RESUMO
OBJECTIVE: To evaluate the experience of prescribing phenosanic acid in the practice of a neurologist/epileptologist when prescribing the second, third anticonvulsant drug (AED) as part of combination therapy for patients with manifestations of fatigue due to epilepsy. MATERIAL AND METHODS: 501 patients with focal epilepsy accompanied by asthenic disorders were included in the observational program. The observation program protocol included 5 visits, including visit 1, at which screening and inclusion in the OP took place. The observation period was 10 months. At baseline and at the end of the 10-month follow-up, the patients' condition was assessed according to the following indicators: frequency and transformation of attacks with focal onset, severity of fatigue (self-assessment scale MFI-20); quality of life (questionnaire QoLiE-10-P); frequency of attacks with focal onset. The safety of phenosanic acid (Dibufelon) was also assessed. RESULTS: In 10 months after the inclusion of Dibufelon as the 2nd, 3rd AED in the treatment regimen, a statistically significant (p<0.01) decrease in the frequency of seizures was observed: in general - in 88% of patients; by 50% or more - in 76% of patients; transition from the group with a large number of seizures to the group with a smaller number of seizures - 74% of patients. Also when taking phenosanic acid, a positive dynamics of seizure type was noted: a reliable decrease in the proportion of patients with seizures with secondary generalization from 70% to 56%; a decrease in the number of focal seizures with impaired consciousness from 65% to 53%. In addition, there was a 38% decrease in the severity of fatigue on the MFI-20 scale (the greatest decrease on the «Mental fatigue¼ scale), improvement in the quality of life - a 2.7-fold increase in the mean values of the QOLIE-10 questionnaire. CONCLUSION: The addition of phenosanic acid to antiepileptic therapy as a second or third AED allows for better control of seizures, leading to a decrease the frequency and severity of attacks and the severity of fatigue both, and an increase of the quality of life of patients with epilepsy.
Assuntos
Anticonvulsivantes , Humanos , Anticonvulsivantes/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Astenia/tratamento farmacológico , Astenia/etiologia , Qualidade de Vida , Adulto Jovem , Epilepsia/tratamento farmacológico , Epilepsia/complicações , Quimioterapia Combinada , Adolescente , Epilepsias Parciais/tratamento farmacológicoRESUMO
AIMS: To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month - 4 years). METHODS: This non-randomized, open-label, and self-controlled real-world study included 105 children (1 month-4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. RESULTS: (1) The 50% response rates at 3, 6, 9, and 12 months of follow-up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure-free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow-up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow-up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). CONCLUSION: Adjunctive lacosamide therapy was effective, safe, and well-tolerated in young Chinese children with focal seizures in this study.
Assuntos
Anticonvulsivantes , Lacosamida , Convulsões , Humanos , Lacosamida/uso terapêutico , Lacosamida/administração & dosagem , Lacosamida/efeitos adversos , Masculino , Feminino , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/administração & dosagem , Lactente , Pré-Escolar , Convulsões/tratamento farmacológico , Resultado do Tratamento , Seguimentos , Quimioterapia Combinada , Epilepsias Parciais/tratamento farmacológicoRESUMO
BACKGROUND: Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. OBJECTIVES: To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. SEARCH METHODS: We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. SELECTION CRITERIA: RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. MAIN RESULTS: We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. AUTHORS' CONCLUSIONS: Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.
Assuntos
Anticonvulsivantes , Carbamatos , Clorofenóis , Epilepsia Resistente a Medicamentos , Quimioterapia Combinada , Epilepsias Parciais , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Carbamatos/uso terapêutico , Carbamatos/efeitos adversos , Clorofenóis/uso terapêutico , Clorofenóis/efeitos adversos , Adulto , Viés , Compostos de Benzil/uso terapêutico , Compostos de Benzil/efeitos adversos , TetrazóisRESUMO
Occipital lobe epilepsy (OLE) is an uncommon type of extratemporal epilepsy constituting roughly 2-13% of symptomatic partial epilepsies and epilepsy surgery cases. Over two-thirds of patients with OLE present with two characteristics: (1) ictal semiology compatible with an occipital seizure focus (e.g., ictal blindness, visual perceptual disturbance, eye blinking, nystagmus), and (2) lateralizing features referable to the posterior cortex (e.g., visual field defects, contralateral head deviation). The remaining one-third of patients present with ≥ 2 seizure types, indicative of spread to other lobes. A common representation of this cortical spread is the altered mental status and generalized tonic-clonic activity seen in patient with OLE. While the key clinical symptoms include visual hallucinations, it may be difficult to elicit on history, especially from children, and are not always present.
Assuntos
Epilepsias Parciais , Procedimentos Neurocirúrgicos , Lobo Occipital , Humanos , Epilepsias Parciais/cirurgia , Lobo Occipital/cirurgia , Procedimentos Neurocirúrgicos/métodos , Convulsões/cirurgia , EletroencefalografiaRESUMO
Children with epilepsy often experience deficits in both executive functioning (EF) and memory. However, how these two domains interact and relate to specific epilepsy types remains unclear. This study compared two groups of children: those with localization-related epilepsy (LRE) and those with genetic generalized epilepsy (GGE). We aimed to understand how performance-based and parent-reported EF differentially contribute to understanding memory function in each group. We examined neuropsychological measures assessing memory and EF in 75 children with LRE and 91 with GGE. Multiple linear regressions explored the impact of EF on memory performance. Performance-based EF scores accounted for greater variance in memory scores than parental EF reports. However, performance-based EF measures explained much more variance in visual memory for LRE than GGE and explained much more variance in verbal memory for the GGE group. Parental reports of EF contributed marginally to understanding variance. These findings suggest differential relationships between EF and memory based on epilepsy type. Performance-based EF measures appear more reliable at understanding memory variance than did parent reports. Our results have potential clinical implications for tailoring neuropsychological assessment and intervention for children with different epilepsy types.
Assuntos
Epilepsia Generalizada , Função Executiva , Memória , Testes Neuropsicológicos , Pais , Humanos , Feminino , Masculino , Função Executiva/fisiologia , Criança , Epilepsia Generalizada/psicologia , Epilepsia Generalizada/fisiopatologia , Pais/psicologia , Adolescente , Memória/fisiologia , Epilepsias Parciais/psicologia , Epilepsias Parciais/fisiopatologia , Transtornos da Memória/psicologiaRESUMO
Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40-200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores > 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy.
Assuntos
Eletrocorticografia , Epilepsias Parciais , Humanos , Epilepsias Parciais/fisiopatologia , Masculino , Feminino , Ritmo Gama/fisiologia , Rede Nervosa/fisiopatologia , Adulto , Adolescente , Eletroencefalografia , Adulto Jovem , Mapeamento Encefálico/métodosRESUMO
OBJECTIVE: Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. MATERIALS AND METHODS: We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. RESULTS: After controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother's education, lower father's and mother's occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father's education, and higher ADI values compared to those who were cognitively intact. CONCLUSION: We provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities.
Assuntos
Epilepsias Parciais , Testes Neuropsicológicos , Determinantes Sociais da Saúde , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Epilepsias Parciais/psicologia , Epilepsias Parciais/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/epidemiologia , Cognição/fisiologia , Características de Residência , Fatores Socioeconômicos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo-electroencephalography (SEEG) is implanted. Although real-world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG-RFTC in real-world research. METHODS: A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post-RFTC outcomes were evaluated using the seizure-free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post-RFTC outcome were considered by comparing different variables. RESULTS: The mean follow-up period was 18.3 months. Eighty-two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure-free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow-up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR-positive is a predictive factor for seizure freedom (p < 0.01) and responders (p < 0.01). Other factors have no predictive value for post-RFTC outcome. INTERPRETATION: SEEG-RFTC is a safe procedure and yields favorable outcomes in numerous cases of focal DRE. The MRI feature and etiology of epilepsy are correlated with the seizure-free rate and response rate. And MRI positivity is the predictor for good RFTC outcome.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Humanos , Masculino , Feminino , Adulto , Epilepsias Parciais/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico , Adulto Jovem , Estudos Retrospectivos , Adolescente , Pessoa de Meia-Idade , Criança , Eletrocoagulação , Eletroencefalografia , Seguimentos , Eletrocorticografia , Resultado do Tratamento , Pré-Escolar , Técnicas EstereotáxicasAssuntos
Epilepsias Parciais , Humanos , Masculino , Epilepsias Parciais/genética , Epilepsias Parciais/fisiopatologia , ATPases Vacuolares Próton-Translocadoras/genética , Convulsões/genética , Convulsões/fisiopatologia , Eletroencefalografia , Feminino , Distrofias Neuroaxonais , Distúrbios do Metabolismo do FerroRESUMO
This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.
Assuntos
Idade de Início , Encéfalo , Epilepsias Parciais , Imageamento por Ressonância Magnética , Humanos , Masculino , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Testes Neuropsicológicos , AdultoRESUMO
A diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 700k Finns and Estonians. We found that a high genetic generalized epilepsy PRS (PRSGGE) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRSGGE standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRSGGE was significantly larger on idiopathic generalized epilepsies, in females and for earlier epilepsy onset. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). Here, we outline the potential of epilepsy specific PRSs to serve as biomarkers after a first seizure event.
Assuntos
Epilepsia Generalizada , Predisposição Genética para Doença , Herança Multifatorial , Convulsões , Humanos , Feminino , Masculino , Adulto , Herança Multifatorial/genética , Convulsões/genética , Pessoa de Meia-Idade , Fatores de Risco , Epilepsia Generalizada/genética , Adulto Jovem , Adolescente , Epilepsia/genética , Epilepsia/epidemiologia , Biomarcadores , Epilepsias Parciais/genética , Criança , Idoso , Estudos Longitudinais , Registros Eletrônicos de Saúde , Estratificação de Risco GenéticoRESUMO
The insula is often referred to as "the fifth lobe" of the brain, and its accessibility used to be very limited due to the deep location under the opercula as well as the sylvian vasculature. It was not until the availability of modern stereo-electroencephalography (SEEG) technique that the intracranial electrodes could be safely and chronically implanted within the insula, thereby enabling anatomo-electro-clinical correlations in seizures of this deep origin. Since the first report of SEEG-recorded insular seizures in late 1990s, the knowledge of insular lobe epilepsy (ILE) has rapidly expanded. Being on the frontline for the diagnosis and management of epilepsy, neurologists should have a precise understanding of ILE to differentiate it from epilepsies of other lobes or non-epileptic conditions. Owing to the multimodal nature and rich anatomo-functional connections of the insula, ILE has a wide range of clinical presentations. The following symptoms should heighten the suspicion of ILE: somatosensory symptoms involving a large/bilateral cutaneous territory or taking on thermal/painful character, and cervico-laryngeal discomfort. The latter ranges from slight dyspnea to a strong sensation of strangulation (laryngeal constriction). Other symptoms include epigastric discomfort/nausea, hypersalivation, auditory, vestibular, gustatory, and aphasic symptoms. However, most of these insulo-opercular symptoms can easily be masked by those of extra-insular seizure propagation. Indeed, sleep-related hyperkinetic (hypermotor) epilepsy (SHE) is a common clinical presentation of ILE, which shows predominant hyperkinetic and/or tonic-dystonic features that are often indistinguishable from those of fronto-mesial seizures. Subtle objective signs, such as constrictive throat noise (i.e., laryngeal constriction) or aversive behavior (e.g., facial grimacing suggesting pain), are often the sole clue in diagnosing insular SHE. Insular-origin seizures should also be considered in temporal-like seizures without frank anatomo-electro-clinical correlations. All in all, ILE is not the epilepsy of an isolated island but rather of a crucial hub involved in the multifaceted roles of the brain.
Assuntos
Córtex Cerebral , Humanos , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/etiologiaRESUMO
Identification of insular lobe epilepsy (ILE) presents a major clinical challenge in the diagnosis and treatment of drug-resistant focal epilepsies. ILE has diverse clinical presentations due to the multifaceted functions of the insula. Surface EEG findings do not provide straightforward information to predict this deeply-situated origin of seizures; they are even misleading, masquerading as those of other focal epilepsies, such as temporal and frontal ones. Non-invasive imagings may disclose insular abnormalities, but extra-insular abnormalities can coexist or even stand out. Careful reading and a second-look guided by other clinical information are crucial in order not to miss subtle insulo-opercular abnormalities. Furthermore, a possible insular origin of seizures should be considered in MRI-negative frontal/temporal/parietal epilepsies. Therefore, exploration/exclusion of insular-origin seizures is necessary for a great majority of surgical candidates. As for the stereo-electroencephalography, considered as the gold standard method for intra-cranial EEG investigations with suspicion of ILE, planning of electrode positions/trajectories require sufficient knowledge of the functional localization and anatomo-functional connectivity of the insula. Dense sampling within the insula is required in patients with probable ILE, because the seizure-onset zone can be restricted to a single insular gyrus or even a part of it. It is also crucial to explore extra-insular regions on the basis of non-invasive investigation results while considering their anatomo-functional relationships with the insula. From a surgical perspective, differentiating seizures strictly confined to the insula from those extending to the opercula is of particular importance. Pure insular seizures can be treated with less invasive measures, such as radiofrequency thermocoagulation. To conclude, close attention must be paid to the possibility of ILE throughout the diagnostic workup. The precise identification/exclusion of ILE is a prerequisite to provide appropriate and effective surgical treatment in pharmaco-resistant focal epilepsies.
Assuntos
Córtex Cerebral , Eletroencefalografia , Epilepsias Parciais , Humanos , Epilepsias Parciais/cirurgia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband's episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene's introns.
Assuntos
Talassemia alfa , Humanos , Masculino , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Criança , Epilepsia/genética , Epilepsia/diagnóstico , Epilepsia/patologia , Epilepsias Parciais/genética , Epilepsias Parciais/diagnóstico , Fenótipo , Cromossomos Humanos Par 16/genética , Haploinsuficiência/genética , Proteínas Ativadoras de GTPaseRESUMO
We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.
Assuntos
Mapeamento Encefálico , Idioma , Lobo Temporal , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , População do Leste Asiático , Estimulação Elétrica , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Japão , Imageamento por Ressonância Magnética , Lobo Temporal/fisiologiaRESUMO
Correctly diagnosing and classifying seizures and epilepsies is vital to ensure a tailored approach to patients with epilepsy. The ILAE seizure classification consists of two main groups: focal and generalized. Establishing if a seizure is focal or generalized is essential to classify the epilepsy type and the epilepsy syndrome, providing more personalized treatment and counseling about prognosis. EEG is one of the most essential tools for this classification process and further localization of the epileptogenic focus. However, some EEG findings are misleading and may postpone the correct diagnosis and proper treatment. Knowing the most common EEG pitfalls in focal and generalized epilepsies is valuable for clinical practice, avoiding misinterpretations. Some atypical features can be challenging in focal epilepsies, such as secondary bilateral synchrony, focal epileptiform activity induced by hyperventilation and photic stimulation, and non-focal slowing. On the other hand, more than 60 % of persons with idiopathic generalized epilepsies have at least one type of atypical abnormality. In this manuscript, we describe and illustrate some of the most common EEG findings that can make even experienced epileptologists question not only where the epileptogenic focus is but also if the patient has focal or generalized epilepsy. This review summarizes the perils and provide some pearls to assist EEG readers.
Assuntos
Eletroencefalografia , Epilepsias Parciais , Epilepsia Generalizada , Humanos , Eletroencefalografia/métodos , Epilepsia Generalizada/fisiopatologia , Epilepsia Generalizada/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico , Encéfalo/fisiopatologiaRESUMO
PURPOSE: To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy. METHODS: MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results. RESULTS: Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p<0.01). Moreover, these two LRCT indices across five distinct frequency bands correlated with EZ. CONCLUSION: HFO and source-level LRTCs are correlated with EZ. Integrating HFO and LRTCs may be an effective approach for presurgical evaluation of epilepsy.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Feminino , Adulto , Masculino , Epilepsias Parciais/cirurgia , Epilepsias Parciais/fisiopatologia , Adulto Jovem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/fisiopatologia , Adolescente , Pessoa de Meia-Idade , Eletroencefalografia/métodos , Córtex Cerebral/fisiopatologia , Córtex Cerebral/cirurgia , Cuidados Pré-Operatórios/métodos , Ondas Encefálicas/fisiologiaRESUMO
Epilepsy surgery may be a curative therapy for patients with drug-resistant epilepsies when focal lesions or foci are identified. Genetic testing is not yet routinely included in many presurgical evaluation programs although recent evidence support that finding a germline genetic mutation could help to better delineate the patient candidacy to surgery and provide valuable information on the expected surgery outcome. In this study, we report nine patients presenting drug-resistant focal epilepsy enrolled in presurgical evaluation. We show how the identification of genetic pathogenic variant in epilepsy known genes led to the interruption of the presurgical work-up and ruled out surgery in 7 of them. We observed that the co-existence of some recurrent clinical characteristics as early seizures' onset, frequent precipitating factors including fever, and developmental delay or intellectual disability may be useful markers for germline genetic pathogenic variants. In this group, genetic assessment should be mandatory during presurgical work up, mainly in patients with negative magnetic resonance imaging (MRI) or doubtful structural lesions. The integration of next generation targeted sequencing into the presurgical evaluation can improve the selection of candidates for resective surgery and fosters a personalized medicine approach with a better outcome. PLAINE LANGUAGE ABSTRACT: Genetic testing is not yet systematically included in the pre-surgical assessment of patients with drug-resistant focal epilepsies. In this study, through the description of nine patients, we underline how the integration of genomics into the presurgical work up can help in evaluating the patient candidacy to surgery and provide valuable information on expected surgery outcome.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Testes Genéticos , Humanos , Epilepsias Parciais/genética , Epilepsias Parciais/cirurgia , Feminino , Masculino , Criança , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/cirurgia , Pré-Escolar , Adolescente , Cuidados Pré-Operatórios , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Seizures are characterized by periictal autonomic changes. Wearable devices could help improve our understanding of these phenomena through long-term monitoring. In this study, we used wearable electrocardiogram (ECG) data to evaluate differences between temporal and extratemporal focal impaired awareness (FIA) seizures monitored in the hospital and at home. We assessed periictal heart rate, respiratory rate, heart rate variability (HRV), and respiratory sinus arrhythmia (RSA). METHODS: We extracted ECG signals across three time points - five minutes baseline and preictal, ten minutes postictal - and the seizure duration. After automatic Rpeak selection, we calculated the heart rate and estimated the respiratory rate using the ECG-derived respiration methodology. HRV was calculated in both time and frequency domains. To evaluate the influence of other modulators on the HRV after removing the respiratory influences, we recalculated the residual power in the high-frequency (HF) and low-frequency (LF) bands using orthogonal subspace projections. Finally, 5-minute and 30-second (ultra-short) ECG segments were used to calculate RSA using three different methods. Seizures from temporal and extratemporal origins were compared using mixed-effects models and estimated marginal means. RESULTS: The mean preictal heart rate was 69.95 bpm (95 % CI 65.6 - 74.3), and it increased to 82 bpm, 95 % CI (77.51 - 86.47) and 84.11 bpm, 95 % CI (76.9 - 89.5) during the ictal and postictal periods. Preictal, ictal and postictal respiratory rates were 16.1 (95 % CI 15.2 - 17.1), 14.8 (95 % CI 13.4 - 16.2) and 15.1 (95 % CI 14 - 16.2), showing not statistically significant bradypnea. HRV analysis found a higher baseline power in the LF band, which was still significantly higher after removing the respiratory influences. Postictally, we found decreased power in the HF band and the respiratory influences in both frequency bands. The RSA analysis with the new methods confirmed the lower cardiorespiratory interaction during the postictal period. Additionally, using ultra-short ECG segments, we found that RSA decreases before the electroclinical seizure onset. No differences were observed in the studied parameters between temporal and extratemporal seizures. CONCLUSIONS: We found significant increases in the ictal and postictal heart rates and lower respiratory rates. Isolating the respiratory influences on the HRV showed a postictal reduction of respiratory modulations on both LF and HF bands, suggesting a central role of respiratory influences in the periictal HRV, unlike the baseline measurements. We found a reduced cardiorespiratory interaction during the periictal period using other RSA methods, suggesting a blockade in vagal efferences before the electroclinical onset. These findings highlight the importance of respiratory influences in cardiac dynamics during seizures and emphasize the need to longitudinally assess HRV and RSA to gain insights into long-term autonomic dysregulation.