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Samuel F Berkovic - One of the best experts on this subject based on the ideXlab platform.
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the severe Epilepsy Syndromes of infancy a population based study
Epilepsia, 2021Co-Authors: Katherine B Howell, Jeremy L Freeman, Mark T Mackay, Michael C Fahey, John S Archer, Samuel F Berkovic, Eunice ChanAbstract:OBJECTIVE: To study the Epilepsy Syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy Epilepsy Syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for Epilepsy Syndromes at presentation, and 16 (14%) had "variants" of Epilepsy Syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" Epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common Syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of Epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" Epilepsy (100%), unifocal Epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal Epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an Epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing Epilepsy Syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.
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inherited rorb pathogenic variants overlap of photosensitive genetic generalized and occipital lobe Epilepsy
Epilepsia, 2020Co-Authors: Lynette G Sadleir, Samuel F Berkovic, Guillem De Vallesibanez, Chontelle King, Matthew Coleman, Stuart Mossman, Sarah Paterson, John Nguyen, Saul A Mullen, Melanie BahloAbstract:Variants in RORB have been reported in eight individuals with Epilepsy, with phenotypes ranging from eyelid myoclonia with absence Epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three Epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital Epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and Epilepsy Syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with Epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital Epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of Epilepsy Syndromes.
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inherited rorb pathogenic variants overlap of photosensitive genetic generalized and occipital lobe Epilepsy
Epilepsia, 2020Co-Authors: Lynette G Sadleir, Samuel F Berkovic, Guillem De Vallesibanez, Chontelle King, Stuart Mossman, Sarah Paterson, John Nguyen, Saul A Mullen, Matthew J Coleman, Melanie BahloAbstract:Variants in RORB have been reported in eight individuals with Epilepsy, with phenotypes ranging from eyelid myoclonia with absence Epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three Epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital Epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and Epilepsy Syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with Epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital Epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of Epilepsy Syndromes.
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Genetics of Epilepsy Syndromes in families with photosensitivity
Neurology, 2013Co-Authors: Isabella Taylor, Samuel F Berkovic, Ingrid E. SchefferAbstract:Objective: To use family studies to investigate the clinical genetics of photosensitivity to understand the interrelationship of different photosensitive Epilepsy Syndromes. Methods: Twenty-nine families were recruited in which at least 2 members had idiopathic Epilepsy and either clinical or electrical photosensitivity on EEG studies. We performed electroclinical analysis of these individuals and all other affected family members and analyzed the phenotypic patterns in families. Results: An earlier age at seizure onset was observed in photosensitive patients compared with nonphotosensitive individuals. A significant female bias for photosensitivity was confirmed. All subjects with visual seizures were photosensitive. Subjects could be classified into 3 main photosensitive phenotypes: genetic (idiopathic) generalized epilepsies (GGE), idiopathic photosensitive occipital Epilepsy (IPOE), and mixed GGE/IPOE. Within each category, subjects with purely photosensitive seizures were observed. We report a distinctive syndrome of early-onset photosensitive absence Epilepsy, with onset beginning by 4 years of age, which was more refractory than childhood absence Epilepsy. Conclusions: The clinical genetics of the idiopathic photosensitive epilepsies show a phenotypic spectrum from the GGEs to IPOE with overlap between the focal features of IPOE and all the GGE Syndromes. Shared genetic determinants are likely to contribute to the complex inheritance pattern of photosensitivity, IPOE, and the GGEs.
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genetic association studies in Epilepsy the truth is out there
Epilepsia, 2004Co-Authors: John C Mulley, Samuel F BerkovicAbstract:Summary: Success has been achieved in identifying many mutations in rare monogenic Epilepsy Syndromes by using linkage analysis, but dissecting the genetic basis of common Epilepsy Syndromes has proven more difficult. Common epilepsies are genetically complex disorders believed to be influenced by variation in several susceptibility genes. Association studies can theoretically identify these genes, but despite more than 50 association studies in Epilepsy, no consistent or convincing susceptibility genes have emerged, leading to scepticism about the association-study approach. We review the results of existing association studies in focal epilepsies, generalized epilepsies, febrile seizures, and Epilepsy pharmacogenetics. By using an illustrative example, we discuss how methodologic issues of sample size, selection of appropriate controls, population stratification, and significance thresholds can lead to bias and false-positive associations; the importance of biologic plausibility also is emphasized. Newer methodologic refinements for association studies, such as use of two control groups, genomic control, haplotyping, and use of two independent datasets, are discussed. A summary of existing guidelines and a checklist for planning and appraising such association studies in Epilepsy is presented. We remain cautiously optimistic that with methodologic refinements and multicenter collaborations with large sample sizes, association studies will ultimately be useful in dissecting the genetic basis of common Epilepsy Syndromes.
Akshara R Balachandra - One of the best experts on this subject based on the ideXlab platform.
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white matter abnormalities across different Epilepsy Syndromes in adults an enigma Epilepsy study
Brain, 2020Co-Authors: Sean N Hatton, Khoa H Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K M Alvim, Akshara R BalachandraAbstract:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common Epilepsy Syndromes, including temporal lobe Epilepsy, extratemporal Epilepsy, and genetic generalized Epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within Syndromes in a multicentre sample of adult Epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe Epilepsy with hippocampal sclerosis (n = 599), temporal lobe Epilepsy with normal MRI (n = 275), genetic generalized Epilepsy (n = 182) and non-lesional extratemporal Epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each Epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across ‘all epilepsies’ lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe Epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of Epilepsy. Overall, patients with Epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across Epilepsy Syndromes. These data further define the spectrum of white matter abnormalities in common Epilepsy Syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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white matter abnormalities across different Epilepsy Syndromes in adults an enigma Epilepsy study
bioRxiv, 2019Co-Authors: Sean N Hatton, Khoa H Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Akshara R Balachandra, Marina M K Alvim, Nuria Bargallo, Emanuele BartoliniAbstract:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common Epilepsy Syndromes, including temporal lobe Epilepsy, extratemporal Epilepsy, and genetic generalized Epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within Syndromes in a multicentre sample of adult Epilepsy patients. Diffusion-weighted MRI data were analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe Epilepsy with hippocampal sclerosis (N=599), temporal lobe Epilepsy with normal MRI (N=275), genetic generalized Epilepsy (N=182) and nonlesional extratemporal Epilepsy (N=193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fiber tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each Epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at p
Robert L. Macdonald - One of the best experts on this subject based on the ideXlab platform.
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synaptic clustering differences due to different gabrb3 mutations cause variable Epilepsy Syndromes
Brain, 2019Co-Authors: Yiwu Shi, Qi Zhang, Kefu Cai, Sarah Poliquin, Wangzhen Shen, Nathan Winters, Jie Wang, Robert L. MacdonaldAbstract:GABRB3 is highly expressed early in the developing brain, and its encoded β3 subunit is critical for GABAA receptor assembly and trafficking as well as stem cell differentiation in embryonic brain. To date, over 400 mutations or variants have been identified in GABRB3. Mutations in GABRB3 have been increasingly recognized as a major cause for severe paediatric Epilepsy Syndromes such as Lennox-Gastaut syndrome, Dravet syndrome and infantile spasms with intellectual disability as well as relatively mild Epilepsy Syndromes such as childhood absence Epilepsy. There is no plausible molecular pathology for disease phenotypic heterogeneity. Here we used a very high-throughput flow cytometry assay to evaluate the impact of multiple human mutations in GABRB3 on receptor trafficking. In this study we found that surface expression of mutant β3 subunits is variable. However, it was consistent that surface expression of partnering γ2 subunits was lower when co-expressed with mutant than with wild-type subunits. Because γ2 subunits are critical for synaptic GABAA receptor clustering, this provides an important clue for understanding the pathophysiology of GABRB3 mutations. To validate our findings further, we obtained an in-depth comparison of two novel mutations [GABRB3 (N328D) and GABRB3 (E357K)] associated with Epilepsy with different severities of Epilepsy phenotype. GABRB3 (N328D) is associated with the relatively severe Lennox-Gastaut syndrome, and GABRB3 (E357K) is associated with the relatively mild juvenile absence Epilepsy syndrome. With functional characterizations in both heterologous cells and rodent cortical neurons by patch-clamp recordings, confocal microscopy and immunoblotting, we found that both the GABRB3 (N328D) and GABRB3 (E357K) mutations reduced total subunit expression in neurons but not in HEK293T cells. Both mutant subunits, however, were reduced on the cell surface and in synapses, but the Lennox-Gastaut syndrome mutant β3 (N328D) subunit was more reduced than the juvenile absence Epilepsy mutant β3 (E357K) subunit. Interestingly, both mutant β3 subunits impaired postsynaptic clustering of wild-type GABAA receptor γ2 subunits and prevented γ2 subunits from incorporating into GABAA receptors at synapses, although by different cellular mechanisms. Importantly, wild-type γ2 subunits were reduced and less clustered at inhibitory synapses in Gabrb3+/- knockout mice. This suggests that impaired receptor localization to synapses is a common pathophysiological mechanism for GABRB3 mutations, although the extent of impairment may be different among mutant subunits. The study thus identifies the novel mechanism of impaired targeting of receptors containing mutant β3 subunits and provides critical insights into understanding how GABRB3 mutations produce severe Epilepsy Syndromes and Epilepsy phenotypic heterogeneity.
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a structural look at gabaa receptor mutations linked to Epilepsy Syndromes
Brain Research, 2019Co-Authors: Ciria C. Hernandez, Robert L. MacdonaldAbstract:Understanding the genetic variation in GABAA receptor subunit genes (GABRs), GABRA1-6, GABRB1-3, GABRG1-3 and GABRD, in individuals affected by Epilepsy may improve the diagnosis and treatment of Epilepsy Syndromes through identification of disease-associated variants. However, the lack of functional analysis and validation of many novel and previously reported familial and de novo mutations have made it challenging to address meaningful gene associations with Epilepsy Syndromes. GABAA receptors belong to the Cys-loop receptor family. Even though GABAA receptor mutant residues are widespread among different GABRs, their frequent occurrence in important structural domains that share common functional features suggests associations between structure and function.
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molecular pathogenic basis for gabrg2 mutations associated with a spectrum of Epilepsy Syndromes from generalized absence Epilepsy to dravet syndrome
JAMA Neurology, 2016Co-Authors: Jing-qiong Kang, Robert L. MacdonaldAbstract:Objective In this review article, we focus on the molecular pathogenic basis for genetic generalized epilepsies associated with mutations in the inhibitory γ-aminobutyric acid (GABA A ) receptor γ2 subunit gene, GABRG2 (OMIM137164), an established Epilepsy gene. Observations The γ-aminobutyric acid (GABA A ) receptor γ2 subunit gene, GABRG2 , is abundantly expressed in the mammalian brain, and its encoded γ2 subunit is assembled into αβγ2 receptors, which are the major GABA A receptor isoforms in the brain. The γ2 subunits have a critical role in GABA A receptor trafficking and clustering at synapses. They reside inside the endoplasmic reticulum after synthesis, where they oligomerize with other binding partners, such as α and β subunits, and further assemble into pentameric receptors. Only correctly assembled receptors can traffic beyond the endoplasmic reticulum and reach the cell surface and synapses, where they conduct chloride ion current when activated by GABA. Mutations in GABRG2 have been associated with simple febrile seizures and with genetic Epilepsy Syndromes, including childhood absence Epilepsy, generalized Epilepsy with febrile seizures plus, and Dravet syndrome or severe myoclonic Epilepsy in infancy. The mutations include missense, nonsense, and frameshift mutations, as well as splice-site and deletion mutations. The mutations have been identified in both coding and noncoding sequences like splice sites. In the coding sequence, these mutations are found in multiple locations, including the extracellular N-terminus, transmembrane domains, and transmembrane 3–transmembrane 4 intracellular loop. All of these mutations reduced channel function but to different extents and by diverse mechanisms, including nonsense-mediated messenger RNA decay, endoplasmic reticulum–associated protein degradation, dominant negative suppression of partnering subunits, mutant subunit aggregation causing cell stress and cell death, and gating defects. Conclusions and Relevance We conclude that the Epilepsy phenotypic heterogeneity associated with GABRG2 mutations may be related to the extent of the reduction of GABA A receptor channel function and the differential dominant negative suppression, as well to toxicity related to the metabolism of mutant subunit proteins resulting from each mutant γ2 subunit, in addition to different genetic backgrounds.
Ingrid E. Scheffer - One of the best experts on this subject based on the ideXlab platform.
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Genetics of Epilepsy Syndromes in families with photosensitivity
Neurology, 2013Co-Authors: Isabella Taylor, Samuel F Berkovic, Ingrid E. SchefferAbstract:Objective: To use family studies to investigate the clinical genetics of photosensitivity to understand the interrelationship of different photosensitive Epilepsy Syndromes. Methods: Twenty-nine families were recruited in which at least 2 members had idiopathic Epilepsy and either clinical or electrical photosensitivity on EEG studies. We performed electroclinical analysis of these individuals and all other affected family members and analyzed the phenotypic patterns in families. Results: An earlier age at seizure onset was observed in photosensitive patients compared with nonphotosensitive individuals. A significant female bias for photosensitivity was confirmed. All subjects with visual seizures were photosensitive. Subjects could be classified into 3 main photosensitive phenotypes: genetic (idiopathic) generalized epilepsies (GGE), idiopathic photosensitive occipital Epilepsy (IPOE), and mixed GGE/IPOE. Within each category, subjects with purely photosensitive seizures were observed. We report a distinctive syndrome of early-onset photosensitive absence Epilepsy, with onset beginning by 4 years of age, which was more refractory than childhood absence Epilepsy. Conclusions: The clinical genetics of the idiopathic photosensitive epilepsies show a phenotypic spectrum from the GGEs to IPOE with overlap between the focal features of IPOE and all the GGE Syndromes. Shared genetic determinants are likely to contribute to the complex inheritance pattern of photosensitivity, IPOE, and the GGEs.
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Is the ketogenic diet effective in specific Epilepsy Syndromes
Epilepsy research, 2012Co-Authors: Srishti Nangia, Douglas R. Nordli, Roberto Caraballo, Hoon Chul Kang, Ingrid E. SchefferAbstract:Is the ketogenic diet (KD) more effective in certain Epilepsy Syndromes? The KD has been shown to be effective in treating multiple seizure types and Epilepsy Syndromes. We review the effectiveness of the KD in Dravet syndrome, Epilepsy with myoclonic-atonic seizures, mitochondrial disease, tuberous sclerosis, late infantile and juvenile neuronal ceroid lipofuscinosis, and febrile infection-related Epilepsy syndrome. In certain Epilepsy Syndromes, like Epilepsy with myoclonic-atonic seizures, the diet should be considered early in the course of treatment.
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the health related quality of life of childhood Epilepsy Syndromes
Journal of Paediatrics and Child Health, 2003Co-Authors: Mark Sabaz, Ingrid E. Scheffer, David Cairns, Andrew Bleasel, John A Lawson, Bronwyn E Grinton, Ann M E ByeAbstract:Objective: There is increasing awareness of the importance of assessing physical, psychological, social and behavioural well-being in chronic disease. The aim of this study was to examine the health-related quality of life (HRQoL) of children with common Epilepsy Syndromes and to explore if there are HRQoL differences between those Syndromes. Methods: Each child had their Epilepsy syndrome defined according to the International League Against Epilepsy classification. Epilepsy Syndromes included symptomatic frontal, temporal, parietal/occipital lobe and partial unlocalized Epilepsy, and two idiopathic epilepsies, childhood absence Epilepsy (CAE) and benign rolandic Epilepsy (BRE). Seizure semiology and ictal/interictal electroencephalogram (EEG) were determined for symptomatic partial Epilepsy Syndromes by video-EEG monitoring. HRQoL was evaluated with an Epilepsy-specific instrument, the Quality of Life in Childhood Epilepsy Questionnaire, and two generic instruments, the Child Health Questionnaire and Child Behavior Checklist. Results: Children with symptomatic partial Epilepsy Syndromes were affected by Epilepsy in a similar way and did not have unique HRQoL profiles. However, these children had significantly lower HRQoL scores compared to those with CAE or BRE. All children with Epilepsy regardless of syndrome had a higher frequency of behavioural problems compared to normative data. Conclusion: These results indicate that children with Epilepsy regardless of syndrome require evaluation of the psychosocial implications. There is a greater impact on HRQoL in symptomatic Epilepsy compared to idiopathic Epilepsy. Specific symptomatic partial Syndromes did not differ in the degree they affect HRQoL. These findings have important implications for clinicians caring for children with Epilepsy.
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chromosomal abnormalities and Epilepsy a review for clinicians and gene hunters
Epilepsia, 2002Co-Authors: Ingrid E. Scheffer, Samuel F Berkovic, Rita Singh, R Mckinlay J Gardner, Kathryn M CrosslandAbstract:Summary: Purpose: We analyzed databases on chromosomal anomalies and Epilepsy to identify chromosomal regions where abnormalities are associated with clinically recognizable Epilepsy Syndromes. The expectation was that these regions could then be offered as targets in the search for Epilepsy genes. Methods: The cytogenetic program of the Oxford Medical Database, and the PubMed database were used to identify chromosomal aberrations associated with seizures and/or EEG abnormalities. The literature on selected small anomalies thus identified was reviewed from a clinical and electroencephalographic viewpoint, to classify the seizures and Syndromes according to the current International League Against Epilepsy (ILAE) classification. Results: There were 400 different chromosomal imbalances described with seizures or EEG abnormalities. Eight chromosomal disorders had a high association with Epilepsy. These comprised: the Wolf–Hirschhorn (4p-) syndrome, Miller–Dieker syndrome (del 17p13.3), Angelman syndrome (del 15q11-q13), the inversion duplication 15 syndrome, terminal deletions of chromosome 1q and 1p, and ring chromosomes 14 and 20. Many other segments had a weaker association with seizures. The poor quality of description of the epileptology in many reports thwarted an attempt to make precise karyotype–phenotype correlations. Conclusions: We identified certain chromosomal regions where aberrations had an evident association with seizures, and these regions may be useful targets for gene hunters. New correlations with specific Epilepsy Syndromes were not revealed. Clinicians should continue to search for small chromosomal abnormalities associated with specific Epilepsy Syndromes that could provide important clues for finding Epilepsy genes, and the epileptology should be rigorously characterized.
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febrile seizures genetics and relationship to other Epilepsy Syndromes
Current Opinion in Neurology, 1998Co-Authors: Samuel F Berkovic, Ingrid E. SchefferAbstract:The relationship between febrile seizures and Epilepsy has long been debated. We argue that there is some specificity to the types of Epilepsy that follow febrile seizures, rather than febrile seizures being a nonspecific marker of a lowered seizure threshold. The relationship between febrile seizures and later Epilepsy is frequently genetic. Recent clinical and molecular genetic studies suggest that there are a number of syndrome‐specific genes for febrile seizures. Curr Opin Neurol 11:129-134. © 1998 Rapid Science Ltd
Saud Alhusaini - One of the best experts on this subject based on the ideXlab platform.
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white matter abnormalities across different Epilepsy Syndromes in adults an enigma Epilepsy study
Brain, 2020Co-Authors: Sean N Hatton, Khoa H Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K M Alvim, Akshara R BalachandraAbstract:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common Epilepsy Syndromes, including temporal lobe Epilepsy, extratemporal Epilepsy, and genetic generalized Epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within Syndromes in a multicentre sample of adult Epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe Epilepsy with hippocampal sclerosis (n = 599), temporal lobe Epilepsy with normal MRI (n = 275), genetic generalized Epilepsy (n = 182) and non-lesional extratemporal Epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each Epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across ‘all epilepsies’ lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe Epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of Epilepsy. Overall, patients with Epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across Epilepsy Syndromes. These data further define the spectrum of white matter abnormalities in common Epilepsy Syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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white matter abnormalities across different Epilepsy Syndromes in adults an enigma Epilepsy study
bioRxiv, 2019Co-Authors: Sean N Hatton, Khoa H Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Akshara R Balachandra, Marina M K Alvim, Nuria Bargallo, Emanuele BartoliniAbstract:The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common Epilepsy Syndromes, including temporal lobe Epilepsy, extratemporal Epilepsy, and genetic generalized Epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within Syndromes in a multicentre sample of adult Epilepsy patients. Diffusion-weighted MRI data were analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe Epilepsy with hippocampal sclerosis (N=599), temporal lobe Epilepsy with normal MRI (N=275), genetic generalized Epilepsy (N=182) and nonlesional extratemporal Epilepsy (N=193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fiber tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each Epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at p