Spike-wave Activity Research Articles

Learning Disabilities and Epilepsy: About a Clinical Case

Landau-Kleffner syndrome (LKS) is an epilepsy syndrome of childhood, characterized by auditory verbal agnosia and severe electroencephalographic abnormalities. It happens between 3-7 years of age, 20% without seizures. A 6-years-old boy, with normal psychomotor development, who begins to experience difficulties in understanding the meaning of words, sometimes with incoherent speech and writing difficulties (irregular handwriting, spelling mistakes). Neurological evaluation showed loss of comprehensive language with auditory verbal agnosia, difficulties in fine motor skills and in graphomotor coordination. After clinical suspicion, the diagnosis of SLK was confirmed by night video-electroencephalogram (EEG): abundant paroxysmal activity of bilateral and independent fronto-center-temporal spikes and spike-wave activity, with an almost continuous exacerbation during sleep. Initially treated with valproate and clobazam, without improvement, he started prednisolone, with improvement in language, writing and normalization of the EEG. Knowledge of this syndrome is important for differential diagnosis with other neurological disorders, especially learning difficulties.

14 and 6 Hz like spike wave activity is a common finding in young patients with Prader-Willi syndrome.

Our aim was to characterize the 14 and 6 like spike wave activity seen on electroencephalograms (EEG) in children with Prader-Willi syndrome (PWS) undergoing polysomnograms. We performed a retrospective review of children with PWS and healthy controls who underwent diagnostic polysomnograms between January 1, 2007, and December 31, 2020, at SickKids, Toronto, Canada. EEGs from the polysomnograms were reviewed for the presence of the 14 and 6 like spike wave activity and its characteristics. Clinical correlation of the EEG variant with sleep-disordered breathing indices from the polysomnograms was also evaluated. A total of 94 children with PWS and 50 healthy controls were included. The median age and interquartile range for the cohort was 1.42 (0.6, 4.2) years. There were 50 (53.2%) males in the PWS cohort. The EEG variant prevalence in this cohort was 51.0% (n = 48) in children with PWS and 0% for the healthy controls. 14 and 6 Hz like spike wave activity was bilateral in 52% (25/48) children with PWS. The waves had a negative deflection in almost all patients, 44/48 (92%), with PWS. It was predominantly located in the frontal leads for children with PWS, 23/48 (47.9%). It most frequently occurred during non-rapid eye movement stage 2 sleep for children with PWS, 25/48 (52.0%). The mean (standard deviation) frequency was 6.8 (0.97) Hz. The median (interquartile range) length of the waves was 1.1 (0.8, 1.4) seconds in children with PWS. There was no correlation between the presence of the EEG variant and sleep-disordered breathing indices in children with PWS. The 14 and 6 Hz like spike wave activity EEG variant was present in more than 50% of a pediatric cohort of children with PWS compared with 0% in healthy children. This EEG variant did not appear to be associated with sleep-disordered breathing indices in children with PWS and is of unknown clinical significance. Alzaid M, Sunkonkit K, Massicotte C, Otsubo H, Amin R, Al-Saleh S. 14 and 6 Hz like spike wave activity is a common finding in young patients with Prader-Willi syndrome. J Clin Sleep Med. 2024;20(8):1227-1232.

Прогнозування ризику розвитку розладів аутистичного спектра в дітей з епілептичними енцефалопатіями

Predicting the risk of developing autism spectrum disorders (ASD) in children with epileptic encephalopathies (EE) is an important task, which makes it possible to identify the most significant risk factors and develop ways of their modification. Purpose - to develop a model for predicting the risk of developing ASD in young children with EE. Materials and methods. 75 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of EE were examined. The most informative clinical, neurophysiological, and neuroimaging indicators for predicting the risk of clinical manifestations of ASD were determined: age of onset of epileptic seizures, index of spike-wave activity during NREM sleep, frequency and amplitude of alpha rhythm, frequency and amplitude of epileptiform activity, fractional anisotropy and mean diffusion coefficient in the Broca’s center, fractional anisotropy in the Wernicke center and knee of the corpus callosum. The multiple linear regression method was used to predict the risk of developing ASD symptoms. Results. A model for predicting the risk of developing clinical manifestations of ASD in children with EE has been developed. It was established that the risk of developing clinical manifestations of ASD increases with a decrease in the age of onset of epileptic seizures, decrease in the frequency and amplitude of the alpha rhythm according to electroencephalography (EEG) data, increase of the index of spike-wave activity, frequency and amplitude of epileptiform activity, increase in the index of fractional anisotropy in the anterior part of the arcuate tract, decrease in the average diffusion coefficient in the area of the Broca’s center, fractional anisotropy in the Wernicke center and the knee of the corpus callosum according to magnetic resonance tractography. Conclusions. A regression model for predicting the risk of clinical manifestations of ASD in children with EE was developed with an average error of approximation of 13.2% and a coefficient of determination of 0.74, which is recommended for use in clinical practice in order to form groups of children at high risk of ASD. Such children require further dynamic monitoring and early intervention by specialists of a multidisciplinary team for timely identification and correction of ASD symptoms The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Adrenergic mechanisms of absence status epilepticus.

Absence status epilepticus is a prolonged, generalized absence seizure that lasts more than half an hour. The mechanisms underlying the absence of status epilepticus are still not entirely understood. In this study, the study concentrates on alpha2-adrenergic mechanisms of absence status using the WAG/Rij rat model. In this model, a prolonged spike-wave activity was associated with a specific behavioral state in transition between sedation («alpha2-wakefulness»)-resembled absence status in human patients. Pharmacological activation of alpha2-adrenoreceptors may target the locus coeruleus (presynaptic alpha2-adrenoreceptors) and the thalamic part of the seizure-generating thalamocortical system (postsynaptic alpha2B-adrenoreceptors). The duration of EEG-behavioral correlates of absence status was not dose-dependent and was predetermined by the intensity of absence seizures at baseline. This model could help scientists better understand the underlying causes of absence status and develop more effective and personalized treatments for each individual.

Serum Levels of Neuropeptides in Epileptic Encephalopathy With Spike-and-Wave Activation in Sleep

BackgroundEpileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) is a syndrome of childhood, characterized by diffuse or generalized spike-wave activity in electroencephalography during non–rapid eye movement sleep. Neuropeptides have been demonstrated in several studies to function in the sleep-wake cycle and display convulsant and anticonvulsant features. In this study, we aimed to investigate the relationship between EE-SWAS and neuropeptides such as dynorphin, galanin, ghrelin, leptin, melatonin, and orexin. MethodsThis multicenter study was conducted from July 2019 to January 2021. There were three groups: Group 1 contained patients with EE-SWAS. Group 2 consisted of patients with self-limited focal epilepsy of childhood (SeLFE), and group 3 was the control group. Levels of neuropeptides were compared in the sera of these three groups. ResultsThere were 59 children aged between four and 15 years. Group 1 contained 14 children, group 2 contained 24 children, and group 3 contained 21 children. The level of leptin is higher and the level of melatonin is lower in group 1 than in group 3 (P = 0.01 and P = 0.005, respectively). In group 3, the level of orexin was lower than in both groups 2 and 3 (P = 0.01 and P = 0.01). ConclusionsThese data show that the level of leptin was higher and the level of melatonin was lower in patients with EE-SWAS than in the control group. Furthermore, patients with EE-SWAS had lower orexin levels than both the control group and patients with SeLFE. Further research is required to understand the potential role of these neuropeptides in the pathophysiology of EE-SWAS.

Differential diagnosis of familial adult myoclonic epilepsy.

Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. Thedifferential diagnoses and frequent presentations leading to misdiagnosisofFAMEwereinvestigatedfromtheavailableliteratureandreportedbasedonanexpertopinionsurvey. The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder. Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.

Interhemispheric Symmetry and Asymmetry of Absence Type Spike-Wave Discharges Caused by Systemic Administration of Pentylenetetrazole

Absence epilepsy is a specific generalized non-convulsive form occurring almost exclusively in children and adolescents. It is traditionally thought that the resulting seizure is completely generalized in the cortex of both hemispheres, as seen in humans on surface electroencephalograms and magnetoencephalograms. However, most studies were performed on animals, mainly rats – genetic (WAG/Rij and GAERS lines) and pharmacological models, since signals not only from the cortex, but also from subcortical structures such as the thalamus must be measured, what cannot be done on humans, who have no medical indications for intracranial surgery. In animals, measurements of local field potentials were almost always made from one hemisphere in order to cover the maximum number of brain structures involved. At the same time, the degree of synchrony of seizure onsets and terminations in different hemispheres in animals was practically not studied, and the markup itself in the vast majority of cases was done on the basis of one channel from motor or somato-sensory cortex. This work aims to reveal differences and similarities in the course of spike-wave discharges (the main encephalographic marker of absence seizures) in the cortex of the two hemispheres in a known pharmacological model of rats exposed to pentylentetrazole. For discharge detection, a method of automatic discharge marking is proposed and its sensitivity and specificity are evaluated using records of nine animals. We used it to mark seizures in symmetrical cortical sites from both hemispheres separately. According to the results of the analysis of seizure duration it turned out that for five out of nine animals the distribution of discharges significantly differed between the hemispheres, and for the other four was equal. Consequently, in the rat model, spike-wave activity may be generalized both symmetrically and asymmetrically, which may be due to individual peculiarities or different discharge triggering scenarios.

Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy.

Spike-wave discharges are the hallmark of idiopathic generalized epilepsy. They are caused by a disorder in the thalamocortical network. Commercially available anti-epileptic drugs have pronounced side effects (i.e., sedation and gastroenterological concerns), which might result from a low selectivity to molecular targets. We suggest a specific subtype of adrenergic receptors (ARs) as a promising anti-epileptic molecular target. In rats with a predisposition to absence epilepsy, alpha2 ARs agonists provoke sedation and enhance spike-wave activity during transitions from awake/sedation. A number of studies together with our own observations bring evidence that the sedative and proepileptic effects require different alpha2 ARs subtypes activation. Here we introduce a new concept on target pharmacotherapy of absence epilepsy via alpha2B ARs which are presented almost exclusively in the thalamus. We discuss HCN and calcium channels as the most relevant cellular targets of alpha2 ARs involved in spike-wave activity generation.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats.

The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

EEG Network Analysis in Epilepsy with Generalized Tonic-Clonic Seizures Alone.

Many contradictory theories regarding epileptogenesis in idiopathic generalized epilepsy have been proposed. This study aims to define the network that takes part in the formation of the spike-wave discharges in patients with generalized tonic-clonic seizures alone (GTCSa) and elucidate the network characteristics. Furthermore, we intend to define the most influential brain areas and clarify the connectivity pattern among them. The data were collected from 23 patients with GTCSa utilizing low-density electroencephalogram (EEG). The source localization of generalized spike-wave discharges (GSWDs) was conducted using the Standardized low-resolution brain electromagnetic tomography (sLORETA) methodology. Cortical connectivity was calculated utilizing the imaginary part of coherence. The network characteristics were investigated through small-world propensity and the integrated value of influence (IVI). Source localization analysis estimated that most sources of GSWDs were in the superior frontal gyrus and anterior cingulate. Graph theory analysis revealed that epileptic sources created a network that tended to be regularized during generalized spike-wave activity. The IVI analysis concluded that the most influential nodes were the left insular gyrus and the left inferior parietal gyrus at 3 and 4 Hz, respectively. In conclusion, some nodes acted mainly as generators of GSWDs and others as influential ones across the whole network.

Diagnostics and age-related evolution of Lennox–Gastaut syndrome. Management in diverse patient age periods

Lennox–Gastaut syndrome is an epileptic encephalopathy with onset in childhood. The classical triad of diagnostic criteria is well known: 1) presence of various types of refractory epileptic seizures (tonic, atypical absences, myoclonic, tonic/atonic drop attacks, generalized tonic-clonic, focal); 2) cognitive disorders with frequent behavioral disorders (not always evident by the beginning of epileptic seizures); 3) generalized, slow (≤2.5 Hz) spike-wave activity of wakefulness and generalized paroxysmal fast activity on sleep electroencephalogram. Despite the seizure onset usually occurring before the age of 8 (peak at 3–5) years old, the Lennox–Gastaut syndrome is often featured with a lifelong course. Many patients with this syndrome suffer from refractory epilepsy in adulthood, however, not always being provided a proper syndromological diagnosis. Expanding the criteria to diagnose the Lennox–Gastaut syndrome discussed here would allow to choose a proper treatment algorithm. Rufinamide is the drug of the second choice in the adjunctive therapy of epileptic seizures associated with Lennox–Gastaut syndrome. However, a pediatric-to-adult clinic transition of patients with Lennox–Gastaut syndrome may pose some obstacles. Herein, an effective patient management requires not only seizure control, but also improvement of patient's quality of life by influencing cognitive and behavioral issues, sleep disorders, disability (both physical and social), educational problems and employment.

Calcium/calmodulin-dependent protein kinase IIα heterozygous knockout mice show electroencephalogram and behavioral changes characteristic of a subpopulation of schizophrenia and intellectual impairment

Cognitive deficit remains an intractable symptom of schizophrenia, accounting for substantial disability. Despite this, little is known about the cause of cognitive dysfunction in schizophrenia. Recent studies suggest that schizophrenia patients show several changes in dentate gyrus structure and functional characteristic of immaturity. The immature dentate gyrus (iDG) has been replicated in several mouse models, most notably the CaMKIIα heterozygous mouse (CaMKIIα-hKO). The current study characterizes behavioral phenotypes of CaMKIIα-hKO mice and determines their neurophysiological profile using electroencephalogram (EEG) recording from hippocampus. CaMKIIα-hKO mice were hypoactive in home-cage environment; however, they displayed less anxiety-like phenotype, suggestive of impulsivity-like behavior. In addition, severe cognitive dysfunction was evident in CaMKIIα-hKO mice as examined by novel object recognition and contextual fear conditioning. Several EEG phenomena established in both patients and relevant animal models indicate key pathological changes associated with the disease, include auditory event-related potentials and time–frequency EEG oscillations. CaMKIIα-hKO mice showed altered event-related potentials characterized by an increase in amplitude of the N40 and P80, as well as increased P80 latency. These mice also showed increased power in theta range time–frequency measures. Additionally, CaMKIIα-hKO mice showed spontaneous bursts of spike wave activity, possibly indicating absence seizures. The GABAB agonist baclofen increased, while the GABAB antagonist CGP35348 and the T-Type Ca2+ channel blocker Ethosuximide decreased spike wave burst frequency. None of these changes in event-related potentials or EEG oscillations are characteristic of those observed in general population of patients with schizophrenia; yet, CaMKIIα-hKO mice likely model a subpopulation of patients with schizophrenia.

Spectrum of EEG Findings in Patients with Leptomeningeal Carcinomatosis and Seizures: Correlation with Neurodiagnostic Results and Outcome.

Purpose: Leptomeningeal carcinomatosis (LC) is a devastating condition in patients with systemic malignancies or primary brain tumors. Although much is known about neuro-radiologic investigations, there is very little information about EEG findings in these patients. Whether EEG is correlated with cranial magnetic resonance imaging (MRI) results and survival has not been investigated. Methods: Medical records of 2340 adult patients with the diagnosis of brain tumor, either metastatic (Group 1) or primary (Group 2), between 2000-2021 were reviewed for the presence of LC and seizures. Demographic and clinical features, laboratory results and Karnofsky performance scores of included patients were noted. Available routine EEG recordings were re-evaluated. Any possible correlation between EEG findings-MRI and EEG findings-survival were investigated statistically. Results: Sixty-six patients with LC and seizures were identified. The most common malignancies were lung cancer and glioblastoma multiforme. Twenty-six EEG recordings of 17 patients in Group 1, and 13 EEGs of 9 patients in Group 2 were available for final analysis. The most common EEG characteristic was background slowing (73%). The most frequent findings were rhythmic periodic patterns or spike wave activity (27%). Sporadic epileptiform discharges (8%) or ictal recordings (4%) were very rare. None of the EEG features correlated with MRI results or survival. Conclusion: There are various EEG patterns in patients with LC and seizures. The most common findings are related to background activity, with rhythmic periodic patterns or spike wave activity being observed less commonly. EEG characteristics do not predict MRI findings or survival.

Hemimegalencephaly and Epileptic Encephalopathy Associated with a Variant of Uncertain Significance of the TRIO Gene

Objectives: Electrical status epilepticus during sleep (ESES) is a type of EEG pattern seen in children with childhood-onset epileptic seizures and cognitive, language and motor regression. ESES has been associated with different etiologies, with or without structural abnormalities of the brain. To replace the term “ESES”, the recent Position Paper of the ILAE Taskforce on Nosology and Definitions introduced the term Epileptic Encephalopathy with Spike-Wave Activity during Sleep (EE-SWAS), which represents an activation of epileptiform activity, typically 1.5-2.5 Hz during NREM sleep, in a previously normal child and leads to cognitive and motor regression. Pathogenic variants in the TRIO gene are associated with autosomal dominant mental retardation type 44 (MRD44), which is characterized by mildly delayed global development resulting in variable intellectual deficits, learning difficulties, and variable dysmorphic features mostly represented by facial asymmetry, microcephaly, abnormalities of the fingers, and dental anomalies. Materials and methods: We present the case of a 13-year-old girl with onset of atonic seizures at the age of 3 who had undergone different types of antiepileptic drug (AED) therapies and was seizure-free 4 years later. She had an acquired impaired cognitive status as well as hemimegalencephaly, multiple hypopigmented patches on her legs and a large patch of hypopigmentation on the left side of her face extending towards the scalp (Becker’s nevus), dental anomalies (gingival hyperplasia, ogival palate), periventricular gliosis and electroencephalographic and (EEG) findings consistent with SWAS. Outcomes: Genetic testing confirmed a heterozygous variant of uncertain significance (VUS) of the TRIO gene, possibly associated with autosomal dominant MRD44. Although our patient presented with some phenotypic similarities to MRD44, her cognitive impairment improved with control of the SWAS pattern and AED adjustments. Conclusion: Association of structural anomalies of white matter, hemimegalencephaly, and encephalopathy with SWAS and a VUS mutation of the TRIO gene might suggest a different genetic neurocutaneous syndrome altogether.

Childhood Lennox-Gastaut Syndrome, Low Set Ears, Unilateral Cryptorchidism: A New Variant

Background: Childhood Lennox-Gastaut syndrome is a heterogeneous epileptic encephalopathy with onset between the age of one and seven years. It is associated with more than one seizure type that are drug-resistant, a slow spike-wave activity in the EEG recording and mental retardation .The syndrome was first described by William Gordon Lennox in 1950, and later by Henri Gastaut in 1966. The condition was first called “Lennox-Gastaut syndrome” by Ernst Niedermeyer in 1968. The association of Lennox-Gastaut syndrome with low set ears and cryptorchidism has not been reported before. Patients and Methods: A two and three months boy was referred late during February, 2022 because of seizures that started during the last week of December, 2021 and were not controlled with multiple anti-epileptic drugs. The diagnosis was made and an evidence-based therapeutic approach is described. Results: When the boy was first seen he was still experiencing frequent generalized tonic clonic seizures that may last for about ten minutes and myoclonic seizures, despite he was receiving four anti-seizure drugs in good doses including valproic acid, clobazam, levetiracetam, topiramate. The drugs made the boy sleepy most of the day. Brain MRI was performed during August, 2021 for the evaluation of developmental retardation showed normal findings. The presence of more than seizure type, the EEG recording, and the developmental and retardation together with resistance of seizures to polytherapy allowed confident diagnosis of Lennox-Gastaut syndrome. Anti-epileptics were replaced with other drugs and evidence-based agents were used for neuroprotection and improving development and mental retardation. Treatment was associated with a significant improvement. Conclusion: A new variant of childhood Lennox-Gastaut syndrome is reported and the experience with its early treatment is described.

Exacerbation of eyelid myoclonia in patients with epilepsy and eyelid myoclonia receiving cannabidiol.

Epilepsy with eyelid myoclonia or Jeavons Syndrome (JS) is a childhood genetic generalized epilepsy. Its clinical features include eyelid myoclonia (hallmark) with or without brief absences, eyelid closure-induced seizures and/or electroencephalographic (EEG) paroxysms (generalized polyspikes and/or generalized spike-wave activity at 3-6Hz, elicited by closure of eyelid) and photosensitivity. Broad-spectrum anti-seizure medications are often utilized for the management of JS patients. A wide variety of medications may be utilized especially in refractory cases. Efficacy or safety of cannabidiol (CBD) for JS has not been studied. We describe two cases of exacerbation of eyelid myoclonia in JS which correlated with CBD use and resolved after CBD discontinuation. These cases highlight that caution should be practiced when using CBD for JS as it can potentially worsen eyelid myoclonia.

Spike-wave seizures, slow-wave sleep EEG and morphology of substantia nigra pars compacta in WAG/Rij rats with genetic predisposition to absence epilepsy

Spike-wave discharges (SWDs) are EEG hallmarks of absence epilepsy, and they spontaneously appear in adult WAG/Rij rats. SWDs are known to be vigilance-dependent and are modulated by monoaminergic mechanisms. It is also known that loss of neurons in the center of the nigrostriatal dopamine system, substantia nigra pars compacta (SNc), is associated with a variety of sleep disorders. We hypothesized that a disorder of the nigrostriatal dopamine system described for WAG/Rij rats might facilitate generation of SWDs through changes in vigilance state and the quality of sleep. Our study was conducted in ‘epileptic’ and ‘non-epileptic’ phenotype (less than 1 SWDs per h). Analysis included (1) EEG examination, i.e., analysis of SWDs, rudimentary SWDs and slow wave sleep EEG and (2) microstructural examination of SNc, i.e., measuring its size and the number of neurons and glial cells. No differences in size and cellular content of SNc were found between ‘epileptic’ and ‘non-epileptic’ phenotypes. Meanwhile in ‘epileptic’ subjects, the number of SWDs correlated with the number of neurons in SNc (SWDs more frequently occurred in subjects with fewer neurons in SNc). Rudimentary SWDs were found in both phenotypes. No differences in number and duration of rudimentary SWDs were found between ‘epileptic’ and ‘non-epileptic’ phenotypes. Spike-wave EEG activity showed strong association with the number of neurons in SNc: subjects with fewer neurons in SNc were characterized by higher number of SWDs and longer rudimentary SWDs. In sum, our data suggested that intense epileptic EEG activity (in the form of SWDs and rudimentary SWDs) might lead to sleep disruption. However, the lack of direct correlations between sleep parameters and SWDs number indicated that the link between sleep features, SNc cellularity and spike-wave EEG activity could be more complex than we had expected.

Heritability of Magnetoencephalography Phenotypes Among Patients With Genetic Generalized Epilepsy and Their Siblings.

ObjectiveTo assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography resting-state recordings in patients and their healthy siblings.MethodsIn a prospective, cross-sectional design, we investigated source-reconstructed power and functional connectivity in patients, siblings, and controls. We analyzed 5 minutes of cleaned and awake data without epileptiform discharges in 6 frequency bands (1–40 Hz). We further calculated intraclass correlations to estimate heritability for the imaging patterns within families.ResultsCompared with controls (n = 45), patients with GGE (n = 25) showed widespread increased functional connectivity (θ to γ frequency bands) and power (δ to γ frequency bands) across the spectrum. Siblings (n = 18) fell between the levels of patients and controls. Heritability of the imaging metrics was observed in regions where patients strongly differed from controls, mainly in β frequencies, but also for δ and θ power. Network connectivity in GGE was heritable in frontal, central, and inferior parietal brain areas and power in central, temporo-parietal, and subcortical structures. Presence of generalized spike-wave activity during recordings and medication were associated with the network patterns, whereas other clinical factors such as age at onset, disease duration, or seizure control were not.ConclusionMetrics of brain oscillations are well suited to characterize GGE and likely relate to genetic factors rather than the active disease or treatment. High power and connectivity levels co-segregated in patients with GGE and healthy siblings, predominantly in the β band, representing an endophenotype of GGE.

Automated quantification of spike-wave activity may be used to predict the development of electrical status epilepticus in sleep (ESES) in children with perinatal stroke

ObjectiveContinuous spike and wave in slow-wave sleep (CSWS), an epileptic encephalopathy, occurs after perinatal stroke where it is associated with cognitive decline. CSWS features a distinct EEG pattern, electrical status epilepticus in sleep (ESES). Biomarkers for the prediction of ESES have not been identified but will facilitate earlier diagnosis and treatment. We hypothesized that spike-frequency and differences in power spectra would be predictive of subsequent ESES. MethodsA cross-sectional study comparing EEG spike-frequency and Power before the development of ESES in patients with perinatal stroke, patients with focal epilepsy, and appropriate controls. Results43 patients met the inclusion criteria; 11 stroke-ESES, 10 stroke controls, 14 epilepsy-ESES, 8 epilepsy controls. ESES patients had higher pre-diagnosis mean spike-frequency (24.0 ± 24 versus 6.6 ± 9.1 SW/min, p = 0.002) than patients that did not develop ESES; these differences present ~ 3 years before ESES diagnosis. Pre-diagnosis, normalized delta power (1–4 Hz) was higher in the stroke-ESES group (105.7 ± 58 dB/Hz) compared to stroke controls (57.4 ± 45 dB/Hz, p = 0.036). ConclusionSpike-frequency and delta power may represent EEG biomarkers of the risk of developing ESES in children with perinatal stroke. SignificanceEEG biomarkers may be used by clinicians to assess which patients are more at-risk for ESES.Using spike-frequency, clinicians may be able to identify patients at risk of developing ESES.

Active avoidance learning in WAG/Rij rats with genetic predisposition to absence epilepsy

Neurological disorders are often accompanied by impairment of memory, attention deficit that cause learning difficulties. Better understanding of learning problems in neurological patients might help to improve the quality of their life. Here we studied the character of fear-based associative learning using the standard active avoidance test in WAG/Rij rats with genetic predisposition to absence epilepsy. Electroencephalographic properties of spike-wave seizures (i.e., hallmarks of absence epilepsy) were examined at the age of 5 and 7 m. Around 24 % of rats did not express epileptic activity despite genetic predisposition. In the active avoidance test, 6 m old rats with the epileptic phenotype needed more trails to obtain the first avoidance than non-epileptic rats, but showed the same number of avoidances to reach the learning criterion. The total time of spike-wave activity positively correlated with the outcomes of avoidance performance only in subjects with severe epilepsy, but not in subjects with mild epilepsy.In order to evaluate early sensory (epigenetic) factors governing cognitive comorbidities in adult WAG/Rij rats, we performed bilateral whisker trimming during PN1-8 and PN9-16. This led to a quicker development of SWD, but did not influence cognitive abilities at the age of 6 m.In summary, epileptic WAG/Rij rats had difficulties with executive functions before the first avoidance of adverse stimulus, rather than impairment of memory after the first avoidance. Our data assume that cognitive comorbidities in epileptic WAG/Rij rats primarily may relate to executive deficit during the initial stage of avoidance test and secondary - to impairment of short-term memory. This fits well to outcomes of clinical studies in patients with generalized epilepsy.