Feline Temporal Lobe Epilepsy: Review of the Experimental Literature.

Accumulating evidence suggests that epileptic seizures originating from the temporal lobe (TL) occur in cats. Typically, affected animals have clinically focal seizures with orofacial automatisms including salivation, facial twitching, lip smacking, chewing, licking, and swallowing. Motor arrest and autonomic and behavioral signs also may occur.

The alpha2 adrenoreceptor agonist clonidine suppresses evoked and spontaneous seizures, whereas the alpha2 adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens.

Microinfusion of alpha2 adrenoreceptor agonists and antagonists into amygdala has contrasting effects on evoked and spontaneous seizure susceptibility in amygdala-kindled kittens. Subjects were 14 preadolescent kittens between 3 and 4 months old at the beginning of kindling. The same protocol was followed except that half the kittens received microinfusions (1 mul) of the alpha2 agonist clonidine (CLON; 1.

Ontogeny of feline temporal lobe epilepsy in amygdala-kindled kittens: an update.

This report describes amygdala-kindled seizure development and the post-kindling course in 58 cats (29 males and 29 females), including 40 preadolescents between 2.5 and 6.5 months of age and 18 adults >1 year of age at the beginning of kindling.

Sleep and arousal mechanisms in experimental epilepsy: epileptic components of NREM and antiepileptic components of REM sleep.

Neural generators related to different sleep components have different effects on seizure discharge. These sleep-related systems can provoke seizure discharge propagation during nonrapid eye movement (NREM) sleep and can suppress propagation during REM sleep. Experimental manipulations of discrete physiological components were conducted in feline epilepsy models, mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy.

Monoamines and seizures: microdialysis findings in locus ceruleus and amygdala before and during amygdala kindling.

We used microdialysis to determine extracellular concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) before and during a 1-day amygdala kindling paradigm. Subjects were young cats (<1 year old; n=8; 6 female, 2 male). Consecutive 5-min samples (2 microl/min infusion rate) were obtained from left amygdala and ipsilateral locus ceruleus complex (LC) under 3 experimental conditions lasting 1-h each (n=12 samples per cat per condition): (1) just before amygdala stimulation (baseline), (2) during focal afterdischarge (AD) and (3) during generalized AD.

Long-lasting effects of feline amygdala kindling on monoamines, seizures and sleep.

This report describes the relationship between monoamines, sleep and seizures before and 1-month after amygdala kindling in young cats (<1 year old; n=8; six female and two male). Concentrations (fmoles of norepinephrine or NE, dopamine or DA and serotonin or 5-HT) were quantified in consecutive, 5-min microdialysis samples (2 microl/min infusion rate) from amygdala and locus ceruleus complex (LC) during four, 6-8-h polygraphic recordings before (n=2) and 1 month post-kindling (n=2); 5-min recording epochs were temporally adjusted to correspond to dialysate samples and differentiated according to dominant sleep or waking state (lasting > or =80% of 5-min epoch) and degree of spontaneous seizure activity (number and duration of focal versus generalized spikes and spike trains and behavioral seizure correlates). Post-kindling records in each cat were divided into two groups (n=1 record each) based on higher or lower spontaneous EEG and behavioral seizure activity and compared to pre-kindling records.

Physiological basis: how NREM sleep components can promote and REM sleep components can suppress seizure discharge propagation.

Objectives: To describe how the neural generators of different sleep components can provoke seizure discharge propagation during NREM sleep and can suppress it during REM sleep.

Methods: Experimental manipulations of discrete physiological components were conducted in feline epilepsy models (n=64), mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy. Procedures included seizure induction as well as quantifying norepinephrine concentrations (microdialysis) and the sleep-waking state distribution of seizures before and after lesions, systemic and localized drug administration and/or photic stimulation.

Monoamines and sleep: microdialysis findings in pons and amygdala.

This is the first microdialysis report comparing concentrations (pg/microliter) of norepinephrine (NE), serotonin (5-HT) and dopamine (DA) derived from feline locus ceruleus complex (LC) and amygdala. NE and 5-HT declined progressively from waking to slow-wave-sleep (SWS) and then to rapid-eye-movement (REM) sleep. Concentrations of DA did not change at either collection site across the sleep-wake cycle.

Vasodilatory actions of the dietary peptide carnosine.

The objective of this study was to test the hypothesis that the dietary dipeptide carnosine (beta-alanine-L-histidine) causes direct decreases in arterial tone. Isolated descending thoracic aortic rings from male Sprague-Dawley rats were used for all studies. Preconstriction of vessels was accomplished with phenylephrine.

The alpha 2 adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2 adrenoreceptor antagonist idazoxan promotes seizures: pontine microinfusion studies of amygdala-kindled kittens.

This is the first report showing that microinfusion of alpha 2 adrenoreceptor agonists and antagonists into the vicinity of the locus ceruleus (LC) have contrasting effects on evoked amygdala-kindled seizure susceptibility. Microinfusion (1 microliter) of the alpha 2 agonist clonidine (CLON) and of the alpha 2 antagonist idazoxan (IDA) were made over 1 min through cannulae in the LC ipsilateral to the kindled amygdala in 6 kittens. Order of administered drugs (CLON vs.

The alpha 2-adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2-adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens: a comparison of amygdala and pontine microinfusion effects.

Purpose: We sought to determine whether local, in vivo microinfusion of an alpha 2-adrenoreceptor agonist and antagonist into either the amygdala or the pons (locus ceruleus, LC) would have contrasting effects on evoked amygdala-kindled seizure susceptibility.

Methods: The study population consisted of 6 amygdala-kindled kittens, each undergoing the same protocol, in which the amygdala microinfusion paradigm preceded the pontine microinfusion series. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulas adjacent to stimulating electrodes in the kindled amygdala or through cannulas adjacent to recording electrodes in the ipsilateral LC.

Brainstem stimulation during sleep evokes abnormal rhythmic activity in thalamic neurons in feline penicillin epilepsy.

Some periods in the sleep-waking cycle are more seizure prone than others. In absence epilepsy, transition periods between nonrapid-eye-movement (nonREM) sleep and waking or REM sleep can be more seizure prone that stable states. One feature of transition periods that is hypothesized to promote seizure activity is the presence of coincident activity in ascending brainstem reticular formation (RF) arousal systems with synchronized thalamo-cortical activity.

Circadian rhythm, sleep, and epilepsy.

This review article: (1) describes the circadian distribution of ictal and interictal events; (2) differentiates transitional arousal, non-rapid eye movement and rapid eye movement sleep components and their substrates; (3) suggests the means by which the neural generators of these seizure-prone vs. seizure-resistant sleep and arousal states modulate the timing of different seizure manifestations; (4) considers clinical and mechanistic findings for the reciprocal effects of seizures and antiepileptic drugs upon the sleep-wake cycle; and (5) assesses clinical and basic mechanisms of sleep deprivation effects upon seizures.

Paroxysmal microarousals in amygdala-kindled kittens: could they be subclinical seizures?

Amygdala-kindled kittens exhibit frequent epileptiform EEG transients, often in conjunction with phasic arousal events of sleep [k-complexes, pontogeniculo-occipital (PGO) waves, and/or sleep spindles]. In this study, paroxysmal microarousals occurred throughout the sleep-wake cycle after kindling, but were most frequent during seizure-prone states of slow-wave sleep (SWS) and the transition into rapid-eye-movement sleep (REM). Their incidence correlated with interictal sleep fragmentation as well as onset of spontaneous convulsions.

Ontogeny of feline temporal lobe epilepsy. III: Spontaneous sleep and arousal disorders in amygdala-kindled kittens.

We report the ontogeny and persistence of sleep and arousal disorders in amygdala-kindled kittens. We also identify procedural differences that may explain discrepancies in the literature on postkindling sleep disorders. The study population consisted of 12 preadolescent kittens kindled between 2.

The alpha 2-agonist clonidine suppresses seizures, whereas the alpha 2-antagonist idazoxan promotes seizures--a microinfusion study in amygdala-kindled kittens.

This is the first report showing that local, in vivo microinfusion of alpha 2-adrenoreceptor agonists and antagonists have contrasting effects on amygdala-kindled seizure susceptibility. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and of the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulae adjacent to stimulating electrodes in five amygdala-kindled kittens. Order of administered drugs (CLON vs.

Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep epilepsy in amygdala-kindled kittens.

We previously described a model of spontaneous "sleep epilepsy" in kindled kittens with temporal lobe epilepsy (TLE). We now describe the postkindling course of this model from preadolescence to maturity and suggest pathophysiologic mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic convulsions (GTCs), developed 1h to 4 months after amygdala kindling and persisted to adulthood.

Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep.

Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells.

Spontaneous sleep epilepsy in amygdala-kindled kittens: a preliminary report.

We describe a model of 'sleep epilepsy' after amygdala kindling in kittens. Seizure activity was evaluated at different times in the sleep-wake cycle. Susceptibility was documented by thresholds for evoked convulsions in kittens without spontaneous seizures (n = 5) and by polygraphic or split-screen video recordings in kittens with spontaneous seizures (n = 6).

Lesions producing REM sleep without atonia disinhibit the acoustic startle reflex without affecting prepulse inhibition.

This study determined whether the brainstem motor inhibition system that mediates muscle atonia during rapid eye movement (REM) sleep is involved in the elicitation and prepulse inhibition of the acoustic startle reflex. Electrolytic or neurotoxic (glutamate) lesions were made in the dorsolateral pontine tegmentum or the medial medulla, respectively, to produce the syndrome of REM sleep without atonia. Startle responses were released during REM sleep following the lesions.

The ontogeny of feline temporal lobe epilepsy: kindling a spontaneous seizure disorder in kittens.

We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals.

Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking.

Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0-7 Hz) and spindles (8-15 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.

Mechanisms of seizure suppression during rapid-eye-movement (REM) sleep in cats.

REM sleep is the most antiepileptic state in the sleep-wake cycle for human generalized epilepsy, yet the neural mechanism is unknown. This study verified the antiepileptic properties of REM sleep in feline generalized epilepsy and also isolated the responsible factors. Conclusions are based on 20 cats evaluated for generalized EEG and motor seizure susceptibility before and after dissociation of specific REM sleep components.

Anticonvulsant drugs selectively affect kindled and penicillin epilepsy, especially during seizure-prone sleep or awakening states in cats.

Carbamazepine (CBZ) selectively suppressed kindled convulsions, whereas ethosuximide (ESM) suppressed spike-wave activity accompanying systemic penicillin epilepsy in cats. Evoked potential data indicated that CBZ acted at the thalamic level, whereas ESM acted at cortex. Reduction of seizures and thalamic or cortical excitability occurred throughout the sleep-wake cycle, but effects were most pronounced in seizure-prone sleep or awakening states.

Temporal lobe and petit mal antiepileptics differentially affect ventral lateral thalamic and motor cortex excitability patterns.

Evoked potential (EP) analysis of the somatomotor pathway in cats revealed that the temporal lobe anticonvulsant carbamazepine suppresses the thalamic relay, whereas the petit mal antiepileptic ethosuximide acts on the cortex. Moreover, a history of temporal lobe epilepsy (amygdala kindling) maximized thalamic response to carbamazepine, especially during sleep states vulnerable to generalized kindled seizures. Ethosuximide accentuated cortical response during sleep and awakening states vulnerable to generalized spike-wave complexes, regardless of a history of petit mal seizures (systemic penicillin epilepsy).