Idiopathic Generalized Epilepsies Subsyndromes Research Articles

Neuropsychological profile and drug treatment response in Idiopathic Generalized Epilepsy

PurposeThe endophenotype of Idiopathic Generalized Epilepsies (IGE) comprises distinct neuropsychological deficits compared to normal controls. It is unknown if the severity of features of the endophenotype correlates with resistance to anti-seizure medication. Therefore, we here studied the association of neuropsychological profiles with treatment response. MethodsWe evaluated 106 Danish patients aged ≥18 and diagnosed with IGE using a neuropsychological test battery comprising tests for executive dysfunction, visual attention, episodic memory, and verbal comprehension. Tests were complemented by the Purdue Pegboard test. Patients with suspected ongoing psychogenic non-epileptic seizures were excluded. ResultsAt testing, 72 patients were seizure free, and 34 patients had recent seizures despite anti-seizure medication. As compared to age corrected Danish normative values, IGE patients showed significant impairments in semantic fluency and performed significantly worse in the Purdue Pegboard test. The vocabulary subtest of the WAIS-IV suggested lower verbal comprehension in IGE patients. We found no signs of memory impairment. Comparisons between results of the test battery, drug resistance, and the different IGE subsyndromes revealed consistent null-associations in various predefined and exploratory univariate and multivariate analyses. ConclusionWe here found and confirmed the distinct neuropsychological profile comprising impaired executive functions, reduced psychomotor speed, and normal memory previously described in juvenile myoclonic epilepsy. This profile was, however, not restricted to juvenile myoclonic epilepsy but equally affected all IGE patients. The neuropsychological deficits were not significantly associated with drug treatment outcome.

Patterns of Gray Matter Abnormalities in Idiopathic Generalized Epilepsy: A Meta-Analysis of Voxel-Based Morphology Studies.

ObjectiveWe aimed to identify the consistent regions of gray matter volume (GMV) abnormalities in idiopathic generalized epilepsy (IGE), and to study the difference of GMV abnormalities among IGE subsyndromes by applying activation likelihood estimation (ALE) meta-analysis.MethodsA systematic review of VBM studies on GMV of patients with absence epilepsy (AE), juvenile myoclonic epilepsy (JME), IGE and controls indexed in PubMed and ScienceDirect from January 1999 to June 2016 was conducted. A total of 12 IGE studies, including 7 JME and 3 AE studies, were selected. Meta-analysis was performed on these studies by using the pooled and within-subtypes analysis (www.brainmap.org). Based on the above results, between-subtypes contrast analysis was carried out to detect the abnormal GMV regions common in and unique to each subtype as well.ResultsIGE demonstrated significant GMV increase in right ventral lateral nucleus (VL) and right medial frontal gyrus, and significant GMV decrease in bilateral pulvinar. For JME, significant GMV increase was seen in right medial frontal gyrus, right anterior cingulate cortex (ACC), while significant GMV decrease was found in right pulvinar. In AE, the most significant GMV increase was found in right VL, and slight GMV reduction was seen in right medial dorsal nucleus, right subcallosal gyrus, left caudate and left precuneus. No overlapped and unique regions with significant GMV abnormalities were found between JME and AE.SignificanceThis meta-analysis demonstrated that thalamo-frontal network was a structure with significant GMV abnormality in IGE, and the IGE subsyndromes showed different GMV abnormal regions. These observations may provide instructions on the clinical diagnosis of IGE.

Electroclinical syndromes of idiopathic generalized epilepsies in adults

Idiopathic generalized epilepsies (IGE) accounting for 20–40% of all epilepsies. International League against Epilepsy (ILAE) Classification recognizes three main IGE subsyndromes that are manifested in adults: juvenile absence epilepsy (JAE); juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures only (EGTCSO). JAE is mainly manifested with typical absence seizures (TAS), 80% of patients suffer from GTCS, and 20% have myoclonic jerks (MJ). JME is the most common IGE subsyndrome, characterized by MJ on awakening, GTCS in nearly all patients, and TAS in a third of them. EGTCSO with GTCS occurring predominantly on awakening is probably life-long disease with a high incidence of relapse on withdrawal of treatment. Some types of IGE have not yet been recognized by the ILAE: (1) Jeavons syndrome – a purely reflex IGE predominantly manifested with eyelid myoclonia and electroencephalogram (EEG) abnormalities on eye closure, (2) perioral myclonia with absences, (3) IGE with phantom absences – a type of mild absences before the first GTCS, that usually occurs in adulthood. Both perioral myoclonia with absences and phantom absences are clinically significant because they are probably life-long and are associated with a very high incidence of absence status epilepticus that may escape diagnosis and appropriate treatment.

Generalized Spike and Waves: Effect of Discharge Duration on Brain Networks as Revealed by BOLD fMRI

In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG-fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG-fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.

Idiopathic generalized epilepsy (IGE) syndromes in development: IGE with absences of early childhood, IGE with phantom absences, and perioral myoclonia with absences

The classification of idiopathic generalized epilepsies (IGEs) is still controversial, with special reference to absence epilepsy syndromes. Strict, well-defined criteria for syndromic definitions are necessary to delineate homogeneous conditions; however, this approach may leave a considerable group of patients unclassified, leading to the effort to categorize them in possible distinct subsyndromes. In this report, we review some of these possible IGE subsyndromes, such as IGE with absences of early childhood, IGE with phantom absences, and perioral myoclonia with absences, briefly commenting on the issues regarding their recognition as individual entities.

Mutational analysis ofCACNA1Gin idiopathic generalized epilepsy

Recent studies have strongly implicated low voltage-activated/T-type calcium channels (T-channels) in the etiology of epilepsy. Here, we report the results of a mutational analysis of the CACNA1G gene, encoding the T-channel CaV3.1/1G subunit, using a cohort of 123 mostly Japanese and Hispanic patients with idiopathic generalized epilepsies (IGE) and 360 healthy control individuals. We found 13 variants, including five which involved amino acid substitutions. One variant, c.1709C>T (Ala570Val), is present in a sporadic case of juvenile myoclonic epilepsy (JME) with early childhood absence and astatic seizures, but was not found in control samples. Another variant, c.3265G>T (Ala1089Ser), was observed in three family members affected with JME, and also in one control individual. Two JME patients and three control individuals harbored a third variant, c.2968G>A (Asp980Asn). Although not statistically significant, slightly faster inactivation decay rates were observed in some mutant channels. Our collective findings flag CACNA1G as a potential susceptibility locus for IGE subsyndromes that warrants closer investigation. © 2007 Wiley-Liss, Inc.

Voxel-based morphometry in patients with idiopathic generalized epilepsies

Idiopathic generalized epilepsies (IGE) are a group of frequent age-related epilepsy syndromes. IGE are clinically characterized by generalized tonic–clonic, myoclonic and absence seizures. According to predominant seizure type and age of onset, IGE are divided in subsyndromes: childhood absence and juvenile absence epilepsy (AE), juvenile myoclonic epilepsy (JME) and generalized tonic–clonic seizures on awakening (GTCS). The limits between these subsyndromes are not well defined, supporting the existence of only one major syndrome. Visual assessment of routine magnetic resonance imaging (MRI) in patients with IGE is normal. MRI voxel-based morphometry (VBM) uses automatically segmented gray and white matter for comparisons, eliminating the investigator bias. We used VBM to study 120 individuals (47 controls, 44 with JME, 24 with AE and 15 with GTCS) to investigate the presence of subtle structural abnormalities in IGE subsyndromes. VBM was performed searching for abnormalities on gray matter concentration (GMC) between patients groups and controls. Compared to controls, JME presented increased GMC in frontobasal region and AE showed increased GMC in the superior mesiofrontal region. The GTCS group did not differ from controls. There were no areas of reduced GMC with the statistical level selected. Region of interest analysis showed increased GMC in the anterior portion of the thalamus in patients with absence seizures. Our results support subtle GMC abnormalities in patients with JME and AE when compared to controls. These findings suggest the existence of different patterns of cortical abnormalities in IGE subsyndromes.

Brain Imaging in Idiopathic Generalized Epilepsies

While it is generally accepted that there is no neuroimaging abnormality in idiopathic generalized epilepsy (IGE), image processing and quantitative magnetic resonance imaging (MRI) studies suggest that there may be subtle structural abnormalities. Magnetic resonance spectroscopy indicates neuronal dysfunction with differing abnormalities in the IGE subsyndromes, and high concentrations of glutamate and glutamine have been inferred in the frontal lobes, and low gamma-aminobutyric acid levels in the occipital lobe. Studies of cerebral blood distribution at the time of absences have given complex results. The general consensus is of an increase in the thalamus and broad decreases in the neocortex, reflecting a suppression of neuronal activity, but with some increases, that may indicate focal areas of activation. Positron emission tomography (PET) ligand studies with an opioid tracer have inferred neocortical release of endogenous opioids at the time of serial absences. In combination with neurophysiological methods, PET studies with specific ligands have the potential to clarify the functional anatomy and neurochemical circuits that underlie IGE.

Idiopathic generalized epilepsies: clinical and electroencephalogram diagnosis and treatment

This review concentrates on the principles of the clinical and electroencephalogram diagnosis of idiopathic generalized epilepsies and their treatment. The electroclinical variability of the main seizure types is detailed and particular emphasis is placed on the differential diagnosis from other seizures and nonepileptic conditions that is essential for the optimal management of these patients. The authors review the various idiopathic generalized epilepsy subsyndromes and conditions that are included in both the 1989 International League Against Epilepsy classification system and the recently proposed International League Against Epilepsy scheme, but also syndromes and forms that have not been formally recognized. Finally, the authors describe the principles of antiepileptic drug treatment with the old and newer drugs, and their specific indications and contraindications in the various syndromes and seizure types.

Idiopathic Generalized Epilepsies: A Review and Modern Approach

Idiopathic Generalized Epilepsies: A Review and Modern Approach

Paper by Invitation: Imaging Idiopathic Generalized Epilepsy

It has been traditionally held that there is no radiological abnormality in patients with idiopathic generalized epilepsy (IGE). Sophisticated image processing and quantitative magnetic resonance imaging (MRI) studies suggest that, in some cases, there may be a subtle structural abnormality. Magnetic resonance spectroscopy indicates neuronal dysfunction with differing patterns of abnormality in the IGE sub-syndromes, and high levels of glutamate and glutamine have been suggested in the frontal lobes, and low GABA levels in the occipital lobe. Studies reflecting cerebral blood flow at the time of absences have given complex results. The principal consensus is of an increase in the thalamus and broad decreases in the neocortex, reflecting a suppression of neuronal activity, but with the possibility of some increases, that could perhaps reflect focal areas of neuronal activation. PET ligand studies with an opioid tracer have implied neocortical release of endogenous opioids at the time of serial absences. In combination with high time-resolution neurophysiological methods, static and dynamic PET studies with specific ligands have the potential to elucidate the functional anatomy and neurochemical circuits that under-lie IGE.