Unilateral thalamic lesion mimicking genetic generalized epilepsy.
Ontology highlight
ABSTRACT:
SUBMITTER: Kulick-Soper CV
PROVIDER: S-EPMC8327384 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Unilateral thalamic lesion mimicking genetic generalized epilepsy.
Kulick-Soper Catherine V CV Stein Joel M JM Chen Isaac H IH Ellis Colin A CA Davis Kathryn A KA
Epileptic disorders : international epilepsy journal with videotape 20201201 6
Similar Datasets
Project description:ObjectiveSome patients with genetic generalized epilepsy (GGE) may present with ambiguous and atypical findings and even focal brain abnormalities. Correct diagnosis may therefore be difficult.MethodsWe retrospectively collected six patients investigated on the epilepsy monitoring unit with MRI abnormalities mimicking focal cortical dysplasia (FCD-like) or heterotopias, but with semiology and EEG features of GGE. We compared them to four additional patients with GGE and nonmigratory abnormalities.ResultsAll six patients presented with frontal MRI lesions: radial ("transmantle," n = 4), cortical-subcortical (n = 1), and periventricular heterotopia (n = 1). Five had positive family histories. Semiologic lateralizing signs compatible with the lesion were seen in four. Five patients had 3/s spike-wave complexes, with an asymmetric appearance in three. Regional EEG changes matched with the side of the abnormality in three patients. Invasive EEG (n = 2) or postoperative outcomes (n = 3) argued against an ictogenic role of the MRI abnormalities. Histology showed mild malformation of cortical development, but no focal cortical dysplasia. The six patients were finally diagnosed with juvenile myoclonic epilepsy (n = 2), juvenile absence epilepsy (n = 2), or GGE not further specified (nfs, n = 2). Compared to these patients, the other four (final diagnoses: childhood absence epilepsy, n = 1; perioral myoclonia with absences, n = 1; and GGE nfs, n = 2) had no lateralizing EEG findings.SignificancePatients with GGE may have coincidental MRI abnormalities. These cases are challenging as frontal epilepsy and GGE can present with similar semiologies. GGE with coincidental FCD-like lesions/heterotopias is in particular difficult to diagnose as patients have more lateralizing features (in semiology and EEG) than those with tumors. A detailed noninvasive presurgical evaluation may be justified. We point out red flags that may help to distinguish GGE from frontal epilepsy, even in the presence of brain abnormalities: 3/s spike waves (even if asymmetric), changing lateralizing signs at different times, and a positive family history hinting at GGE.
| S-EPMC7278548 | biostudies-literature
Project description:Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20-30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.
| S-EPMC9381751 | biostudies-literature
Project description:Epilepsy has been extensively studied as a common neurological disease. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs for treatment. However, the features of current epilepsy models cannot fully mimic different types of epilepsy in humans, hence non-human primate models of epilepsy are required. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we present a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operations in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that the epileptic phenotype can be inherited. These marmosets were more sensitive to the epilepsy inducers pentylenetetrazol. Using electrocorticogram (ECoG) recordings, we detected epileptiform discharge in marmosets with a history of seizures. In summary, we report a family of marmosets with generalized seizures induced by handling operations. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.
| S-EPMC8832845 | biostudies-literature
Project description:ObjectiveTo investigate the electroclinical characteristics and the prognostic impact of generalized fast discharges in a large cohort of genetic generalized epilepsy (GGE) patients studied with 24-h prolonged ambulatory electroencephalography (paEEG).MethodsThis retrospective multicenter cohort study included 202 GGE patients. The occurrence of generalized paroxysmal fast activity (GPFA) and generalized polyspike train (GPT) was reviewed. GGE patients were classified as having idiopathic generalized epilepsy (IGE) or another GGE syndrome (namely perioral myoclonia with absences, eyelid myoclonia with absences, epilepsy with myoclonic absences, generalized epilepsy with febrile seizures plus, or GGE without a specific epilepsy syndrome) according to recent classification proposals.ResultsGPFA/GPT was found in overall 25 (12.4%) patients, though it was significantly less frequent in IGE compared with other GGE syndromes (9.3 vs. 25%, p = 0.007). GPFA/GPT was found independently of seizure type experienced during history, the presence of mild intellectual disability/borderline intellectual functioning, or EEG features. At multivariable analysis, GPFA/GPT was significantly associated with drug resistance (p = 0.04) and with a higher number of antiseizure medications (ASMs) at the time of paEEG (p < 0.001) and at the last medical observation (p < 0.001). Similarly, GPFA/GPT, frequent/abundant generalized spike-wave discharges during sleep, and a higher number of seizure types during history were the only factors independently associated with a lower chance of achieving 2-year seizure remission at the last medical observation. Additionally, a greater number of GPFA/GPT discharges significantly discriminated between patients who achieved 2-year seizure remission at the last medical observation and those who did not (area under the curve = 0.77, 95% confidence interval 0.57-0.97, p = 0.02).ConclusionWe found that generalized fast discharges were more common than expected in GGE patients when considering the entire GGE spectrum. In addition, our study highlighted that GPFA/GPT could be found along the entire GGE continuum, though their occurrence was more common in less benign GGE syndromes. Finally, we confirmed that GPFA/GPT was associated with difficult-to-treat GGE, as evidenced by the multivariable analysis and the higher ASM load during history.
| S-EPMC8960043 | biostudies-literature
Project description:ObjectiveParoxysmal 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.MethodsConfounding 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.ResultsOur 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.SignificanceOur 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.
| S-EPMC8672363 | biostudies-literature
Project description:Altered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication.
| S-EPMC6796782 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment.MethodsThe baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified.ResultsTwenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy.SignificanceThis case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.
| S-EPMC8483259 | biostudies-literature
Project description:Genetic generalized epilepsy (GGE) including childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy (JME), and GGE with tonic-clonic seizures (TCS) (GGE-TCS), is genetically influenced with a two- to four- fold increased risk in the first-degree relatives of patients. Since large families with GGE are very rare, international studies have focused on sporadic GGE patients using whole exome sequencing, suggesting that GGE are highly genetically heterogeneous and rather involve rare or ultra-rare variants. Moreover, a polygenic mode of inheritance is suspected in most cases. We performed SNP microarrays and whole exome sequencing in 20 families from Sudan, focusing on those with at least four affected members. Standard genetic filters and Endeavour algorithm for functional prioritization of genes selected likely susceptibility variants in FAT1, DCHS1 or ASTN2 genes. FAT1 and DCHS1 are adhesion transmembrane proteins interacting during brain development, while ASTN2 is involved in dendrite development. Our approach on familial forms of GGE is complementary to large-scale collaborative consortia studies of sporadic cases. Our study reinforces the hypothesis that GGE is genetically heterogeneous, even in a relatively limited geographic area, and mainly oligogenic, as supported by the low familial penetrance of GGE and by the Bayesian algorithm that we developed in a large pedigree with JME. Since populations with founder effect and endogamy are appropriate to study autosomal recessive pathologies, they would be also adapted to decipher genetic components of complex diseases, using the reported bayesian model.
| S-EPMC11583555 | biostudies-literature
Project description:Background: Distal 7q11.23 deletions are variably associated with epilepsy, intellectual disability and neurobehavioural abnormalities. The relative importance of different genes in this region in contributing to different phenotypes is not clear, though HIP1 and YWHAG are both thought to play important roles. Patients and Methods: We performed thorough phenotyping on members of a family in which multiple members carried a relatively small 0.8 Mb distal 7q11.23 deletion, affecting 17 genes. Results: Two brothers and a half-brother had all inherited the 7q11.23 deletion from their mother. The eldest two both had global developmental impairment and genetic generalized epilepsy, involving absence, myoclonic or myoclonic-atonic seizures. There was no history of seizures in the mother or her youngest son, but both also had developmental impairment. Conclusion: Distal 7q11.23 deletions affecting HIP1 and YWHAG may cause developmental impairment and genetic generalized epilepsy, with considerable intrafamilial phenotypic variability.
| S-EPMC9036355 | biostudies-literature
Project description:ObjectiveWe studied the frequency of auras in generalized epilepsy (GE) using a detailed semistructured diagnostic interview.MethodsIn this cross-sectional study, participants with GE were drawn from the Epilepsy Phenome/Genome Project (EPGP). Responses to the standardized diagnostic interview regarding tonic-clonic (grand mal) seizures were then examined. This questionnaire initially required participants to provide their own description of any subjective phenomena before their "grand mal seizures." Participants who provided answers to these questions were considered to have an aura. All participants were then systematically queried regarding a list of specific symptoms occurring before grand mal seizures, using structured (closed-ended) questions.ResultsSeven hundred ninety-eight participants with GE were identified, of whom 530 reported grand mal seizures. Of these, 112 (21.3%) reported auras in response to the open-ended question. Analysis of responses to the closed-ended questions suggested that 341 participants (64.3%) experienced at least one form of aura.ConclusionsAuras typically associated with focal epilepsy were reported by a substantial proportion of EPGP subjects with GE. This finding may support existing theories of cortical and subcortical generators of GE with variable spread patterns. Differences between responses to the open-ended question and closed-ended questions may also reflect clinically relevant variation in patient responses to history-taking and surveys. Open-ended questions may underestimate the prevalence of specific types of auras and may be in part responsible for the underrecognition of auras in GE. In addition, structured questions may influence participants, possibly leading to a greater representation of symptoms.
| S-EPMC4206156 | biostudies-literature