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)

A great number of clinical observations show a relationship between epilepsy and depression. Idiopathic generalized epilepsy, including absence epilepsy, has a genetic basis. The review provides evidence that WAG/Rij rats can be regarded as a valid genetic animal model of absence epilepsy with comorbidity of depression. WAG/Rij rats, originally developed as an animal model of human absence epilepsy, share many EEG and behavioral characteristics resembling absence epilepsy in humans, including the similarity of action of various antiepileptic drugs. Behavioral studies indicate that WAG/Rij rats exhibit depression-like symptoms: decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased sucrose consumption and preference (anhedonia). In addition, WAG/Rij rats adopt passive strategies in stressful situations, express some cognitive disturbances (reduced long-term memory), helplessness, and submissiveness, inability to make choice and overcome obstacles, which are typical for depressed patients. Elevated anxiety is not a characteristic (specific) feature of WAG/Rij rats; it is a characteristic for only a sub-strain of WAG/Rij rats susceptible to audiogenic seizures. Interestingly, WAG/Rij rats display a hyper-response to amphetamine similar to anhedonic depressed patients. WAG/Rij rats are sensitive only to chronic, but not acute, antidepressant treatments, suggesting that WAG/Rij rats fulfill a criterion of predictive validity for a putative animal model of depression. However, more and different antidepressant drugs still await evaluation. Depression-like behavioral symptoms in WAG/Rij rats are evident at baseline conditions, not exclusively after stress. Experiments with foot-shock stress do not point towards higher stress sensitivity at both behavioral and hormonal levels. However, freezing behavior (coping deficits) and blunted response of 5HT in the frontal cortex to uncontrollable sound stress, increased c-fos expression in the terminal regions of the meso-cortico-limbic brain systems and greater DA response of the mesolimbic system to forced swim stress suggest that WAG/Rij rats are vulnerable to some, but not to all types of stressors. We propose that genetic absence epileptic WAG/Rij rats have behavioral depression-like symptoms, are vulnerable to stress and might represent a model of chronic low-grade depression (dysthymia). Both 5HT and DAergic abnormalities detected in the brain of WAG/Rij rats are involved in modulation of vulnerability to stress and provocation of behavioral depression-like symptoms. The same neurotransmitter systems modulate SWDs as well. Recent studies suggest that the occurrence and repetition of absence seizures are a precipitant of depression-like behavior. Whether the neurochemical changes are primary to depression-like behavioral alterations remains to be determined. In conclusion, the WAG/Rij rats can be considered as a genetic animal model for absence epilepsy with comorbidity of dysthymia. This model can be used to investigate etiology, pathogenic mechanisms and treatment of a psychiatric comorbidity, such as depression in absence epilepsy, to reveal putative genes contributing to comorbid depressive disorder, and to screen novel psychotropic drugs with a selective and/or complex (dual) action on both pathologies.
 ...
PMID:The WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression [corrected]. 2109 20

Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF), in which memories are retained normally over short delays but are then lost at an accelerated rate over days or weeks. The causes of ALF, and whether it represents a consolidation deficit distinct from the one associated with forgetting over short delays, remain unclear. In addition, methodological issues have made results of some previous studies difficult to interpret. This study used improved methodology to investigate the role of seizure activity in ALF. Forgetting was assessed in participants with TLE (who have involvement of temporal lobe structures) and idiopathic generalised epilepsy (IGE; in which seizures occur in the absence of identified structural pathology in the temporal lobes). Learning of novel stimuli was matched between patients with TLE, patients with IGE and healthy controls matched for age and IQ. Results indicated that the TLE group showed accelerated forgetting between 30-min and three-weeks, but not between 40-s and 30-min. In contrast, rates of forgetting did not differ between patients with IGE and controls. We conclude that (1) ALF can be demonstrated in TLE in the absence of methodological confounds; (2) ALF is unlikely to be related to the experience of epilepsy that does not involve the temporal lobes; (3) neither seizures during the three-week delay nor polytherapy was associated with ALF.
 ...
PMID:Accelerated long-term forgetting in temporal lobe but not idiopathic generalised epilepsy. 2154 34

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/- mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/- males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/- female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/- vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/- mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/- mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE.
 ...
PMID:GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy. 2188 91

Epilepsy and sleep have a profound bidirectional influence. Idiopathic generalized epilepsy (IGE) comprises a fascinating group of syndromes that constitute nearly one-third of all epilepsies. These syndromes are genetically determined and affect otherwise normal people of both sexes and all races. IGE manifests with typical absences, myoclonic jerks, and generalized tonic-clonic seizures, alone or in varying combinations and severity. IGE syndromes are typically modulated by the sleep-wake cycle, and particularly by the sleep-wake transition process, both in terms of the occurrence of seizures and interictal epileptiform discharges (IED), with pronounced susceptibility to sleep deprivation. IGE analysis from the point of view of arousal modulation enhances the concept of a biological continuum existing among IGE syndromes. At the same time, this analysis broaches the problem of syndromic diagnosis and identification of the factors influencing the phenotypic expression of some epileptic phenomena over the course of life with potential bidirectional influences between epileptic manifestations and sleep-wake processes.
 ...
PMID:Pre- and post-dormitum epilepsies: idiopathic generalized epilepsies. 2213 92

Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes based on clinical and electroencephalography (EEG) features. The EEG signature of IGE is bisynchronous, symmetric, and generalized spike-wave complex; although focal, irregular, and so called "fragments" of discharges are not uncommon. Other characteristic EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, and photoparoxysmal response. Both human and animal data suggest involvement of the thalamus and the cortex in the generation of spike-wave discharges in IGE. Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. Those discharges tend to occur more often after awakening and during cyclic alternating pattern phase-A of non-rapid eye movement sleep. Activation procedures such as hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are useful techniques to increase the yield of both interictal and ictal EEG abnormalities. Although not in routine use, specific triggers such as pattern stimulation and cognitive tasks may also be of value in eliciting rare reflex seizure-related EEG abnormalities. Variations of EEG abnormalities are evident between different electroclinical syndromes. EEG is also affected by certain external as well as internal factors, which should be borne in mind when interpreting EEG studies in IGE.
 ...
PMID:The electroencephalogram of idiopathic generalized epilepsy. 2215 May 83

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.
 ...
PMID:Default mode network abnormalities in idiopathic generalized epilepsy. 2238 87

We studied 279 women, aged 18-40 years old, with epilepsy. The study included the evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, MRI of the brain. The period of observation was 6 months - 8 years. Idiopathic generalized epilepsy (IGE) was diagnosed in 85 cases, cryptogenic focal epilepsy in 107 cases, symptomatic focal epilepsy in 51 cases, unclassified epilepsy in 32 cases. In the end of study, remission was achieved in 70.8% of patients of the IGE group, the substantial reduction in the number of seizures was identified in 13.8%, no effect was seen in 15.4%. Adverse events were found in 22 of 63 (34.9%) patients treated with valproates, 9 of 25 (36%) patients treated with topiramate, 5 of 39 (1.8%) patients treated with carbamazepine, 3 of 7 (42.9%) patients treated with levetiracetam and in 2 of 5 (40%) patients treated with lamotrigine. The aggravation of absences with carbamazepine was diagnosed in 2 cases, myoclonic seizures - in 2 cases. Therapeutic strategies of young women with juvenile forms of IGE were described and analyzed.
 ...
PMID:[Idiopathic generalized epilepsy in young women: choise of treatment strategy]. 2298 42

We studied 479 epileptic patients. The study included the evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, MRI of the brain. The period of observation was 1-8 years (on average 2.5 years). Idiopathic generalized epilepsy was diagnosed in 55 cases, cryptogenic focal epilepsy in 228 cases and symptomatic focal epilepsy in 196 cases. In the end of study, remission was achieved in 29.2%, the serious reduction in the number of seizures in 31.7%, no effect was seen in 39.1%. There were 261 attempts of therapy with carbamazepine (CBZ), 298 with valproates (VPA), 173 with topiramate (TPM), 48 with levetiracetam (LEV), 18 with lamotrigine (LTG), 23 with benzodiazepines (BDZ), 62 with barbiturates (BRB), 3 with ethosuximide (ESM), 15 with oxcarbazepine (OXC), 1 with lacosamide (LAS) and 8 with phenytoin (PHT). The total efficacy (remission plus seizure reduction) was similar for VPA (48%), TPM (47.4%) and CBZ (44.5%). Stopping treatment due to adverse effects was significantly higher in TPM (12,1%) versus LEV (4,2%) (p<0,05).
 ...
PMID:[Efficacy of epilepsy treatments with different drugs]. 2323 10

Eventually, glutamate and gamma-aminobutyric acid (GABA) are both excitatory; the first cortical synapses start to appear, some myelin is found in the cerebral hemispheres, and the long tracts are barely visible. The premature activation of N-methyl-D-aspartate (NMDA) transmission seems to generate neonatal myoclonic encephalopathy. Benign neonatal seizures and migrating partial seizures of infancy may result from an excessive or premature excitability in the deep layers. Benign rolandic epilepsy and continuous spikes and waves during slow sleep are associated with an excess of excitatory and inhibitory cortical synapses. West and Lennox-Gastaut syndromes are related to an age-dependent, diffuse cortical hyperexcitability; the clinical presentation depends on the age at onset, and spike synchronization is achieved by myelination. Idiopathic generalized epilepsy is driven by brain maturation, which induces a frontal hyperexcitability responsible for myoclonic-astatic seizures at an age comprised between that of infantile and juvenile myoclonic epilepsies. The extensive physiological time frame preceding the maturation of the hippocampal-neocortical system could explain the scarcity of cortical injuries resulting from a lesion in infants.
 ...
PMID:[Brain maturation and epilepsy]. 2342 14

At full term, both glutamate and gamma-amino-butyric acid (GABA) are excitatory; cortical synapses are beginning to appear, there is little myelin in the cerebral hemispheres, and long tracts hardly start to develop. Neonatal myoclonic encephalopathy can result from premature activation of N-methyl-D-aspartate (NMDA) transmission. Benign neonatal seizures and migrating partial seizures in infancy could involve excessive or premature excitability of deep cortical layers. Benign rolandic epilepsy and continuous spike waves in slow sleep are consistent with an excess of both excitatory and inhibitory cortical synapses. West and Lennox-Gastaut syndromes express age-related diffuse cortical hyperexcitability, the pattern depending on the age of occurrence; synchronization of spikes is becoming possible with maturation of the myelin. Idiopathic generalized epilepsy is itself modulated by maturation that causes frontal hyperexcitability generating myoclonic-astatic seizures, between the ages of infantile and juvenile myoclonic epilepsies. Physiological delay of hippocampo-neocortical pathways maturation could account for the delayed occurrence of mesial temporal epilepsy following infantile damage, whereas premature maturation could contribute to fronto-temporal damage characteristic of fever-induced epileptic encephalopathy in school-age children, a dramatic school-age epileptic encephalopathy.
 ...
PMID:Brain maturation and epilepsy. 2362 92


<< Previous 1 2 3 4 5 6 Next >>