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Suncica Lah - One of the best experts on this subject based on the ideXlab platform.
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accelerated long term forgetting in children with Genetic Generalized Epilepsy the temporal trajectory and contribution of executive skills
Epilepsy & Behavior, 2020Co-Authors: Samantha Joplin, Belinda Barton, Deepak Gill, Richard Webster, John A Lawson, Anna Mandalis, Mark Sabaz, Michael Gascoigne, Suncica LahAbstract:Abstract Purpose Long-term memory, which is critical for social and vocational functioning, is impaired in children with Genetic Generalized Epilepsy (GGE). In this study, we examined the relationship between the temporal pattern of long-term forgetting for visual and verbal materials and executive skills in children with GGE. Method Thirty-two children, 17 with GGE and 25 typically developing age-matched controls completed standardized tests of short-term memory (recall after a 30-minute delay), executive skills, and experimental long-term memory tasks (one verbal and one visual) involving recall after one short (30-minute), and two long (1-day, 2-week) delays. Results On the long-term visual memory task, children with GGE performed comparably with typically developing children at a 30-minute delay (p = .298), although obtained lower object placement accuracy score, at 1 day (p = .039) and at 2 weeks (p = .022) relative to typically developing children. On the verbal task, the between-group difference was not significant at any delay. In children with GGE, poorer object placement accuracy at two weeks correlated with lower visuospatial short-term memory (r = − 0.624, p = .005) and verbal working memory (r = − 0.448, p = .041). Conclusions This study provided several novel findings. For the first time, accelerated long-term forgetting (ALF) was found in long-term visual memory in children with GGE, despite comparable learning and recall at 30 min. Study results indicated that deficits in long-term visual memory are present after one day, increase over time, and may relate to reduced executive skills. Our findings can be used to inform our understanding of the temporal trajectory of ALF and contribution of executive skills.
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accelerated long term forgetting is not evident in adults with Genetic Generalized Epilepsy irrespective of the paradigm used
Epilepsy & Behavior, 2020Co-Authors: Jessica Elise Beilharz, Zoe Thayer, Armin Nikpour, Suncica LahAbstract:Abstract Accelerated long-term forgetting (ALF) is a recently discovered memory disorder characterized by intact acquisition and retention over short delays, followed by abnormally fast rates of forgetting. Accelerated long-term forgetting has been repeatedly found in children, but not in adults, with Genetic Generalized Epilepsy (GGE). It is possible that this discrepancy is due to a difference in paradigms used in these studies. The current study aimed to determine whether adults with GGE displayed ALF using two paradigms, one that required complete learning and another one that did not. In addition, we explored the relationships with everyday memory difficulties, working memory, mood, and Epilepsy variables. Fourteen adults with GGE were compared with 16 healthy controls on two verbal memory tests: a modified version of the California Verbal Learning Test learned to a criterion of 100% (complete learning) and Logical Memory from the Wechsler Memory Scale (Fourth Edition) presented only once (incomplete learning). Recall was tested at 2 min, 30 min, and 1 week, and recognition at 1 week only. Working memory, everyday memory, and mood were also assessed. We found no evidence of ALF on either of the two verbal memory paradigms on recall or recognition tests although patients displayed significantly poorer working memory. Moreover, patients with GGE reported significantly more memory difficulties in everyday life, and these were associated with greater mood disturbances but not with memory tests scores. Greater number of antiepileptic drugs and Epilepsy severity also related to memory scores on some tests. Our study suggests that a difference in paradigms used to investigate ALF in children and adults with GGE is unlikely to explain the differences in findings. The study tentatively raises a hypothesis that developmental factors may play a role in ALF in patients with GGE; children with GGE may grow out of ALF. Nevertheless, this hypothesis would need to be tested in a longitudinal study that would follow patients from childhood to early adulthood.
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longitudinal study of accelerated long term forgetting in children with Genetic Generalized Epilepsy evidence of ongoing deficits
Cortex, 2017Co-Authors: Jasmin Graysoncollins, Michael B Gascoigne, Belinda Barton, Richard M Webster, Deepak Gill, Suncica LahAbstract:Accelerated long-term forgetting (ALF) is a recently described memory disorder characterised by adequate recall after short, but not long delays. Currently, the prevailing conceptualisation of ALF is of a seizure related phenomenon. The main aim of this study was to assess whether ALF subsides as Epilepsy severity and seizures abate in children with Genetic Generalized Epilepsy (GGE). Eighteen children with GGE were compared over time to 29 healthy controls on a range of cognitive measures. The primary outcome was a modified version of the California Verbal Learning Test for Children with a long delay (seven day) recall component. At approximately two years follow up, ALF was apparent, although Epilepsy severity subsided and seizures resolved in many children. This result contrasts with the dominant conceptualisation of ALF being a seizure related phenomenon. Moreover, at follow-up, worse recall at the long delay was related to greater Epilepsy severity at baseline and earlier age of seizure onset, but not to being seizure free at follow-up. While at follow-up worse recall at the long delay related to the worse baseline recall at the long delay, this recall did not relate to scores obtained on standardised memory tests at baseline. Our study suggests that ALF may not be seizure related and identifies factors associated with risk of ALF in children with GGE.
Wendyl Dsouza - One of the best experts on this subject based on the ideXlab platform.
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the effect of antiepileptic drugs on epileptiform discharges in Genetic Generalized Epilepsy a systematic review
Epilepsy & Behavior, 2019Co-Authors: Claire Gunawan, Udaya Seneviratne, Wendyl DsouzaAbstract:Abstract Objective The objective of this study was to evaluate the current evidence regarding the effect of antiepileptic drugs (AEDs) on epileptiform discharge (ED) burden in Genetic Generalized Epilepsy (GGE). Methods We conducted a comprehensive literature search of PubMed, Embase, PsycINFO, and the Web of Science Core Collection databases using the keywords ‘Genetic Generalized Epilepsy’, ‘antiepileptic drugs’ and ‘epileptiform discharge’. Primary human studies published in English that reported the effect of AEDs on EDs captured on electroencephalogram (EEG) recordings of at least 24 h in duration in patients with GGE were included. Results Six studies published between 1984 and 2017, which reported the effect of AEDs on EDs, involving a total of 116 patients with GGE, were analyzed. Our systematic review found a tendency for AEDs to reduce ED density, frequency, cumulative duration, and burst duration in GGE. Furthermore, we found evidence that the AED-mediated reduction in ED burden was associated with improved seizure control and cognitive outcomes. Conclusions Antiepileptic drugs tend to reduce ED burden in GGE, but the significance of this association remains uncertain.
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electroencephalography in the diagnosis of Genetic Generalized Epilepsy syndromes
Frontiers in Neurology, 2017Co-Authors: Udaya Seneviratne, Mark J. Cook, Wendyl DsouzaAbstract:Genetic Generalized Epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical and electroencephalographic (EEG) features. The EEG signature of GGE is bisynchronous, symmetric and Generalized spike-wave complex. Other typical EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of Generalized epileptiform discharges. Activation procedures such as sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure and fixation-off are useful techniques to increase the yield of EEG abnormalities. Specific triggers such as pattern stimulation and cognitive tasks are useful in eliciting reflex seizure-related EEG abnormalities in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes.
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a comprehensive assessment of cognitive function in the common Genetic Generalized Epilepsy syndromes
European Journal of Neurology, 2017Co-Authors: Stephen C Bowden, Amy Loughman, Wendyl DsouzaAbstract:Considered to be benign conditions, the common Genetic Generalized Epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction. Methods: A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities. Results: Scores on tests of overall cognitive ability, acquired knowledge, long-term retrieval and speed of information processing were significantly below the normative mean. Long-term retrieval was a pronounced weakness with a large reduction in scores (d = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function. Conclusions: This study confirms previous meta-analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common Epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE.
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self and informant report ratings of psychopathology in Genetic Generalized Epilepsy
Epilepsy & Behavior, 2017Co-Authors: Stephen C Bowden, Amy Loughman, Wendyl DsouzaAbstract:The psychological sequelae of Genetic Generalized epilepsies (GGE) is of growing research interest, with up to a third of all adults with GGE experiencing significant psychiatric comorbidity according to a recent systematic review. A number of unexplored questions remain. Firstly, there is insufficient evidence to determine relative prevalence of psychopathology between GGE syndromes. Secondly, the degree to which self-report and informant-report questionnaires accord in adults with Epilepsy is unknown. Finally, while Epilepsy severity is one likely predictor of worse psychopathology in GGE, evidence regarding other possible contributing factors such as Epilepsy duration and antiepileptic drugs (AEDs) has been equivocal. The potential impact of subclinical epileptiform discharges remains unexplored. Self-report psychopathology symptoms across six DSM-Oriented Subscales were prospectively measured in 60 adults with GGE, with informant-report provided for a subset of 47. We assessed the burden of symptoms from both self- and informant-report, and the relationship between clinical Epilepsy variables and self-reported symptoms. Results showed elevated symptoms in almost half of the sample overall. Depression and anxiety were the most commonly reported types of symptoms. There was a trend towards greater symptoms endorsement by self-report, and relatively modest interrater agreement. Symptoms of ADHD were significantly positively associated with number of AEDs currently prescribed. Other psychopathology symptoms were not significantly predicted by Epilepsy duration, seizure-free duration or total duration of epileptiform discharges over a 24-hour period. The high prevalence of psychological needs suggests that routine screening of psychopathology and provision of psychoeducation may be essential to improving patient care and outcomes. Further investigation is required to better understand predictive and causal factors for psychopathology in GGE.
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consistent topography and amplitude symmetry are more typical than morphology of epileptiform discharges in Genetic Generalized Epilepsy
Clinical Neurophysiology, 2016Co-Authors: Udaya Seneviratne, Mark J. Cook, Wendyl DsouzaAbstract:Abstract Objective To provide a quantitative evaluation of typical electroencephalographic (EEG) abnormalities in Genetic Generalized Epilepsy (GGE). Methods We prospectively performed 24-h ambulatory EEG recordings in a cohort of patients with GGE. The diagnosis was established according to the International League Against Epilepsy criteria. Details of all epileptiform discharges across the 24-h time scale were entered into an electronic database. We carried out descriptive statistics to provide a quantitative breakdown of typical EEG abnormalities. Results A total of 6923 epileptiform discharges from 105 abnormal 24-h ambulatory EEGs were analyzed. 96% of discharges were symmetric in amplitude with fronto-central maximum topographically. Only 24% of the paroxysms had typical morphology while 43% were regular. Photoparoxysmal response, eye-closure sensitivity and hyperventilation-induced Generalized paroxysms were less common in around 10%, whereas occipital intermittent rhythmic delta activity was very rare (2%). Conclusion Our results indicate that Generalized discharges with symmetric amplitude and fronto-central maxima are the most consistent findings in GGE, and other features are observed less frequently. Significance Epileptiform discharges displaying highly consistent amplitude symmetry coupled with fronto-central topography should provoke consideration of GGE. Recognition of variations from typical abnormalities is important to avoid the risk of misdiagnosis and delayed diagnosis.
Udaya Seneviratne - One of the best experts on this subject based on the ideXlab platform.
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the effect of antiepileptic drugs on epileptiform discharges in Genetic Generalized Epilepsy a systematic review
Epilepsy & Behavior, 2019Co-Authors: Claire Gunawan, Udaya Seneviratne, Wendyl DsouzaAbstract:Abstract Objective The objective of this study was to evaluate the current evidence regarding the effect of antiepileptic drugs (AEDs) on epileptiform discharge (ED) burden in Genetic Generalized Epilepsy (GGE). Methods We conducted a comprehensive literature search of PubMed, Embase, PsycINFO, and the Web of Science Core Collection databases using the keywords ‘Genetic Generalized Epilepsy’, ‘antiepileptic drugs’ and ‘epileptiform discharge’. Primary human studies published in English that reported the effect of AEDs on EDs captured on electroencephalogram (EEG) recordings of at least 24 h in duration in patients with GGE were included. Results Six studies published between 1984 and 2017, which reported the effect of AEDs on EDs, involving a total of 116 patients with GGE, were analyzed. Our systematic review found a tendency for AEDs to reduce ED density, frequency, cumulative duration, and burst duration in GGE. Furthermore, we found evidence that the AED-mediated reduction in ED burden was associated with improved seizure control and cognitive outcomes. Conclusions Antiepileptic drugs tend to reduce ED burden in GGE, but the significance of this association remains uncertain.
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electroencephalography in the diagnosis of Genetic Generalized Epilepsy syndromes
Frontiers in Neurology, 2017Co-Authors: Udaya Seneviratne, Mark J. Cook, Wendyl DsouzaAbstract:Genetic Generalized Epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical and electroencephalographic (EEG) features. The EEG signature of GGE is bisynchronous, symmetric and Generalized spike-wave complex. Other typical EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of Generalized epileptiform discharges. Activation procedures such as sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure and fixation-off are useful techniques to increase the yield of EEG abnormalities. Specific triggers such as pattern stimulation and cognitive tasks are useful in eliciting reflex seizure-related EEG abnormalities in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes.
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Can EEG Differentiate Among Syndromes in Genetic Generalized Epilepsy
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2017Co-Authors: Udaya Seneviratne, Graham Hepworth, Mark J. Cook, Wendyl D'souzaAbstract:PURPOSE To evaluate EEG differences among syndromes in Genetic Generalized Epilepsy based on quantified data. METHODS Twenty-four-hour ambulatory EEGs were recorded in consecutive patients diagnosed with Genetic Generalized Epilepsy. All epileptiform EEG abnormalities were quantified into density scores (total duration of epileptiform discharges per hour). One-way analysis of variance was conducted to find out differences in EEG density scores among the syndromes. Generalized linear mixed models were also fitted to explore the association between the proportion of "pure" Generalized spike-wave paroxysms and fragments (without intervening polyspikes/polyspike-waves) and the syndromes. RESULTS In total, 6,923 epileptiform discharges were analyzed from 105 abnormal EEGs. In the analysis of variance, six EEG variables were significantly different among syndromes: total spike density (P = 0.001), total polyspike and polyspike-wave density (P = 0.049), Generalized spike-wave-only density (P < 0.001), Generalized paroxysm density (P < 0.001), Generalized paroxysm duration mean (P = 0.018), and Generalized paroxysm duration maximum (P = 0.009). The density of epileptiform discharges and the paroxysm durations were the highest in juvenile absence Epilepsy followed by juvenile myoclonic Epilepsy, childhood absence Epilepsy, and Generalized Epilepsy with tonic-clonic seizures only. Generalized linear mixed models revealed that "pure" Generalized spike-wave discharges (without intervening polyspikes/polyspike waves) tended to be more frequent in absence epilepsies, although the difference was not statistically significant (P = 0.21). CONCLUSIONS The findings of this study suggest that the density and duration of epileptiform discharges can help differentiate among Genetic Generalized Epilepsy syndromes.
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Electroencephalography in the Diagnosis of Genetic Generalized Epilepsy Syndromes
Frontiers Media S.A., 2017Co-Authors: Udaya Seneviratne, Mark J. Cook, Wendyl Jude D’souzaAbstract:Genetic Generalized Epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical features and electroencephalographic (EEG) abnormalities. The main EEG feature of GGE is bilateral, synchronous, symmetric, and Generalized spike-wave complex. Other classic EEG abnormalities are polyspikes, epileptiform K-complexes and sleep spindles, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity, and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of Generalized epileptiform discharges. Sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are often used as activation techniques to increase the diagnostic yield of EEG recordings. Reflex seizure-related EEG abnormalities can be elicited by the use of triggers such as cognitive tasks and pattern stimulation during the EEG recording in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes
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epileptiform k complexes and sleep spindles an underreported phenomenon in Genetic Generalized Epilepsy
Journal of Clinical Neurophysiology, 2016Co-Authors: Udaya Seneviratne, Mark J. Cook, Wendyl DʼsouzaAbstract:Purpose: To study the frequency of epileptiform K-complexes and sleep spindles as well as clinical variables influencing those abnormalities. Methods: We prospectively performed 24-hour ambulatory EEGs in a cohort of patients with Genetic Generalized Epilepsy diagnosed and classified according to the International League against Epilepsy criteria. Overlapping of epileptiform discharges with K-complexes and sleep spindles was defined as epileptiform K-complexes and epileptiform sleep spindles. The presence of epileptiform K-complexes and sleep spindles was tabulated for each patient, and frequencies were calculated. We performed multiple regression analysis to study the influence of clinical predictors on the occurrence of epileptiform K-complexes and sleep spindles. The predictor variables tested in the model were seizure-free duration, Epilepsy duration, Genetic Generalized Epilepsy syndrome, number of antiepileptic drugs, use of sodium valproate, and use of lamotrigine. Results: A total of 107 patients (37 males and 70 females) were studied. The mean age was 28.5 ± 10.7 years (range, 13-58). Juvenile absence Epilepsy was the most common Epilepsy syndrome in the cohort (31.8%), followed by Generalized Epilepsy with tonic-clonic seizures only (26.2%), juvenile myoclonic Epilepsy (26.2%), and childhood absence Epilepsy (14%). Epileptiform K-complexes and sleep spindles were seen in 65.4% and 10.3% of patients, respectively. None of the clinical variables had any significant impact on the occurrence of epileptiform K-complexes and sleep spindles in our multivariable analysis. Conclusions: Epileptiform K-complexes are common in the sleep EEGs of patients diagnosed with Genetic Generalized Epilepsy. This underreported phenomenon highlights the important association of arousals and epileptiform discharges in Genetic Generalized Epilepsy.
Jesus Gonzalez De La Aleja - One of the best experts on this subject based on the ideXlab platform.
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antisaccades and memory guided saccades in Genetic Generalized Epilepsy and temporal lobe Epilepsy
Epilepsy & Behavior, 2021Co-Authors: Maria Paz Guerreromolina, Rosa Ana Saizdiaz, Claudia Rodriguezlopez, Luisa Panadesde Oliveira, David Uriarte Perez De Urabayen, Nicolas Garzocaldas, Cecilia E Garciacena, Julian Benitoleon, Jesus Gonzalez De La AlejaAbstract:Abstract Objective Oculomotor tasks can be used to measure volitional control of behavior sensitive to frontal dysfunction. This study aimed to examine the saccadic eye movement in Genetic Generalized Epilepsy (GGE) which could correlate with the abnormality of the frontal lobe or the thalamo-frontal network. Methods Twenty-one patients with GGE were compared with 22 patients with Temporal Lobe Epilepsy (TLE) and 39 healthy controls. Visual-guided saccades, Antisaccades, and Memory-guided saccades as oculomotor tasks were performed using a novel gaze-tracker designed for clinical practice use. Results Patients with Epilepsy (either GEE or TLE) had similar latency, accuracy, and velocity in visual-guided saccades and memory-guided saccades. Patients with Epilepsy had similar latencies and correct antisaccade number. However, healthy volunteers, matched by age, had faster responses and more accurate results than patients with Epilepsy. Conclusions Our investigations did not reveal differences between TLE and GGE patients’ groups in visually guided saccades, antisaccades, and memory-guided saccades, thus suggesting that the frontal cortical mechanisms responsible for them are not explicitly impaired in patients with GGE.
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peripapillary retinal nerve fibre layer thinning in Genetic Generalized Epilepsy
Seizure-european Journal of Epilepsy, 2019Co-Authors: Jesus Gonzalez De La Aleja, Maripaz Guerreromolina, Rosa Ana Saizdiaz, Francisco Lopezmunoz, Isidoro Ragamartinez, Jesus Hernandezgallego, Patricia Navarretechamorro, Francisco Javier PovedanomonteroAbstract:Abstract Purpose The purpose of this study was to compare the peripapillary retinal nerve fibre layer (RNFL) between patients with Genetic Generalized Epilepsy (GGE) and healthy controls. Methods This prospective observational study was conducted on adults aged 18–60 years. The study group comprised 26 consecutive patients who met the inclusion criteria and 26 healthy age- and sex-matched healthy adults. Peripapillary RNFL thickness was measured by spectral domain optical coherence tomography. Results The average peripapillary RNFL thickness was significantly thinner for GGE patients (98.61 μm) than for healthy controls (104.77 μm) (p = 0.016). Similar results were obtained for the left eye. The peripapillary RFNL thickness of all quadrants was lower for GGE patients than for healthy controls, but it was significant only in the superior (p = 0.009) and inferior (p = 0.024) quadrants for both eyes. Conclusions Our results suggest that the peripapillary RNFL is significantly thinner in GGE patients than in healthy participants. We concluded that this microstructural feature might be an intrinsic feature of GGE.
Roiza A. Rodrigues Baldez - One of the best experts on this subject based on the ideXlab platform.
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shared Genetic basis between Genetic Generalized Epilepsy and background electroencephalographic oscillations
Epilepsia, 2021Co-Authors: Remi Stevelink, Jurjen J. Luykx, Costin Leu, Dennis Lal, Dick Schijven, Johannes A. Carpay, Koen Rademaker, Bochao D Lin, Alexander W Smith, Roiza A. Rodrigues BaldezAbstract:Objective Paroxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent Epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the Genetic correlation between Epilepsy and background EEG oscillations. Methods Confounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with Epilepsy. To overcome this limitation, we compared Genetic data from a genome-wide association study (GWAS) on Epilepsy (n = 12 803 people with Epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without Epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent Epilepsy replication dataset (n = 4851 people with Epilepsy and 20 428 controls). To assess the Genetic overlap between these phenotypes, we performed Genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses. Results Our analyses show strong Genetic correlations of Genetic Generalized Epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having Generalized Epilepsy. Mendelian randomization analyses suggest a causal effect of GGE Genetic liability on beta oscillations. Significance Our results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of Epilepsy.
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converging evidence for shared Genetic underpinnings of Genetic Generalized Epilepsy and background eeg oscillations
bioRxiv, 2020Co-Authors: Remi Stevelink, Jurjen J. Luykx, Costin Leu, Dennis Lal, Alexander Smith, Dick Schijven, Johannes A. Carpay, Koen Rademaker, Bochao D Lin, Roiza A. Rodrigues BaldezAbstract:Abstract Paroxysmal epileptiform abnormalities on EEG are the hallmark of epilepsies, but it is uncertain to what extent Epilepsy and background EEG oscillations share neurobiological underpinnings. Confounding factors, including the heterogeneous etiology of epilepsies and medication effects hamper studies on background brain activity in people with Epilepsy. To overcome this limitation, using Genetic correlation, polygenic risk score (PRS), Mendelian Randomization and meta-analyses, we here provide consistent evidence for shared Genetic underpinnings between Genetic Generalized Epilepsy (GGE) and EEG beta power. Subjects in the highest 10% quantile of beta-power PRS scores are 1.4 fold more likely to suffer from GGE compared to the lowest 10% quantile. Moreover, we find increased enrichment of brain-expressed genes relative to the Epilepsy and the EEG GWASs individually. In conclusion, our results point to shared biological mechanisms underlying background EEG and the susceptibility for seizures, opening avenues to investigate the clinical utility of beta oscillations in GGE.
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Converging evidence for shared Genetic underpinnings of Genetic Generalized Epilepsy and EEG beta power
2019Co-Authors: Remi Stevelink, Jurjen J. Luykx, Bochao Lin, Costin Leu, Dennis Lal, Alexander Smith, Dick Schijven, Johannes A. Carpay, Koen Rademaker, Roiza A. Rodrigues BaldezAbstract:Paroxysmal epileptiform abnormalities on EEG are the hallmark of epilepsies, but it is uncertain to what extent Epilepsy and background EEG oscillations share neurobiological underpinnings. Confounding factors, including the heterogeneous etiology of epilepsies and medication effects hamper studies on background brain activity in people with Epilepsy. To overcome this limitation, using Genetic correlation, polygenic risk score (PRS), Mendelian Randomization and meta-analyses, we here provide consistent evidence for shared Genetic underpinnings between Genetic Generalized Epilepsy (GGE) and EEG beta power. Subjects in the highest 10% quantile of beta-power PRS scores are 1.4 fold more likely to suffer from GGE compared to the lowest 10% quantile. Moreover, we find increased enrichment of brainexpressed genes relative to the Epilepsy and the EEG GWASs individually. In conclusion, our results point to shared biological mechanisms underlying background EEG and the susceptibility for seizures, opening avenues to investigate the clinical utility of beta oscillations in GGE.
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Genetic correlation between background eeg oscillations and Genetic Generalized Epilepsy
bioRxiv, 2019Co-Authors: Remi Stevelink, Jurjen J. Luykx, Costin Leu, Dennis Lal, Alexander Smith, Dick Schijven, Johannes A. Carpay, Koen Rademaker, Bochao D Lin, Roiza A. Rodrigues BaldezAbstract:Abstract Paroxysmal epileptiform abnormalities on EEG are the hallmark of epilepsies, but it is uncertain to what extent Epilepsy and background EEG oscillations share neurobiological underpinnings. Confounding factors, including the heterogeneous etiology of epilepsies and medication effects hamper studies on background brain activity in people with Epilepsy. This limitation may be partly overcome by assessing the Genetic overlap between Epilepsy and EEG power spectra based on genome-wide association studies (GWASs). We used the summary statistics of the recently published EEG (n=8,425) and Epilepsy (n=37,021) GWASs to compute estimates of Genetic overlap between EEG power spectra and Epilepsy subtypes using linkage disequilibrium score regression (LDSC) and polygenic risk scoring (PRS). We found significant Genetic correlations between Genetic Generalized Epilepsy (GGE) and EEG beta power (rg=0.44; p=0.01) and between GGE and theta power (rg =0.25; p=0.02), which were replicated in an independent GGE cohort. Supporting this finding, beta and theta powers’ PRSs were both strongly and positively associated with Generalized Epilepsy (p-values ranging from 5.3×10−8 to 8.5×10−4), suggesting that Genetic predisposition to GGE and to altered background brain activity partially overlap. All PRS directions of effect were replicated in an independent cohort of people with Epilepsy and controls (n=25,303; p=0.023). Furthermore, subjects in the highest 10% quantile of beta-power PRS scores were 1.4 fold more likely to suffer from GGE compared to subjects in the lowest 10% quantile (OR: 1.40; 95%CI: 1.18-1.67; p=1.5×10−4). Moreover, by meta-analyzing EEG and Epilepsy GWASs data for gene-based tests and by imputing gene expression, we found increased enrichment of brain-expressed genes relative to both the Epilepsy and the EEG GWASs individually. Finally, Mendelian Randomization analyses suggested a causal effect of GGE Genetic liability on beta oscillations. In conclusion, our results point to shared biological mechanisms underlying background EEG and the susceptibility for seizures. Our findings thus open avenues to investigate the clinical utility of theta and beta oscillations in GGE. They may also inspire preclinical research into the links between background EEG oscillations and epilepsies.