Childhood Absence Epilepsy Patients Research Articles

Focality in childhood absence epilepsy

ABSTRACT Background and purpose Childhood absence epilepsy (CAE) has a typical electroencephalography (EEG) pattern of generalized 3 Hz spike and wave discharges (SWD). Focal interictal discharges were also documented in a small number of documents. The aim was to investigate the amplitudes of interictal 3 Hz SWD within the 1st second in drug-naïve CAE patients. In this way, areas with maximal electronegativity at the beginning of clinically generalized discharges will be documented. Methods The EEG records of children with drug-naïve CAE were evaluated retrospectively by two child neurologists first for 3 Hz SWD. Then, a machine-learning model evaluated the amplitudes of 3 Hz in the 1st second of SWD. Maximum electronegativity areas were documented and classified as focal, bilateral, and generalized. Results One hundred and twelve 3 Hz SWD were evaluated in 11 patients. Among discharges within the 1st second, maximum electronegativity areas were documented as focal for 44 (39.2%), bilateral for 8 (7.1%), generalized for 60 (53.5%). Among focal electronegativity areas, mostly right central, left occipital and midline parietal areas were documented in 12 (10.7%), 7 (6.2%), and 6 (5.3%), respectively. Eight (7.1%) of the maximum electronegativity areas were detected bilaterally, of which 7 (6.2%) originated from the frontopolar areas. Conclusions Focal maximal electronegativity areas were frequently observed in drug-naïve CAE patients, comprising approximately half of non-generalized discharges. Focal discharges might be misleading in diagnosis. Focal areas within the brain may be responsible for and contribute to absence seizures that appear bilaterally symmetrical and generalized clinically. Although its clinical implication is unknown, this warrants further study.

The sound of silence: Quantification of typical absence seizures by sonifying EEG signals from a custom-built wearable device.

To develop and validate a method for long-term (24-h) objective quantification of absence seizures in the EEG of patients with childhood absence epilepsy (CAE) in their real home environment using a wearable device (waEEG), comparing automatic detection methods with auditory recognition after seizure sonification. The waEEG recording was acquired with two scalp electrodes. Automatic analysis was performed using previously validated software (Persyst® 14) and then fully reviewed by an experienced clinical neurophysiologist. The EEG data were converted into an audio file in waveform format with a 60-fold time compression factor. The sonified EEG was listened to by three inexperienced observers and the number of seizures and the processing time required for each data set were recorded blind to other data. Quantification of seizures from the patient diary was also assessed. Eleven waEEG recordings from seven CAE patients with an average age of 8.18 ± 1.60 years were included. No differences in the number of seizures were found between the recordings using automated methods and expert audio assessment, with significant correlations between methods (ρ > .89, p < .001) and between observers (ρ > .96, p < .001). For the entire data set, the audio assessment yielded a sensitivity of .830 and a precision of .841, resulting in an F1 score of .835. Auditory waEEG seizure detection by lay medical personnel provided similar accuracy to post-processed automatic detection by an experienced clinical neurophysiologist, but in a less time-consuming procedure and without the need for specialized resources. Sonification of long-term EEG recordings in CAE provides a user-friendly and cost-effective clinical workflow for quantifying seizures in clinical practice, minimizing human and technical constraints.

Dysfunction of the glymphatic system in childhood absence epilepsy.

This study aimed to evaluate the glymphatic system in childhood absence epilepsy (CAE) using diffusion tensor image analysis along the paravascular space (DTI-ALPS) index. Methods: Forty-two CAE patients and 50 age- and gender-matched healthy controls (HC) were included in this study. All participants underwent scanning using a Siemens 3.0 T magnetic resonance scanner, and the DTI-ALPS index was calculated. The study compared the differences of DTI-ALPS index between CAE patients and the healthy controls. Additionally, this study also assessed the relationship between the DTI-ALPS index and clinical characteristics such as age, seizure frequency, and duration of epilepsy. The DTI-ALPS index was lower in CAE patients compared to the healthy controls (1.45 ± 0.36 vs. 1.66 ± 0.30, p < 0.01). The DTI-ALPS index showed a negative correlation with the duration of epilepsy (r = -0.48, p < 0.01) and a positive correlation with age (r = 0.766, p < 0.01) in CAE patients. However, no significant correlation was observed between the DTI-ALPS index and seizure frequency. The results of this study indicate that children with CAE exhibit dysfunction in the glymphatic system of the brain, which might contribute to understanding the pathophysiological mechanism of CAE. The DTI-ALPS, as a non-invasive diagnostic marker, can be used to assess the function of the glymphatic system in CAE patients, providing promising applications in the diagnosis and research of CAE.

Changes in awake and sleep electroencephalography characteristics after 1-year treatment for childhood and juvenile absence epilepsy

PurposeTo compare electroencephalography (EEG) features of newly diagnosed drug-naive childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) patients and analyze their response to anti-seizure medications (ASMs). MethodEEG characteristics between CAE and JAE patients and responders and non-responders to ASM at baseline and 12 months were compared, and the changes from baseline were analysed. ResultsA total of 62 patients (32 CAE and 30 JAE) were included. Discharges in baseline awake and sleep EEGs and interictal and polyspike discharges in baseline sleep EEGs were more frequent in JAE patients. Although the median discharge densities (discharge containing seconds per minute) were similar in baseline awake and sleep EEGs between the groups, the median was higher in the JAE group at 12 months and decreased significantly in both groups at 12 months compared to the baseline values. Responses to initial ASMs were 94% and 77% in the CAE and JAE groups, respectively. In initial sleep EEGs of non-responders with JAE, focal onset generalized spike and slow wave discharges (GSWDs) were more frequent, and the median ictal and interictal discharge densities were higher. ConclusionJAE patients had more frequent disorganized discharges at baseline in both awake and sleep EEGs and interictal and polyspike discharges in sleep EEGs than those of CAE patients. Improvement in EEG was more pronounced in CAE patients than in JAE patients. Focal-onset GSWDs and higher ictal and interictal discharge densities on baseline EEG were associated with a poor response to initial ASMs in JAE patients.

Altered neuromagnetic activity in default mode network in childhood absence epilepsy.

The electrophysiological characterization of resting state oscillatory functional connectivity within the default mode network (DMN) during interictal periods in childhood absence epilepsy (CAE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in CAE. Using a cross-sectional design, we analyzed MEG data from 33 children newly diagnosed with CAE and 26 controls matched for age and sex. The spectral power and functional connectivity of the DMN were estimated using minimum norm estimation combined with the Welch technique and corrected amplitude envelope correlation. Default mode network showed stronger activation in the delta band during the ictal period, however, the relative spectral power in other bands was significantly lower than that in the interictal period (p corrected < 0.05 for DMN regions, except bilateral medial frontal cortex, left medial temporal lobe, left posterior cingulate cortex in the theta band, and the bilateral precuneus in the alpha band). It should be noted that the significant power peak in the alpha band was lost compared with the interictal data. Compared with controls, the interictal relative spectral power of DMN regions (except bilateral precuneus) in CAE patients was significantly increased in the delta band (p corrected < 0.01), whereas the values of all DMN regions in the beta-gamma 2 band were significantly decreased (p corrected < 0.01). In the higher frequency band (alpha-gamma1), especially in the beta and gamma1 band, the ictal node strength of DMN regions except the left precuneus was significantly higher than that in the interictal periods (p corrected < 0.01), and the node strength of the right inferior parietal lobe increased most significantly in the beta band (Ictal: 3.8712 vs. Interictal: 0.7503, p corrected < 0.01). Compared with the controls, the interictal node strength of DMN increased in all frequency bands, especially the right medial frontal cortex in the beta band (Controls: 0.1510 vs. Interictal: 3.527, p corrected < 0.01). Comparing relative node strength between groups, the right precuneus in CAE children decreased significantly (β: Controls: 0.1009 vs. Interictal: 0.0475; γ 1: Controls:0.1149 vs. Interictal:0.0587, p corrected < 0.01) such that it was no longer the central hub. These findings indicated DMN abnormalities in CAE patients, even in interictal periods without interictal epileptic discharges. Abnormal functional connectivity in CAE may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction, and prognosis in CAE patients.

Childhood absence epilepsy patients with cognitive impairment have decreased sleep spindle density

ObjectiveTo explore the differences in sleep spindle (SS) characteristics during stage N2 sleep between children with childhood absence epilepsy and healthy controls, and between children with childhood absence epilepsy with or without cognitive impairment. MethodsWe recruited 29 children (14 females, 15 males, mean age: 8 (2.5) years) with childhood absence epilepsy who did not undergone antiseizure treatments previously and 30 age-matched controls (14 females, 16 males, mean age: 9 (3.0) years). For all patients, data on medical history were collected. Each child was monitored overnight by long-term video electroencephalography and was evaluated by the Wechsler Intelligence Scale for Children-Fourth Edition. Next, we compared anterior SS characteristics, including density, frequency, cycle length, duration, amplitude, and percentage of sleep stages. ResultsThe childhood absence epilepsy group exhibited lower spindle density and duration in the first 37.5 min of stage N2 sleep than the control group (P < 0.01). A decrease in spindle density could be observed in the childhood absence epilepsy group with aggravated cognition impairment. The spindle density was substantially lower in the cognitively impaired group than in the cognitively unimpaired group (P < 0.01). No significant differences were observed in SS amplitude, SS frequency, SS cycle length, and the distribution of sleep stages. ConclusionsReduction in spindle density and duration is associated with the mechanisms underlying childhood absence epilepsy. The deficit in SS density is related with impaired cognition. This deficiency in SSs may be a useful predictive indicator of cognitive impairment in children with absence epilepsy, indicating that SSs may become a useful biomarker and potential adjuvant anti-seizure target for cognitive impairment caused by childhood absence epilepsy.

Neuronal networks underlying ictal and subclinical discharges in childhood absence epilepsy

Childhood absence epilepsy (CAE), involves 3 Hz generalized spikes and waves discharges (GSWDs) on the electroencephalogram (EEG), associated with ictal discharges (seizures) with clinical symptoms and impairment of consciousness and subclinical discharges without any objective clinical symptoms or impairment of consciousness. This study aims to comparatively characterize neuronal networks underlying absence seizures and subclinical discharges, using source localization and functional connectivity (FC), to better understand the pathophysiological mechanism of these discharges. Routine EEG data from 12 CAE patients, consisting of 45 ictal and 42 subclinical discharges were selected. Source localization was performed using the exact low-resolution electromagnetic tomography (eLORETA) algorithm, followed by FC based on the imaginary part of coherency. FC based on the thalamus as the seed of interest showed significant differences between ictal and subclinical GSWDs (p < 0.05). For delta (1–3 Hz) and alpha bands (8–12 Hz), the thalamus displayed stronger connectivity towards other brain regions for ictal GSWDs as compared to subclinical GSWDs. For delta band, the thalamus was strongly connected to the posterior cingulate cortex (PCC), precuneus, angular gyrus, supramarginal gyrus, parietal superior, and occipital mid-region for ictal GSWDs. The strong connections of the thalamus with other brain regions that are important for consciousness, and with components of the default mode network (DMN) suggest the severe impairment of consciousness in ictal GSWDs. However, for subclinical discharges, weaker connectivity between the thalamus and these brain regions may suggest the prevention of impairment of consciousness. This may benefit future therapeutic targets and improve the management of CAE patients.

In vitro identification of CACN1h 9 axonal SNP in epileptic patients

Childhood absence epilepsy (CAE) is an autosomal dominant disorder and a heterogeneous familial condition in which family members express absence seizures initially and then show multiple phenotypes of myoclonic epilepsy, including partial or absence seizures and generalized tonic conic seizures. Multiple types of genetic mutations are involved in epilespy. This study was aimed at investigating the coding regions of CACNA1H gene for analyzing the mutations involved in epilepsy. Blood samples of mutually unrelated true representatives of CAE were collected from the psychiatry department of various hospitals in Lahore. DNA was extracted using the standard protocol and the amplification of the CACNA1H region was achieved with specially designed primers. Later on, the analysis of the results was carried out via the sequencing of target fragments. Sequences were analyzed using the BioEdit software and then aligned with the help of the ClustalW2 software. A series of 12 unrelated patients with CAE were screened for mutations in the CACNA1H gene. No mutation was found in exon 9a. As already reported, mutations in the exonic sequence of CACNA1H gene were found in 5 out of 14 CAE patients. These changes were observed in a PCR fragment amplified by primer 2 in the region of the 9th exon. Subsequent analysis of these fragments identified transition mutations (2025G&gt;A) in exon 9. To conclude, there is a need to explore the site of the gene along with other gene mutations causing epilepsy in the local population of Punjab, Pakistan. It will help to develop genetic counseling strategies, gene therapies, and prenatal diagnostic procedures for the said population.

Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study

Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy.Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders.Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8–12 and 30–80 Hz, especially 8–12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80–250 Hz.Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80–250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.

Graph-theory based degree centrality combined with machine learning algorithms can predict response to treatment with antiepileptic medications in children with epilepsy

Background and purposeThe purpose of the current study is to detect changes of graph-theory-based degree centrality (DC) and their relationship with the clinical treatment effects of anti-epileptic drugs (AEDs) for patients with childhood absence epilepsy (CAE) using resting-state functional MRI (RS-fMRI). MethodsRS-fMRI data from 35 CAE patients were collected and compared with findings from 35 age and gender matched healthy controls (HCs). The patients were treated with AEDs for 46.03 weeks before undergoing a second RS-fMRI scan. ResultsCAE children at baseline showed increased DC in thalamus, postcentral and precentral and reduced DC in medial frontal cortex, superior frontal cortex, middle temporal cortex, angular and precuneus. However, those abnormalities showed a clear renormalization after AEDs treatments. We then explored the viability of graph-theory-based degree centrality to accurately classify effectiveness to AEDs. Support Vector Machine analysis using leave-one-out cross-validation achieved a correct classification rate of 84.22% [sensitivity 78.76%, specificity 89.65%, and area under the receiver operating characteristic curve (AUC) 0.96] for differentiating effective subjects from ineffective subjects. Brain areas that contributed most to the classification model were mainly located within the right thalamus, bilateral middle temporal gyrus, right medial frontal gyrus, right inferior frontal gyrus, left precuneus, bilateral angular right precentral and left postcentral. Furthermore, the DC change within the bilateral angular are positively correlated with the symptom improvements after AEDs treatment. ConclusionThese findings suggest that graph-theory-based measures, such as DC, combined with machine-learning algorithms, can provide crucial insights into pathophysiological mechanisms and the effectiveness of AEDs.

The interictal activities load and cognitive performance of children with typical absence epilepsy

BackgroundThe description of childhood absence epilepsy (CAE) a benign self-limited generalized epilepsy has become a matter of debate. The objectives of this work were to evaluate the existence of psychiatric and cognitive impairments among patients with typical CAE and to correlate their possible relation to seizure frequency, duration of epilepsy, IISL, and valproate therapy.MethodsThe study was conducted on 19 typical CAE patients receiving valproate therapy, 11 newly diagnosed CAE patients not receiving AEDs, and 30 healthy control subjects (HCS). Participants were subjected to medical history taking, EEG monitoring, child behavior checklist (CBCL), Stanford Binet Intelligence Scale 5th edition, and computerized psychometric tests that assess cognitive domains and executive functions.ResultsThe study revealed a high rate of cognitive and psychiatric dysfunctions in CAE patients. 53.3% of patients had psychiatric problems versus 16.6% in HCS. Attention deficit hyperactive disorder (ADHD) (26.6%), anxiety (16.6%), and depression (6.6%) were the most common psychiatric disorders in the patient group. Withdrawn/depressed symptoms, thought problems, social problems, and attention problems in CAE patients were significantly increased compared to HCS. At the same time, CAE patients perform worse in cognitive scales than HCS with comparable intelligent quotient (IQ) scores.ConclusionCognitive and psychiatric impairments in typical CAE patients appear multifactorial in origin with epilepsy-related factors including the duration of epilepsy and interictal spike load (IISL).

Altered spontaneous brain activity in patients with childhood absence epilepsy: associations with treatment effects.

The study aims to detect resting-state functional MRI (RS-fMRI) changes and their relationships with the clinical treatment effects of anti-epileptic drugs (AEDs) for patients with childhood absence epilepsy (CAE) using the fractional amplitude of low-frequency fluctuation (fALFF). RS-fMRI data from 30 CAE patients were collected and compared with findings from 30 healthy controls (HCs) with matched sex and age. Patients were treated with first-line AEDs for 46.2 months before undergoing a second RS-fMRI scan. fALFF data were processed using DPABI and SPM12 software. Compared with the HCs, CAE patients at baseline showed increased fALFF in anterior cingulate cortex, inferior parietal lobule, inferior frontal lobule, supplementary motor area and reduced fALFF in putamen and thalamus. At follow-up, the fALFF showed a clear rebound which indicated a normalization of spontaneous brain activities in these regions. In addition, the fALFF changes within thalamus showed significant positive correlation with the seizure frequency improvements. Our results suggest that specific cortical and subcortical regions are involved in seizure generation and the neurological impairments found in CAE children and might shed new light about the AEDs effects on CAE patients.

High-power, frontal-dominant ripples in absence status epilepticus during childhood

ObjectiveAbsence status epilepticus (ASE) is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity accompanied by behavioral and cognitive changes. Herein, we assessed high-frequency oscillations in the ripple band in patients with ASE and typical absence seizures. MethodsWe enrolled five patients with ASE, 26 patients with childhood absence epilepsy (CAE), and 15 patients with juvenile absence epilepsy (JAE). We performed time–frequency analysis of electroencephalogram data for ictal absence seizures at each electrode to assess the high frequency activity (HFA) rate, peak frequency, and peak power. ResultsThe average HFA rates were 60.7%, 20.8%, and 12.9% in ASE, CAE, and JAE patients, respectively. The average peak frequencies were 126.4 Hz, 120.9 Hz, and 126.1 Hz in ASE, CAE, and JAE patients, respectively. The average peak power values were 2,388.8 μV2, 120.9 μV2, and 126.1 μV2 in ASE, CAE, and JAE patients, respectively, and all epilepsy groups exhibited frontal-dominant ripple distribution. ConclusionASE patients presented higher power and frontal dominant ripples of absence seizure, compared to CAE and JAE patients. SignificanceFuture studies should utilize scalp-recorded ripples as a biomarker of absence epilepsy. This may aid in the development of novel treatment strategies for ASE.

Changes in Interictal Pretreatment and Posttreatment EEG in Childhood Absence Epilepsy.

Spike and wave discharges (SWDs) are a characteristic manifestation of childhood absence epilepsy (CAE). It has long been believed that they unpredictably emerge from otherwise almost normal interictal EEG. Herein, we demonstrate that pretreatment closed-eyes theta and beta EEG wavelet powers of CAE patients (20 girls and 10 boys, mean age 7.4 ± 1.9 years) are much higher than those of age-matched healthy controls at multiple sites of the 10–20 system. For example, at the C4 site, we observed a 100 and 63% increase in power of theta and beta rhythms, respectively. We were able to compare the baseline and posttreatment wavelet power in 16 patients. Pharmacotherapy brought about a statistically significant decrease in delta and theta wavelet power in all the channels, e.g., for C4 the reduction was equal to 45% (delta) and 63% (theta). The less pronounced attenuation of posttreatment beta waves was observed in 13 channels (36% at C4 site). The beta and theta wavelet power were positively correlated with the percentage of time in seizure (defined as the ratio of the duration of all absences which patients experienced to the duration of recording) for majority of channels. We hypothesize that the increased theta and beta powers result from cortical hyperexcitability and propensity for epileptic spike generation, respectively. We argue that the distinct features of CAE wavelet power spectrum may be used to define an EEG biomarker which could be used for diagnosis and monitoring of patients.

De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy

This study aimed to identify monogenic mutations from Chinese patients with childhood absence epilepsy (CAE) and summarize their characteristics. A total of 100 patients with CAE were recruited in Peking University First Hospital from 2005 to 2016 and underwent telephone and outpatient follow-up review. We used targeted disease-specific gene capture sequencing (involving 300 genes) to identify pathogenic variations for these patients. We identified three de novo epilepsy-related gene mutations, including missense mutations of SCN1A (c. 5399 T > A; p. Val1800Asp), SCN8A (c. 2371 G > T; p. Val791Phe), and CLCN2 (c. 481 G > A; p. Gly161Ser), from three patients, separately. All recruited patients presented typical CAE features and good prognosis. To date, CAE has been considered a complex disease caused by multiple susceptibility genes. In this study, we observed that 3% of typical CAE patients had a de novo mutation of a known monogenic epilepsy-related gene. Our study suggests that a significant proportion of typical CAE cases may be monogenic forms of epilepsy. For genetic generalized epilepsies, such as CAE, further studies are needed to clarify the contributions of de novo or inherited rare monogenic coding, noncoding and copy number variants.

Mutational screening of GABRG2 gene in Pakistani population of Punjab with generalized tonic clonic seizures and children with childhood absence epilepsy

BackgroundEpilepsy is a multifaceted and multistep disorder that disrupts the proper functioning of neurons. It is becoming increasingly clear that the responsiveness of neurons depends on the appropriate trafficking of ions across the channels in the membrane of neurons. In line with this notion, impairment among these ion channels due to mutations has gain increasing attention in molecular neuroscience. MethodsMutation analysis of the coding exons (exon 3, 5 and 9) was performed by sequencing GABRG2 to identify any complex biological entities among two different types of epilepsies. ResultsSequencing of the candidate gene “GABRG2” revealed a single polymorphic site in exon 3 in the children with absence epilepsy and generalized tonic clonic seizures. However, this single nucleotide alteration was more common in the patients with childhood absence epilepsy patients compared to the generalized cases. ConclusionA silent mutation was identified at locus 27,909 C > T in 30.66% of the total screened or analyzed cases. However, no single nucleotide polymorphism was identified in exon 5 of GABRG2 in a Pakistani population, in contrast to a study of Chinese patients with childhood absence epilepsy.

Disrupted topological organization of structural brain networks in childhood absence epilepsy

Childhood absence epilepsy (CAE) is the most common paediatric epilepsy syndrome and is characterized by frequent and transient impairment of consciousness. In this study, we explored structural brain network alterations in CAE and their association with clinical characteristics. A whole-brain structural network was constructed for each participant based on diffusion-weighted MRI and probabilistic tractography. The topological metrics were then evaluated. For the first time, we uncovered modular topology in CAE patients that was similar to healthy controls. However, the strength, efficiency and small-world properties of the structural network in CAE were seriously damaged. At the whole brain level, decreased strength, global efficiency, local efficiency, clustering coefficient, normalized clustering coefficient and small-worldness values of the network were detected in CAE, while the values of characteristic path length and normalized characteristic path length were abnormally increased. At the regional level, especially the prominent regions of the bilateral precuneus showed reduced nodal efficiency, and the reduction of efficiency was significantly correlated with disease duration. The current results demonstrate significant alterations of structural networks in CAE patients, and the impairments tend to grow worse over time. Our findings may provide a new way to understand the pathophysiological mechanism of CAE.

Epileptic characteristics and sleep architecture of drug naïve patients in childhood absence epilepsy spectrum. A prospective study

Objective: Childhood absence epilepsy (CAE) is a common pediatric epileptic disorder. Few studies examine the relationship of sleep architecture and epileptic activity, but none comprises overnight-recordings before treatment. Our aim is to describe sleep architecture and its relationship with epileptic activity by using an EEG-polygraphy study in a cohort of CAE patients before and after treatment. Methods: Twenty-eight drug-naive, healthy children were recruited (21 girls, 7 boys) with mean age of 90.1±32.6 months. Patients were separated in 3 age-groups (A: <60 mo, B: >60 mo to <120 mo and C: >120 mo). Routine and overnight EEG-polygraphy were conducted upon diagnosis, 3 and 12 months after treatment onset. Twenty-two children were treated with valproic (13: monotherapy, 7: with ethosuxomide, 2: with other drugs) and six with ethosuxomide alone. Sleep parameters, epileptic activity and arousals were measured. Results: Awake: Electroclinical absences were activated in all patients with HV (mean duration 106.25 s). Seven female patients developed photosensitivity. Sleep: Group-B demonstrated significant improvement (p < 5%) of sleep parameters a year after treatment onset. The discharges were decreased significantly in all groups, mostly in group-B. Children treated with valproic demonstrated improvement in discharges and sleep parameters (p < 5%) independently of the age group. Polyspikes were observed mainly in group-C (p=0,013). Half patients demonstrated focal discharges. All children with photosensitivity recurred after drug discontinuation. Conclusion: Improvement of sleep parameters after treatment in CAE patients is age and regiment dependent (observed in children between 5–10 years and those whose regiment included valproic). The presence of polyspikes in older children may be an explanation of the resistancy of sleep improvement in this age-group.

Altered Effective Connectivity Network in Childhood Absence Epilepsy: A Multi-frequency MEG Study.

Using multi-frequency magnetoencephalography (MEG) data, we investigated whether the effective connectivity (EC) network of patients with childhood absence epilepsy (CAE) is altered during the inter-ictal period in comparison with healthy controls. MEG data from 13 untreated CAE patients and 10 healthy controls were recorded. Correlation analysis and Granger causality analysis were used to construct an EC network at the source level in eight frequency bands. Alterations in the spatial pattern and topology of the network in CAE were investigated by comparing the patients with the controls. The network pattern was altered mainly in 1-4Hz, showing strong connections within the frontal cortex and weak connections in the anterior-posterior pathways. The EC involving the precuneus/posterior cingulate cortex (PC/PCC) significantly decreased in low-frequency bands. In addition, the parameters of graph theory were significantly altered in several low- and high-frequency bands. CAE patients display frequency-specific abnormalities in the network pattern even during the inter-ictal period, and the frontal cortex and PC/PCC might play crucial roles in the pathophysiology of CAE. The EC network of CAE patients was over-connective and random during the inter-ictal period. This study is the first to reveal the frequency-specific alteration in the EC network during the inter-ictal period in CAE patients. Multiple-frequency MEG data are useful in investigating the pathophysiology of CAE, which can serve as new biomarkers of this disorder.

Altered degree centrality in childhood absence epilepsy: A resting-state fMRI study

Modern network studies have suggested that the pathology of many neurological diseases is in fact not equally distributed over the brain but preferentially affects the hub regions. This study aims to investigate how hub regions were affected in Children with Childhood absence epilepsy (CAE) using resting-state fMRI (rs-fMRI). As one important measures obtained from rs-fMRI, degree centrality (DC) calculates the number of direct connections between a given node and the rest of the brain within the entire connectivity matrix of the brain. In this study, twenty-five CAE children and 25 healthy controls were recruited to investigate the DC changes in CAE patients. Compared with healthy controls, children with CAE showed significantly decreased DC in default mode network (DMN, medial prefrontal cortex, posterior cingulate cortex, precuneus and middle temporal cortex) and increased DC in thalamus. Importantly, significant negative correlation between the epilepsy duration and DC was found in precuneus. Our results suggested selective and specific disruption of hub nodes, especially thalamus and the highly connected brain regions within DMN, might underlie the pathophysiological mechanism of CAE.