Paroxysmal EEG Discharges Research Articles

Physiological sleep myoclonus in baboons

Physiological sleep myoclonus (sleep onset myoclonus and myoclonus during paradoxical sleep) was recorded from the tails of 6 baboons (2 Papio hamadryas and 4 Papio papio) and its relationship with spontaneously occurring EEG paroxysmal discharges was studied. It was observed that during light slow wave sleep tail myoclonus (sleep onset myoclonus) was almost always associated with EEG paroxysmal discharges predominating in the fronto-rolandic cortex. During deep slow wave sleep the number of EEG paraxysmal discharges decreased and tail myoclonus disappeared. In contrast, during paradoxical sleep tail myoclonus became more frequent even in the absence of cortical paroxysmal discharges. Though at present we do not know whether sleep onset myoclonus is triggered or not by cortical paroxysmal discharges, we propose that sleep myoclonus (sleep onset myoclonus and myoclonus of paradoxical sleep) is independent of these discharges but that, at a given moment, the two phenomena may be coupled by a hypothetical subcortical pacemaker.

Alumina cream-induced focal motor seizures in cats. V. unilateral lesions of the brain-stem reticular formation

The effect of unilateral mesencephalic (MRF) and pontine (PRF) lesions on EEG-EMG patterns of type B and C alumina cream induced focal motor seizures was studied on cats with chronically implanted elecrode and cannula lesion systems. EEG patterns included number, amplitude and contralateral propagation of type B spikes and occurrence and duration of type C tonic-clonic discharges. EMG patterns included changes in muscular multiple unit activity (EMG-MUA) time locked to the onset of type B spikes and to the onset (tonic OTCD) and the end (clonic ETCD) of type C tonic-clonic EEG paroxysmal discharges. 1. (1) MRF lesions ipsilateral to the cortical epileptogenic focus significantly increased number, amplitude and propagation of type B EEG spikes and the occurrence, but not the duration, of type C EEG tonic-clonic discharges. They also reduced amplitude of type B muscular jerks and blocked type C tonic contradversion with a significant decrease in EMG-MUA time locked to the onset of type B spikes and type C paroxysmal EEG discharges. 2. (2) PRF lesions contralateral to the cortical epileptogenic focus produced an effect on muscular contractions of type B and C seizures similar to that produced by ipsilateral MRF lesions. PRF lesions, however, did not significantly change the EEG patterns of type B and C seizures. 3. (3) Neither MRF lesions contralateral nor PRF lesions ipsilateral to the cortical epileptogenic focus produced significant changes on EEG and EMG patterns of types B and C epileptic seizures.

Push-pull perfusion of pentylenetetrazol in the brain stem of ‘encéphale isolé’ cats

Nine ‘encéphale isolé’ cats had ‘push-pull’ perfusions of pentylenetetrazol (PTZ) in various loci of the brain stem, while the EEG from the right and left motor cortices, EMG from neck muscles, ocular movements and clinical changes were recorded. Perfusions in the rostral MRF induced bilateral rhythmic paroxysmal EEG discharges and myoclonic twitching of neck and head, more prominent in the muscles contralateral to the perfused side. PTZ in the caudal MRF induced tonic-clonic paroxysmal EEG discharges and EMG seizures, similar to those seen when PTZ is injected systemically. Perfusion in the PRF induced EEG spindle bursts, muscular hypotonia and myosis. When perfusion in the MRF inducing rhythmic paroxysmal EEG discharges and myoclonic twitching was followed by perfusion in the PRF, the EEG discharges were not modified, but the myoclonic movements were abolished. Perfusions outside the MRF and PRF did not produce obvious changes other than tonic gaze deviation to the contralateral side or nystagmus. The results suggest that PTZ has a differential effect in various structures of the CNS, producing primary generalized convulsive seizures when acting directly on the MRF.

Differential effects of the benzodiazepine antagonist Ro 15-1788 on two types of myoclonus in baboon Papio papio

Certain benzodiazepines (BZs) like lorazepam, diazepam or clonazepam induce myoclonus jerks in photosensitive and non-photosensitive baboons, Papio papio, which are not accompanied by EEG paroxysmal discharges (type B). The effect of the selective BZ antagonist Ro 15-1788 was evaluated in this myoclonus. Ro 15-1788 completely blocked type B myoclonus without decreasing the level of vigilance in the two types of baboons, and reversed the antiepileptic action of the BZs in photosensitive ones, permitting the reappearance of myoclonus following EEG paroxysmal discharges (type A). l-5-hydroxytryptophan and progabide also blocked type B myoclonus, but the blockade was only transiently effective and was always accompanied by slight drowsiness.

Effect of sagittal transections of the brain stem tegmentum on alumina cream-induced focal motor seizures in cats

The effect of extensive and circumscribed sagittal transections of the brain stem tegmentum on types B (epilepsia partialis continua) and C (contradversive tonic-clonic seizures) alumina cream-induced focal motor seizures in cats was investigated. The neurological abnormalities of cats with transections and differences in the EEG-EMG patterns of types B and C seizures between operated and intact animals were statistically analyzed. Animals with either extensive or superior central nucleus transections showed bilateral neglect and internuclear palsy syndromes, no tonic type C seizures (contradversion), and a significant decrease in electromyogram multiple-unit activity (EMG MUA) from 0 to 10 s or more after the onset of EEG paroxysmal tonic-clonic discharges. Animals with rostral transections showed a unilateral neglect and internuclear palsy or ataxic syndromes with a concomitant partial reduction of contradversive seizures and a significant decrease in EMG MUA from 0 to 5 s or less after the onset of EEG tonic-clonic discharges; those with dorsal and caudal transections showed a transient neglect and insomniac syndromes with no differences in contradversion and EMG MUA at the onset of EEG tonic-clonic discharges in relation to intacts. Experimental and intact animals showed neither differences in types C and B EEG patterns nor in EMG MUA at the end of type C EEG tonic-clonic discharges and type B EEG spikes. These results support the idea that tonic and clonic muscular seizures are due to epileptic impulses originating in the cerebral cortex and mediated at the level of the brain stem by different pathways.

Alumina cream-induced focal motor epilepsy in cats. IV. Peduncular and midline tegmental lesions

The effect of peduncular and midline tegmental lesions on EEG-EMG patterns of type B and C alumina cream-induced focal motor seizures was studied on cats with chronically implanted electrodes and cannula lesion systems. EEG patterns included number, amplitude and contralateral propagation of type spikes and occurrence and duration of type C tonic-clonic discharges. EMG patterns included phasic multiple unit activity (EMG MUA) time locked to the onset of type B EEG spikes and time locked to the onset (contradversive OTCD) and end (clonic ETCD) of type C tonic-clonic EEG paroxysmal discharges. 1. (1) Lesions of the middle third of the cerebral peduncle, ipsilateral to the cortical epileptogenic focus, blocked type B muscular convulsions and significantly decreased phasic EMG MUA at contralateral face, neck and limbs. 2. (2) Bilateral peduncular lesions blocked clonic type C muscular convulsions and significantly decreased phasic clonic ETCD EMG MUA at the same body regions. 3. (3) Midline tegmental lesions blocked phasic type C muscular convulsions and significantly decreased phasic contradversive OTCD EMG MUA at neck muscles. 4. (4) Bilateral peduncular lesions significantly increased and midline tegmental lesions significantly decreased (below the previous interictal) contradversive OTCD EMG MUA. 5. (5) Neither peduncular nor midline tegmental lesions significantly changed EEG patterns of type B and C seizures.

Specific and nonspecific multiple-unit activities during pentylenetetrazol seizures in animals with pretrigeminal brain stem transection

The sequence of activation and deactivation of multiple-unit activity (MUA) in the mesencephalic and pontine reticular formations, pyramidal tract, and the electromyogram (from neck and temporalis muscles) in relation to the onset and the end of EEG paroxysmal discharges induced by pentylenetetrazol was studied in cats with brain stem “pretrigeminal” transection. The following events were observed: (i) A significant increment of the MUA in the mesencephalic reticular formation followed 6 s later by the onset of EEG paroxysmal discharges and significant increase of pyramidal tract MUA, while pontine reticular MUA increased slowly before or after the onset of EEG paroxysmal discharges and the electromyogram remained unchanged. (ii) A decrease of mesencephalic reticular and pyramidal tract MUA at the end of EEG paroxysmal discharges, while the pontine reticular MUA remained very active. Comparing the observations made in “pretrigeminal” preparations with those previously published in “encéphale isolé” preparations, we conclude that in normal conditions pentylenetetrazol induced a peculiar sequence of activation of MUA starting at the mesencephalic reticular formation and followed by other brain stem structures and the cerebral cortex, that the mesencephalic reticular seizures propagate to the spinal cord through both pyramidal and “extrapyramidal” (perhaps the brain stem motor apparatus) pathways, and that inhibitory mechanisms of seizure activity in this model of epilepsy, situated above the transection level, exclude the cerebellum.

Cortical unit activity during intermittent photic stimulation in Papio Papio. Relationship with paroxysmal fronto-rolandic activity

Extracellular records have been made in the fronto-rolandic (FR), parietal and occipital cortical areas in Papio papio injected with allylglycine and paralysed with a synthetic curarizing agent. The organization of the unit discharges in the absence of intermittent light stimulation (ILS) is normal. During ILS, unit discharges in the FR cortex are organized in bursts of high frequency that are synchronous with the spikes of the EEG paroxysmal discharges (PD) in the same territory; this burst-organized FR activity is reversible, and bursts disappear when the ILS stops. In addition, in the FR cortex, triple or single flashes induced paroxysmal visual evoked potentials (PVEP) whose spikes were accompanied by bursts identical to the preceding ones. The slow waves which constituted The PD and the PVEP corresponded to a transitory inhibition of the FR neuronal activity. From the unit discharge patterns, no difference was observed between the two EEG paroxysmal activities recorded. No pattern of discharge in bursts was ever observed in the parietal and occipital cortex. The synchronizing role of the light stimulation in the FR cortex in Papio papio under allylglycine is discussed and the results are used to compare the experimental model with the naturally highly photosensitive animal. The Particular reactivity of the FR cortex with respect to other regions is also discussed. Finally, the results bring forth new information in favour of a similarity between PD and PVEP.

Effect of carbachol “push-pull” perfusion in the reticular formation on alumina cream-induced focal motor seizures in cats

The effect of carbachol perfusion in pontine (PRF) and mesencephalic reticular formations (MRF) on type B and C focal motor seizures induced by alumina cream was studied in a group of cats, in an attempt to reproduce (totally or partially) that observed under spontaneous sleep-waking states and state transitions. During carbachol perfusion in the PRF, there was a pure hypotonic response: significant decrease in mean tonic and phasic electromyographic multiple-unit activities (MUAs) with no changes in number of electroencephalogram (EEG) type B spikes and duration of type C paroxysmal discharges. This response lasted 60 to 80 min and was followed by a slow-wave-sleep-like response: further significant decrease in mean tonic and phasic electromyographic MUA and increase in number of EEG type B spikes and duration of type C paroxysmal discharges, which lasted until 180 min after carbachol perfusion. During carbachol perfusion in the MRF, there was an arousal-like response: significant increase in type B mean tonic and phasic electromyographic MUA and decrease in number of EEG spikes and prevention of occurrence of electroencephalogram-electromyogram patterns of type C seizures. This response lasted 60 to 80 min after perfusion and was followed by a paradoxical-sleep-like response: significant decrease in type B mean tonic and phasic electromyographic MUA and number of EEG spikes and delay of type C phasic electromyographic MUA and decreased duration of EEG paroxysmal discharges.

Consequences de l'impregnation medicamenteuse de longue duree sur le developpement de l'enfant; etude clinique et electrophysiologique au cours du sevrage

The case of a child under continuous anticonvulsant medication, especially barbiturate, since the age of 8 months for atypical seizures is reported. Medication was withdrawn when the child was 7.7 years old. The child was then under care in a Day Hospital with an autistic-like syndrome associated with important disturbances of sleep-waking regulation, complete learning incapability and major EEG abnormalities. The EEG paroxysmal discharges observed in the waking and all-night sleep records gradually decreased and then disappeared as the withdrawal was pursued over a period of several months. During the same period, the child's behaviour markedly improved and his sleep disturbances disappeared. The possibility of iatrogenic effects of early and continuous anti-convulsant therapies is discussed, even though the drug plasma levels remain within ranges generally considered as non-toxic.

THE EFFECT OF FRUSEMIDE, MEXILETINE, (+)‐PROPRANOLOL AND THREE BENZODIAZEPINE DRUGS ON INTERICTAL SPIKE DISCHARGES IN THE ELECTROENCEPHALOGRAMS OF EPILEPTIC PATIENTS

The effects of single intravenous doses of diazepam, clonazepam, lorazepam, frusemide, mexiletine and (+)‐propranolol on the frequency of electroencephalographic (EEG) interictal spike discharges were assessed in three double‐blind placebo‐controlled trials in fourteen epileptic patients. Diazepam (5 mg) produced a significant mean decrease of spike discharges to about one third of the control frequency. The effect developed rapidly and persisted for the duration of the study (up to 25 min after injection). A larger dose (10 mg) failed to produce a further reduction in the frequency of the spike discharges. Clonazepam (0.5 mg), frusemide (40 mg) and lorazepam (2 mg) appeared to be as effective as diazepam in reducing spike discharges, although the effect of the latter drug seemed to develop with some delay. Mexiletine (100 mg) and (+)‐propranolol (50 mg) did not reduce paroxysmal EEG discharges, their effects being not significantly different from that of saline. EEG spike counting after intravenous administration of single test‐doses appeared to be both a simple and promising technique for the rapid preliminary evaluation of the clinical efficacy of new anti‐epileptic drugs.

Influence of chlordiazepoxide on paroxysmal EEG activity induced by hippocampal and-or thalamic cobalt foci.

The influence of chlordiazepoxide (Librium) on the paroxysmal 7–9/sec spike and wave and polyspike EEG discharges induced by chronic cobaltgelatine implantation into the dorsal hippocampus and/or nonspecific thalamus has been studied in rats with electrodes in the frontal cortices, dorsal hippocampi and the mesencephalic reticular formation. Both low (1.5–9 mg/kg i.p.) and high (9–15 mg/kg i.p.) doses of chlordiazepoxide reduced the incidence of paroxysmal EEG manifestations and shortened their duration (when present). Both effects were more pronounced after higher doses. The frequency of spike-wave complexes or spikes within the paroxysmal EEG discharges did not change systematically after chlordiazepoxide. The influence of the drug on the paroxysmal discharges is independent of whether the EEG after chlordiazepoxide is desynchronized or synchronized. In the latter case desynchronization of the EEG by reticular stimulation does not facilitate the occurrence of paroxysmal EEG dischartes.

Autonomic changes during paroxysmal EEG activity

1. 1. Changes in skin resistance, heart rate, skin temperature, respiration and finger vasomotor activity during paroxysmal EEG discharges were evaluated in 54 epileptic patients and five non-epileptic photo-sensitive subjects. Simultaneous recording of autonomic variables and EEG enabled an evaluation to be made of the association of autonomic changes with seizure discharges. 2. 2. All discharges recorded were generalized, bilaterally synchronous, and symmetrical. They were evaluated as to type of wave form and organization, length of burst, whether spontaneous or photically induced, and whether they were accompanied by clinical phenomena. 3. 3. Analysis indicated that no autonomic responses were associated with slow wave bursts and few autonomic responses were present during “subclinical” spike and slow wave discharges. “Clinical” spike and slow wave bursts ( i.e. bursts associated with objective or subjective signs) were usually accompanied by autonomic involvement, the degree of which correlated with the extent of clinical phenomena. Changes in skin resistance and HR were most frequently associated with paroxysmal activity. A GSR and change in heart rate were present during nearly all petit mal discharges, but respiration and temperature responses were variable. 4. 4. The latency of the GSR differed significantly for spike and slow wave complexes and petit mal discharges. Regardless of duration of the burst the GSR usually occurred within 2 sec following the first spike of the atypical spike and wave bursts, whereas it occurred several seconds after onset, or more frequently, following the cessation of the petit mal discharge. These observations of the GSR suggest that awareness of the manifestations of the discharge may be an important determinant of autonomic response.

Cyclic conditioning of epileptic discharges

Eight patients with high voltage polyspike or spike-wave response to flickered light were subjected to a cyclic conditioning procedure which failed to produce consistent evidence of conditioning of the S-W to a paired tone signal. However, paroxysmal EEG discharges preceding the occurrence of positive (light-reinforced) and especially negative (not light-reinforced) stimuli suggest that the mental set anticipation, and especially unfulfilled anticipation favor the occurrence of EEG paroxysms. The possible obliteration of a conditioned S-W response by a prepotent conditioned blocking response is considered, as is the possibility that the epileptic discharge represents an “error” of conversion from conditioned desynchronization through physiological hypersynchrony to eventual extinction. A principal interest in the study lies in the possibility of defining some of the behavioral factors which contribute to the occurrence of “spontaneous” unpredictable spiking in the EEG of individuals with epileptic disorders.

Epileptic activation of single cortical neurons and their relationship with electroencephalographic discharges

1. 1. Epileptogenic foci were elicited in the suprasylvian (parietal) gyrus of unanesthetized cats by means of local application of different drugs (strychnine, penicillin, curare, Metrazol). 2. 2. The paroxysmal EEG discharges were simultaneously monitored, from their early development, with routine cortical electrodes and with tungsten microelectrodes. 3. 3. The activity of one or of several units from a given microelectrode placement and of a large number of units from different placements through the cortical layers was correlated with the paroxysmal EEG discharge. 4. 4. The most characteristic pattern of unit behavior, in coincidence with the EEG paroxysmal event, is a burst of high frequency spikes; other units may fire only one or two spikes and occasionally units are found which are apparently unaffected during the EEG discharges. The activity of “injured” elements as well as that of elements characterized by high frequency repetitive firing in the absence of EEG paroxysms, suddenly stops when the latter occur. 5. 5. Hypersynchrony of firing of a large number of unitary elements, though not strictly absolute, is another characteristics feature of epileptic activation. 6. 6. There exists a close correlation between morphology of the slow EEG discharge and firing pattern of given units. 7. 7. These various findings together with the topographical distribution of active units within the cortex are analyzed and discussed.

Electroencephalographic changes in man during use and withdrawal of barbiturates in moderate dosage

1. 1. In contrast to doses of over 0.6 g. per day, the withdrawal of 0.4 g. daily of seconbarbital or pentobarbital after three months was not followed by psychotic or convulsive manifestations in any of 18 nonepileptic subjects. 2. 2. Seven of 13 individuals demonstrated some evidence of EEG tolerance to 0.4 g. daily of secobarbital or pentobarbital during 90 days. 3. 3. During withdrawal from this same barbiturate regimen, 5 of 18 subjects developed paroxysmal EEG discharges which later disappeared and were not associated with observable clinical abnormalities.