Carlos Cepeda

Spontaneous secondarily generalized seizures induced by a single microinjection of kainic acid into unilateral amygdala in cats

Electrographic and clinical observations were made for 6 months after the injection of kainic acid (KA) solution (1 microgram in 1 microliter of phosphate buffer solution) through a chronically implanted cannula into a unilateral amygdala of freely moving and non-anesthetized cats. The control group (phosphate buffer group) showed no change during the observation period. After the injection of kainic acid, focal status epilepticus in the limbic system was observed for 3 days. Cats recovered clinically but persistent IIDs were observed at the injected site of the amygdala. These IIDs increased in amplitude and frequency and began to trigger spontaneous amygdaloid seizures. Secondary epileptogenic foci were then established in the contralateral amygdala, and amygdaloid seizures began to occur alternatively on both sides and finally trigger frequent limbic seizures from 20 to 40 days after KA injection. Spontaneous secondarily generalized seizures developed about 30 days after KA injection and occurred once or twice a week thereafter. The animals were completely normal in their behavior during the interictal phase. This is an excellent model of experimental epilepsy for the investigation of the mechanism of limbic seizure development and further study using this model will provide informations useful for the therapy of temporal lobe epilepsy in man.

Wakefulness-sleep modulation of cortical and subcortical somatic evoked potentials in man

Abstract Amplitude changes of early and late components of cortical and subcortical somatic evoked potentials (SEP) were determined during wakefulness-sleep steady state shifts in patients with implanted electrodes used as an electrophysiological procedure for the surgical treatment of unilateral tremor and rigidity. SEP were produced by threshold motor stimulation of the median nerve and simultaneously recorded from contralateral scalp, thalamic and subthalamic regions, while patients spontaneously shifted from initial wakefulness (W1), to slow wave sleep (SWS I, II, IV), paradoxical sleep (PS) and final wakefulness (W2). 1. (1) During W1, cortical responses were formed by early (P50) and late (P100, 200, 300) components. Subcortical type A responses were formed only by early (N or P20) components recorded within a circumscribed region including VPL thalamic nucleus and medial lemniscus. Subcortical type B and C responses were formed by only late components (P100 and P100, 300 respectively) and were recorded intermixed within a widespread region including VL and Ce thalamic nuclei, zona incerta, nucleus subthalamicus, prelemniscal radiations and reticular formation. 2. (2) Early cortical and subcortical components significantly increased when patients shifted from PS to W2 but showed no systematic changes during other wakefulness-sleep state shifts. 3. (3) Late cortical and subcortical components significantly decreased when patients shifted from W1 to SWS I and increased from PS to W2. In addition, late cortical components significantly decreased from SWS I to II and remained unchanged from SWS II to IV while late subcortical components remained unchanged from SWS I to II and significantly decreased from SWS II to IV. These components were maximally depressed during SWS IV and PS; however new cortical (P150, N250, P450) and subcortical (P250 or N300) components appeared during SWS IV but not during PS.

Alumina cream induced focal motor epilepsy in cats. II. Wakefulness--sleep modulation of pyramidal tract multiple unit activity.

Abstract Quantitative changes in tonic and phasic multiple unit activities of the pyramidal tract (PT MUA) were determined during wakefulness-sleep state shifts of a group of cats with alumina cream induced focal motor epilepsy. In addition, tonic multiple unit activity from neck muscles (EMG MUA) was recorded as an indicator of peripheral neuromuscular tonic excitability. Changes in PT MUA and EMG MUA were related to other EEG and clinical epileptogenic events. 1. [1] During wakefulness (W), animals showed both EEG spikes and clinical convulsions. Tonic PT MUA and EMG MUA were high and phasic PT MUA showed a pronounced and significant transient increase time locked to the EEG spike. During slow wave sleep (SWS), animals showed EEG spikes with no (or discrete) clinical convulsions. Tonic PT MUA and EMG MUA were low and phasic PT MUA showed a slight although significant transient increase time locked to the EEG spike. During paradoxical sleep (PS) animals showed EEG spikes with no clinical convulsions. Tonic PT MUA was high while EMG MUA was low and phasic PT MUA showed a pronounced and significant trandient increase time locked to the EEG spikes. 2. [2] A significant decrease in tonic and phasic PT MUA and tonic EMG MUA was found when animals shifted from W to SWS. A significant increase in tonic and phasic PT MUA and decrease in tonic EMG MUA were found when animals shifted from SWS to PS. No significant changes in tonic and phasic PT MUA and a significant decrease in EMG MUA were found when animals indirectly shifted from W to PS. These data suggest that wakefulness-sleep states modulate initiation and propagation of epileptic impulses at two different levels of the CNS: cortical and spinal. Accordingly, W activates both, SWS deactivates both and PS activates the cortical while deactivates the spinal one.

Alumina cream induced focal motor epilepsy in cats. I. Wakefulness-sleep modulation of cortical paroxysmal EEG spikes

Abstract Quantitative changes in amplitude, density and temporal distribution of cortical paroxysmal EEG spikes from motor cortex (spikes) during wakefulness-sleep state shifts were studied in a group of cats with alumina cream induced focal motor epilepsy. Special care was taken in analyzing various types of spikes and in operationally defining wakefulness-sleep states. Main results and conclusions referred to type B spikes since it was present in all cats during the convulsive stage and in all wakefulness-sleep states within the same cat. 1. (1) During wakefulness (W), individual type B spikes showed a mean amplitude of 215 ± 28 μV, density of 60 ± 13/min and interval of 462 ± 36 msec. Correlation coefficient between individual spike and EMG clonic contractions (convulsions) was equal to one. 2. (2) There was a significant increase spike density (decreased interval) when cats shifted from W to slow wave sleep (SWS) and significant decrease spike density (increase interval) when cats shifted from SWS to paradoxical sleep (PS). In contrast, no significant changes in spike density and interval were found in cats between W and PS. 3. (3) No significant differences in spike amplitude and interval variance were found during wakefulness-sleep shifts. 4. (4) Arousal shifted cats from SWS to W and produced changes in amplitude density and interval similar to those spontaneously observed in shifts from SWS to PS. 5. (5) Spike/convulsion correlation coefficient was reduced from one to zero (or near zero) when cats spontaneously shifted from W to SWS and PS, and it was increased from zero (or near zero) to one when cats shifted from SWS to W by means of an arousal stimulus presentation.

Wakefulness-sleep modulation of thalamic multiple unit activity and EEG in man ☆

Quantitative changes in the number of EEG waves and MUA neuronal spikes of various thalamic nuclear groups were studied during steady and transitional wakefulness-sleep states in a group of patients with implanted electrodes, used as an electrophysiological procedure for the surgical treatment of unilateral tremor and rigidity. Thalamic nuclei included ventroposterolateral (VPL), ventrolateral (VL) and centromedian (CM). Steady states included initial wakefulness (W1), slow wave sleep (SWS) I, II, IV and IIL, paradoxical sleep phasic (PSP) and tonic (PST) and final wakefulness (W2). Transitional states included transition from SWS to PSP (transition) and from sleep to W2 (arousal). (1) There was a significant correlation in EEG and MUA between different thalamic nuclei simultaneously recorded in the same patient during different steady-states. (2) Thalamic MUA significantly decreased from W to SWS, increased from SWS to PS and SWS to W2, while thalamic EEG significantly decreased from W to SWS, increased from SWS to W2 but was not significantly modified from SWS to PS, consecutive steady-state shifts. (3) Thalamic MUA significantly decreased while EEG remained unchanged from PSP to PST consecutive steady-state shifts. (4) Both thalamic MUA and EEG significantly decreased from SWS II to IIL while they were not systematically modified from W1 to W2 indirect steady-state shifts. (5) Thalamic MUA significantly increased 1 sec before transition and arousal while EEG increased 5 sec after arousal and did not change during transition.

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 B 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) 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) Bilateral peduncular lesions blocked clonic type C muscular convulsions and significantly decreased phasic clonic ETCD EMG MUA at the same body regions. (3) Midline tegmental lesions blocked phasic type C muscular convulsions and significantly decreased phasic contradversive OTCD EMG MUA at neck muscles. (4) Bilateral peduncular lesions significantly increased and midline tegmental lesions significantly decreased (below the previous interictal) contradversive OTCD EMG MUA. (5) Neither peduncular nor midline tegmental lesions significantly changed EEG patterns of type B and C seizures.

Effect of a new thienodiazepine (We-941) on sleep patterns of normal and insomniac subjects.

Abstract The effect of a new thienodiazepine We-941 (0.5 mg, oral) on sleep patterns of normal and insomniac subjects was quantitatively determined and statistically compared with (a) the sleep patterns obtained under base line conditions and with placebo in 10 normal subjects; (b) with those obtained under initial and final placebo in a series of 8 insomniac subjects; and (c) with those obtained with flurazepam (30 mg, oral) in another series of 8 insomniac subjects. 1. 1. The spontaneous arousal episodes shown by some normal subjects under base line conditions and with placebo were abolished by We-941. However, no significant differences in wakefulness-sleep parameters were found in normal subjects under We-941 compared with base line or placebo. 2. 2. The duration of wakefulness and number of arousal episodes were decreased by We-941 which increased the duration of sleep, decreased the latency of slow wave sleep I and II and increased the duration of slow wave sleep III. These results were significantly different to initial, but not to final, placebos in the same insomniac subjects. Flurazepam decreased the duration of wakefulness and number of arousal episodes and increased the duration of sleep and duration of rapid eye movement sleep. These results were significantly different from initial, but not from final, placebos in the same insomniac subjects. 3. 3. No significant differences were found between the effects of We-941 and flurazepam on slow wave sleep III and rapid eye movement sleep in different insomniac subjects.

Alumina cream-induced epilepsy in cats. III. Wakefulness-sleep modulation of multiple unit activity in the reticular formation

Abstract Quantitative changes in tonic and phasic multiple unit activities (MUA) of the mesencephalic (MRF) and pontine reticular formations (PRF), pyramidal tract (PT) and neck muscles (EMG) during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS) were determined in alumina cream-induced epileptic cats showing two types of EEG/EMG seizures: type B characterized by continuous isolated EEG spikes and EMG jerks (epilepsia partialis continua) and type C characterized by episodic tonic-clonic EEG spikes and EMG jerks (adversive seizures). 1. (1) Tonic PT, MRF and PRF MUA were large during W and PS and low during SWS while EMG MUA was large during W, low during SWS and almost abolished during PS. PT and EMG MUA significantly decreased while MRF and PRF MUA did not change when cats shifted from W to SWS. PT, MRF and PRF MUA significantly increased while EMG MUA decreased from SWS to PS. PRF MUA significantly increased and EMG MUA significantly decreased while PT and MRF MUA did not change from W to PS. 2. (2) During W, type B phasic PT, MRF, PRF and EMG MUA significantly increased time-locked to the onset of isolated EEG spikes. During SWS and PS, PT, MRF and PRF MUA significantly increased while EMG MUA remained unchanged at the onset of EEG spikes. Type B phasic PT MUA significantly decreased when cats shifted from W and PS to SWS, EMG MUA decreased from W to SWS and PS while MRF and PRF did not change systematically through different wakefulness-sleep state shifts. 3. (3) During W, type C phasic PT, MRF and PRF MUA significantly increased 1 sec before while EMG MUA increased 1 sec after the onset of EEG tonic-clonic discharges. During PS, PT, MRF and PRF MUA significantly increased 5-4 sec before, decreased 2–3 sec after and increased 5–6 sec after while EMG MUA remained low and unchanged until it significantly increased 4 sec after the onset of tonic-clonic EEG discharges. PT MUA significantly increased 3 sec before, PRF MUA decreased 3 sec after and EMG MUA decreased 1–4 sec after the onset of tonic-clonic EEG discharges when cats shifted from W and SWS to PS.

Kainic acid-induced limbic seizures in cats: some reflections on sleep-epilepsy interactions

Summary: Sleep–epilepsy interactions were investigated in a model of temporal lobe seizures induced in cats by intra‐amygdaloid kainic acid (KA) microinjections. We found that limbic status epilepticus disrupted sleep for 2 or 3 days after injection. Sleep, in turn, modulated the frequency of interictal discharges. However, such modulation was variable depending on the time elapsed since KA injection. For this and other reasons (such as the occurrence of subclinical seizures during paradoxical sleep), we postulate a dual effect—facilitatory or inhibitory—of paradoxical sleep on limbic epilepsy. A role in seizure induction for bulbopontine structures is proposed on the basis of seizure precipitation during phasic paradoxical sleep. Propagated limbic seizures and paradoxical sleep without atonia displayed similar behavioral patterns. This fact and the possibility that a seizure may substitute for paradoxical sleep, lead us to think that limbic seizures and paradoxical sleep subserve similar functions. One of them might be the elimination of a potentially Neuroloxic endogenous product.

A peculiar rhythmic EEG activity from ventrobasal thalamus during paradoxical sleep in man

A peculiar 3/sec rhythmic EEG activity (named Vc rhythm) was consistently found at the ventrobasal thalamus (nucleus ventrocaudalis) during paradoxical sleep of patients with implanted electrodes used as an electrophysiological procedure for identification of the thalamic targets for the surgical treatment of tremor and rigidity. The Vc rhythm was formed by high voltage, sharp biphasic positive negative potentials which were absent during wakefulness, rare and isolated during slow wave sleep, increased in number and organized in trains during paradoxical sleep and blocked during arousal. Significant changes in number of Vc waves were found when patients shifted through these wakefulness-sleep states. Integrated EMG multiple unit activity also showed significant changes during these wakefulness-sleep shifts, which were parallel although inverse to those showed by Vc waves. A significant negative correlation (r = -0.7126) between number of Vc waves and EMG units was found. In contrast, Vc waves showed no correlation with other electrophysiological indicators of thalamic excitability (multiple unit activity and early evoked potentials) and sleep (scalp EEG frequency and ocular movements).