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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of systemic administration of a single dose (50 mg/kg) of ethosuximide (ESM) on extracellularly recorded thalamic (nucleus centralis lateralis, CL; nucleus reticularis, RE) and cortical neurons and on cortical EEG activity of acute cats, have been studied. In intact animals ESM led to: (a) desynchronization of cortical EEG activity; (b) reduction of cortical recruiting responses to 6 Hz stimulation of nucleus centralis medialis (CeM); (c) increased firing rate of CL units; and (d) reduction of incremental responses (IRs) of CL neurons to CeM stimulation. In midbrain reticular formation (MRF)-lesioned animals, ESM induced: (a) reduction of cortical spindle waves; (b) increment of their intraburst frequency; (c) reduction of the IR of CL neurons to 3 and 6 Hz CeM stimulation; (d) shortening of the inhibitory period following each response; and (e) no increment of spontaneous firing rate of CL units. Moreover, ESM led to important changes in the spontaneous activity of RE neurons: spike barrages, typical of these neurons in MRF-lesioned animals, became less frequent and of longer duration, being also constituted by longer interspike intervals. However, responses of RE neurons to low frequency CeM stimulation, when present, did not show any incremental phenomenon and appeared unchanged after ESM. Responses of cortical neurons to paired stimuli, applied with different interstimulus intervals, to nucleus ventralis posterolateralis or in animals with isolated cortex, to subcortical white matter, disclosed a reduction of the cortical inhibitory period following the response to the conditioning stimulus. These data suggest that ESM exerts a moderate diffuse anti-inhibitory action at both cortical and thalamic levels and an activating effect on MRF, which could also be accomplished through disinhibition. The reduction of the inhibitory phases in thalamic nuclei would alter spontaneous intrathalamic synchronizing mechanisms, leading to a decreased effectiveness of thalamocortical volleys, which are believed to be fundamental for the appearance of cortical spike and wave discharges. This hypothesis would therefore explain the specific efficacy of ESM against absence seizures.
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PMID:Ethosuximide alters intrathalamic and thalamocortical synchronizing mechanisms: a possible explanation of its antiabsence effect. 281 30

Kindling is an animal model of epilepsy produced by focal electrical stimulation of the brain. This chapter: describes the kindling phenomenon; considers the validity of kindling as an animal model and proposes a hypothesis as to how kindling might contribute to human epileptogenesis; presents a critical review of current insights into the underlying mechanisms; and emphasizes that, if progress is to be made in understanding the mechanisms, the network of brain structures underlying kindling must be elucidated. Recent investigations directly related to the network issue are considered, namely studies demonstrating that a brainstem structure, the substantia nigra (SN), can regulate the kindled seizure threshold. Thus, either microinjection of a GABA receptor agonist or a GABA transaminase inhibitor into SN, but not into nearby sites, elevates kindled-seizure threshold. Likewise, destruction of SN, but not of adjacent structures, is associated with an increase of kindled-seizure threshold. These treatments suppress not only clonic motor seizures, but also complex partial seizures and afterdischarge at the site of stimulation. These findings demonstrate that the SN can regulate the intrinsic neuronal excitability of forebrain structures. A hypothesis is advanced that generation of a complex partial seizure requires activation of neurons in the SN which in turn feed back through polysynaptic connections to influence neurons at the site of seizure origin. This nigral influence on neurons at the site of seizure origin is either a direct excitation or a disinhibition. Thus, the seizure represents reverberatory activity within a network of brain structures which includes the SN. Other investigators have proposed that the centrencephalic system subserved seizure propagation; the relationship of the hypothesis proposed here to these earlier ideas is discussed.
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PMID:Kindling model of epilepsy. 287 21

The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state.
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PMID:Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. 287 52

The present study was designed to test the hypothesis that chronic gamma-aminobutyric acid (GABA) disinhibition of granule cells could explain permanent kindled epileptogenicity. Quantitative and statistical comparisons of glutamate decarboxylase immunoreactivity (GAD-IR), the synthesizing enzyme for GABA, were made of GAD-IR cells and puncta in stratum granulosum of the fascia dentata. The use of GAD immunocytochemistry in kindled and control tissue was used to allow direct anatomic confirmation that we were measuring changes in GAD-IR which would represent GABA synthesis for release by the recurrent inhibitory system of the fascia dentata. Immediately after the last kindled seizure, optically detected GAD-IR puncta densities were significantly reduced in stratum granulosum. At 3 or 7 days after the last kindled seizure, GAD-IR was normal in puncta, indicating that the transient GAD-IR loss was probably a metabolic response to the recent seizure represented by over-use of GAD needed for synthesis of GABA after a prolonged kindled seizure. When the prolonged kindled seizures were discontinued GAD-IR recovered in the puncta. This transient effect did not occur in other areas such as Ammon's horn (CA3) or substantia nigra. The extent of the GAD-IR loss showed no correlation with the severity of the final behavioral seizure (R = 0.23), or the final afterdischarge (AD) duration in entorhinal cortex (R = 0.17) or motor cortex (R = 0.53). A massed stimulation control group given 19 shorter-duration ADs every 10 min (non-kindling) did not reduce GAD-IR. These findings support the hypothetical model that prolonged kindled seizures release excessive GABA which depletes GAD in axon terminals for 1 day after the seizure. However, such a transient suppression of GAD-IR provides no evidence that disinhibition contributes to the kindling process, because kindling proceeds normally with inter-seizure intervals as long as 1 week. The finding of full recovery of GAD-IR within 1 week does not support the model of loss of GABA inhibition to explain the permanency of kindled epileptogenesis.
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PMID:Recovery of decreased glutamate decarboxylase immunoreactivity after rat hippocampal kindling. 291 45

A 13-year-old girl had a reversible frontal syndrome secondary to partial complex seizures. She developed sudden and dramatic behavioral changes including sexual disinhibition, loss of concern for personal hygiene, physical and verbal aggression, and pressured and tangential speech. Although the basic neurologic examination was normal, neuropsychological testing revealed selective impairment on tasks sensitive to frontal dysfunction with relatively normal performance on other tests. This case demonstrates that a frontal syndrome can be caused by partial complex seizures and that behavior comparable to that observed in adults with frontal dysfunction may occur in young adolescents.
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PMID:Neuropsychological and behavioral abnormalities in an adolescent with frontal lobe seizures. 335 16

The effect of kainic acid (KA) microinjected into the dorsal raphe nucleus (NRD) of the cat through glass micropipette by means of an air pressure system in doses ranging from 2.3 to 23.5 nmol on the electroencephalographic (EEG)-reactions elicited by repetitive (6-10 Hz) peripheral (somatic and visual) or central electrical stimulation was investigated. A significant facilitation of the driving reaction evoked by rhythmic subcutaneous electrical stimulation of the forepaw was found after KA, while the driving reaction elicited by repetitive photostimulation did not change. The cortical rhythmic reactions to repetitive electrical stimulation of the specific and nonspecific nuclei of the thalamus and of the caudate nucleus (where inhibitory mechanisms are known to be involved) diminished or disappeared when generalized paroxysmal spontaneous activity occurred after kainic acid. The EEG-reaction to stimulation of the mesencephalic reticular formation was significantly facilitated after KA. The repetitive electrical stimulation of the ventral posterolateral nucleus, the centre median and the mesencephalic reticular formation also provoked the appearance of paroxysmal EEG activity or afterdischarge which in some cases developed into epileptic seizures. The data show that kainic acid injected into the dorsal raphe nucleus increases (probably by disinhibition) the excitability level of some forebrain structures connected with the nucleus.
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PMID:Changes in the EEG-reactions to repetitive peripheral and central electrical stimulation by intraraphedorsal kainic acid in the cat. 357 67

The brains of seizure-sensitive (SS) and seizure-resistant (SR) gerbils were studied with an immunocytochemical method to localize glutamic acid decarboxylase (GAD) to determine whether a defect existed in the inhibitory GABAergic system similar to that which has been reported in animal models of focal epilepsy in which GABAergic cell bodies and terminals are decreased in number. A major difference between the two strains of gerbils was found in the number of GABAergic neurons in the hippocampal formation. Specifically, a paradoxical increase occurred in the number of glutamate decarboxylase GAD-immunoreactive neurons: there were approximately 65% more GABAergic cells within the dentate gyrus and the CA3 region of the hippocampus in the SS gerbils. Furthermore, the density of GAD-immunoreactive puncta, the light microscopic correlates of synaptic boutons, was greater in the SS animals. Other histological methods were used to determine if the difference between SS and SR gerbils was specific for the GABAergic system. Nissl-stained preparations showed that the number of granule cells in the dentate gyrus was 20% greater in SS gerbils than in SR gerbils. An examination of some hippocampal afferents, efferents, and intrinsic connections with acetylcholinesterase histochemistry and the Timm's stain for heavy metals demonstrated no differences between the two strains. In addition, Golgi-stained preparations of the dentate gyrus indicated that the morphology of basket cells did not differ between the two strains nor between the gerbil and the rat. Several brain regions in addition to the hippocampus were studied to determine whether or not the increased number of GAD-immunoreactive neurons was specific for the hippocampal formation. These regions included the substantia nigra, motor cortex, and nucleus reticularis thalami and were selected because they contain large populations of GABAergic neurons and have been implicated in seizure activity. No differences between the two strains were detected in any of these regions. Therefore, a major morphological difference between the brains of SS and SR gerbils exists in the hippocampal formation of SS gerbils in which an increase occurs in the number of GABAergic neurons and granule cells. If these additional inhibitory neurons act mainly to inhibit other inhibitory neurons, the net effect would be increased disinhibition of the principal excitatory neurons of the hippocampal formation. This could lead to seizure activity within the hippocampal formation and at distant sites through multiple synaptic connections.
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PMID:Hippocampus of the seizure-sensitive gerbil is a specific site for anatomical changes in the GABAergic system. 361 18

The Capgras syndrome of delusions that familiar persons are being impersonated by identical doubles has occasionally been associated with cerebral disease, often of the nondominant hemisphere. A patient with chronic right cerebral hemisphere dysfunction and complex partial seizures of right temporal origin manifested the Capgras syndrome in the postictal state, and the delusions ceased with optimal seizure control. The delusions could result from postictal disinhibition of dominant hemisphere recognition functions, or from dysfunction of nondominant hemisphere centers involved in perceptual integration.
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PMID:Postictal Capgras syndrome. 369 Sep 33

Inhibitory gamma-aminobutyric acidergic (GABAergic) neurons were identified in the dentate gyrus of seizure-sensitive (SS) and seizure-resistant (SR) gerbils by immunocytochemical localization of glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA. Increases in both the number of GAD+ somata and terminals were found in the dentate gyrus of the SS brains compared to the SR. The magnitude of the increase was positively correlated with the recorded seizure intensity. The increased number of GABAergic neurons in the dentate gyrus of SS gerbils could result in disinhibition of the granule cells, thereby allowing propagation of epileptiform activity through the hippocampus.
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PMID:A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil. 389 6

A right-handed woman with independent left- and right-sided temporal lobe discharges was studied by continuous EEG and videotape monitoring for 3 weeks. Changes in affect were noted in the immediate and extended postictal periods and varied with the side of discharge. After a left-sided discharge, she became globally aphasic and depressed. Right-sided discharges evoked laughing and postictal hypomania. These manifestations were attributed to contralateral hemispheric disinhibition after ipsilateral seizure inactivation. This case provides evidence that the speech-dominant hemisphere subserves positive feelings and the nondominant hemisphere negative ones.
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PMID:Cerebral organization of affect suggested by temporal lobe seizures. 402 80


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