Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 micrograms/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.
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PMID:Bacterial alkaloids mitigate seizure-induced hippocampal damage and spatial memory deficits. 881 62

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.
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PMID:Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy. 1500 53

Nicotinic acetylcholine receptors are important for maintaining optimal memory performance. In order to more fully characterize the involvement of nicotinic systems in memory, the contributions of nicotinic acetylcholine receptor subtypes were investigated. This study targeted the alpha 7 and alpha 4 beta 2 nicotinic receptors in the ventral hippocampus, an area known to be important for spatial working memory. Antagonists of alpha 7 and alpha 4 beta 2 receptors were locally infused into the ventral hippocampus of rats and the effects on memory were examined with the radial-arm maze. The subtype-specific competitive antagonists infused into separate groups of rats were methyllycaconitine citrate (an alpha 7 antagonist) and dihydro-beta-erythroidine hydrobromide (an alpha 4 beta 2 antagonist). Their effects on radial-arm maze performance were contrasted with the non-specific competitive antagonist, D-tubocurarine chloride. Significant deficits in radial-arm maze choice accuracy performance were found at 78.7 micrograms/side for methyllycaconitine and at 106.9 micrograms/side for dihydro-beta-erythroidine. Increased response latency was also seen at these doses. Tubocurarine induced seizures at doses previously reported to have no effect. Wet dog shakes were seen in most rats at 0.1 microgram/side with tubocurarine, 26.3 micrograms/side with methyllycaconitine and 106.9 micrograms/side with dihydro-beta-erythroidine. This study suggests that both alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptor subtypes are involved in working memory formation and that the hippocampus is a critical site for nicotinic cholinergic involvement in memory function, though the high doses of antagonists needed to produce the memory impairment may have had less than completely specific effects.
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PMID:Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats. 933 Mar 63

The association between epilepsy and amnesia is studied in patient J.T. who presented with a very unusual pattern of memory loss with retention of information for hours to days but rapid forgetting of information that exceeded this time frame. J.T.'s unusual memory profile was studied with several tests administered over week-long intervals of time. There was evidence that his retention decreased in conjunction with increased seizures. During a trial of paraldehyde, a decrease in seizure frequency was associated with enhanced memory. J.T.'s memory problem was unlike that described in prototypical cases of amnesia. His day-long retention of new information alongside his absolute loss of that information days later is consistent with the idea that consolidation is a process that occurs over lengthy periods of time.
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PMID:Accelerated forgetting in association with temporal lobe epilepsy and paraneoplastic encephalitis. 933 3

In this study, the anticonvulsant and adverse effects of compounds that belong to four different categories of systemically available N-methyl-D-aspartate (NMDA) receptor ligands were compared, namely the competitive antagonist CGP 40116, the noncompetitive antagonist MK-801 (dizocilpine), the glycineB receptor antagonist L-701,324, and the glycineB receptor high-efficacy partial agonist D-cycloserine. The maximal electroshock seizures (MES), which are widely used to detect drug efficacy against generalized tonic-clonic seizures in humans, were produced by transcorneal electrical stimulation. Abolition of tonic hind-limb extension was taken as the end-point. The drug-induced motor and long-term memory deficits were quantified by using the inverted screen test and the step-through passive-avoidance test, respectively. All tested compounds exhibited significant anticonvulsant effect. The rank order of potency for the respective compounds was: MK-801 = CGP 40116 > L-701,324 >> D-cycloserine. All of these compounds induced motor impairment at doses close to those found to be anticonvulsant, however, hyperlocomotion and stereotyped behavior occurred only with MK-801. The highest protective indices [PI = TD50 (inverted screen)/ED50 (MES)] were calculated for CGP 40116 and D-cycloserine (2.4 and 2.2, respectively). When tested for memory impairment at one-half the MES ED50, again only MK-801 induced significant memory disruption in the passive avoidance test. In conclusion, these results suggest that glycineB receptor high-efficacy partial agonists and competitive NMDA receptor antagonists may be advantageous to noncompetitive NMDA antagonists and glycineB receptor antagonists as potential antiepileptic drugs.
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PMID:Anti-convulsant and adverse effects of the glycineB receptor ligands, D-cycloserine and L-701,324: comparison with competitive and non-competitive N-methyl-D-aspartate receptor antagonists. 974 91

Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of gamma-aminobutyric acid (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain. The absorption and elimination of tiagabine follow linear pharmacokinetics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzyme-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral contraceptives. In the perforant pathway stimulation model of status epilepticus, tiagabine reduced the seizure number and severity, and also prevented the loss of pyramidal cells in the hippocampus as well as alleviated impairment of the spatial memory impairment associated with hippocampal damage. Tiagabine has both antiepileptogenic and anticonvulsant effects in the kindling model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has been also possible in substantial amount of patients with partial seizures in three trials. Tiagabine is generally well-tolerated. The most common adverse events in controlled studies involve the central nervous system; for example, dizziness, asthenia, nervousness, tremor, depressed mood and emotional lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagabine represents an important new therapeutic option for patients with treatment-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially emphasized since tiagabine has a low side-effect profile in the cognitive area.
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PMID:Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy. 1003 Apr 35

Previous studies have demonstrated that remacemide and its desglycinyl metabolite, AR-R 2495AA, reduce neuronal damage in animal models of ischemia, subarachnoid hemorrhage, and traumatic brain injury. The aim of the present study was to investigate whether remacemide hydrochloride also alleviates seizure-induced neuronal damage in a model of status epilepticus induced by the stimulation of the perforant pathway (PP) in the rat. Chronic oral remacemide treatment (3 x 25 mg/kg/day) was started either 2 days before or 2 h after the beginning of PP stimulation (2 mA, 20 Hz, 0.1 ms pulse duration for 60 min). The effects of remacemide treatment on the severity of seizures, electroencephalogram (EEG) parameters, seizure-induced neuronal damage in the temporal lobe regions, and memory impairment were compared to unstimulated and stimulated vehicle-treated controls, and carbamazepine-pre-treated (3 x 40 mg/kg/day) rats. Both remacemide and carbamazepine pretreatments, but not remacemide posttreatment, decreased pyramidal cell damage in the CA3 and CA1 subregions of the hippocampus (P < 0.05). In addition, overall neuronal damage in the extrahippocampal temporal lobe regions (the piriform cortex, entorhinal cortex, and the amygdaloid complex) was milder in remacemide-pretreated rats compared to stimulated control rats (P < 0.01). The neuroprotective effect was most evident on the side contralateral to stimulation. Remacemide or carbamazepine pretreatment had no evident effect on the number or duration of behavioral seizures during PP stimulation. Neither drug altered the spectral parameters of the baseline EEG or prevented status epilepticus-induced EEG slowing observed 2 weeks after PP stimulation. Nor did remacemide or carbamazepine treatment alleviate spatial memory impairment determined in a Morris water-maze task 2 weeks after PP stimulation. Our data provide evidence that pretreatment with remacemide has a moderate neuroprotective effect against status epilepticus-induced neuronal damage.
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PMID:Neuroprotective effect of remacemide hydrochloride in a perforant pathway stimulation model of status epilepticus in the rat. 1021 40

We report a retrospective analysis of MRI in 206 patients with intractable seizures and describe the findings in bilateral mesial temporal sclerosis (MTS) on fast spin-echo (FSE) and fast fluid-attenuated inversion-recovery (fFLAIR) sequences. Criteria for MTS were atrophy, signal change and loss of the digitations of the head of the hippocampus. In patients with bilateral MRI signs of MTS, correlation with clinical electro, volumetric MRI data and neuropsychological tests, when available, was performed. Bilateral MTS was observed in seven patients. Bilateral loss of the digitations and signal change on fFLAIR was seen in all seven. In three, bilateral atrophy was obvious. In two patients, mild bilateral atrophy was observed and in two others, the hippocampi were: asymmetrical, with obvious atrophy on only one side. Volumetric data confirmed bilateral symmetrical atrophy in five patients, and volumes were at the lowest of the normal range in the other two. The EEG showed temporal abnormalities in all patients, unilateral in five and bilateral in two. All patients had memory impairment and neuropsychological data confirmed visual and verbal memory deficits; two patients failed the Wada test on both sides. High-resolution T2-weighted FSE and fFLAIR sequences allow diagnosis of bilateral MTS, which has important therapeutic and prognostic implications.
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PMID:Bilateral mesial temporal sclerosis: MRI with high-resolution fast spin-echo and fluid-attenuated inversion-recovery sequences. 1045 Aug 38

Traumatic brain injury (TBI) can be associated with memory impairment, cognitive deficits, or seizures, all of which can reflect altered hippocampal function. Whereas previous studies have focused on the involvement of neuronal loss in post-traumatic hippocampus, there has been relatively little understanding of changes in ionic homeostasis, failure of which can result in neuronal hyperexcitability and abnormal synchronization. Because glia play a crucial role in the homeostasis of the brain microenvironment, we investigated the effects of TBI on rat hippocampal glia. Using a fluid percussion injury (FPI) model and patch-clamp recordings from hippocampal slices, we have found impaired glial physiology 2 d after FPI. Electrophysiologically, we observed reduction in transient outward and inward K(+) currents. To assess the functional consequences of these glial changes, field potentials and extracellular K(+) activity were recorded in area CA3 during antidromic stimulation. An abnormal extracellular K(+) accumulation was observed in the post-traumatic hippocampal slices, accompanied by the appearance of CA3 afterdischarges. After pharmacological blockade of excitatory synapses and of K(+) inward currents, uninjured slices showed the same altered K(+) accumulation in the absence of abnormal neuronal activity. We suggest that TBI causes loss of K(+) conductance in hippocampal glia that results in the failure of glial K(+) homeostasis, which in turn promotes abnormal neuronal function. These findings provide a new potential mechanistic link between traumatic brain injury and subsequent development of disorders such as memory loss, cognitive decline, seizures, and epilepsy.
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PMID:Impaired K(+) homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia. 1047 15

The epilepsy patients whose seizures will prove to be refractory should be identified as early as possible, and thus the need for new prognostic factors of intractable epilepsy is evident. The aim of the study was to investigate predictors of seizure outcome in a multivariate analysis. Neurological, electroencephalography (EEG) and neuropsychological variables were analyzed as potential predictors of epilepsy. Eighty-nine newly diagnosed adult patients with partial epilepsy were, after a prospective 2-year follow-up period, categorized into one of the two groups: patients with satisfactorily controlled epilepsy, and patients with refractory epilepsy. Six variables predicted 2-year seizure outcome: presence of spike focus in EEG, partial complex or mixed seizure type, remote symptomatic etiology, moderately impaired memory performance in immediate recall and in delayed recognition of the word list, and age at the time of diagnosis. The correct seizure outcome could be predicted with the model in 94% of newly diagnosed epilepsy patients. The presence of verbal memory impairment at the time of the diagnosis of partial epilepsy is a significant predictor of seizure outcome and, together with clinical and EEG variables, it predicts seizure outcome in the majority of the patients. Memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting.
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PMID:Predictors of seizure outcome in newly diagnosed partial epilepsy: memory performance as a prognostic factor. 1051 Sep 82


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