Idiopathic Epilepsy Syndromes Research Articles

Cognitive disorders with epilepsy: clinical-psychopathological and neuropsychological characteristics, non-pharmacological correction

IntroductionCognitive dysfunction affects the development, treatment compliance, significantly worsens the quality of life and social functioning of the patients with epilepsy.Objectives146 patients with epilepsy aged 18 to 65 participated in the study (М-40.7±2.42) were diagnosed with focal, idiopathic epilepsy and epileptic syndromes (G40.1, G40.2, G40).MethodsClinical-anamnestic, social-demographic, clinical-psychopathological, psycho-diagnostic and statistical.ResultsThe study of the attention selectivity was carried out using the Munsterberg test. Only 9 examined patients (6.16%) of the total group had sufficient indices, 35 (23.97%) patients refused from the test, while the rest – 102 (69.87%) had low test results. The overall treatment group score was 7.72, which is by 13.28 lower than in the control group, where the attention selectivity index was 21 (р<0,001), which shows a considerable attention selectivity decrease in patients with epilepsy compared to the healthy persons. According to the МоСА test results, the first treatment group patients showed better cognitive functions (1.4, р<0.001), higher attention selectivity under the Munsterberg test (0.63, р<0.001), lower anxiety level under HARS (1.45, р<0.001), lower depression level under HDRS (1.7, р<0.001) and higher subjective assessment of the life quality (2.77, р<0.05). According to the МоСА test results, the second treatment group patients showed better cognitive functions (0.73, р<0.001), higher attention selectivity under the Munsterberg test (0.27, р<0,05), lower anxiety level under HARS (4.27, р<0.05), lower depression level under HDRS (2.32, р<0.05) and higher subjective assessment of the life quality (1.21, р<0.05). According to the МоСА test results, the comparison group patients demonstrated lower cognitive functions (0.22, р<0.05), higher attention selectivity under the Munsterberg test (0.15, р<0.05), lower anxiety level under HARS (2.61, р<0.001), lower depression level under HDRS (2.49, р<0.001) and higher subjective assessment of the life quality (1.0, р<0.05). The cognitive training showed its effectiveness in healthy persons of the control group: according to the МоСА test results, cognitive functions improved (0.79, р<0.001), compared to the treatment group 2 patients (0.73, р<0.001).ConclusionsAccording to the follow-up study data 12 months after the cognitive training and psychoeducation, follow-up study showed better values under depression and anxiety scales, and improved life quality levels in the patients of treatment groups. Patients with epilepsy show a reliable cognitive functioning improvement after a 3-month computerized cognitive training. The study results indicate a more significant cognitive functioning improvement in the patients provided the combined use of the methods of psychoeducation and cognitive training, compared to the use of a cognitive training only.Disclosure of InterestNone Declared

Etiological profile of new-onset seizures among adult Egyptians

BackgroundNew-onset seizure (NOS) is defined as the first seizure within a 24-h period ever experienced by the patient. A first-ever seizure can be the first manifestation of epilepsy. Or it may be a symptom of a brain tumor, a systemic disorder, an infection, or a syndrome that deserves special attention and treatment. This study aims to identify the etiology of NOS among different age and sex groups of adult Egyptian patients. A hundred and twenty adult Egyptian patients (> 18 years) presented with acute NOS were enrolled in a hospital-based cross-sectional observational study from the emergency room and neurology outpatient clinics of our hospitals within a time period of 6 months from March till September 2018. All patients were subjected to neurological examination, laboratory, neuroimaging, and electroencephalogram investigations.ResultsAmong 120 adult patients presented with NOS, males were prevalent (63%). Older adults (age group > 55 years) were the most prevalent cohort (60%). Cerebrovascular diseases (CVDs) were the most common identified etiology of NOS (44.17%), followed by idiopathic epilepsy syndrome (18.33%), symptomatic mainly “metabolic” (11%), brain tumors (9.17%), post-traumatic epilepsy (6.67 %), encephalitis (5.83%), and cryptogenic (5%). Idiopathic epilepsy syndrome was the most common etiology (55.56%) of new-onset seizures among the young adult age group (< 36 years), while CVDs were the most common etiology (65.28%) among older adults (> 55 years). Also, CVDs were the most common etiology among males (43.4%) as well as females (45.4%). However, male predominance was the highest among post-traumatic seizures (87.5%). And female predominance was the highest among brain tumors identified etiology of NOS (54.5%).ConclusionNOS among adults are prevalent in elder males. CVDs are the most commonly identified etiology of adult NOS across males and females. Idiopathic epilepsy syndromes are the predominant etiology among younger adults.

Computational Evidence for a Competitive Thalamocortical Model of Spikes and Spindle Activity in Rolandic Epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy syndrome, characterized by sleep-activated epileptiform spikes and seizures and cognitive deficits in school age children. Recent evidence suggests that this disease may be caused by disruptions to the Rolandic thalamocortical circuit, resulting in both an abundance of epileptiform spikes and a paucity of sleep spindles in the Rolandic cortex during non-rapid eye movement sleep (NREM); electrographic features linked to seizures and cognitive symptoms, respectively. The neuronal mechanisms that support the competitive shared thalamocortical circuitry between pathological epileptiform spikes and physiological sleep spindles are not well-understood. In this study we introduce a computational thalamocortical model for the sleep-activated epileptiform spikes observed in RE. The cellular and neuronal circuits of this model incorporate recent experimental observations in RE, and replicate the electrophysiological features of RE. Using this model, we demonstrate that: (1) epileptiform spikes can be triggered and promoted by either a reduced NMDA current or h-type current; and (2) changes in inhibitory transmission in the thalamic reticular nucleus mediates an antagonistic dynamic between epileptiform spikes and spindles. This work provides the first computational model that both recapitulates electrophysiological features and provides a mechanistic explanation for the thalamocortical switch between the pathological and physiological electrophysiological rhythms observed during NREM sleep in this common epileptic encephalopathy.

The Correlation of ELP4-PAX6 With Rolandic Spike Sources in Idiopathic Rolandic Epilepsy Syndromes.

Objective: To study the single nucleotide polymorphism rs662702 of ELP4-PAX6 in patients with idiopathic rolandic epilepsy syndromes (IRES) in China and explore the relationship between the distribution of rolandic spike sources and the single nucleotide polymorphism rs662702 in ELP4-PAX6.Methods: First, clinical information was obtained from patients diagnosed with IRES. Next, the single nucleotide polymorphism rs662702 of ELP4 was analyzed by using the Sanger method. Resting-state magnetoencephalography data were collected from 17 patients. We analyzed the epileptic spike sources using the single equivalent current dipole (SECD) model and determined the spike distributions across the whole brain. Finally, Fisher's test was performed to assess the correlation between the single nucleotide polymorphism rs662702 of ELP4-PAX6 and rolandic spike sources.Results: ELP4 rs662702 T alleles were found in 10.7% of IRES patients and occurred four times more frequently in these patients than in the healthy controls. TT homozygosity was found in one IRES patient (1.3%), while no TT homozygosity was found in the healthy control group. The IRES rolandic spike sources were unilateral in sixteen patients (94.1%) and were mainly located in the anterior central gyrus (58.8%). The spike source of patients without the ELP4 rs662702 T allele was correlated with the central region (p < 0.05). The rolandic spikes sources were significant correlated with the non-central gyrus (frontal and temporal lobes) in patients with the ELP4 rs662702 T allele (p < 0.05).Conclusion: The rolandic spike sources of the IRES patients with the ELP4 rs662702 T allele were significantly associated with the non-central gyrus, including the frontal and temporal lobes. Our study confirmed for the first time in vivo that ELP4 rs662702 T allele overexpression is correlated with the rolandic spike distribution in patients with IRES and provides important insights into how genetic abnormalities can lead to brain dysfunction and into the precise targeting of abnormal discharge sources in the brain.

Connectome-based prediction of brain age in Rolandic epilepsy: a protocol for a multicenter cross-sectional study.

BackgroundRolandic epilepsy (RE) is a common pediatric idiopathic partial epilepsy syndrome. Children with RE display varying degrees of cognitive impairment. In epilepsy, age-related neuroanatomic and cognitive changes differ greatly from those observed in the healthy brain, and may be defined as accelerated brain aging. Connectome-based predictive modeling (CPM) is a recently developed machine learning approach that uses whole-brain connectivity measured with neuroimaging data (“neural fingerprints”) to predict brain-behavior relationships. The aim of the study will be to develop and validate a CPM for predicting brain age in patients with RE.MethodsA multicenter, cross-sectional study will be conducted in 5 Chinese hospitals. A total of 100 RE patients (including 50 patients receiving anti-epileptic drugs and 50 drug-naïve patients) and 100 healthy children will be recruited to undergo a neuropsychological test using the Wechsler Intelligence Scale. Magnetic resonance images will also be collected. CPM will be applied to predict the brain age of children with RE based on brain functional connectivity.DiscussionThe findings of the study will facilitate our understanding of developmental changes in the brain in children with RE and could also be an important milestone in the journey toward developing effective early interventions for this disorder.Trial registrationThe study has been registered with Chinese Clinical Trial Registry (ChiCTR2000032984).

Focal Sleep Spindle Deficits Reveal Focal Thalamocortical Dysfunction and Predict Cognitive Deficits in Sleep Activated Developmental Epilepsy.

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common focal epilepsy syndrome, yet the cause of this disease remains unknown. Now recognized as a mild epileptic encephalopathy, children exhibit sleep-activated focal epileptiform discharges and cognitive difficulties during the active phase of the disease. The association between the abnormal electrophysiology and sleep suggests disruption to thalamocortical circuits. Thalamocortical circuit dysfunction resulting in pathologic epileptiform activity could hinder the production of sleep spindles, a brain rhythm essential for memory processes. Despite this pathophysiologic connection, the relationship between spindles and cognitive symptoms in epileptic encephalopathies has not been previously evaluated. A significant challenge limiting such work has been the poor performance of available automated spindle detection methods in the setting of sharp activities, such as epileptic spikes. Here, we validate a robust new method to accurately measure sleep spindles in patients with epilepsy. We then apply this detector to a prospective cohort of male and female children with CECTS with combined high-density EEGs during sleep and cognitive testing at varying time points of disease. We show that: (1) children have a transient, focal deficit in spindles during the symptomatic phase of disease; (2) spindle rate anticorrelates with spike rate; and (3) spindle rate, but not spike rate, predicts performance on cognitive tasks. These findings demonstrate focal thalamocortical circuit dysfunction and provide a pathophysiological explanation for the shared seizures and cognitive symptoms in CECTS. Further, this work identifies sleep spindles as a potential treatment target of cognitive dysfunction in this common epileptic encephalopathy.SIGNIFICANCE STATEMENT Childhood epilepsy with centrotemporal spikes is the most common idiopathic focal epilepsy syndrome, characterized by self-limited focal seizures and cognitive symptoms. Here, we provide the first evidence that focal thalamocortical circuit dysfunction underlies the shared seizures and cognitive dysfunction observed. In doing so, we identify sleep spindles as a mechanistic biomarker, and potential treatment target, of cognitive dysfunction in this common developmental epilepsy and provide a novel method to reliably quantify spindles in brain recordings from patients with epilepsy.

Clinico - aetiological profile of new onset seizures among adult Egyptians

Abstract Objectives We aimed to evaluate the clinical and etiological profile of new onset seizures in adults with the help of laboratory and neuroimaging studies in a tertiary care hospital in Cairo. Methods An observational hospital based cross sectional analytical study of 120 cases with new onset seizures were included in the study, who had their first seizure above the age of 18, and admitted to Neurology OPCs and ER of Ain Shams University and Nasr city Health Insurance Hospitals between March 2018 to September 2018. We determined the type of seizure and etiological factors. Results In the 120 patients, whose specific incidence of acute new onset seizures was found to be highest in males in the age group &amp;gt; 55 years 48 (66.67 %), we found the most common seizure type was generalized seizure 56 (46.67%) and the most common etiologic factor was cerebrovascular diseases 58 (48.33 %). Patients presented with cluster seizures was 31 (25.83 %) and status epileptics was 14 (11.67 %). The most common metabolic insult was hypocalcemia 12 (10%) and hyponatremia 8 (6.76%). Conclusion Cerebrovascular disease was the most common etiology after 55 years of age whereas Idiopathic epilepsy syndrome and Metabolic insults were common in younger individuals (18-35) years of age. Patients presented with cluster seizures were mostly found to have SOL.

Network analysis of prospective brain development in youth with benign epilepsy with centrotemporal spikes and its relationship to cognition.

Benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood idiopathic localization-related epilepsy syndrome. BECTS presents normal routine magnetic resonance imaging (MRI); however, quantitative analytic techniques have captured subtle cortical and subcortical magnetic resonance anomalies. Network science, including graph theory (GT) analyses, facilitates understanding of brain covariance patterns, potentially informing in important ways how this common self-limiting epilepsy syndrome may impact normal patterns of brain and cognitive development. GT analyses examined the developmental covariance among cortical and subcortical regions in children with new/recent onset BECTS (n=19) and typically developing healthy controls (n=22) who underwent high-resolution MRI and cognitive assessment at baseline and 2years later. Global (transitivity, global efficiency, and modularity index [Q]) and regional measures (local efficiency and hubs) were investigated to characterize network development in each group. Associations between baseline-based GT measures and cognition at both time points addressed the implications of GT analyses for cognition and prospective cognitive development. Furthermore, an individual contribution measure was investigated, reflecting how important for cognition it is for BECTS to resemble the correlation matrices of controls. Groups exhibited similar Q and overall network configuration, with BECTS presenting significantly higher transitivity and both global and local efficiency. Furthermore, both groups presented a similar number of hubs, with BECTS showing a higher number in temporal lobe regions compared to controls. The investigated measures were negatively associated with 2-year cognitive outcomes in BECTS. Children with BECTS present a higher-than-normal global developmental configuration compared to controls, along with divergence from normality in terms of regional configuration. Baseline GT measures demonstrate potential as a cognitive biomarker to predict cognitive outcome in BECTS 2years after diagnosis. Similarities and differences in developmental network configurations and their implications for cognition and behavior across common epilepsy syndromes are of theoretical interest and clinical relevance.

Autism spectrum disorder and attention-deficit/hyperactivity disorder-related symptoms in benign childhood epilepsy with centrotemporal spikes: A prospective case–control study

BackgroundBenign childhood epilepsy with centrotemporal spikes (BECTS), one of the most common idiopathic epilepsy syndromes in children, has been associated with neuropsychological problems. PurposeThe objective of this study was to investigate the frequency of symptoms related to comorbid neurodevelopmental disorders, the autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children with typical BECTS, and to identify corresponding risk factors. MethodsChildren and adolescents with typical BECTS aged 6–16 years were included in the study period from January 1, 2017, to December 31, 2017. Children with atypical presentations of BECTS, other neurological disorders, and preexisting neuropsychiatric disorders were excluded. The ASD and ADHD were assessed by the Social Communication Questionnaire (SCQ) and the Turgay Diagnostic and Statistical Manual of Mental Disorders – 4th Edition – Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S), respectively. Patients' scores were compared with those of healthy subjects. Correlation analyses were performed to evaluate the association between the age at seizure onset, the total number of seizures and the SCQ and T-DSM-IV-S scores. ResultsFifty-eight children with BECTS and 60 healthy children participated in the study. The total SCQ score, the SCQ reciprocal social interaction score, and the SCQ communication score significantly differed between children with BECTS and the control group (p = 0.001, p < 0.001, p = 0.001, respectively). The total ADHD score was significantly different between patients and controls (p < 0.001). A significant difference was observed between patients and controls in terms of the T-DSM-IV-S hyperactivity–impulsivity score and the T-DSM-IV-S inattention score (p = 0.012, p < 0.001, respectively). The age at seizure onset was significantly correlated with the total SCQ score (p = 0.03). The Spearman's correlation coefficient was 0.352 for the total SCQ score, indicating a positive association between the age at seizure onset and the total SCQ score. ConclusionChildren with typical BECTS may have an increased risk of suffering from symptoms of ASD and ADHD. Children with late onset of seizures may be more likely to develop neuropsychological disturbances regarding ASD and ADHD.

Dysfunctional white-matter networks in medicated and unmedicated benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white-matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white-matter structural architecture, it cannot detect neural activity or white-matter functions. Recent studies demonstrated the functional organization of white-matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white-matter dysfunctions in BECT. Resting-state fMRI data were collected from 24 new-onset drug-naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white-matter functional networks were obtained using a clustering analysis on voxel-by-voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub-bands (Slow-5:0.01-0.027, Slow-4:0.027-0.073, Slow-3:0.073-0.198, and Slow-2:0.198-0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white-matter networks based on their correlations with multiple gray-matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency-specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow-3 and Slow-4. This study provided further support on the existence of white-matter functional networks which exhibited frequency-specific properties, and extended abnormalities of rolandic area from the perspective of white-matter dysfunction in BECT.

De novo absence status epilepticus in three paediatric patients: a new idiopathic epilepsy syndrome?

Absence status epilepticus (ASE) is a prolonged generalized absence seizure that usually lasts for hours and can even last for days. The main symptom is the altered content of consciousness while the patient may be alert and partly responsive. We describe the electroclinical features, treatment, and evolution of three paediatric patients with de novo ASE with an excellent response to valproic acid (VPA). Three paediatric patients presented with non-convulsive status epilepticus and an acute confusional state with impaired consciousness and EEG abnormalities compatible with typical ASE, associated with generalized spike-and-wave paroxysms at 2.5-4Hz, as the first epileptic manifestation at eight, three, and nine years of age, respectively. No significant personal and/or family history was reported. None of the patients had absence seizures or any other type of seizure before the occurrence of the ASE. All of them responded well to VPA and had a benign disease course. Neuroradiological imaging was normal in all patients. These three cases presented with ASE as the first manifestation of their epilepsy; none of them had any other type of seizure before the event or during their follow-up, which was long-term in one. All patients had an excellent response to VPA. Our three cases presented with generalized typical ASE as the first manifestation of their epilepsy. De novo ASE might be considered as a well-defined idiopathic epilepsy syndrome or a variant of an idiopathic generalized epilepsy syndrome, such as a particular type or variant of childhood absence epilepsy.

Photosensitivity in generalized epilepsies.

Photosensitivity, which is the hallmark of photosensitive epilepsy (PSE), is described as an abnormal EEG response to visual stimuli known as a photoparoxysmal response (PPR). The PPR is a well-recognized phenomenon, occurring in 2-14% of patients with epilepsy but its pathophysiology is not clearly understood. PPR is electrographically described as 2-5Hz spike, spike-wave, or slow wave complexes with frontal and paracentral prevalence. Diagnosis of PPR is confirmed using intermittent photic stimulation (IPS) as well as video monitoring. The PPR can be elicited by certain types of visual stimuli including flicker, high contrast gratings, moving patterns, and rapidly modulating luminance patterns which may be encountered during e.g., watching television, playing video games, or attending discotheques. Photosensitivity may present in different idiopathic (genetic) epilepsy syndromes e.g. juvenile myoclonic epilepsy (JME) as well as non-IGE syndromes e.g. severe myoclonic epilepsy of infancy. Consequently, PPR is present in patients with diverse seizure types including absence, myoclonic, and generalized tonic-clonic (GTC) seizures. Across syndromes, abnormalities in structural connectivity, functional connectivity, cortical excitability, cortical morphology, and behavioral and neuropsychological function have been reported. Treatment of photosensitivity includes antiepileptic drug administration, and the use of non-pharmacological agents, e.g. tinted or polarizing glasses, as well as occupational measures, e.g. avoidance of certain stimuli.

Gender aspects of medico-social adaptation in adults with early onset of epilepsy

To study the relationship between indicators of clinical picture and social adaptation in idiopathic and symptomatic epilepsies with onset before adulthood depending on patient's gender. The cross-sectional study was carried out. The study group included 212 women and 171 men, aged 24-60 years, with confirmed diagnosis of epilepsy with onset before 18 years. Seventy-three patients were diagnosed with symptomatic epilepsy, 310 with idiopathic epilepsy. In 120 patients, the frequency of seizures was rarer than once a year. All patients had secondary education and were on treatment with antiepileptic drugs. In symptomatic epilepsy with early onset, gender differences in family and educational status were not identified. Regardless of gender, patients with myoclonus had higher education more frequently than patients with absence and tonic-clonic seizures. Patients with the combination of different types of seizures, irrespective from etiology and gender, had secondary education more frequently. Women with rare generalized seizures more frequently had higher education and were married. Unmarried men with rare generalized seizures lived separately from their relatives more frequently. To author's opinion, the contradiction in indicators of social adaptation in men with rare generalized seizures, to the great extent, is related to the phenomenon of self-stigmatization than to the influence of disease. The results can be used in rehabilitation of patients with idiopathic epilepsy syndromes.

Jeavons syndrome – updated review

Summary Introduction. Eyelid myoclonia and absences (ELMA) was first described by Jeavons in 1977 as a separate type of photosensitive epilepsy. Aim and method. The aim is to consider the updated electro-clinical pathophysiology and to discuss terminology, classification and differential diagnosis. The review includes our own research and relevant papers on the subject of Jeavons syndrome (JS). Review and differential diagnosis. Definition: Jeavons syndrome is a generalized idiopathic (genetic) epilepsy syndrome (IGE) characterized by eyelid myoclonia, other seizures (absences, myoclonic and or generalized tonic-clonic) and EEG paroxysms induced by voluntary or on command eye closure, in the light and photosensitivity. Demographical data: The prevalence of JS has been reported to vary from 7.3% to 12.9% among idiopathic generalized epilepsies and 2.5% to 2.7% among all patients with epileptic disorders. Etiology: JS, as is the case for all idiopathic generalized epilepsies, is genetic and the familial preponderance and concordance is high. Pathophysiology: Three factors are important in order for JS to manifest clinically; the genetic predisposition, the voluntary or on command eye closure and the light input. Clinical forms of JS: we have identified four forms of JS; early onset (&lt; 4 years), mild form, classical form and an ELMA-JME form. Diagnosis: the diagnosis of JS is based on the history, clinical observation and provocation and the confirmation with an EEG. Differential diagnosis: is easily made from tics, other idiopathic generalized or focal cryptogenic/symptomatic epilepsies. Conclusion. JS is characterized by unique electro-clinical features evoked by voluntary or on command eye closure in the light and photosensitivity.

Altered Structural and Functional Feature of Striato-Cortical Circuit in Benign Epilepsy with Centrotemporal Spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common form of childhood idiopathic focal epilepsy syndrome. We investigated quantitative evidence regarding brain morphology and functional connectivity features to provide insight into the neuroanatomical foundation of this disorder, using high resolution T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI in 21 patients with BECT and in 20 healthy children. The functional connectivity analysis, seeded at the regions with altered gray-matter (GM) volume in voxel-based morphometry (VBM) analysis, was further performed. Then, the observed structural and functional alteration were investigated for their association with the clinical and behavior manifestations. The increased GM volume in the striatum and fronto-temporo-parietal cortex (striato-cortical circuit) was observed in BECT. The decreased connections were found among the motor network and frontostriatal loop, and between the default mode network (DMN) and language regions. Additionally, the GM of striatum was negatively correlated with age at epilepsy onset. The current observations may contribute to the understanding of the altered structural and functional feature of striato-cortical circuit in patients with BECT. The findings also implied alterations of the motor network and DMN, which were associated with the epileptic activity in patients with BECT. This further suggested that the onset of BECT might have enduring structural and functional effects on brain maturation.

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy.

Idiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires. Cognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9-14years, were assessed and compared with 27 age- and education-matched healthy controls. Compared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p<0.0001), working memory deficits (p<0.003), auditory verbal long-term memory deficits (p<0.0021), and more frequent psychosocial symptoms (p<0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls. Results suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms.

Risk factors of cognitive outcome in patients with atypical benign partial epilepsy/pseudo-Lennox syndrome (ABPE/PLS) and continues spike and wave during sleep (CSWS)

BackgroundAtypical benign partial epilepsy/pseudo-Lennox syndrome (ABPE/PLS) and continues spike and wave during sleep (CSWS) belong to a spectrum of idiopathic focal epilepsy syndromes ranging from benign Rolandic epilepsy to more severe seizure disorders, which are commonly characterized by the association of various epileptic seizure types, aggravation of spike-wave discharges during slow sleep, and cognitive and/or behavioral disturbances.The Aim of our study was to evaluate the risk factors that influence cognitive outcome in patients with ABPE/PLS and CSWS in a retrospective analysis. MethodsThirty patients fulfilled the diagnostic criteria for ABPE/PLS and 12 for CSWS and were chosen for the descriptive analysis. Cognitive achievement was evaluated according to psychological tests and school performances. ResultsSevere global and specific cognitive disturbances occurred almost regularly in cases of ABPE. Already at the time of epilepsy presentation the level of cognitive performance was lower than that of the normal population. At the time of disease presentation only 56% of the children had IQ within the standard range (≥85). We observed that the level of cognitive developmental delay did not change significantly during the disease process. We were not able to observe any statistically significant connection between the development of EEG abnormalities and cognitive development. The conclusion can be drawn that many patients exhibit cognitive impairment at disease presentation which is not affected significantly during the treatment process. Judging from the observed data, we assume that EEG abnormalities, duration of active epilepsy, and antiepileptic medication have less influence on the cognitive development than was previously assumed.

RBFOX1 and RBFOX3 Mutations in Rolandic Epilepsy

Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1 have been reported in a range of neurodevelopmental diseases, including idiopathic generalized epilepsy. The RBFOX1 protein and its homologues (RBFOX2 and RBFOX3) regulate alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. In this study, we explored if structural microdeletions and exonic sequence variations in RBFOX1, RBFOX2, RBFOX3 confer susceptibility to rolandic epilepsy (RE), a common idiopathic focal childhood epilepsy. By high-density SNP array screening of 289 unrelated RE patients, we identified two hemizygous deletions, a 365 kb deletion affecting two untranslated 5′-terminal exons of RBFOX1 and a 43 kb deletion spanning exon 3 of RBFOX3. Exome sequencing of 242 RE patients revealed two novel probably deleterious variants in RBFOX1, a frameshift mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3 (p.Y287*). Although the three variants were inherited from unaffected parents, they were present in all family members exhibiting the RE trait clinically or electroencephalographically with only one exception. In contrast, no deleterious mutations of RBFOX1 and RBFOX3 were found in the exomes of 6503 non-RE subjects deposited in the Exome Variant Server database. The observed RBFOX3 exon 3 deletion and nonsense mutation suggest that RBFOX3 represents a novel risk factor for RE, indicating that exon deletions and truncating mutations of RBFOX1 and RBFOX3 contribute to the genetic variance of partial and generalized idiopathic epilepsy syndromes.

Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy

To explore the potential contribution of genetic variation in voltage-gated chloride channels to epilepsy, we analyzed CLCN family (CLCN1-7) gene variant profiles in individuals with complex idiopathic epilepsy syndromes and determined the expression of these channels in human and murine brain. We used parallel exomic sequencing of 237 ion channel subunit genes to screen individuals with a clinical diagnosis of idiopathic epilepsy and evaluate the distribution of missense variants in CLCN genes in cases and controls. We examined regional expression of CLCN1 in human and mouse brain using reverse transcriptase PCR, in situ hybridization, and Western immunoblotting. We found that in 152 individuals with sporadic epilepsy of unknown origin, 96.7% had at least one missense variant in the CLCN genes compared with 28.2% of 139 controls. Nonsynonymous single nucleotide polymorphisms in the "skeletal" chloride channel gene CLCN1 and in CLCN2, a putative human epilepsy gene, were detected in threefold excess in cases relative to controls. Among these, we report a novel de novo CLCN1 truncation mutation in a patient with pharmacoresistant generalized seizures and a dystonic writer's cramp without evidence of variants in other channel genes linked to epilepsy. Molecular localization revealed the unexpectedly widespread presence of CLCN1 mRNA transcripts and the ClC-1 subunit protein in human and murine brain, previously believed absent in neurons. Our findings support a possible comorbid contribution of the "skeletal" chloride channel ClC-1 to the regulation of brain excitability and the need for further elucidation of the roles of CLCN genes in neuronal network excitability disorders.

Ictal Priapism as an Autonomic Manifestation of Panayiotopoulos Syndrome

Panayiotopoulos syndrome is an idiopathic epilepsy syndrome presenting with a large variety of autonomic symptoms. The mechanism of autonomic symptoms is still not well understood. A neurologically normal 13-month-old boy presented on 2 occasions with complex partial status epilepticus that included significant ictal priapism. Inpatient brain magnetic resonance imaging (MRI) scan showed restricted diffusion-weighted imaging within his left temporal lobe and electroencephalograms (EEGs) left temporal slowing only. An outpatient EEG 6 months later showed abundant multifocal, predominantly posterior, as well as irregular generalized spike-and-slow-wave discharges on normal background consistent with the diagnosis of Panayiotopoulos syndrome. Ictal priapism is a previously undescribed phenomenon that is consistent with parasympathetic manifestations noted in this young boy. Acute postictal MRI and EEG findings suggest that this undeniably fascinating seizure semiological sign may be localized to the left temporal region.