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

The last ten years of the 20th century is called in neuroscience "decade of the brain". This period has brought many new antiepileptic drugs (AEDs) to the practising physician. New AEDs include: vigabatrin, lamotrigine, topiramate, tiagabine, gabapentin, oxcarbazepine, levetiracetam and zonisamide (not registered in Poland). The development of these drugs was under the current epilepsy theory (balance-disturbances between inhibitory and excitatory neurotransmitters in the brain). Mechanism of action of the new AEDs is due to increase of the GABA-system activity and/or reaction with ion-channels events in neurons. The aim of the study was an overview of the current literature on the new AEDs in the treatment of seizures and epileptic syndromes. Data from literature show that the new AEDs are better tolerated, have fewer drug interactions and seem to affect cognitive functions to a lesser degree compared to the conventional drugs. Most of them are recommended to an add-on therapy of partial seizures with/without second generalization, although there are more evidences on efficacy of new AEDs in monotherapy. The new AEDs seemed to be similar to the conventional drugs in efficacy, but superior in tolerability. New AEDs with more selective activity and lower toxicity have been significant improved the quality of life in the epileptic patients. Numerous chemical compounds with potential antiepileptic activity are in experimental and clinical development.
 ...
PMID:New antiepileptic drugs--an overview. 1611 37

Accumulating evidence indicates that agmatine (AGM--an endogenous neuromodulator/neurotransmitter in the brain) exerts the anticonvulsant action in various in vivo experiments. Therefore, the aim of this study was to assess the influence of AGM on the protective action of numerous conventional and newer antiepileptic drugs [carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM) and valproate (VPA)] in the mouse maximal electroshock seizure (MES) model. Results indicate that AGM (up to 100 mg/kg, i.p., 45 min before the test) neither altered the threshold for electroconvulsions nor protected the animals against MES-induced seizures in mice. Moreover, AGM (100 mg/kg, i.p.) significantly enhanced the anticonvulsant effects of PB and VPA in the MES test by reducing their ED50 values from 22.54 to 16.82 mg/kg (P < 0.01) for PB, and from 256.1 to 210.6 mg/kg (P < 0.05) for VPA, respectively. In contrast, AGM at 100 mg/kg (i.p.) had no significant effect on the antielectroshock action of the remaining drugs tested (CBZ, LTG, OXC, PHT, and TPM) in mice. Estimation of total brain PB and VPA concentrations revealed that the observed interactions between AGM and PB or VPA in the MES test were pharmacodynamic in nature because neither total brain PB, nor total brain VPA concentrations were altered after i.p. administration of AGM at 100 mg/kg. Moreover, none of the examined combinations of AGM (100 mg/kg) with CBZ, LTG, OXC, PB, PHT, TPM, and VPA (at their ED50 values from the MES test) affected motor coordination in the chimney test, long-term memory in the passive avoidance task, and muscular strength in the grip-strength test in mice, indicating no acute adverse effects in animals. In conclusion, one can ascertain that the selective potentiation of the antielectroshock action of PB and VPA by AGM, lack of any pharmacokinetic interactions between drugs and no acute adverse effects, make the combinations of AGM with PB or VPA of pivotal importance for epileptic patients. It seems that modulation of AGM concentration in the brain may occur favorable in further clinical practice.
 ...
PMID:Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model. 1837 17

Intramuscular injection of selective NMDA receptor antagonists memantine and arcaine 4-fold decreased the incidence of pentylenetetrazole-induced generalized tonic-clonic seizures in rats, while the incidence of clonic seizures decreased by 1.2-1.3 times. Memantine and arcaine are characterized by low therapeutic index, i.e. induced ataxia in rats in doses exceeding the effective anticonvulsant dose by only 3.5-10 times. Intramuscular injection of IEM-1913 (combined blockade of NMDA and AMPA receptors in the brain) decreased the incidence of pentylenetetrazole-induced clonic and tonic-clonic seizures in rats by 4-8 times. The therapeutic index of IEM-1913 surpassed that of memantine and arcaine by 200-600 times.
 ...
PMID:Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia. 1911 May 62

Acquired epilepsy (i.e., after an insult to the brain) is often considered to be a progressive disorder, and the nature of this hypothetical progression remains controversial. Antiepileptic drug treatment necessarily confounds analyses of progressive changes in human patients with acquired epilepsy. Here, we describe experiments testing the hypothesis that development of acquired epilepsy begins as a continuous process of increased seizure frequency (i.e., proportional to probability of a spontaneous seizure) that ultimately plateaus. Using nearly continuous surface cortical and bilateral hippocampal recordings with radiotelemetry and semiautomated seizure detection, the frequency of electrographically recorded seizures (both convulsive and nonconvulsive) was analyzed quantitatively for approximately 100 d after kainate-induced status epilepticus in adult rats. The frequency of spontaneous recurrent seizures was not a step function of time (as implied by the "latent period"); rather, seizure frequency increased as a sigmoid function of time. The distribution of interseizure intervals was nonrandom, suggesting that seizure clusters (i.e., short interseizure intervals) obscured the early stages of progression, and may have contributed to the increase in seizure frequency. These data suggest that (1) the latent period is the first of many long interseizure intervals and a poor measure of the time frame of epileptogenesis, (2) epileptogenesis is a continuous process that extends much beyond the first spontaneous recurrent seizure, (3) uneven seizure clustering contributes to the variability in occurrence of epileptic seizures, and (4) the window for antiepileptogenic therapies aimed at suppressing acquired epilepsy probably extends well past the first clinical seizure.
 ...
PMID:Development of spontaneous recurrent seizures after kainate-induced status epilepticus. 1982 8

The aim of this study was to assess the influence of agmatine (an endogenous neuromodulator/neurotransmitter in the brain) on the protective action of numerous classical and second-generation antiepileptic drugs (clonazepam, ethosuximide, gabapentin, phenobarbital, tiagabine, vigabatrin, and valproate) in the mouse pentetrazole-induced clonic seizure model. The results indicate that agmatine (up to 100 mg/kg, ip, 45 min before the test) did not alter the threshold for pentetrazole-induced clonic seizures in mice. However, agmatine (100 mg/kg, ip) significantly attenuated the anticonvulsant effects of vigabatrin against pentetrazole-induced clonic seizures by elevating the ED(50) value of vigabatrin from 517.5 to 790.3 mg/kg (p < 0.01). In contrast, agmatine at a dose of 50 mg/kg did not significantly affect the anticonvulsant action of vigabatrin, although an increase in the ED(50) value of the antiepileptic drug from 517.5 to 629.1 mg/kg was documented. Moreover, agmatine at doses of 50 and 100 mg/kg (ip) had no significant impact on the anticonvulsant action of clonazepam, ethosuximide, gabapentin, phenobarbital, tiagabine, or valproate in pentetrazole-induced seizures in mice. In conclusion, the combination of agmatine with vigabatrin seems to be unfavorable due to the reduction of the anticonvulsant effect of vigabatrin after concomitant administration of agmatine in the pentetrazole-induced seizure model. Therefore, the utmost caution is advised when combining agmatine with vigabatrin in further clinical settings.
 ...
PMID:Influence of agmatine on the protective action of numerous antiepileptic drugs against pentetrazole-induced seizures in mice. 1944 36

Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron-astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures.
 ...
PMID:An excitatory loop with astrocytes contributes to drive neurons to seizure threshold. 2040 49

Hydranencephaly is a rare congenital condition where the greater portions of the cerebral hemispheres and the corpus striatum are replaced by cerebrospinal fluid and glial tissue. The meninges and the skull are well formed, which is consistent with earlier normal embryogenesis of the telencephalon. Bilateral occlusion of the internal carotid arteries in utero is a potential mechanism. Clinical features include intact brainstem reflexes without evidence of higher cortical activity. The infant's head size and the spontaneous reflexes such as sucking, swallowing, crying, and moving the arms and legs may all seem normal at birth. However, after a few weeks the infant usually becomes irritable and has increased muscle tone and after a few months of life, seizures and hydrocephalus (excessive accumulation of cerebrospinal fluid in the brain) may develop. Other symptoms may include visual impairment, lack of growth, deafness, blindness, spastic quadriparesis (paralysis), and intellectual deficits. Since the early behaviour appears to be relatively normal, the diagnosis may be delayed for months sometimes. There is no definitive treatment for hydranencephaly. The outlook for children with hydranencephaly is generally poor, and many children with this disorder die before their first birthday.
 ...
PMID:Hydranencephaly. 2120 13

The present study has been undertaken in a tertiary care centre of North-west India to know the clinical profile of epilepsy and response to drug therapy with special reference to study the effect of reduction of dosage of anti-epileptic drug after a seizure-free interval of two years. A total of 904 patients were selected during the period January, 2001 to October, 2006 who attended OPD clinic of the department of neurology, SMS Medical College and Hospital, Jaipur. Datailed clinical history was taken, general physical examination, routine blood examination, ECG and CT scan along with MRI (brain) in some cases were carried out. Of all the cases, sex ratio (male : female) was 2:1. A high proportion of cases (62.83%) were from low socio-economic group, 41.15% had normal EEG, 532 patients had normal CT scan (out of 800 cases). Single drug therapy was instituted in 71.67% cases. Patients went follow-up for 3 years. Most of the cases proved to be seizure-free after 2 years. Average maintenance dosage in patients on monotherapy can be reduced after a seizure-free interval of 2 years.
 ...
PMID:Clinical profile of epilepsy, in a tertiary care centre of North-west India. 2188 53

WHO grade II glioma, i.e. diffuse low-grade glioma, is a pre-malignant tumour, usually revealed by seizures in young patients with a normal life. This tumour has a constant growth, and will inescapably become anaplastic. Surgical resection significantly increases the overall survival by delaying the malignant transformation. Thus, the dilemma is to perform early surgery in order to optimise the extent of resection (and thus the median survival) by removing smaller tumours while preserving the quality of life. To this end, the new concept proposed in this review is to achieve surgical resection according to functional and not to oncological boundaries. In other words, the principle is to first understand the cerebral anatomo-functional organisation at the individual level (because of a major inter-individual variability), with the aim of resecting a part of the brain invaded by a diffuse chronic disease, on the condition nonetheless that this part of the brain can be functionally compensated-i.e. with no consequences on the quality of life. To this end, in addition to the preoperative functional neuroimaging and the intraoperative electrical cortical mapping in awake patients, it is also crucial to map both horizontal cortico-cortical connectivity (long-distance association fibres) as well as vertical cortico-subcortical connectivity (projection fibres), with the aim to preserve the networks underlying the minimal common core of the brain. Interestingly, this "hodotopical" workframe, based on the study of both cortical epicentres and subcortical pathways, opens the door to mechanisms of functional reshaping. These recent technical and conceptual advances in the hodotopical and plastic view of brain processing have allowed a dramatic improvement of the benefit-to-risk ratio of surgery, concerning both oncological and functional outcomes. In summary, it is time to move towards "functional neurooncology" and "preventive neurosurgery" in low-grade gliomas. Stronger interactions with fundamental neurosciences should be developed, in order (1) to build updated models of cognition and brain plasticity; (2) to elaborate biomathematical models of low-grade glioma growth and migration; (3) to study in silico the dynamic interactions between the natural course of this disease and the adaptative behaviour of its host (the brain), with the goal to adapt the best individualised therapeutic strategy.
 ...
PMID:The challenge to remove diffuse low-grade gliomas while preserving brain functions. 2227 63

It was shown that the preliminary single i.p. injection of antibodies (AB) to glutamate (GLU) 1,5 hours prior to the first injection pentylenetetrazole (prior to the beginning of kindling) did not have an effect on latency period of appearance and the severity of convulsive reactions in the mice of C57Bl/6. The administrations of AB to GLU at the different stages of kindling animals with different severity of seizures did not have an effect on their severity. Thus, AB to GLU did not posses antiepileptic effect. However, AB to GLU posses anticonvulsive action on the acute seizures reaction, inducing an increase in the thresholds of clonic seizures and tonic phase seizures with lethal outcome as well as an extended latency period of occurrance these seizures in mice with enhanced kindling-producing convulsive readiness of the brain. This effect was revealed at the different stages of kindling in animals with the severity of seizures 2-3 and 4-5 marks. Possible to assume, that the mechanisms of chronic epileptogenesis (in this case, in the form kindling-dependent enhanced convulsive readiness of the brain) and those of the acute convulsive reaction are not similar.
 ...
PMID:[Influence of antibodies to the glutamate on convulsive reaction to mice C57Bl/6 in term of chronic epileptogenesis]. 2227 35


<< Previous 1 2 3 4 5 Next >>