scholarly journals Polygenic risk scores of several subtypes of epilepsies in a founder population

2020 ◽  
Vol 6 (3) ◽  
pp. e416
Author(s):  
Claudia Moreau ◽  
Rose-Marie Rébillard ◽  
Stefan Wolking ◽  
Jacques Michaud ◽  
Frédérique Tremblay ◽  
...  
Keyword(s):  
Mixed Model ◽  
Focal Epilepsy ◽  
Population Based ◽  
Risk Scores ◽  
Founder Population ◽  
Idiopathic Generalized Epilepsy ◽  
Polygenic Risk ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy ◽  
Variance Explained

ObjectivePolygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.MethodsWe first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls. We fitted a logistic mixed model to calculate the variance explained by the PRS using pseudo-R2 statistics.ResultsWe show that the PRS explains more of the variance in idiopathic generalized epilepsy than in patients with nonacquired focal epilepsy. We also demonstrate that the variance explained is different within each epilepsy subtype.ConclusionsGlobally, we support the notion that PRSs provide a reliable measure to rightfully estimate the contribution of genetic factors to the pathophysiologic mechanism of epilepsies, but further studies are needed on PRSs before they can be used clinically.

scholarly journals Polygenic risk scores of several subtypes of epilepsies in a founder population

2019 ◽  
Author(s):  
Claudia Moreau ◽  
Rose-Marie Rébillard ◽  
Stefan Wolking ◽  
Jacques Michaud ◽  
Frédérique Tremblay ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Random Effect ◽  
Area Under The Curve ◽  
Risk Scores ◽  
Pathophysiological Mechanism ◽  
Founder Population ◽  
French Canadian ◽  
Pairwise Identity ◽  
Polygenic Risk ◽  
Genetic Mechanisms

ABSTRACTImportanceEpilepsy is defined as a group of neurological disorders characterized by epileptic seizures, brief episodes of symptoms that are caused by abnormal or excessive neuronal activity in the brain. Epilepsy affects around 3 percent of individuals. In the past 10 years, many groups have been working to better understand the complex genetic mechanisms underlying epilepsy. Together, they studied many different genetic mechanisms, but there is still a substantial missing heritability component in epilepsy genetics.ObjectiveHere, we used polygenic risk scores (PRS) to quantify the cumulative effects of a number of variants, which may individually have a very small effect on susceptibility.DesignWe calculated PRS in 522 French-Canadian epilepsy patients divided into seven subtypes and French-Canadian controls.SettingAll study participants (cases and controls) were selected based on their French-Canadian ancestry.ParticipantsThe epilepsy cohort was composed of families of at least three affected individuals with Idiopathic Generalized Epilepsy (IGE) or Non-acquired Focal Epilepsy (NAFE) previously collected and diagnosed by neurologists following the International League Against Epilepsy (ILAE) criteria.ExposuresAll samples were processed on a common genotyping array.Main outcomes and ResultsWe show that the area under the curve (AUC) is almost always slightly greater than 0.5, especially in patients with IGE and subtypes. We also looked at the association of the PRS with the different phenotypes using a linear mixed effects model estimated by generalized estimating equation (GEE) with the pairwise identity-by-descent (IBD) matrix as a random effect. P-values of GEE were consistent with AUC calculations.Conclusions and RelevanceGlobally, we support the notion that PRS and SNP-based heritability provide reliable measures to rightfully estimate the contribution of genetic factors to the pathophysiological mechanism of epilepsies, but further studies are needed on PRS before they can be used clinically.

CORTICAL EXCITABILITY AND REFRACTORY EPILEPSY: A THREE-YEAR LONGITUDINAL TRANSCRANIAL MAGNETIC STIMULATION STUDY

2012 ◽  
Vol 23 (01) ◽  
pp. 1250030 ◽  
Author(s):  
RADWA A. B. BADAWY ◽  
GRAEME D. JACKSON ◽  
SAMUEL F. BERKOVIC ◽  
RICHARD A. L. MACDONELL
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Refractory Epilepsy ◽  
Cortical Excitability ◽  
Focal Epilepsy ◽  
Idiopathic Generalized Epilepsy ◽  
Generalized Epilepsy ◽  
Effective Medication ◽  
Over Time

Transcranial magnetic stimulation was used to study the effect of recurrent seizures on cortical excitability over time in epilepsy. 77 patients with firm diagnoses of idiopathic generalized epilepsy (IGE) or focal epilepsy were repeatedly evaluated over three years. At onset, all groups had increased cortical excitability. At the end of follow-up the refractory group was associated with a broad increase in cortical excitability. Conversely, cortical excitability decreased in all seizure free groups after introduction of an effective medication.

scholarly journals Jumping to conclusions, general intelligence, and psychosis liability: findings from the multi-centre EU-GEI case-control study

2020 ◽  
pp. 1-11 ◽  
Author(s):  
Giada Tripoli ◽  
Diego Quattrone ◽  
Laura Ferraro ◽  
Charlotte Gayer-Anderson ◽  
Victoria Rodriguez ◽  
...  
Keyword(s):  
Cognitive Biases ◽  
Population Based ◽  
Case Control ◽  
Risk Scores ◽  
First Episode ◽  
Polygenic Risk Score ◽  
General Intelligence ◽  
Polygenic Risk ◽  
Jumping To Conclusions ◽  
Episode Psychosis

Abstract Background The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. Methods A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. Results The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients. Conclusions Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

scholarly journals Efficacy of Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Is it the Stimulation or Medication?

2017 ◽  
Vol 44 (5) ◽  
pp. 532-537 ◽  
Author(s):  
Jaylynn Arcand ◽  
Karen Waterhouse ◽  
Lizbeth Hernandez-Ronquillo ◽  
Aleksander Vitali ◽  
Jose F. Tellez-Zenteno
Keyword(s):  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Drug Resistant ◽  
Idiopathic Generalized Epilepsy ◽  
Drug Resistant Epilepsy ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy ◽  
Seizure Classification

AbstractBackground: Vagus nerve stimulation (VNS) therapy has been widely recognized as an alternative for the treatment of drug-resistant epilepsy, although modification of antiepileptic drugs (AEDs) during VNS treatment could explain the improvement in patients. Methods: We retrospectively assessed the efficacy of VNS in 30 adult patients with epilepsy treated with >6 months of follow-up. The criteria for implantation were the following: (1) not a candidate for resective epilepsy surgery, (2) drug-resistant epilepsy, (3) impairment of quality of life, (4) no other option of treatment, and (5) patients with idiopathic generalized epilepsy who fail to be controlled with appropriate AEDs. We assessed sociodemographics, seizure etiology, seizure classification, and AEDs used during treatment with VNS. We assessed adverse effects and efficacy. Responder rate was defined as >50% seizure improvement from baseline. Results: Thirty patients (females, 18; males, 12; age, 35.1±13.3 years) were included. After 6, 12, 24, and 36 months of follow-up, the response rates were: 13/30 (43%), 13/27 (48%), 9/22 (41%), and 8/16 (50%), respectively; none was seizure free. Fifty-seven percent, 33%, 59%, and 81% of patients had changes of medication type or dose at 6, 12, 24, and 36 months respectively. In the majority of patients, the change of medication consisted of an increase in the dose of AEDs. Conclusions: Our study shows that VNS is an effective therapy, although significant changes in medications were done along with the therapy; therefore, the real effect of VNS could be controversial.

scholarly journals Patterns of depressive symptoms in epilepsy

2013 ◽  
Vol 71 (4) ◽  
pp. 213-215
Author(s):  
Nikolaos I. Triantafyllou ◽  
Stergios Gatzonis ◽  
Evangelia Kararizou ◽  
Charalampos C. Papageorgiou
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Focal Epilepsy ◽  
Self Rating ◽  
Increasing Trend ◽  
Epileptic Patients ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy

Objective: The purpose of this study was to determine the nature and extent of depressive symptoms among patients with epilepsy. Methods: Ninety patients were investigated over a three-month period: 42 were suffering from generalized epilepsy, 29 from focal epilepsy and 19 from undetermined epilepsy. All completed the Zung self-rating scale for assessment of the depressive symptoms. Results: Sixty-seven patients felt stigmatized because of epilepsy (67%): 73.6% in the undetermined epilepsy group, 55.1% in the focal epilepsy group and 88% in the generalized epilepsy group. Moreover, among the 90 epileptic patients studied, symptoms of irritability, indecisiveness, personal devaluation and emptiness showed a constant increasing trend for their presence from the undetermined epilepsy group through the generalized epilepsy group to the focal epilepsy group. Conclusions: These findings indicate that although the focal epilepsy patients felt less stigmatized, they did not differ greatly in terms of depressive symptoms, in relation to the undetermined epilepsy and generalized epilepsy patients.

scholarly journals Estimating prevalence of human traits among populations from polygenic risk scores

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Britney E. Graham ◽  
Brian Plotkin ◽  
Louis Muglia ◽  
Jason H. Moore ◽  
Scott M. Williams
Keyword(s):  
Phenotypic Variation ◽  
Significant Proportion ◽  
Population Level ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Diverse Populations ◽  
Polygenic Risk ◽  
Risk Variants ◽  
Complex Architecture ◽  
Variance Explained

AbstractThe genetic basis of phenotypic variation across populations has not been well explained for most traits. Several factors may cause disparities, from variation in environments to divergent population genetic structure. We hypothesized that a population-level polygenic risk score (PRS) can explain phenotypic variation among geographic populations based solely on risk allele frequencies. We applied a population-specific PRS (psPRS) to 26 populations from the 1000 Genomes to four phenotypes: lactase persistence (LP), melanoma, multiple sclerosis (MS) and height. Our models assumed additive genetic architecture among the polymorphisms in the psPRSs, as is convention. Linear psPRSs explained a significant proportion of trait variance ranging from 0.32 for height in men to 0.88 for melanoma. The best models for LP and height were linear, while those for melanoma and MS were nonlinear. As not all variants in a PRS may confer similar, or even any, risk among diverse populations, we also filtered out SNPs to assess whether variance explained was improved using psPRSs with fewer SNPs. Variance explained usually improved with fewer SNPs in the psPRS and was as high as 0.99 for height in men using only 548 of the initial 4208 SNPs. That reducing SNPs improves psPRSs performance may indicate that missing heritability is partially due to complex architecture that does not mandate additivity, undiscovered variants or spurious associations in the databases. We demonstrated that PRS-based analyses can be used across diverse populations and phenotypes for population prediction and that these comparisons can identify the universal risk variants.

scholarly journals Two schizophrenia imaging signatures and their associations with cognition, psychopathology, and genetics in the general population

2022 ◽  
Author(s):  
Ganesh B Chand ◽  
Pankhuri Singhal ◽  
Dominic B Dwyer ◽  
Junhao Wen ◽  
Guray Erus ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Gray Matter Volume ◽  
Control Sample ◽  
Population Level ◽  
Population Based ◽  
Risk Scores ◽  
Support Vector ◽  
Cross Sectional ◽  
Polygenic Risk ◽  
Independent Population

The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume, and signature 2 with increased striatal volume, could be replicated in an independent schizophrenia sample, and investigate whether expression of these signatures can be detected at the population-level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. This cross-sectional study used an independent schizophrenia-control sample (n=347; age 16-57 years) for replication of imaging signatures, and then examined two independent population-level datasets: Philadelphia Neurodevelopmental Cohort [PNC; n=359 typically developing (TD) and psychosis-spectrum symptoms (PS) youth] and UK Biobank (UKBB; n=836; age 44-50 years) adults. We quantified signature expression using support-vector machine learning, and compared cognition, psychopathology, and polygenic risk between signatures. Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youth with PS than TD youth, whereas signature 2 frequency was similar. In both youth and adults, signature 1 had worse cognitive performance than signature 2. Compared to adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. We successfully replicate two neuroanatomical signatures of schizophrenia, and describe their prevalence in population-based samples of youth and adults. We further demonstrate distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

scholarly journals Cannabis Treatment in Children with Epilepsy: Practices of Canadian Neurologists

2020 ◽  
Vol 47 (4) ◽  
pp. 511-518 ◽  
Author(s):  
Stephanie M. DeGasperis ◽  
Richard Webster ◽  
Daniela Pohl
Keyword(s):  
Online Survey ◽  
Focal Epilepsy ◽  
Poor Quality ◽  
Dravet Syndrome ◽  
Pediatric Epilepsy ◽  
Medical Cannabis ◽  
Idiopathic Generalized Epilepsy ◽  
Community Based ◽  
Drug Resistant Epilepsy ◽  
Generalized Epilepsy

ABSTRACT:Background:Medical cannabis has recently emerged as a treatment option for children with drug-resistant epilepsy. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about the attitudes of neurologists toward cannabinoid treatment of children with epilepsy.Methods:A 21-item online survey was distributed via email to 148 pediatric neurologists working in hospitals and community clinics across Canada. Questions were related to clinical practice and demographics.Results:This survey achieved a response rate of 38% (56 Canadian neurologists). These neurologists were treating 668 pediatric epilepsy patients with cannabinoids. While 29% of neurologists did not support cannabis treatment in their patients, 34% prescribed cannabis, and 38% referred to another authorizing physician, mostly to community-based non-neurologists. The majority of neurologists considered cannabis for patients with Dravet syndrome (68%) and Lennox–Gastaut syndrome (64%) after an average of three failed anticonvulsants. Twenty-seven percent considered it for patients with idiopathic generalized epilepsy, and 18% for focal epilepsy. No neurologist used cannabis as a first-line treatment. All neurologists had at least one hesitation regarding cannabis treatment in pediatric epilepsy. The most common one was poor evidence (66%), followed by poor quality control (52%) and high cost (50%).Conclusions:The majority of Canadian pediatric neurologists consider using cannabis as a treatment for epilepsy in children. With many gaps in evidence and high patient-driven demand for cannabis therapy, this survey provides immediate information from the “wisdom of the crowd,” to aid neurologists until further evidence is available.

scholarly journals Seizure Exacerbation and Developmental Regression with Carbamazepine

1998 ◽  
Vol 25 (4) ◽  
pp. 287-294 ◽  
Author(s):  
A.N. Prasad ◽  
M. Stefanelli ◽  
L Nagarajan
Keyword(s):  
Seizure Control ◽  
Tertiary Care ◽  
Dramatic Improvement ◽  
Idiopathic Generalized Epilepsy ◽  
Careful Patient ◽  
Developmental Regression ◽  
Group I ◽  
Neurological Exam ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy

ABSTRACT:Background:Unexpected exacerbation of seizures may occur following initiation of treatment with carbamazepine (CBZ). We reviewed the occurrence of such reactions in our patient population at a tertiary care children's hospital.Methods:A retrospective analysis of our clinic database identified 129/691 (18.6%) patients with epilepsy treated with CBZ, as monotherapy. 38/129 children were later switched to another drug. In 11/38 (28.5 %) clinical and/or EEG deterioration was observed. Two patients identified at another institution with similar exacerbation were also included in our analysis. We report on the findings in these 13 cases.Results:Two groups were identified: Group I - 6 patients with normal neurological exam, normal EEG background, and a diagnosis of idiopathic generalized epilepsy. Group II - 7 patients with an abnormal neurological exam and/or abnormal EEG background. Following introduction of CBZ therapy, worsening of preexisting seizures, appearance of new seizure types, behavioral regression, and accompanying EEG deterioration were reported in both groups. Dramatic improvement in seizure control occurred, following withdrawal of CBZ and substitution of another anticonvulsant.Conclusion:Physicians treating epilepsy must be aware that CBZ can exacerbate seizures, and cause developmental regression in children. Careful patient selection, when choosing CBZ as treatment, and prompt recognition of clinical deterioration and intervention, may help avoid or reverse these paradoxical reactions.

Electroencephalography: Evaluation of Neurologic Disorders

2021 ◽  
pp. 255-263
Author(s):  
David B. Burkholder ◽  
Jeffrey W. Britton
Keyword(s):  
Brain Death ◽  
Slow Wave ◽  
Focal Epilepsy ◽  
Focal Lesions ◽  
Steep Ascent ◽  
Sharp Waves ◽  
Epileptiform Discharges ◽  
Neurologic Disorders ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy

Electroencephalography (EEG) is a useful diagnostic and prognostic tool for evaluation of patients with epilepsy, encephalopathy, focal lesions, coma, or brain death. The 3 main types of epileptiform discharges are spikes, sharp waves, and spike-and-wave discharges. Spikes have a steep ascent and descent and are brief (duration ≤70 milliseconds). Sharp waves, in contrast, are longer (70-200 milliseconds). Spike-and-wave discharges consist of a spike followed by an after-coming slow wave. All the discharges may occur singly or in trains, and any may be present in either focal epilepsy or generalized epilepsy.

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