Seizures In Cats Research Articles

Disposition and clinical use of bromide in cats.

To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. Prospective and retrospective studies. 7 healthy adult male cats and records of 17 cats with seizures. Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane.

We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg.kg(-1) of bicuculline was administered i.v.. In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD ( P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model.

Claustral lesions delay amygdaloid kindling in the rat.

Lesions of the claustrum in cats and primates have been shown to disrupt the development and expression of amygdaloid-kindled seizures in cats and primates. Because the structure and connectivity of the claustrum can vary between species, we wanted to examine the effects of claustral lesions on kindling in rats. One group of rats received bilateral radiofrequency lesions of both anterior and posterior regions of the claustrum before amygdaloid kindling. Another group of rats received bilateral anterior and posterior radiofrequency lesions of the claustrum after amygdaloid kindling. Some rats were tested for transfer of kindling to the contralateral amygdala after claustral lesions. Small lesions that destroyed 13% of the claustrum were capable of delaying, but not blocking, amygdaloid kindling. The delay in kindling was due to an increase in the stimulation trials required to kindle to stage 5 seizures. The lesions had no effect on established kindled seizures or on transfer to the contralateral amygdala. As in other species, the claustrum in the rat appears to play a role in kindling from the amygdala. Because of the restricted size of our claustral lesions, however, we were unable to conclusively assess the full extent of the claustrum's participation in limbic kindling.

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats.

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg x kg(-1) x min(-1) was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130%+/-56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.

Membrane capacitance of cortical neurons and glia during sleep oscillations and spike-wave seizures.

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5-3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5-0.8 s). The repolarization of the glial membrane (duration, 0.5-0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1-2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation ( approximately 0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.

Change in cerebral glucose metabolism during limbic seizures elicited from lateral septal nucleus.

The roles of the amygdala and hippocampus have been extensively studied in limbic seizures. Although the septal nuclei have a close connection to the hippocampus and affect emotional behavior, the effect on limbic seizures is still unclear. We have reported that characteristic sham-rage seizures were observed in cats, by administering a local injection of kainic acid (KA) into the lateral septal nucleus (LSN). This study investigated the electrophysiological features of KA-induced septal seizures in rats and analyzed the process in relation to the cerebral glucose metabolism using [14C]deoxyglucose autoradiography. On EEG, epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus and the amygdala. Behavioral change was similar to that in limbic seizures induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats. However, the local cerebral glucose metabolism during the seizures increased not only in the limbic structures including the LSN but also in the hypothalamus and periaqueductal grey matter of the midbrain. The findings were distinctive of septal seizures as compared with amygdaloid seizures. The results suggested that sham-rage seizures in cats might be caused by a secondary epileptogenic excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The septal nuclei may play an important role in emotional behavior associated with limbic seizures even if there is a species difference in its function.

Diagnostic evaluation of cats with seizure disorders: 30 cases (1991-1993)

Objective To investigate causes of seizure disorders in cats. Design Case series. Animals 30 cats referred to the Ontario Veterinary College for recurrent seizures. Procedures Signalment and seizure pattern were evaluated. Diagnostic procedures included physical, neurologic, and fundic examinations; CBC; serum biochemical analyses, including determination of pre- and postprandial bile acid concentrations; urinalysis; serologic assays for FeL V and feline immunodeficiency virus, feline infectious peritonitis, and Toxoplasma gondii; magnetic resonance imaging of the brain; CSF analysis; and neuropathologic examination of euthanatlzed cats and of surgical biopsy specimens. Results All cats were found to have structural brain diseases; nonsuppurative meningoencephalitis of unknown cause was found in 14 cats, feline ischemic encephalopathy in 6, meningioma in 2, polycythemia vera with secondary brain lesions in 2, posttraumatic epilepsy in 1, and cerebral abscess in 1. A definitive diagnosis could not be reached in 4 cats. Clinical Implications The most common cause of seizures in cats is structural brain disease. Structural brain lesions often can be detected on the basis of seizure pattern and results of neurologic examination. Cerebrospinal fluid analysis and brain imaging are essential to determine the cause of these lesions. Causes of seizures found in the cats of this study differ from those reported to be the most common. Nonsuppurative meningoencephalitis of unknown origin appears to be a frequent cause of neurologic disorders in cats, including seizure disorders. Feline ischemic encephalopathy appears to exist in a milder form than the classic disease and may be a common cause of seizures in cats. (J Am Vel Med Assoc 1997;210:65–71)

Seizures in Cats

Seizures in cats are caused by active structural disease or secondary epilepsy. The most common structural causes are inflammatory diseases, many of which are probably viral (non-FIP) in origin. Toxoplasmosis, FIP, FeLV, and FIV are rare causes of recurrent seizures in cats. The incidence of primary epilepsy is unknown; it is unlikely to occur in domestic cats. The pattern (type and frequency) of the seizures and the age at onset of the seizures are important factors in establishing a differential diagnosis. More than 50% of cats with seizures experience nonconvulsive (mild generalized or partial complex) seizures. Though many cats experience severe cluster seizures and status epilepticus, severity of seizures is not a good predictor of outcome. Many cats stop having seizures or are controlled well with AEDs regardless of the severity of their seizure activity.

Respiratory motor nerve activities during experimental seizures in cats.

We evaluated respiratory motor nerve activities during experimental seizures induced with subcortical penicillin. The activities of the phrenic (PH), nasolabial (NL), and hypoglossal (HG) nerves and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 13 anesthetized, vagotomized, paralyzed, and ventilated cats. During ictal and interictal phases of seizures, nerve activities became irregular and peak integrated nerve activities increased, particularly in the case of the PH nerve. The ictal phase of seizures was associated with increased tonic activity and decreased phasic respiratory discharges, particularly in the cases of the HG, NL, and PCA nerves. During some prolonged ictal discharges, entrainment of nerve activities by cortical spiking was associated with irregular uncoordinated activation, particularly in the TA nerve. These studies help explain respiratory impairment during seizures by providing evidence of impaired coordination between activation of muscles that regulate upper airway patency and activation of the diaphragm.

Kainic acid-induced thalamic seizures in cats: A possible model of petit mal seizure

Kainic acid-induced thalamic seizures in cats: A possible model of petit mal seizure

The cerebral cortex origin of enflurane-induced generalized seizure in cats.

The role of sensorimotor cortex (anterior and posterior sigmoid gyri) as the origin of enflurane-induced generalized seizures was examined and compared to that of lidocaine-induced seizures in cats. The inhaled enflurane concentration was adjusted at 3.5% in oxygen, the maximum potency to induce generalized seizures. Repetitive electrical stimulation with supramaximum intensity at a forepaw (2 Hz, 0.5 ms, 10 V) induced generalized seizures, which ended with a sudden appearance of isoelectricity in the electroencephalogram (EEG), the so-called "postictal depression." Repetitive auditory stimuli also induced similar grand mal-type EEGs. Unilateral ablation of the sensorimotor cortex completely blocked the induction of generalized seizures by contralateral somatosensory stimuli. However, it had little effect on the induction of seizures by ipsilateral somatosensory stimuli or bilateral auditory stimuli. In contrast, bilateral ablation of the sensorimotor cortex did not have a significant effect on the lidocaine-induced seizures. These findings indicate that the involvement of the sensorimotor cortex is essential for the development of enflurane-induced but not lidocaine-induced seizures.

Changes in the threshold of pentylenetetrazol-induced seizures in cats with a chronic granuloma in brain amygdala

A parenchymal brain granuloma is the final consequence of a localized inflammatory reaction against an infectious agent, particularly parasites. In humans, these lesions are frequent causes of epilepsy. We studied the pattern of seizures induced by pentylenetetrazol (PTZ) in cats with a chronic granuloma induced 1 year earlier by injection of silicates into the brain amygdala. Compared with controls, the seizure threshold to myoclonic seizures was significantly decreased in cats with granuloma, while the threshold for tonic-clonic seizures was not altered. Thus, the difference in PTZ doses between the initial and final components of the seizure became significantly enlarged ( P<0.001). Our results indicate that a granulomatous lesion in amygdala facilitates the generation and propagation of myoclonic seizures, whereas other components of PTZ-induced seizures are not affected.

Kainic acid-induced thalamic seizure in cats — a possible model of petit mal seizure

Bipolar depth electrodes were implanted stereotaxically in the thalamus, hippocampus and midbrain reticular formation of cats. Cortical screw electrodes were placed over the bilateral sensorimotor cortex. A guide cannula with an inner injection cannula was inserted unilaterally into the posterolateral ventral nuclei (VPL) of the thalamus. Eight days after the procedures, kainic acid (2.0 βg) was injected unilaterally into the VPL via the injection cannula in freely moving animals and electro-clinical observations were made. About 1 h after the kainic acid injection, multiple spikes were observed in the VPL (injection site), which propagated to the subcortical structures. These seizures finally propagated bilaterally to the cortex about 2 h after the injection. About 3—4 h after the injection, small spike and wave complexes repeatedly appeared for a short period of time in cortical leads and cats exhibited behavioral arrest with unrespohsiveness during the seizures. About 24 h after the injection, generalized small spike and wave complexes were observed intermittently in cortical and subcortical structures. They per- isted for 4–5 s and were associated with behavioral arrest and staring. The results demonstrate that a unilateral microinjection of kainic acid into VPL induced petit mal-like seizure, and suggest that VPL plays an important role in the generation or transfer of spike and wave complexes.

Neural respiratory responses to cortically induced seizures in cats

Seizure activity can lead to profound respiratory stimulation in spontaneously breathing animals with intact respiratory feedback mechanisms (Paydarfar et al., Am. J. Physiol. 260, R934, 1991). The present study was designed to test the hypothesis that peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea. Studies were performed in 16 anesthetized, vagotomized, glomectomized cats whose end-tidal P CO 2 (P et CO 2 ) was kept constant. Integrated phrenic nerve activity was used to represent respiration. Seizures were induced by injection of penicillin into the parietal cortex and electrocorticographic (ECoG) and biceps femoris nerve activities, arterial pressure, airway P CO 2 and brain temperature were recorded continuously. Progressive seizure activity was associated with progressive increases of respiratory frequency and peak phrenic activity, despite constancy of P et CO 2 and brain temperature . Patterns of entrainment were identified among ECoG spikes, biceps femoris nerve and phrenic nerve activities. Phrenic nerve activity became highly irregular during generalized ictal seizures and ceased to respond to changes of P et CO 2 . Acute intercollicular decerebration in all experiments resulted in normalization of respiratory rhythm even while ictal ECoG activity continued. We conclude that simulation of breathing during seizures occurs in the absence of respiratory feedback mechanisms. The findings suggest that an important cause of the respiratory response is a feedforward mechanism, whereby activation of subcortical structures above medulla and pons results in stimulation of breathing.

Serotonergic inhibition of limbic and thalamic seizures in cats.

To clarify the role of the serotonergic system in limbic and thalamic epileptic activity, we examined the effects of 5-hydroxytryptophan (5-HTP, 20 and 40 mg/kg) on fully kindled seizures from the hippocampus and lateral geniculate nucleus. The intraperitoneal administration of 20 mg/kg 5-HTP exerted no anticonvulsant effect on hippocampal kindled seizures, and a higher dose (40 mg/kg) produced a significant reduction in the behavioral seizure stage. 5-HTP at 20 mg/kg displayed no suppressive effect on lateral geniculate seizures, and 5-HTP at 40 mg/kg significantly reduced both the seizure stage and afterdischarge duration. Our data suggest that serotonergic mechanisms play an inhibitory role in seizures kindled from these brain regions.

The Role of Interhemispheric Pathways in Generalization of Kindled Seizures in Cats and Subhuman Primates

The role of interhemispheric pathways in generalization of partial seizures was evaluated in the kindling model of epilepsy. The generalized seizure kindled from the amygdala was asymmetrical in cats with callosal bisection, destruction of massa intermedia of the thalamus or bilateral ventral hippocampus. The generalized convulsion of amygdala kindled cats became asymmetrical or changed into partial seizures by callosal bisection. The fully-kindled amygdala seizure of a split-brain epileptic baboon and rhesus monkey was a hemiconvulsion or an asymmetrical generalized convulsion. The amygdala-kindled bisymmetrical generalized convulsion of the epileptic baboon was changed into a hemiconvulsion or an asymmetrical generalized convulsion. These results indicate that the corpus callosum plays an important, although not exclusive, role in bilateralization of epileptic activity, and its role becomes more important when the animal ascends the phylogenetic scale.

Respiratory responses to focal and generalized seizures in cats

We studied the effects on breathing of seizures induced by focal injection of penicillin G into the parietal cortex in 13 anesthetized cats. Electrocorticograms, ventilation, end-tidal PCO2, and intrapleural and arterial pressures were monitored; changes of these variables were related to the stages of motor seizure. The first respiratory responses, tachypnea and hyperpnea, usually occurred before any peripheral muscular contractions developed. Progression of the seizure was always accompanied by further tachypnea and hyperpnea. The hyperpnea associated with all stages of seizure activity resulted in hypocapnia, which was sustained even during prolonged tonic-clonic motor convulsions that caused a threefold increase of metabolic rate. The extreme tachypnea of tonic generalized convulsions led to increased end-expiratory lung volume because of dynamic hyperinflation associated with very short expiratory durations in the tonic phase. We suggest that the profound effects of seizures on respiration are by feedforward mechanisms from the cortical focus itself and from subcortical circuits, such as hypothalamus, that become involved during seizure propagation and generalization. Peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea.

Quantitative EEG analysis of carbamazepine effects on amygdaloid kindled seizures in cats

We studied the effects of carbamazepine (CBZ) on seizure behaviour and electroencephalographic (EEG) activity in 6 amygdala kindled cats. CBZ reduced the behavioural severity of kindled seizures and prolonged the earlier seizure stages (latency to stage 4). These effects were not always parallel by a reduction in the duration of seizure activity. EEG activity paradoxically increased in amplitude during early and mid-seizure, then fell in late seizure after CBZ. CBZ also caused an overall decrease in EEG coherence during mid and late seizure. These observations represent a first attempt to use quantitative EEG analysis to investigate the effects of anticonvulsants on electrographic seizure activity. The duration of postictal EEG suppression was reduced after CBZ treatment. The results support the view that CBZ has a major effect on limiting the spread of seizure discharges.

Ibotenic acid-induced nigral lesion and limbic seizure in cats

The degenerative lesions of bilateral substantia nigra (SN) were made by means of microinjections of ibotenic acid (IBO) solutions and influences upon kainic acid (KA)-induced seizures were studied. IBO solutions were injected bilaterally into SN and circumscribed degenerative lesions were made within the bilateral SN. In a control group, phosphate buffer solutions were injected in the bilateral SN. More than one week after the procedures, 1 μg KA was injected into unilateral amygdala via implanted cannula and limbic seizures were induced. The descruction of SN accelerated the secondary generalization of the limbic seizure within 3 days after the KA injection while no secondary generalization was observed within 3 days in the control group. The fact suggests that GABAergic systems of the substantia nigra and/or ascending norepinephrine pathway have a strong inhibitory influence on the secondary generalization of limbic seizures. The hypothesis of nigral mechanisms as a control system for secondary generalization is discussed.

Regional cerebral blood flow and kainic acid-induced focal limbic seizures in cats

An experimental limbic seizure was induced in cats by microinjection of kainic acid into the left amygdala. Measurement of regional cerebral blood flow (rCBF) in the limbic structure and cerebral cortex was performed by means of the hydrogen clearance method. Immediately after the development of continuous multiple spikes, rCBF increased about 2-fold in the left amygdala (LA) and remained so during the seizure. When continuous multiple spikes were transmitted to the left hippocampus (LH), rCBF in the LH increased to 140% of the baseline value, but in the right amygdala (RA) and left sensorimotor cortex (LCx) it remained unchanged. During limbic seizure in which spike discharges propagated to the LCx, rCBF in the LA, RA, LCx and LH increased to 220%, 130%. 120% and 190%. respectively. In the interictal stage in which interjetai spike discharges intermittently appeared in the LA. rCBF returned to baseline values in the primary and secondary foci. The results show that rCBF increased almost simultaneously with the development of the seizure in the primary focus and the areas where seizure propagation were observed, and returned to baseline value once the seizure had disappeared. During the interictal stage, rCBF in the primary focus was only slightly increased in spite of persistence of interictal spike discharges.