Disease relevance of Epilepsy, Generalized

• Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel alpha-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+) [1].
• It is an epilepsy-related electroencephalographic trait with high prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy [2].
• In studies in which patients were diagnosed as having one of the primary generalized epilepsies, the response rate of tonic-clonic seizures to valproate establishes valproate as the drug of choice in the epilepsy syndromes with primary generalized tonic-clonic seizures [3].
• OBJECTIVE: To replicate and extend the previously reported association between the opioid receptor mu subunit gene (OPRM1) and idiopathic absence epilepsy (IAE), using a sample of 230 probands with idiopathic generalized epilepsy (IGE) [4].
• Analysis of concordance of epilepsy syndromes in families has been used to assess shared versus distinct genetic influences on generalized epilepsy (GE) and localization-related epilepsy (LRE) [5].

High impact information on Epilepsy, Generalized

• Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies [6].
• Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified [7].
• Ligand-gated ion channels, such as nicotinic acetylcholine receptors and GABA receptor subunits, are associated with specific syndromes of frontal and generalized epilepsies, respectively [8].
• The mapping of the GABABR1 gene to human chromosome 6p21.3, in the vicinity of a susceptibility locus (EJM1) for idiopathic generalized epilepsies, identifies a candidate gene for inherited forms of epilepsy [9].
• CHRNA4 led the way to mutation identifications in 15 ion channel genes, most causing primarily generalized epilepsies [10].

Chemical compound and disease context of Epilepsy, Generalized

• In all primary generalized epilepsies, valproate has in many studies produced an excellent response, with one comparative study showing that valproate was as effective as phenytoin [11].
• Vigabatrin is rarely associated with seizure worsening, and then mainly in patients with resistant generalized epilepsies [12].
• Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies [13].
• PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies [14].
• Although valproate is considered to be the drug of first choice for the treatment of idiopathic generalized epilepsies (IGEs), other antiepileptic drugs (AEDs), both old (ethosuximide, clobazam, and clonazepam) and new (lamotrigine, levetiracetam, topiramate, and zonisamide) are also available [15].

Biological context of Epilepsy, Generalized

• The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus, CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome [16].
• Brain-derived neurotrophic factor (BDNF) is associated with each of these processes in normal brain and shows acute up-regulation in models of generalized epilepsy [17].
• We review the results of existing association studies in focal epilepsies, generalized epilepsies, febrile seizures, and epilepsy pharmacogenetics [18].
• Exclusion of linkage between idiopathic generalized epilepsies and the GABAA receptor alpha 1 and gamma 2 subunit gene cluster on chromosome 5 [19].
• Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsies [20].

Anatomical context of Epilepsy, Generalized

• In animals submitted to amygdala kindling, a nonlesional model of secondarily generalized epilepsy, no such reexpression of E-NCAM was observed [21].
• METHODS: The authors studied 207 consecutive patients with intractable seizures referred to a University Hospital for presurgical evaluation between 1998 and 2002: 135 had temporal lobe epilepsy (TLE); 23, frontal lobe epilepsy (FLE); 29, generalized epilepsies (GEs); and 20 had extratemporal or multifocal epilepsy [22].
• Wisconsin Card Sorting Test (WCST) performance was investigated in patients with complex partial seizures (CPS) of dominant (n = 16) or nondominant (n = 19) temporal-lobe origin as well as in an epilepsy control group (n = 6) which consisted largely of patients with primary generalized epilepsies [23].
• PET: central benzodiazepine neuroreceptor mapping in generalized epilepsies [24].
• SES occurred in different types of partial and generalized epilepsies of childhood but in nearly 50% of the cases with epilepsy, there was a benign condition involving mainly the parietal lobe with versive, unilateral and sleep-generalized seizures [25].

Gene context of Epilepsy, Generalized

• The present replication study tested the initial finding that the KCNJ10 Cys271 allele is associated with seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE) [26].
• Some families with LGI1 mutations contain individuals with idiopathic generalized epilepsies [27].
• GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies [28].
• PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs) [29].
• RECENT FINDINGS: Mutations in the chloride channel gene CLCN2 have been associated with the most common forms of idiopathic generalized epilepsies [30].

Analytical, diagnostic and therapeutic context of Epilepsy, Generalized

• Both substances when diffusely applied on a wide cortical area of both hemispheres at very low concentration produced an EEG pattern consisting of spike-wave bursts similar to the electrographic manifestations seen in feline generalized epilepsy induced by large parenteral doses of sodium penicillin [31].
• The major aim of this study was to elucidate the role of nitric oxide (NO) in the development of pentylenetetrazole (PTZ)-kindling as an animal model of primary generalized epilepsy [32].
• The immunohistochemical localization of c-fos protein in the CNS neurons was studied in a model of generalized epilepsy induced by the intraperitoneal injection of 4-aminopyridine to adult Wistar rats [33].
• Focal perfusion of DZP therefore effectively reduced spiking in this cobalt chloride/pilocarpine model of focal and secondarily generalized epilepsy [34].
• Epilepsy research using positron emission tomography (PET) has advanced our understanding of the pathophysiology and neurochemical correlates of both focal and generalized epilepsies, but from the clinical viewpoint its major contribution has been in the presurgical evaluation of patients with medically intractable partial seizures [35].

References