A comparative study of multiple resting state functional magnetic resonance imaging indices to detect epileptic activity in childhood absence epilepsy / 中华神经科杂志

Objective:To comprehensively evaluate the ability of common resting state functional magnetic resonance imaging (rs-fMRI) indices to detect abnormal brain activity in childhood absence epilepsy (CAE).Methods:Simultaneous electroencephalography-functional magnetic resonance imaging (fMRI) data of 20 patients with CAE who were treated in the Jinling Hospital, Nanjing University School of Medicine from February 2010 to September 2021 were retrospectively collected. After excluding 2 patients with CAE with greater head movement, 44 fMRI data containing discharges from 18 patients were obtained finally. The generalized spike and slow-wave discharges (GSWD) related fMRI activation mappings were obtained by using the generalized linear model. At the same time, 94 age- and sex-matched healthy controls underwent rs-fMRI scanning. Meanwhile, 12 indices of rs-fMRI were calculated respectively [amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF), regional homogeneity (ReHo), functional connectivity density (FCD), long FCD, local FCD, granger causality density (GCD)-in, GCD-out, GCD-int, resting state functional magnetic resonance imaging lag analysis (RSLA), Hurst index and brain entropy]. Two-sample t-tests were employed to detect significant differences in 12 indices of rs-fMRI. The Dice coefficient was used to evaluate the overlap between different brain maps of 12 indices of rs-fMRI and the GSWD-related blood oxygenation level dependent (BOLD) activation. Results:Positive activation of GSWD-related BOLD in CAE was mainly in the bilateral thalamus, and negative activation was mainly in default mode network (DMN) related brain regions. There was a significant overlap between the abnormal brain regions detected by various resting-state indicators: compared with normal controls, ALFF, fALFF, ReHo, GCD-in, GCD-out and local FCD were elevated in the bilateral thalamus, while FCD, long FCD, GCD-int and RSLA were decreased in CAE; ALFF, fALFF, ReHo, local FCD, GCD-out, RSLA and brain entropy were decreased in the DMN, while FCD, long FCD, GCD-in and GCD-int were increased in CAE. The Dice coefficient of long FCD was the highest (0.365),FCD was 0.362, while the Hurst index showed the lowest (0.142).Conclusions:Rs-fMRI indices variously revealed abnormal brain activity in CAE, in which the FCD is better for detection of epileptic activity. Rs-fMRI could be helpful to understand the pathophysiological mechanism of CAE, and to find reliable imaging markers.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective@#To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.@*Methods@#The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords " SLC6A1" and " myoclonic-atonic epilepsy" . The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.@*Results@#A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in SLC6A1 gene. A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before epilepsy onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear.@*Conclusions@#The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures, cognition before epilepsy onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.Methods The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected.The related literatures were reviewed from Wanfang Data,China National Knowledge Infrastructure,PubMed (until July 2019) by using keywords "SLC6A1" and "myoclonic-atonic epilepsy".The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.Results A 8 year and 8 months old girl was enrolled in the study.Her first attack happened at the age of 19 months,and multiple seizure types including myoclonic-atonic,atonic and absence were observed.The seizures were well controlled by valproate (VPA),but she has mild-moderate intellectual disability.Whole exome-sequencing study identified a de novo nonsense variant of c.46G ＞ T(p.Glu16 *)in SLC6A1 gene.A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed.22 mutations were identified,including 11 missense mutations,5 nonsense mutations,3 frameshift mutations,2 splicing mutation and 1 with chromosome microdeletion.Among them 26 patients had more one type of seizures,20 cases had absence seizures,17 cases had atonic seizures,14 cases had myoclonic seizures,11 cases had myoclonic-atonic seizures,4 cases had generalized tonic-clonic seizures,3 cases had eyelid myoclonias,2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure.24 patients had described intelligence assessment.Among them,18 had developmental delay before epilepsy onset,11 had developmental regression after onset.There were 9 cases with autistic features,4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia.The seizures of 17 cases were controlled,4 cases had partial seizure control,3 cases had no significant improvement,and other 3 cases were unclear.Conclusions The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures,cognition before epilepsy onset can be impaired,and some patients had behavioral problems,such as autistic features or attention deficit hyperactivity disorders.VPA is recommend as first-line treatment.

Electroclinical study of patients with juvenile absence epilepsy / 中华神经科杂志

Objective To investigate the electroclinical,treatment response and prognosis of juvenile absence epilepsy (JAE).Methods Thirty-two patients diagnosed as JAE from Epilepsy Center of Xijing Hospital between January 2014 and August 2017 were investigated.All of them underwent 24-hour video-electroencephalography (EEG) recording.Clinical aspects,electroencephalographic features,and antiepileptic drugs (AEPs) received were reviewed.The follow-up time was 6-44 months,with an average of (18.6 ± 11.6) months.Results Five patients (15.6％) had family history of epilepsy.Four patients (12.5％) had history of febrile seizures.Twenty-six patients (81.3％) showed absence seizures,11 patients (34.4％) were hyperventilation test positive,five patients (15.6％) were intermittent flash stimulation test positive.All the 32 patients received AEDs treatments,21 cases (65.5％) with monotherapy,nine patients (28.1％) with two AEDs,two patients (6.3％) with three AEDs.The most commonly used AED was valproic acid,and the second was levetiracetam.At the end of follow-up,five patients (15.6％) had complete seizure free and 27 patients (84.4％) had poor seizure control.Conclusions It is necessary to give electroclinical study on more samples of JAE and establish detailed practical diagnostic criteria about JAE as early as possible.More than half of JAE patients seizure control were not ideal.The monotherapy of JAE was less effective than combined treatment.

Expressão gênica em larga escala em modelos genéticos de epilepsia / Large-scale gene expression in genetic models of epilepsy

Wistar audiogenic rat (WAR) é um modelo genético de epilepsia de crises audiogênicas desencadeadas após alta intensidade de estimulação sonora. Outro modelo genético recentemente identificado é o da epilepsia generalizada com crises de ausência (GEAS). O objetivo do presente estudo foi caracterizar o perfil de expressão gênica destas duas cepas através de uma análise em larga escala. Para os estudos de expressão foi utilizada inicialmente a tecnologia de microarranjos seguida da validação dos resultados por técnica quantitativa de PCR em tempo real. Os resultados foram analisados em ambiente R, utilizando os pacotes AFFY e RankProd do bioconductor, utilizando o algoritmo MAS 5 os array foram normalizados e calculou-se a intensidade do sinal e a detecção (presença ou ausência de expressão). Após a detecção, os transcritos que estavam ausentes foram removidos. Para a análise estatística foi utilizado o teste RankProd, que é biologicamente projetado para testar e detectar genes diferencialmente expressos em experimentos de microarranjos. Foi utilizado um valor de p ? 0,01 e pfp ? 0,05, a fim de considerar os transcritos diferencialmente expressos. No geral, nossos resultados mostram uma assinatura molecular similar nos dois modelos de ratos genéticos analisados. Houve uma sobreposição na lista de genes diferencialmente expressos encontrados em ambos os modelos, quando comparado com controles. Além disso, descobrimos que duas importantes vias moleculares para epileptogênese: neurotransmissão GABAérgica e potencialização de longo prazo pós-sináptica NMDA-dependente, foram encontrados em ambos os modelos, quando combinamos os dados dos animais WAR e GEAS. No entanto, algumas diferenças nas vias de sinalização expressas nos dois modelos também foram identificadas. Portando os resultados mostram claramente a natureza heterogênea e complexa dos mecanismos moleculares envolvidos na epileptogênese.

Wistar audiogenic rat (WAR) is a genetic epilepsy model susceptible to audiogenic seizures, after high-intensity sound stimulation. Another genetic model we have recently identified is the generalized epilepsy with absence seizures (GEAS) rat. The aim of the present study was to characterize and compare the genetic profile of these two strains using gene expression analysis. Experiments were performed initially using microarray technology followed by quantitative real-time PCR. Results were analyzed in R environment using the Affy and RankProd packages from Bioconductor, using the algorithm MAS 5 we normalized the arrays and calculated the signal intensity and the detection (presence or absence of expression), after the detection, transcripts which were absent in all samples were removed. For statistical analysis we used the Rank Product test, which is biologically motivated and designed to test and detect differentially expressed genes in replicated microarray experiments. This is a simple non-parametric statistical method based on ranks of fold changes. We used a p-value ? 0.01 and a pfp ? 0.05 in order to consider a given transcript to be differentially expressed Overall, the results show a different molecular signature in the two genetic rat models analyzed, since different enriched gene ontology categories were found. However, there was some overlap in the list of genes differentially expressed found in both models when comparing to controls. In addition, we found that two important molecular pathways for epileptogenesis: GABAergic neurotransmission and: Neurophysiological process NMDA-dependent postsynaptic long-term potentiation in CA1 hippocampal neurons, were found to be present in both models when combining data from WAR and GEAS animals.

The clinical-electroencephalographic features of the 6 patients with idiopathic generalized epilepsy in adults with phantom absences / 中华神经科杂志

Objective To investigate the clinical and electroencephalogram (EEG) features of patients with idiopathic generalized epilepsy in adults with phantom absences.Methods Six patients were referred to the clinic of epilepsy from April,2007 to December,2011.They all had clinical assessment,EEG,or video EEG confirming absences seizure.Results Six patients showed the following similar clinical-EEG features:(1) mild ictal impairment of consciousness associated with generalized 3.0-3.5 Hz spike and slow wave discharges; (2) late-onset generalized tonic-clonic seizures; (3) absence status epilepticus with or without secondary generalized tonic-clonic seizures; (4) generalized discharges were mostly seen in three types in the awaking stage:fragmented discharge (＜4 s),brief discharge (4-10s) and long-time discharge (＞ 10 s).None of the patients had myoclonic jerks or photosensitivity.One patient' s mother had a history of generalized tonic clonic seizures.One patient had a history of children absence epilepsy and one patient had a history of febrile convulsion in the age of 1-3.Conclusion Idiopathic generalized epilepsy with phantom absences has distinct clinical and EEG features and may become a new idiopathic generalized epilepsy syndrome in adults.

Monotherapy with levetiracetam for absence epilepsy in children / 中华全科医师杂志

Objective To assess the efficacy and safety of levetiracetam (LEV) monotherapy in children with absence epilepsy.Methods Fifty five children [ 34 males,21 females,aged (8.1 ± 4.8) y ] with typical absence seizures were treated with LEV ( n =25 ) or valproic acid ( VPA,n =30) from Jan 2009 to Jun 2010.Patients were followed up for 1y; the seizure frequency,electroencephalogram (EEG) and side effect were observed at 6th month and 12th month after the initiation of therapy.Results During the follow-up,none had aggravated symptoms of epilepsy.There were no significant differences in seizure frequency(t =0.76,P =0.450; t =0.67,P =0.504),abnormal EEG ( x2 =0.120,P =0.729 ; x2 =0.043,P =0.836 ) and seizure control ( x2 =0.051,P =0.821 ; x2 =0.078,P =0.780) after 6 and 12 months of treatment between two groups.No death or severe side effects were observed; 2 cases (8.0％) in LEV group had mild adverse effect( drowsiness and restlessness)and 2 cases (6.7％ ) in VPA group had weight gain and nausea.Conclusion The results suggest that monotherapy with LEV is effective and safe for treatment of childhood absence epilepsy.

GABA_B receptor subunit GBR1b pan mRNA in absence seizure model / 中华神经科杂志

Objective To explore the possible mechanism of GABA B receptor subunit and epileptogenesis in absence seizure animal model Methods AY 9944 absence seizure model is developed by abdomenal injection of a cholesterol biosynthesis inhibitor Ay 9944 to neonatal Lon Evan hooded rats In situ hybridization is applied to detect GABA B receptor subunit GBR1b pan mRNA in rat brain of absence seizure Result There is increased hybridization signal in cortex, hippocampus and thalamus, especially in cortex (361?48 nCi/g) and hippocampus CA1 region (327?83 nCi/g)( P value 0 020 and 0 027 respectively) Conclusion The result of this study support the hypothesis that GABA B receptor subunit may be involved and induce seizures in absence epilepsy The finding of subunit change may direct the screen of new antiepileptic drug This finding deserves further study