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OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.
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Epilepsia Generalizada , Epilepsia , Adulto , Humanos , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Eletroencefalografia/métodos , Mapeamento Encefálico , Epilepsia Generalizada/genética , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.
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Convulsões por Abstinência de Álcool , Alcoolismo , Fraturas Cranianas , Síndrome de Abstinência a Substâncias , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Convulsões por Abstinência de Álcool/complicações , Convulsões por Abstinência de Álcool/induzido quimicamente , Convulsões por Abstinência de Álcool/tratamento farmacológico , Alcoolismo/complicações , Síndrome de Abstinência a Substâncias/complicações , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Benzodiazepinas/uso terapêutico , Recidiva , Fraturas Cranianas/induzido quimicamente , Fraturas Cranianas/complicações , Fraturas Cranianas/tratamento farmacológicoRESUMO
BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.
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Epilepsia , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Epilepsia/diagnóstico , Convulsões/diagnóstico , Prognóstico , Imageamento por Ressonância Magnética , EletroencefalografiaRESUMO
Ecstatic epilepsy is a rare form of focal epilepsy, so named because the seizures' first symptoms consist of an ecstatic/mystical experience, including feelings of increased self-awareness, mental clarity, and "unity with everything that exists," accompanied by a sense of bliss and physical well-being. In this perspective article, we first describe the phenomenology of ecstatic seizures, address their historical context, and describe the primary brain structure involved in the genesis of these peculiar epileptic seizures, the anterior insula. In the second part of the article, we move onto the possible neurocognitive underpinnings of ecstatic seizures. We first remind the reader of the insula's role in interoceptive processing and consciously experienced feelings, contextualized by the theory of predictive coding. This leads us to hypothesize that temporary disruptions to activity in the anterior insula could interrupt the generation of interoceptive prediction errors, and cause one to experience the absence of uncertainty, and thereby, a sense of bliss. The absence of interoceptive prediction errors would in fact mimic perfect prediction of the body's physiological state. This sudden clarity of bodily perception could explain the ecstatic quality of the experience, as the interoceptive system forms the basis for unified conscious experience. Our alternative hypothesis is that the anterior insula plays an overarching role in the processing of surprise and that the dysfunction caused by the epileptic discharge could interrupt any surprise exceeding expectations, resulting in a sense of complete control and oneness with the environment.
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Epilepsias Parciais , Epilepsia , Humanos , Epilepsia/diagnóstico por imagem , Emoções/fisiologia , Convulsões , Córtex Cerebral/diagnóstico por imagemRESUMO
For the first time, an ecstatic aura has been evoked through the electrical stimulation of the dorsal anterior insula during presurgical invasive intracerebral monitoring in a patient who did not suffer from an ecstatic form of epilepsy. This case provides more evidence that the anterior insula is the major generator of such a mystical-type experience even in individuals with no underlying brain network changes related to a preexisting ecstatic epilepsy. ANN NEUROL 2022;91:289-292.
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Córtex Cerebral/fisiologia , Estimulação Elétrica , Euforia/fisiologia , Córtex Cerebral/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Misticismo/psicologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP. METHODS: Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5c/- ), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures. RESULTS: Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic-ECG records on Depdc5c/- mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event are not preceded by cardiac arrhythmia. INTERPRETATION: Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. ANN NEUROL 2022;91:101-116.
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Epilepsias Parciais/complicações , Proteínas Ativadoras de GTPase/genética , Coração , Morte Súbita Inesperada na Epilepsia/etiologia , Adolescente , Adulto , Animais , Eletrocardiografia , Eletroencefalografia , Epilepsias Parciais/genética , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.
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Epilepsia , Convulsões , Adulto , Humanos , Estudos de Coortes , Convulsões/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Imageamento por Ressonância MagnéticaRESUMO
Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy to epilepsy of infancy with migrating focal seizures (EIMFS) and include developmental and epileptic encephalopathies. This study aims to provide a comprehensive overview of the phenotypic and genotypic spectrum of KCNT1 mutation-related epileptic disorders in 248 individuals, including 66 previously unpublished and 182 published cases, the largest cohort reported so far. Four phenotypic groups emerged from our analysis: (i) EIMFS (152 individuals, 33 previously unpublished); (ii) developmental and epileptic encephalopathies other than EIMFS (non-EIMFS developmental and epileptic encephalopathies) (37 individuals, 17 unpublished); (iii) autosomal dominant or sporadic sleep-related hypermotor epilepsy (53 patients, 14 unpublished); and (iv) other phenotypes (six individuals, two unpublished). In our cohort of 66 new cases, the most common phenotypic features were: (i) in EIMFS, heterogeneity of seizure types, including epileptic spasms, epilepsy improvement over time, no epilepsy-related deaths; (ii) in non-EIMFS developmental and epileptic encephalopathies, possible onset with West syndrome, occurrence of atypical absences, possible evolution to developmental and epileptic encephalopathies with sleep-related hypermotor epilepsy features; one case of sudden unexplained death in epilepsy; (iii) in autosomal dominant or sporadic sleep-related hypermotor epilepsy, we observed a high prevalence of drug-resistance, although seizure frequency improved with age in some individuals, appearance of cognitive regression after seizure onset in all patients, no reported severe psychiatric disorders, although behavioural/psychiatric comorbidities were reported in â¼50% of the patients, sudden unexplained death in epilepsy in one individual; and (iv) other phenotypes in individuals with mutation of KCNT1 included temporal lobe epilepsy, and epilepsy with tonic-clonic seizures and cognitive regression. Genotypic analysis of the whole cohort of 248 individuals showed only missense mutations and one inframe deletion in KCNT1. Although the KCNT1 mutations in affected individuals were seen to be distributed among the different domains of the KCNT1 protein, genotype-phenotype considerations showed many of the autosomal dominant or sporadic sleep-related hypermotor epilepsy-associated mutations to be clustered around the RCK2 domain in the C terminus, distal to the NADP domain. Mutations associated with EIMFS/non-EIMFS developmental and epileptic encephalopathies did not show a particular pattern of distribution in the KCNT1 protein. Recurrent KCNT1 mutations were seen to be associated with both severe and less severe phenotypes. Our study further defines and broadens the phenotypic and genotypic spectrums of KCNT1-related epileptic conditions and emphasizes the increasingly important role of this gene in the pathogenesis of early onset developmental and epileptic encephalopathies as well as of focal epilepsies, namely autosomal dominant or sporadic sleep-related hypermotor epilepsy.
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Epilepsia/genética , Proteínas do Tecido Nervoso/genética , Canais de Potássio Ativados por Sódio/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Genótipo , Humanos , Lactente , Masculino , Mutação , Fenótipo , Adulto JovemRESUMO
Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain and play an important role in the neuromodulation of brain networks implicated in attentional processes. Previous work in humans showed that heteromeric α4ß2 nAChRs are abundant in the cingulo-insular network underlying attentional control. It has been proposed that cholinergic neuromodulation by α4ß2 nAChRs is involved in attentional control during demanding tasks, when additional resources are needed to minimize interference from task-irrelevant stimuli and focus on task-relevant stimuli. Here we investigate the link between the availability of α4ß2 nAChRs in the cingulo-insular network and behavioral measures of interference control using two versions of the Stroop paradigm, a task known to recruit cingulo-insular areas. We used a previously published PET dataset acquired in 24 non-smoking male subjects in the context of a larger study which investigated the brain distribution of nAChRs in two clinical groups using 2-[(18)F]F-A-85380 PET. We found that higher availability of α4ß2 nAChRs in the dorsal anterior cingulate cortex (ACC) predicted better interference control independently of group and age. In line with animal models, our results support the view that the availability of α4ß2 nAChRs in the dorsal ACC is linked with more efficient attentional control.
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Atenção/fisiologia , Giro do Cíngulo/metabolismo , Receptores Nicotínicos/metabolismo , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Teste de Stroop , Adulto JovemRESUMO
OBJECTIVE: Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by hypermotor seizures and may be caused by gain-of-function mutations affecting the nicotinic acetylcholine receptor (nAChR). Benefit from nicotine consumption has been reported in adult patients with this disorder. For the first time, the effect of transdermal nicotine is evaluated in children. METHODS: Transdermal nicotine was applied to three boys, two aged 10â¯years (7â¯mg/24â¯h) and one six years (3.5â¯mg/24â¯h). Autosomal dominant sleep-related hypermotor epilepsy was caused by the p.S280F-CHRNA4 (cholinergic receptor, nicotinic, alpha polypeptide 4) mutation. The children suffered from frequent, persistent nocturnal seizures and had developed educational and psychosocial problems. Seizure frequency and cognitive and behavioral parameters were assessed before and after treatment. RESULTS: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions. SIGNIFICANCE: Nicotine appears to be a mechanistic treatment for this specific disorder, probably because of desensitization of the mutated receptors. It may control seizures resistant to conventional drugs for epilepsy and impact socioeducational function in children. This mode of precision therapy should receive more attention and should be available to more patients with uncontrolled CHRNA4-related ADSHE across the age span.
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Epilepsia Reflexa/tratamento farmacológico , Epilepsia Reflexa/genética , Nicotina/administração & dosagem , Receptores Nicotínicos/genética , Sono/genética , Dispositivos para o Abandono do Uso de Tabaco , Adolescente , Criança , Epilepsia Reflexa/diagnóstico , Humanos , Masculino , Mutação/genética , Sono/efeitos dos fármacos , Resultado do TratamentoRESUMO
The literature points to a large distributed brain network involved in the estimation of time. Among these regions, the role of the insular cortex is still poorly understood. At the confluence of emotional, interoceptive, and environmental signals, this brain structure has been proposed to underlie awareness of the passage of time and emotion related time dilation. Yet, this assumption has not been tested so far. This study aimed at exploring how a lesion of the insula affects subjective duration, either in an emotional context or in a non-emotional context. Twenty-one patients with a stroke affecting the insula, either left or right, were studied for their perception of sub and supra second durations. A verbal estimation task and a temporal bisection task were used with either pure tones or neutral and emotional sounds lasting between 300 and 1500 ms and presented monaurally. Results revealed that patients with a right insular lesion, showed less temporal sensitivity than both control participants and patients with a left insular lesion. Unexpectedly, emotional effects were similar in patients and control participants. Altogether, these results suggest a specific role of the right insula in the discrimination of durations, but not in emotion related temporal distortion. In addition, an ear × emotion interaction in control participants suggests that temporal processing of positive and negative sounds may be lateralized in the brain.
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Córtex Cerebral/fisiopatologia , Emoções , Percepção do Tempo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Percepção Visual , Adulto JovemRESUMO
The original version of this article contained an error in the spelling of the author Erik H. Niks, which was incorrectly given as Erik Niks. This has now been corrected in both the PDF and HTML versions of the article.
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PURPOSE: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants. RESULTS: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign. CONCLUSION: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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Epilepsia/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Síndrome de Brugada/genética , Síndrome de Brugada/mortalidade , Síndrome de Brugada/fisiopatologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Epilepsia/complicações , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Mutação INDEL/genética , Lactente , Recém-Nascido , Mutação com Perda de Função/genética , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Complexos Multiproteicos/genética , Linhagem , Convulsões/complicações , Convulsões/epidemiologia , Convulsões/genética , Convulsões/fisiopatologia , Transdução de Sinais/genéticaRESUMO
The original version of this Article contained an error in the author list where the corresponding author Stéphanie Baulac was repeated twice. This has now been corrected in the HTML, the PDF was correct at the time of publication.
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PURPOSE: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4ß2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. METHODS: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. RESULTS: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy. CONCLUSIONS: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4ß2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.
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Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/metabolismo , Receptores Nicotínicos/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto JovemRESUMO
PURPOSE: FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation. METHODS: A total of 130 patients who underwent PET imaging between 2006 and 2015 matched our inclusion criteria, and of these, 86 were operated on (72% with a favourable surgical outcome, Engel class I). Areas of focal hypometabolism were identified using statistical parametric mapping and concordance with MRI, EEG and intracranial EEG was evaluated. In the surgically treated patients, postsurgical outcome was used as the gold standard for correctness of localization (minimum follow-up 12 months). RESULTS: PET sensitivity and specificity were both 95% in 86 patients with temporal lobe epilepsy (TLE) and 80% and 95%, respectively, in 44 patients with extratemporal epilepsy (ETLE). Significant extratemporal hypometabolism was observed in 17 TLE patients (20%). Temporal hypometabolism was observed in eight ETLE patients (18%). Among the 86 surgically treated patients, 26 (30%) had hypometabolism extending beyond the SOZ. The presence of unilobar hypometabolism, included in the resection, was predictive of complete seizure control (p = 0.007), with an odds ratio of 5.4. CONCLUSION: Additional hypometabolic areas were found in one of five of this group of nonselected patients with focal epilepsy, including patients with "simple" lesional epilepsy, and this finding should prompt further in-depth evaluation of the correlation between EEG findings, semiology and PET. Hypometabolism confined to the epileptogenic zone as defined by EEG and MRI is associated with a favourable postoperative outcome in both TLE and ETLE patients.
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Epilepsias Parciais/metabolismo , Epilepsias Parciais/cirurgia , Valor Preditivo dos Testes , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2â nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra-spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057â spindles per min; 95% confidence interval: [0.025-0.089]; pâ =â .0004), have higher amplitude (average amplification: 0.260â µV; confidence interval: [0.119-0.402]; pâ =â .0032) and last longer (average lengthening: 0.025â s; confidence interval: [0.017-0.032]; pâ =â 2.7e-11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles.
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Eletroencefalografia/métodos , Nicotina/efeitos adversos , Fases do Sono/efeitos dos fármacos , Sono/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Método Simples-Cego , Adulto JovemRESUMO
First seizures are a diagnostic challenge in the emergency room. The differential diagnosis includes epileptic seizures, syncopes and psychogenic non-epileptic seizures. Importantly, amongst first epileptic seizures, acute symptomatic seizures should be distinguished from unprovoked seizures that define epilepsy. The early accurate diagnosis of first seizures is an important issue because of the therapeutic and prognostic implications at stake. In addition to gathering a detailed history, some ancillary tests may be warranted early on in patients' management. In this article, we present some definitions and describe clinical and work up features that might help accurately classify and appropriately manage such cases in the emergency room.
Les crises épileptiques inaugurales arrivant aux urgences représentent un enjeu diagnostique de taille. Le diagnostic différentiel d'une première crise épileptique comprend notamment les syncopes convulsivantes et les crises psychogènes non épileptiques. En cas de première crise épileptique, savoir identifier une crise provoquée d'une crise d'épilepsie-maladie est un autre défi. L'enjeu diagnostique initial est donc important car les implications thérapeutiques et pronostiques sont différentes selon l'étiologie retenue. Outre l'anamnèse très détaillée, un certain nombre d'examens spécialisés doivent être réalisés de manière précoce. Nous présentons dans cet article des éléments diagnostiques cliniques et paracliniques à mettre en Åuvre dans la prise en charge précoce des patients.
Assuntos
Epilepsia , Convulsões , Diagnóstico Diferencial , Eletroencefalografia , Serviço Hospitalar de Emergência , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Humanos , Convulsões/tratamento farmacológico , Convulsões/etiologia , SíncopeRESUMO
OBJECTIVE: Evaluation for surgical treatment is offered to patients who do not respond to antiepileptic drugs. Pseudo-pharmacoresistance (PPR) has been described in the context of impaired compliance, incorrect diagnosis of epilepsy or pharmacological interference resulting in too low blood levels. We were interested to determine the frequency and causes of PPR in patients admitted for presurgical evaluation. METHODS: We reviewed 553 drug levels in 199 patients and analyzed the relative frequency of drugs below reference range (10 and 20% below the range). RESULTS: Patients who had at least one serum level below the 10% cut-off amounted to 33% and 9% of patients had at least one serum level below the 20% cut-off. Only in 2 patients (1%), this was due to poor compliance. Low levels were equally frequent in mono- or polytherapy. Drugs that were most frequently found out of range were phenytoin, valproate, and topiramate. In monotherapy, lamotrigine was often prescribed in too low dosages. CONCLUSION: Low drug levels are frequently observed in surgical candidates due to pharmacological interference or insufficient dosing. Poor compliance or incorrect diagnosis does not appear to be a significant concern in this patient group. Our data strengthen the need for regular drug monitoring even in advanced chronic epilepsy to avoid unnecessary health costs by too low and ineffective dosages.