEP) changes were studied during kindling of the right pericruciate cortex and in the right hippocampus in 7 cats. The test electric stimuli were delivered to left and right anterior paw. The ipsi- and contralateral SSEPs were averaged before kindling and about every 35th day during kindling. Paroxysmal epileptic discharges developed in all cats. The main consistent changes in all the SSEPs involved components N2-P3-N3, i.e., those with latencies of 90--330 msec. Specifically we noted (1) a gradual decrease in the duration and latency of the N3 component (2) an increase in the slope of the P3-N3 component and (3) a decrease in the duration and latency of the p3 component. These changes were present in both hemispheres, ipsi- and contralateral to both right and left paw stimulation, though favoring the contralateral responses. The changes started to develop before the appearance of spontaneous epileptic activity and seem to be independent of the epileptogenic effect of kindling. Thus, during kindling two types of neuronal function modification seem to take place: epileptogenic and nonepileptogenic. The nonepileptogenic nature of kindling is discussed from the point of view that some forms of learning and kindling are based on similar neurophysiological processes, which lead to permanent neuronal bioelectrical changes. These plastic changes underlie the development of such processes as memory and epilepsy. The difference between these two processes may be in the disturbance of spatiotemporal distribution of coherence in neuronal ensembles.
The problem of the relationship between stimulus intensity and kindling effect was studied in three groups of cats with bipolar stimulating electrodes implanted in the right posterior sigmoid gyrus (sensorimotor cortex). Daily stimulation with a 1-sec train of 60-Hz rectangular pulses was carried out in 17 cats over a period of from 27 to 265 days. Group I, 3 cats, was stimulated with a current intensity of 200 microA, peak-to-peak, which was subthreshold for afterdischarges (ADs); 6 animals from group II were stimulated with near-threshold currents (0.8--1.1 mA); and in the 8 animals of the group III, the ADs were evoked by threshold currents of 1.0--1.6 mA. The EEG was recorded from the sensorimotor and visual cortices, hippocampus, caudate nucleus, dentate nucleus, and cerebellar cortex. It was found that the low-current stimulation (200 microV) was not effective in inducing kindling. Near-threshold stimulation (below 1 mA) resulted in the development of bioelectrical epileptic activity in most cats. Threshold stimulation for AD resulted in the development of bioelectrical spontaneous activity and in an increase in the duration of ADs, as well as in generalized tonic-clonic seizures during cortical stimulations, in the majority of cats. Differences in hippocampal and neocortical kindling in cats are discussed in terms of ADs and seizure development. It was found that (1) a longer time was required for neocortical than for hippocampal kindling (3--10 weeks), and (2) there was greater variability in the effects of neocortical kindling. Secondary generalized seizures developed in the group with threshold stimulation for AD and were preceded by an increase in the number of ADs. The interictal epileptic activity developed in some cats in the absence of ADs.
After short introduction in which mile-stones of brain electrical stimulation are mentioned, author discusses kindling as a model of epilepsy and learning. The plastic nature of these two neuronal processes is discussed from the point of view: 1. similarities of these two processes and 2. relation between epileptic discharges (seizures) and learning (memory). The lack of quantitative analysis of afterdischarge duration and its effect on retention is emphasized. Author presents his own study of relation between performance of formed motor avoidance conditioned reflex (CR) and epileptic spontaneous spike activity in hippocampi and duration of afterdischarges (AD) in hippocampi and amygdala in hippocampal kindling in cats. It was shown that spontaneous hippocampal spikes, dissipated over a time, have no effect on performance or retention of the CR. However, there is clear relation between duration of AD and retention of the CR. When duration of the AD was to 15 seconds, correct CRs were obtained in 75% and in 25% the result was negative CR. However, when duration of the AD was longer, the CS presentation between 16-30 sec. resulted in 75% of negative CR and 25% of positive CRs. When the CS was presented during ADs which were longer than 30 sec. almost in all cases the CR was negative, however, in a few instances still possible. Complex effect of brain stimulation are discussed and value of weak stimulation like in kindling technique is emphasized.
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The inhibitory effect of cerebellar cortex (Cb) and dentate nucleus (DN) electrical stimulation were studied on 7 cats. After kindling in right hippocampus or in right somato-sensory motor cortex the both Cb and left DN were stimulated monopolarly or bipolarly in each cat. The stimulation was 1 sec train of impulses of 1 ms duration and 60 Hz. The current intensity was 0.3-1.7 mA, 10-12 stimulations were performed in each animal in each structure and the results of stimulations were averaged. The following indices of the stimulation effect were taken into consideration: 1) Number of epileptic spontaneous discharges during 2 min of EEG records before and after stimulation. 2) sum of the epileptic discharges within the periods, 3) time between spontaneous epileptic discharges, 4) time to first paroxysmal discharge after electrical stimulation of the Cb or DN. Results showed prolonged time to the first spontaneous epileptic discharge after stimulation of both structures, thus, indicating statistically significant inhibitory effect of stimulation. The other indices showed no statistically significant inhibitory effects.
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