Multiple epileptiform waves detection algorithm based on improved VMD and multidimensional feature fusion.

Auditory-evoked changes in slow oscillations and spindles correlate with memory consolidation in children with epilepsy and controls.

Anatomo-Electro-Functional Investigations in Rolandic and Peri-Rolandic Epilepsies: A conceptual framework for Stereo-EEG.

PurposeBenign rolandic epilepsy or benign epilepsy in childhood with centrotemporal spikes (BECTS) and developmental dyslexia (DD) are two of the most studied disorders in childhood. Despite decades of research, the neurophysiological mechanisms underpinning these disorders are largely unknown. Here, we use auditory event-related potentials (AERPs) to shed light on these issues, since several authors have reported the existence of language and learning impairments. AERPs reflect the activation of different neuronal populations and are suggested to contribute to the evaluation of auditory discrimination (N1), attention allocation and phonological categorization (N2), and echoic memory (mismatch negativity (MMN]).Patients and MethodsThis study aims to investigate and document AERP changes in a group of children with BECTS and another group with DD. AERPs were recorded to pure-tones and consonant–vowel (CV) stimuli in an auditory oddball paradigm in eight children with BECTS, seven with DD, and 11 gender- and age-matched controls.ResultsThe results revealed perceptual deficits for pure-tone and CV stimuli (pre-attentional and auditory discrimination) in DD, related to N1 reduced amplitude (p<0.05; Fz: 2.57 μV, Cz: 2.75 μV). The BECTS group revealed no significant results for N1; however, there was an increase in N2b latency.ConclusionThe findings in the DD group support the anchor-deficit hypothesis as an explanation for neurolinguistic deficits. The increased N2b latency in the BECTS group could be related to a potential lack of inhibitory mechanisms of pyramidal neurons, as justified by the process of epileptogenesis.

Aims: This case study explores the psychiatric and physical health complexities in a 28-year-old female service user with Autism Spectrum Disorder (ASD) and Intellectual Disability, focusing on the interplay between neuropsychiatric diagnoses, hormonal treatments, and significant mental health deterioration. It also examines the impact of hormonal changes on mood and behaviour, highlighting potential misdiagnosis of emotional instability versus neurodevelopmental conditions. The service user has a history of polycystic ovary syndrome (PCOS), irritable bowel syndrome, and Benign Rolandic Epilepsy (seizure-free since age 13). She has engaged with mental health services since adolescence, carrying multiple diagnoses including generalized anxiety disorder, post-traumatic stress disorder and emotionally unstable personality disorder (EUPD). Her mental health worsened suddenly and significantly following a switch from an oral progesterone contraceptive to the Depo-Provera injection, prompting inpatient psychiatric care.Methods: A thorough medical and psychiatric evaluation was conducted during the nine-month inpatient admission. This included a mental state examination, routine blood tests, CT head imaging, and extensive collateral history collection. Medication adjustments were made including trials of SNRI and SSRI medication, and multidisciplinary therapeutic interventions were provided. Her Depo-Provera was not re-administered. Her PCOS diagnosis was confirmed and she was started on metformin. A diagnosis of ASD was implemented seven months into the admission and her EUPD diagnosis removed. Her depressive and anxious symptoms were noted to be cyclical, worsening before her menstruation. Following MDT review, she was started on an oral contraceptive with good evidence in pre-menstrual syndrome and PCOS (estradiol with nomegestrol)Results: The service user presented with severe depression, anxiety, and active suicidal ideation, including multiple attempts to leave the ward to act on her plans. Initial physical and neurological workups were unremarkable. The pre-admission switch to Depo-Provera was identified as a likely contributing factor to her deterioration, as no other psychosocial triggers were found. She was subsequently detained under the Mental Health Act due to ongoing suicidality. Despite intensive psychiatric and therapeutic interventions, her mood remained persistently low – however after initiating an appropriate contraceptive, her symptoms showed some stabilization. Her risk of self-harm persisted.Conclusion: This case highlights the potential influence of hormonal changes on psychiatric symptoms in women with complex neurodevelopmental disorders such as ASD. It also raises important considerations about the potential misdiagnosis of personality disorders in neurodivergent individuals and the need for careful management of hormonal treatments in this population. Further research into the hormonal impact on mood disorders in neurodivergent patients is warranted.

Background:Sleep-dependent memory consolidation is supported by sleep spindles during stages 2 and 3 non-rapid eye movement sleep. Sleep spindles and sleep-dependent memory consolidation are both decreased in Rolandic epilepsy (RE). Non-invasive auditory stimulation evokes SOs and SO-spindle complexes in healthy adults but the impact on memory consolidation has been inconsistent.Objective:We investigated the effects of auditory stimulation during sleep on SOs, SO-spindle complexes, and sleep-dependent memory consolidation in children with RE and controls.Methods:A prospective cross-over study was conducted in children with RE and control. Children completed two nap visits with auditory or sham stimulation. SOs and SO-spindle complexes rates were measured offline using validated detectors. Sleep-dependent memory consolidation was assessed using the motor sequence typing task.Results:Auditory stimulation evoked SOs and SO-spindle complexes broadly with maximal effect over frontal electrodes. Compared to sham, stimulation delivered during background activity evoked SOs (29.8% increase, p<0.001) and SO-spindle complexes (16.8% increase, p<0.001) and stimulations delivered near the peak of an ongoing SO upstate maximally evoked SOs (51.3% increase, p<0.001) and SO-spindle complexes (32.3% increase, p<0.001). Changes in frontal SO (1.9% improvement per increase in SO/min; p<0.001) and SO-spindle complexes (9.5% improvement per increase in SO-spindle/min) event rates due to auditory stimulation positively predicted changes in sleep-dependent memory consolidation.Conclusion:Auditory stimulation reliably modulates sleep oscillations when delivered on background activity and during the upstate of SOs. As increased event rates improve memory consolidation, stimulation paradigms to increase SO and SO-spindle complex rates are required to enhance memory.

ABSTRACTLoss‐of‐function ZDHHC9 variants are associated with X‐linked intellectual disability (XLID), rolandic epilepsy (RE) and developmental language difficulties. This study integrates human neurophysiological data with a computational model to identify a potential neural mechanism explaining ZDHHC9‐associated differences in cortical function and cognition. Magnetoencephalography (MEG) data was collected during an auditory roving oddball paradigm from eight individuals with a ZDHHC9 loss‐of‐function variant (ZDHHC9 group) and seven age‐matched individuals without neurological or neurodevelopmental difficulties (control group). Auditory‐evoked fields (AEFs) were larger in amplitude and showed a later peak latency in the ZDHHC9 group but demonstrated normal stimulus‐specific properties. Magnetic mismatch negativity (mMMN) amplitude was also increased in the ZDHHC9 group, reflected by stronger neural activation during deviant processing relative to the standard. A recurrent neural network (RNN) model was trained to mimic group‐level auditory‐evoked responses, and subsequently perturbed to test the hypothesised impact of ZDHHC9‐driven synaptic dysfunction on neural dynamics. Results of model perturbations showed that reducing inhibition levels by weakening inhibitory weights recapitulates the observed group differences in evoked responses. Stronger reductions in inhibition levels resulted in increased peak amplitude and peak latency of RNN prediction relative to the pre‐perturbation predictions. Control experiments in which excitatory connections were strengthened by the same levels did not result in consistently stable activity or AEF‐like RNN predictions. Together, these results suggest that reduced inhibition is a plausible mechanism by which loss of ZDHHC9 function alters cortical dynamics during sensory processing.

AB-434. The effect of seizure age of onset and number of seizure focus hemispheres on cognitive, behavior comorbidities in children with Rolandic epilepsy

Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions. In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using an automated sleep spindle detector validated for use in children with and without epilepsy. Twenty-three children with RE (9 with active disease, 5F, age 6.9-12.8 years; 14 with resolved disease, 8F, age 8.8-17.8 years) and 19 age-matched and sex-matched controls (8F, age 6.9-18.7 years) were enrolled. Children with active epilepsy had decreased memory consolidation compared with control children (p = 0.001, mean percentage reduction 25.7%, 95% CI 10.3%-41.2%) and compared with children with resolved epilepsy (p = 0.007, mean percentage reduction 21.9%, 95% CI 6.2%-37.6%). Children with active epilepsy had decreased sleep spindle rates in the centrotemporal region compared with controls (p = 0.008, mean decrease 2.5 spindles per minute, 95% CI 0.7-4.4 spindles per minute). Spindle rate, but not spike rate or spike-wave index, correlated with sleep-dependent memory consolidation (p = 0.004, mean MST improvement of 3.9%, 95% CI 1.3%-6.4%, for each unit increase in spindles per minute). Children with RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.

Abstract Brain networks provided powerful tools for the analysis and diagnosis of epilepsy. This paper performed a pairwise comparative analysis on the brain networks of Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS): spike group (spike), non‐spike group (non‐spike), and control group (control). In this study, fragments with and without interictal spikes in electroencephalograms of 13 BECTS children during non‐rapid eye movement sleep stage I (NREMI) were selected to construct dynamic brain function networks to explore the functional connectivity (FC). Graph theory and statistical analysis were exploited to investigate changes in FC across different brain regions in different frequency bands. From this study, we can draw the following conclusions: (1) Both spike and non‐spike have lower energy in each brain region on the γ band. (2) With the increase of the frequency band, the FC strength of spike, non‐spike and control groups are all weakened. (3) Spikes are correlated with brain network efficiency and the small‐world property. (4) Spikes increase the FC of temporal, parietal and occipital regions except in the γ band and the absence of spikes weakens the FC of the entire brain region.

ABSTRACT Idiopathic epilepsy (IE), is a group of epileptic syndromes with no structural brain lesion, but with microstructural changes in neuronal networks leading to neuropsychological consequences. Therefore, the assessment of saccadic eye movements can provide insight into the integrity of cerebral networks as it involves large cortical and subcortical brain areas and circuitries. Describe saccadic eye movement abnormalities in patients with IE and correlate them with disease characteristics and antiseizure medication. Case–control study including IE patients followed in the Neurology Department of Razi University Hospital and healthy controls matched. Participants underwent a recording of saccadic eye movements. Pursuit, prosaccade, and anti-saccade tasks were performed. 115 patients and 98 matched healthy controls were included. The gender ratio (male to female) was 0.6. The mean age at onset was 16.3 ± 12 years. Diagnosed epileptic syndromes were juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, and rolandic epilepsy. Saccadic eye movements were impaired in 52.2% of our patients and significantly more altered in those with JME (p = .021). Prolonged horizontal saccades latencies were the most frequent eye movement abnormalities (32.1%), followed by altered horizontal smooth pursuit (22.6%). A positive correlation was found between age at eye movements recording, age at onset, disease duration, global cognitive impairment, and saccadic eye movements. However, no definite relationship was identified. Saccadic eye movement illustrates extending anatomic alterations in IE including frontal and temporoparietal cortical areas and cortico-subcortical circuits. Eye movement recording is a useful and reproducible tool in the assessment of epileptic patients and provides a better understanding of neuronal mechanisms in epilepsy.

Diagnosis of Rolandic Epilepsy in a Patient Presenting with Attention Deficit Hyperactivity Disorder

Individual-based morphological brain network changes in children with Rolandic epilepsy

Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy. In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector. Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute). Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.

This review aims to summarize the available evidence on the efficacy and tolerability of sulthiame for different forms of epilepsy. The analysis of international publications suggests that sulthiame is considered as a first-line drug for the treatment of age-dependent epilepsy with central temporal spikes (rolandic epilepsy). Sulthiame is highly effective in children with epileptic encephalopathies manifesting with spike-and-wave activity during sleep, including Landau-Kleffner syndrome, as well as in patients with myoclonic seizures. The drug might be also effective in patients with other forms of focal epilepsy, including those resistant to therapy. The tolerability of sulthiame is higher that that of old antiepileptic drugs and even levetiracetam; thus, it is associated with a lower risk of treatment interruptions due to adverse events. Moreover, sulthiame can be used for behavioral disorders (such as hyperkinetic behavior, aggressiveness) and cognitive impairments. Sulthiame can be effective in patients with epilepsy and sleep apnea.

ObjectiveWith research progress on Rolandic epilepsy (RE), its “benign” nature has been phased out. Clinicians are exhibiting an increasing tendency toward a more assertive treatment approach for RE. Nonetheless, in clinical practice, delayed treatment remains common because of the “self‐limiting” nature of RE. Therefore, this study aimed to identify an imaging marker to aid treatment decisions and select a more appropriate time for initiating therapy for RE.MethodsWe followed up with children newly diagnosed with RE, classified them into medicated and non‐medicated groups according to the follow‐up results, and compared them with matched healthy controls. Before beginning follow‐up visits, interictal magnetic data were collected using magnetoencephalography in treatment‐naïve recently diagnosed patients. The spectral power of the whole brain during initial diagnosis was determined using minimum normative estimation combined with the Welch technique.ResultsA difference was observed in the magnetic source intensity within the left caudal anterior cingulate and precentral and postcentral gyri in the delta band between the medicated and non‐medicated groups. The results revealed good discriminatory ability within the receiver operator characteristic curve. In the medicated group, there was a specific change in the frontotemporal magnetic source intensity, which shifted from high to low frequencies, compared with the healthy control group.SignificanceThe intensity of the precentral gyrus magnetic source within the delta band showed good specificity. Considering the rigor of initial treatment, the intensity of the precentral gyrus magnetic source can provide some help as an imaging marker for initial RE treatment, particularly for the timing of treatment initiation.

Insights into epileptic aphasia: Intracranial recordings in a child with a left insular ganglioglioma

Abstract ObjectivesWe describe an unusual patient with self‐limited epilepsy in childhood to aid in the accurate diagnosis and timely treatment of an atonic variant of self‐limited focal epilepsy of childhood with centrotemporal spikes.MethodsWe reviewed the medical records documenting the clinical presentation, diagnostic evaluation, and treatment. We also reviewed the relevant video electroencephalograms (EEGs).Patient DescriptionThis 3‐year‐old girl with self‐limited focal epilepsy of childhood (formerly called benign rolandic epilepsy) began having recurrent falls. Multiple clinical seizures were recorded on video EEG. The video documented generalized loss of tone resulting in falls, while the ictal EEG revealed one‐second paroxysms of 4 Hz spike‐slow‐wave discharges in the left centrotemporal region, followed by a brief generalized electrodecrement for 400 milliseconds. These findings support the diagnosis of an atypical variant of benign epilepsy with centrotemporal spikes (BECTS), known as atonic‐BECTS. Valproic acid was maximized. On follow‐up, the patient was seizure‐free with a normal EEG and normal development.DiscussionFew prior publications describe atonic‐BECTS. We present a child with atonic‐BECTS whose ictal video EEG confirms atonic seizures. While atonic seizures typically occur with generalized epilepsies, our report highlights that they can present as an atypical manifestation of self‐limited focal epilepsy in childhood.

Benign Rolandic epilepsy (BRE) is the most common cause of epilepsy in childhood. Childhood epilepsies have high heritability, and many BRE cases show an autosomal dominant inheritance pattern. Thanks to the advancement of genomics, the causal genes of BRE were being elucidated. Although BRE is a genetic disorder, most BRE cases cannot be explained by known causal genes. Pleiotropy is a common phenomenon in genes related to epilepsy. For example, the same variant in a gene related to BRE can cause diverse epileptic syndromes from mild BRE to Landau-Kleffner syndrome, a severe form of epilepsy. Although BRE is classified as idiopathic focal epilepsy, BRE can be caused by the same genes or loci related to idiopathic generalized epilepsy (IGE). Using whole exome sequencing, we tried to find causal variants and copy number variations in the known genes for BRE and IGE. We found a novel missense variant in SLC12A5 as a cause of a familial BRE. Although SLC12A5 is a known causal gene for IGE, it may cause BRE, because many genes related to BRE can cause diverse epilepsy syndromes including IGE.

ObjectiveSelf-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child’s life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. MethodsAt baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. ResultsLongitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044).There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words.Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. ConclusionsThere is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.