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Epilepsy Research Aug 2021Absence epilepsy shows age-related clinical features, as is observed in childhood and juvenile absence epilepsy. Electroencephalogram (EEG) is characterized by bursts of...
OBJECTIVE
Absence epilepsy shows age-related clinical features, as is observed in childhood and juvenile absence epilepsy. Electroencephalogram (EEG) is characterized by bursts of 3 Hz spike-and-wave complex (SWC). We noticed a morphological variation of the slow-wave component of SWCs between patients. This study investigated whether the waveform of SWC might be associated with the child's age of this epilepsy.
METHODS
Digitally-recorded EEGs under medication-free conditions were collected from 25 children who received the diagnosis of childhood or juvenile absence epilepsy. The morphology of slow wave in SWC in the frontal midline region was quantitatively compared between younger and older children using a cluster-based permutation test.
RESULTS
At <7 years of age (2.9-6.5 years of age, n = 6), the electrical potential of the descending slope in the slow wave was positively correlated with age whereas this correlation was not observed in patients of ≥7 years of age (7.1-12.9 years, n = 19). A cluster-based permutation test confirmed the results-among the entire slow wave period (0-285 msec), the period of the descending slope (195-260 msec) showed significantly lower potential in patients of <7 years of age in comparison to patients of ≥7 years of age (sum of t-values: 46.57, p-value: 0.011).
CONCLUSIONS
The current study demonstrated an age-dependent morphological difference in the slow-wave components of SWCs in EEGs of patients with pediatric absence epilepsy. This finding may provide a clue to understanding the age-related clinical manifestations of this epilepsy.
Topics: Adolescent; Child; Child, Preschool; Electroencephalography; Epilepsy, Absence; Humans
PubMed: 33915304
DOI: 10.1016/j.eplepsyres.2021.106647 -
Epilepsia Open Dec 2022Despite introduction of several antiseizure medications over the past two decades, treatment options for childhood absence epilepsy (CAE) and juvenile absence epilepsy... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Despite introduction of several antiseizure medications over the past two decades, treatment options for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) remain limited. We report the innovative adaptive design of an ongoing phase 2/3 trial to evaluate efficacy, safety, and tolerability of brivaracetam (BRV) monotherapy in patients 2-25 years of age with CAE or JAE.
METHODS
N01269 (ClinicalTrials.gov: NCT04666610; start: July 2021; expected completion: 2024) is a randomized, dose-finding and confirmatory, double-blind, placebo-controlled, parallel-group, multicenter trial. The trial consists of a dose-selection and assessment for futility stage, followed by an optimal-dose stage after interim analysis. Both stages include an up to 2-week screening period, a 2-week placebo-controlled period, and an 11-week active treatment period (10 weeks of initial treatment followed by a 24-hour electroencephalogram [EEG] and an additional week of active treatment for 24-hour EEG assessment). Patients who are absence seizure-free will enter an up to 4-week randomized withdrawal period. Efficacy assessments will be based on 24-hour EEG and seizure diaries.
SIGNIFICANCE
This two-stage adaptive trial design allows investigation of two potentially efficacious BRV doses, where one dose is dropped in favor of the other dose with a better benefit-risk profile. This allows for a combined phase 2 dose-finding and phase 3 confirmatory efficacy trial, which reduces the number of patients needed to be recruited and reduces trial duration. A randomized withdrawal period is included to evaluate sustainability of treatment effect over time and to allow for placebo control while minimizing placebo exposure. Use of EEG capture in addition to seizure diaries offers a robust mechanism of detecting seizure activity and measuring treatment effect. Positive efficacy and safety/tolerability data may support the use of BRV as monotherapy for CAE or JAE, providing another treatment option and representing long-delayed progress in the treatment of absence seizures in these populations.
Topics: Humans; Epilepsy, Absence; Anticonvulsants; Drug Therapy, Combination; Treatment Outcome; Seizures
PubMed: 35844134
DOI: 10.1002/epi4.12628 -
Journal of Neurology Mar 2023Childhood absence epilepsy (CAE), involves 3 Hz generalized spikes and waves discharges (GSWDs) on the electroencephalogram (EEG), associated with ictal discharges...
Childhood absence epilepsy (CAE), involves 3 Hz generalized spikes and waves discharges (GSWDs) on the electroencephalogram (EEG), associated with ictal discharges (seizures) with clinical symptoms and impairment of consciousness and subclinical discharges without any objective clinical symptoms or impairment of consciousness. This study aims to comparatively characterize neuronal networks underlying absence seizures and subclinical discharges, using source localization and functional connectivity (FC), to better understand the pathophysiological mechanism of these discharges. Routine EEG data from 12 CAE patients, consisting of 45 ictal and 42 subclinical discharges were selected. Source localization was performed using the exact low-resolution electromagnetic tomography (eLORETA) algorithm, followed by FC based on the imaginary part of coherency. FC based on the thalamus as the seed of interest showed significant differences between ictal and subclinical GSWDs (p < 0.05). For delta (1-3 Hz) and alpha bands (8-12 Hz), the thalamus displayed stronger connectivity towards other brain regions for ictal GSWDs as compared to subclinical GSWDs. For delta band, the thalamus was strongly connected to the posterior cingulate cortex (PCC), precuneus, angular gyrus, supramarginal gyrus, parietal superior, and occipital mid-region for ictal GSWDs. The strong connections of the thalamus with other brain regions that are important for consciousness, and with components of the default mode network (DMN) suggest the severe impairment of consciousness in ictal GSWDs. However, for subclinical discharges, weaker connectivity between the thalamus and these brain regions may suggest the prevention of impairment of consciousness. This may benefit future therapeutic targets and improve the management of CAE patients.
Topics: Humans; Epilepsy, Absence; Patient Discharge; Magnetic Resonance Imaging; Brain; Electroencephalography; Seizures
PubMed: 36370186
DOI: 10.1007/s00415-022-11462-8 -
Epilepsia Oct 2023The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2)...
OBJECTIVE
The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics.
METHODS
We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy.
RESULTS
Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance.
SIGNIFICANCE
JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.
Topics: Humans; Epilepsy, Absence; Siblings; Epilepsy, Generalized; Cognition; Myoclonic Epilepsy, Juvenile; Phenotype; Neuropsychological Tests; Immunoglobulin E
PubMed: 37475704
DOI: 10.1111/epi.17719 -
Seizure Nov 2022We tried to differentiate childhood absence epilepsy (CAE) from juvenile absence epilepsy (JAE) based on their clinical characteristics. We planned to identify a cutoff...
PURPOSE
We tried to differentiate childhood absence epilepsy (CAE) from juvenile absence epilepsy (JAE) based on their clinical characteristics. We planned to identify a cutoff point for the age at onset of seizures between CAE and JAE that is able to reliably predict the presence of generalized tonic-clonic seizures (GTCS) (that has important implications for treatment strategy and outcome prediction).
METHODS
This was a retrospective database study. All patients with an electro-clinical diagnosis of CAE or JAE were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. The receiver operating characteristic (ROC) curve was used for the statistical analysis to predict a cutoff point for the age at onset of seizures between the syndromes.
RESULTS
One hundred and ninety-six patients were studied. Generalized tonic-clonic seizure was reported by 134 patients (68.4%). The ROC curve of the age at seizure onset was an acceptable indicator to anticipate GTCS; the best cutoff point was at 9.65 years; 87 patients (44.4%) had CAE and 109 people (55.6%) had JAE. The odds ratio of the presence of GTCS in JAE compared with CAE was 3.6.
CONCLUSION
Syndrome diagnosis of CAE vs. JAE has important practical implications. The age at onset of seizures serves as a reliable and meaningful variable to differentiate CAE from JAE.
Topics: Child; Humans; Epilepsy, Absence; Retrospective Studies; Electroencephalography; Seizures; Prognosis; Epilepsy, Generalized
PubMed: 36223676
DOI: 10.1016/j.seizure.2022.10.008 -
Neurologia May 2019Childhood absence epilepsy (CAE) is considered easily manageable with medication provided that a strict patient classification system is employed. It accounts for 10% of...
INTRODUCTION
Childhood absence epilepsy (CAE) is considered easily manageable with medication provided that a strict patient classification system is employed. It accounts for 10% of all childhood epilepsy cases starting before the age of 15 and it is most frequent in school-aged girls. The aim of this study is to analyse long-term outcomes of patients diagnosed with CAE according to the Loiseau and Panayiotopoulos criteria and treated during childhood.
METHODS
We conducted a retrospective study including 69 patients with CAE who are currently older than 11; data were gathered from medical histories, EEG records, and telephone questionnaires.
RESULTS
52 patients met the Loiseau and Panayiotopoulos criteria. Mean age is now 17.16 years. Female-to-male ratio was 1.65:1; mean age at onset was 6 years and 2 months; mean duration of treatment was 3 years and 9 months. A family history of epilepsy was present in 30.8% of the patients and 7.7% had a personal history of febrile convulsions. Absence seizures were simple in 73.5% of the patients and complex in 26.5%. Response rates to first-line treatment were as follows: valproic acid, 46.3%; and valproic acid plus ethosuximide, 90.9%. The rate of response to second-line therapy (ethosuximide or lamotrigine) was 84.2%; 4% of the patients experienced further seizures after treatment discontinuation, 78.8% achieved seizure remission, and 25% needed psychological and academic support.
CONCLUSIONS
Our data show that epileptic patients should be classified according to strict diagnostic criteria since patients with true CAE have an excellent prognosis. The relapse rate was very low in our sample. Despite the favourable prognosis, psychological and academic support is usually necessary.
Topics: Adolescent; Anticonvulsants; Child; Disease Progression; Epilepsy, Absence; Ethosuximide; Female; Humans; Male; Prognosis; Retrospective Studies; Treatment Outcome; Valproic Acid
PubMed: 28325560
DOI: 10.1016/j.nrl.2016.12.005 -
Progress in Brain Research 2005Epileptic seizures cause dynamic, reversible changes in brain function and are often associated with loss of consciousness. Of all seizure types, absence seizures lead... (Review)
Review
Epileptic seizures cause dynamic, reversible changes in brain function and are often associated with loss of consciousness. Of all seizure types, absence seizures lead to the most selective deficits in consciousness, with relatively little motor or other manifestations. Impaired consciousness in absence seizures is not monolithic, but varies in severity between patients and even between episodes in the same patient. In addition, some aspects of consciousness may be more severely involved than other aspects. The mechanisms for this variability are not known. Here we review the literature on human absence seizures and discuss a hypothesis for why effects on consciousness may be variable. Based on behavioral studies, electrophysiology, and recent neuroimaging and molecular investigations, we propose absence seizures impair focal, not generalized brain functions. Impaired consciousness in absence seizures may be caused by focal disruption of information processing in specific corticothalamic networks, while other networks are spared. Deficits in selective and varying cognitive functions may lead to impairment in different aspects of consciousness. Further investigations of the relationship between behavior and altered network function in absence seizures may improve our understanding of both normal and impaired consciousness.
Topics: Behavior; Consciousness; Electroencephalography; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Humans; Magnetic Resonance Imaging; Tomography, Emission-Computed, Single-Photon
PubMed: 16186030
DOI: 10.1016/S0079-6123(05)50020-7 -
Journal of the Formosan Medical... Mar 2011The diagnosis of benign epilepsy syndrome should meet the following criteria: age-related and self-limited; good response to medication; and no obvious neurological... (Review)
Review
The diagnosis of benign epilepsy syndrome should meet the following criteria: age-related and self-limited; good response to medication; and no obvious neurological sequelae after seizure. However, the current concept of benign epilepsy syndrome has been challenged because of the advancements in genetic studies, neuroimaging, and molecular techniques. Many studies have revealed that the prevalence of behavioral problems and learning difficulties as well as subtle cognitive deficits is higher among patients with benign epilepsy, compared with the normal population. Here, we review updated results of these studies to show the latest and broad comprehensive knowledge of benign epilepsy in children.
Topics: Adolescent; Child; Child, Preschool; Epilepsy, Absence; Epilepsy, Benign Neonatal; Epilepsy, Rolandic; Humans; Infant; Infant, Newborn; Myoclonic Epilepsy, Juvenile
PubMed: 21497276
DOI: 10.1016/S0929-6646(11)60023-5 -
Seizure Oct 2018Children with Childhood Absence Epilepsy (CAE) may develop generalized tonic-clonic seizure or juvenile myoclonic epilepsy. A possible evolution to Eyelid Myoclonia with...
PURPOSE
Children with Childhood Absence Epilepsy (CAE) may develop generalized tonic-clonic seizure or juvenile myoclonic epilepsy. A possible evolution to Eyelid Myoclonia with Absence Epilepsy (EMA) hasn't been documented yet. We report the electroclinical features of a case series of children with CAE that evolved to EMA after therapy withdrawal.
METHOD
Of 108 patients with CAE referred at our Epilepsy Center in the last ten years, 5 satisfied the inclusion criteria: CAE diagnosis, a minimum of 3 years follow-up, a progression to EMA after therapy withdrawal.
RESULTS
All the six subjects were females. CAE was characterized by typical absences induced by hyperventilation; intermittent photic stimulation (IPS) was negative. All subjects were treated successfully with valproate. After drug withdrawal, all the six girls presented EMA. EMA was characterized by eyelid myoclonia with or without brief absences related to generalized spike/polyspike-waves discharges induced by IPS and less frequently by eye-closure.
CONCLUSIONS
Our study documented another possible evolution of CAE into EMA. These results support the hypothesis that these two epileptic conditions are dynamic processes evolving into one another. CAE and EMA could be considered "system epilepsy" characterized by a high susceptibility to changes in the brain networks during specific life periods such as childhood and puberty.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Disease Progression; Electroencephalography; Epilepsy, Absence; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Myoclonic Epilepsy, Juvenile; Retrospective Studies; Valproic Acid
PubMed: 30029089
DOI: 10.1016/j.seizure.2018.07.009 -
Epilepsia Jan 2018Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type...
OBJECTIVE
Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE.
METHODS
The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABA , and GABA synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABA conductance.
RESULTS
Decreasing cortical GABA conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type.
SIGNIFICANCE
These results provide a window into mechanisms underlying polygenic inheritance in CAE, as well as a mechanism for treatment effects and failures mediated by these channels. Although the model is a simplification of the human thalamocortical network, it serves as a useful starting point for predicting the implications of ion channel electrophysiology in polygenic epilepsy such as CAE.
Topics: Cerebral Cortex; Epilepsy, Absence; Humans; Ion Channels; Models, Biological; Neural Pathways; Neurons; Receptors, GABA; Thalamus
PubMed: 29265352
DOI: 10.1111/epi.13962