Video Electroencephalography Research Articles

Protocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study.

BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl's Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes.

Mild encephalitis/encephalopathy with a reversible splenial lesion associated with systemic Mycoplasma pneumoniae infection in North America: a case report

BackgroundMild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent.Case presentationsA 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, and abnormal tensing movements for 2 days, following a 6-day period of fatigue, fever, and spastic abdominal pain. Emergent work-up in our department ruled out acute gastrointestinal pathologies. Given the high fevers and encephalopathy, there was concern for meningitis or encephalitis. His cerebrospinal fluid profile was concerning for viral meningitis, however extensive infectious workup was negative. Magnetic resonance imaging of his brain demonstrated a T2 fluid-attenuated inversion recovery sequence hyperintensity in the splenium of the corpus callosum, read as postictal changes by radiology. Continuous video electroencephalography demonstrated mild diffuse encephalopathy without electrographic correlate of his tensing episodes. He was determined to have mild encephalitis/encephalopathy with a reversible splenial lesion in the setting of a postinfectious etiology. He was treated with a single pulse-dose of intravenous methylprednisolone, following which he gradually returned to his baseline the next day. Repeat magnetic resonance imaging and cerebrospinal fluid evaluation demonstrated resolution of previous findings. He was ultimately diagnosed with an acute M. pneumoniae infection, which was determined to be the etiology of his mild encephalitis/encephalopathy with a reversible splenial lesion.ConclusionsThe presentation of mild encephalitis/encephalopathy with a reversible splenial lesion is often nonspecific, with behavioral symptoms ranging from irritability to disturbances in consciousness. Its prevalence is higher in the pediatric population, and is thought to be more of an infection-associated encephalopathy syndrome in this group. The infections are typically viral, more so than bacterial. M. pneumoniae, a small, atypical bacterium lacking a peptidoglycan cell wall, is a common respiratory tract pathogen found in children. Despite infection being so rampant in the pediatric community, very few cases of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States have been reported. In Eastern and Southern Asian countries, however, M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion is much more commonly reported. This difference may potentially lie in the prevalence of macrolide-resistant M. pneumoniae, which is significantly higher in Asian countries given more liberal antibiotic use in M. pneumoniae infections. Infections with macrolide-resistant M. pneumoniae are reportedly greater in severity and duration. This amplified state may suggest a correlation between intensity of inflammatory response and the development of mild encephalitis/encephalopathy with a reversible splenial lesion. Given the rarity of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States, much remains unknown regarding predilection and optimum treatment strategy. As rates of macrolide-resistant M. pneumoniae begin to rise in the United States, maintaining a high level of suspicion remains key in better understanding this unique phenomenon.

Local glucose metabolism is unaltered in reversible splenial lesion syndrome.

Transient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES. We retrospectively analysed patients with RESLES after reductions in antiseizure medications during in-hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests. Local glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p=0.902 and p=0.535, respectively). We found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible.

Towards a wearable multi-modal seizure detection system in epilepsy: A pilot study

ObjectiveTo explore the possibilities of wearable multi-modal monitoring in epilepsy and to identify effective strategies for seizure-detection. MethodsThirty patients with suspected epilepsy admitted to video electroencephalography (EEG) monitoring were equipped with a wearable multi-modal setup capable of continuous recording of electrocardiography (ECG), accelerometry (ACM) and behind-the-ear EEG. A support vector machine (SVM) algorithm was trained for cross-modal automated seizure detection. Visualizations of multi-modal time series data were used to generate ideas for seizure detection strategies. ResultsThree patients had more than five seizures and were eligible for SVM classification. Classification of 47 focal tonic seizures in one patient found a sensitivity of 84% with a false alarm rate (FAR) of 8/24 h. In two patients each with nine focal nonmotor seizures it yielded a sensitivity of 100% and a FAR of 13/24 h and 5/24. Visual comparisons of features were used to identify strategies for seizure detection in future research. ConclusionsMulti-modal monitoring in epilepsy using wearables is feasible and automatic seizure detection may benefit from multiple modalities when compared to uni-modal EEG. SignificanceThis study is unique in exploring a combination of wearable EEG, ECG and ACM and can help inform future research on monitoring of epilepsy.

Case Report: Multisystem Autoimmune and Overlapping GAD65-Antibody-Associated Neurological Disorders With Beneficial Effect of Epilepsy Surgery and Rituximab Treatment

Glutamic acid decarboxylase (GAD) antibodies are associated with disabling conditions such as stiff person syndrome, temporal lobe epilepsy (TLE), limbic encephalitis, cerebellar ataxia (CA), and ocular movement disorders, which are usually chronic and difficult to treat. GAD-related TLE has poor response to anti-seizure medications and immune therapies, and epilepsy surgery is rarely successful. We report on a 47-year-old female with history of migraine, autoimmune thyroid disease, ankylosing spondylitis, and drug-resistant TLE. A video electroencephalography recorded frequent seizures with temporo-insular semiology, correlating to left temporal epileptiform activity and left mesiotemporal hyperintensity on magnetic resonance imaging. GAD autoimmunity was confirmed by very high GAD antibody titers in serum and cerebrospinal fluid. Steroids, immunoglobulins, and cyclophosphamide had no effect, and selective left amygdalectomy was performed based on very restricted hypermetabolism on positron-emission tomography. After transient seizure freedom, significant epilepsy improvement was observed in spite of memory decline. Transient worsening was noted 1 year later during diabetes mellitus manifestation and 5 years later during presentation of progressive CA, which stabilized on rituximab treatment. We believe this case illustrates the diversity and the frequent overlap of GAD-associated disorders, the need of early and aggressive immunotherapy in severe patients, as well as the possible benefit from epilepsy surgery in some GAD-TLE.

Calidad de vida en pacientes con epilepsia y crisis no epilépticas psicógenas: una revisión sistemática

Psychogenic non epileptic seizures (PNES) are disruptive changes in behaviour, thought, or emotion that resemble an epileptic seizure, but without paroxysmal neuronal discharge detectable by electroencephalography (EEG), and are not caused by another medical condition. On the other hand, epileptic seizures (ES) are defined as clinical events that reflect the presence of hypersynchronous discharges of neurons located in the cerebral cortex, which have the particularity of starting and ending abruptly. The diagnosis of epilepsy is made when an epileptic seizure was experienced and there is a risk of having another. The objective of this paper is to present the results of a systematic review of articles that have studied quality of life in people with PNES and ES. This review has been performed following the PRISMA guide (Preferred Reporting Items for Systematic reviews and Meta-Analyses). Prior to the beginning of the search, a protocol was carried out and it is published for consultation in the International prospective register of systematic reviews (PROSPERO). The review includes randomized and non-randomized, quantitative or mixed, cross-sectional or longitudinal studies, published in english or spanish until 2020. In addition, participants had to be over 16 years old. PNES diagnosis must have been confirmed by video-electroencephalography (VEEG) or a similar procedure-which is considered the gold standard for the diagnosis of PNES. In regards to research, PubMed, SciELO, Cochrane Library, Lilacs, Dialnet and Science Direct databases were reviewed. In addition, authors from epilepsy centers in Argentina were contacted in order to obtain local data and references of included studies were reviewed. The quality of the articles was evaluated using the guidelines of a tool created in a previous review by Brown and Reuber for PNES studies. It has been chosen to present the data in a narrative synthesis. As a result of the search, 678 references were obtained and after eliminating duplicates, 614 results were left. After filtering the results according to the selection criteria, 11 articles and a doctoral thesis were included. Their publication years date from 1998 to 2020. Most of them (10) were developed in the United States, one in Turkey and one in Argentina. English language was prevalent, being the doctoral thesis the only one written in spanish. Regarding the quality of the studies, most of them (9) were rated as medium quality; two of them as low quality and one as high quality. In regard to the scales employed to measure quality of life, the most widely used was Quality Of Life in Epilepsy (QOLIE), and QOLIE-31 was the most frequently used version of the instrument. It was found that people with PNES had a lower quality of life, mostly associated with the presence of psychopathology. Depression constitutes the most recurrent factor, followed by anxiety and personality traits. These results are consistent with previous research and gain importance when analysing the high rates of psychiatric comorbidity found in both groups of patients. To a lesser extent, other factors have shown a relationship with quality of life: taking anti-epileptic drugs, seizure-related factors (frequency, severity, duration of the disease), family functioning, demographic factors (sex), trauma and somatization. This study has potential limitations, including methodological problems of the articles included (non-randomized studies, dissimilar sample sizes between groups), quality of life scales dissimilarity among studies, and not having performed a meta-analysis, which would have provided more detailed information. Nevertheless, in conclusion, it could be stated that, in general, people with PNES have a lower quality of life than people with epileptic seizures. https://doi.org/10.1688/interd.2022.39.2.6

A Retrospective Analysis of Psychiatric Presurgical Evaluation of Children and Adolescents Evaluated for Epilepsy Surgery in a Comprehensive Epilepsy Care Unit of Mumbai.

Background Epilepsy being one of the most prevalent neurological diseases in children is associated with psychopathology and academic concerns. Epilepsy surgery is considered for refractory epilepsy at some centers in India and hence this study was undertaken to find out prevalence and type of psychopathology in children and adolescents with refractory epilepsy before epilepsy surgery. Methods All data were analyzed from the records of patients undergoing preepilepsy surgery protocol workup in comprehensive center of epilepsy care at a general municipal hospital in Mumbai. A record of 150 children and adolescents in the age group of 3 to 18 years over a period of 10 years was taken and all details of demographics, epilepsy, and psychopathology were recorded. Results The mean age for our sample was 11.4 ± 3.4 years and a male preponderance was seen. Majority (80%) of the children were pursuing education. The duration of seizure disorder was approximately 4.41 + 2.36 years and complex partial seizures were seen commonly in 50% of the children. Both magnetic resonance imaging (MRI) and video electroencephalography (VEEG) findings revealed right sided lateralization followed by left in majority of the patients. Psychopathology was seen in 70 (46%) patients with mental retardation, hyperkinetic disorders affecting attention and activity and oppositional defiant disorder, and unspecified mental disorder due to underlying brain damage being the type of International Classification of Disease-10th Revision (ICD-10) disorders seen. Patients with psychopathology showed a left-sided predominance on their MRI and VEEG findings for laterality of the epileptogenic focus as compared with right side. Conclusion Refractory seizures and associated psychopathology impact family life, friendships, and academics and worsen prognosis and quality of life. Screening for psychopathology in children with epilepsy would therefore lead to better outcomes especially prior to epilepsy surgery.

Comparison of Semiologic Characteristics of Psychogenic Nonepileptic Seizures and Frontal and Temporal Lobe Seizures

Introduction: Video electroencephalography monitoring (VEM) is the gold standard for differentiating epileptic seizures and psychogenic nonepileptic seizures (PNES). This study aimed to compare the semiologic characteristics of PNES and frontal and temporal seizures. Materials and Methods: This study was conducted retrospectively on the records of patients aged over 18 years with PNES and frontal and temporal lobe seizures, who were followed up as inpatients in the Ufuk University Neurology Clinic VEM unit between 2016 and 2020. Seventy-two patients who met the study criteria and were hospitalized during this period were included in the study. The preictal, ictal, and postictal semiologic characteristics of the patients were examined and compared in terms of the seizure type. Results: Of the 72 patients included in the study, 29.2% had PNES, 15.3% had frontal lobe epilepsy, and 41.7% had temporal lobe epilepsy. The mean age of the patients was 32.74 ± 9.84 years. In patients with PNES, frequent semiologic changes, frequent medical visits, ability to execute commands, remembering test words, forced eye closure, subjective sensory symptoms, ictal crying, tremor in extremities, gradual onset, fluctuating course, postictal pseudo-sleep, pelvic thrusting movement, and arrhythmic synchronous extremity movement manifestations were determined to be significantly higher compared with frontal and temporal lobe epilepsies. Conclusion: Seizure semiology is important in the differential diagnosis of epileptic seizures and PNES. VEM remains the gold standard for differentiating PNES and epileptic seizures.

Whole Genome Sequencing: Early Diagnostic Tool in Newborns with Refractory Seizures.

Whole Genome Sequencing: Early Diagnostic Tool in Newborns with Refractory Seizures.

Comparison of Acute Withdrawal and Slow Taper of Antiseizure Medications during Video Electroencephalographic Monitoring: Efficacy for Shortening of Hospital Stay.

Antiepileptic medications (ASMs) are withdrawn at the epilepsy monitoring unit to facilitate seizure recordings. The effect of rapid tapering of ASMs on the length of hospital stay has not been well documented. We compared the mean length of hospital stay between patients who underwent acute ASM withdrawal and slow dose tapering during long-term video electroencephalography (EEG) monitoring. We retrospectively investigated 57 consecutive patients admitted to the epilepsy monitoring unit regarding the mean length of hospital stay in the acute ASM withdrawal group (n = 30) and slow-taper group (n = 27). In the acute-withdrawal group, all ASMs were discontinued once the patients were admitted. In the slow-taper group, the doses of ASMs were gradually reduced by 15–30% daily. We also evaluated the safety of the acute-withdrawal and slow-taper protocols. The mean lengths of hospital stay were 3.8 ± 1.92 and 5.2 ± 0.69 days in the acute-withdrawal and slow-taper groups, respectively (p < 0.005). No severe adverse events, including status epilepticus, were observed. Acute ASM withdrawal has the advantage of significantly reducing the length of hospital stay over slow tapering, without any severe adverse effects.

Clinical analysis of 15 patients with epileptic spasms and focal seizures as a single ictal event in neonatal period

Objective: To investigate the phenomenon of epileptic spasms (ES) and focal seizures (FS) in a single ictal event (FS-ES phenomenon) and to study the etiology, manifestations, and prognosis of this phenomenon. Methods: The data of the 15 neonates who had ES and FS in a single ictal event, according to video-electroencephalography (VEEG) recording in Department of Neonatology of Children's Hospital of Fudan University during the period of January 2018 to December 2019, was analyzed retrospectively. Results: Of the 15 neonates, 7 were male and 8 were female. Gestational age was 39 (32-42) weeks. Birth weight was 3 100 (1 825-3 850) g. The initial onset age of convulsions was 2 (1-10) days. The age of the first discovery of FS-ES phenomenon was 25 (14-32) days. The age of seizure-free was 7(1-27) months. All of the initial seizure types were FS. The FS-ES phenomenon of 15 patients started with FS. The FS-ES phenomenon manifested in 2 forms: FS followed by ES (12 cases), ES appeared during an FS without interrupting FS (2 cases). In 1 neonate the spasm occurred in both forms. The etiology included genetic factors (9 cases), intracranial infection (1 case), abnormal brain tissue structure (2 cases), and etiology was unknown in 3 cases. All the neonates had a poor prognosis except one. Conclusions: The FS-ES phenomenon in the neonatal period starts with FS. There are various etiologies. Etiologies of most patients are genetic factors. Most of the patients have a poor prognosis.

Detecting Tonic-Clonic Seizures in Multimodal Biosignal Data From Wearables: Methodology Design and Validation.

BackgroundVideo electroencephalography recordings, routinely used in epilepsy monitoring units, are the gold standard for monitoring epileptic seizures. However, monitoring is also needed in the day-to-day lives of people with epilepsy, where video electroencephalography is not feasible. Wearables could fill this gap by providing patients with an accurate log of their seizures.ObjectiveAlthough there are already systems available that provide promising results for the detection of tonic-clonic seizures (TCSs), research in this area is often limited to detection from 1 biosignal modality or only during the night when the patient is in bed. The aim of this study is to provide evidence that supervised machine learning can detect TCSs from multimodal data in a new data set during daytime and nighttime.MethodsAn extensive data set of biosignals from a multimodal watch worn by people with epilepsy was recorded during their stay in the epilepsy monitoring unit at 2 European clinical sites. From a larger data set of 243 enrolled participants, those who had data recorded during TCSs were selected, amounting to 10 participants with 21 TCSs. Accelerometry and electrodermal activity recorded by the wearable device were used for analysis, and seizure manifestation was annotated in detail by clinical experts. Ten accelerometry and 3 electrodermal activity features were calculated for sliding windows of variable size across the data. A gradient tree boosting algorithm was used for seizure detection, and the optimal parameter combination was determined in a leave-one-participant-out cross-validation on a training set of 10 seizures from 8 participants. The model was then evaluated on an out-of-sample test set of 11 seizures from the remaining 2 participants. To assess specificity, we additionally analyzed data from up to 29 participants without TCSs during the model evaluation.ResultsIn the leave-one-participant-out cross-validation, the model optimized for sensitivity could detect all 10 seizures with a false alarm rate of 0.46 per day in 17.3 days of data. In a test set of 11 out-of-sample TCSs, amounting to 8.3 days of data, the model could detect 10 seizures and produced no false positives. Increasing the test set to include data from 28 more participants without additional TCSs resulted in a false alarm rate of 0.19 per day in 78 days of wearable data.ConclusionsWe show that a gradient tree boosting machine can robustly detect TCSs from multimodal wearable data in an original data set and that even with very limited training data, supervised machine learning can achieve a high sensitivity and low false-positive rate. This methodology may offer a promising way to approach wearable-based nonconvulsive seizure detection.

Clinical spectrum of pediatric drug refractory epilepsy secondary to parieto-occipital gliosis

BackgroundParieto-occipital (PO) gliosis secondary to perinatal insult, is often associated with neurologic sequelae such as epilepsy, which can be drug resistant. ObjectiveTo evaluate the spectrum of epilepsy among patients presenting with seizures in association with PO gliosis and to determine factors that influence the development of epileptic encephalopathy (EE) in these patients. MethodsWe retrospectively evaluated patients aged < 16 years with drug refractory epilepsy and PO gliosis who underwent video electroencephalography (Video EEG). We evaluated the clinical, electrophysiological and radiological profile including treatment responsiveness of subjects with EE. ResultsOne hundred one patients (M: F=3:1) with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited into the study. Based on video EEG findings, Based on video EEG findings, the commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from parieto occipital region were observed in 28 patients. Ictal onset from frontal, temporal and fronto temporal region were observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively. Comparison of the seizure types and ictal onset among subgroups of patients with occipital gliosis, parieto-occipital gliosis and parieto-occipital with frontal gliosis revealed that the extent of gliosis did not significantly affect seizure semiology or ictal onset. EE was significantly associated with presence of neonatal seizures (p = 0.04), hypoglycaemia (p = 0.005), longer duration of ICU stay (Z score = −3.55, p < 0.001) and younger age of onset of seizures (Z score = - 2.97, p = 0.03). Eleven out of eighteen (64.7%) subjects with EE showed greater than 50% improvement in seizure frequency following three months of pulse intravenous methylprednisolone therapy. ConclusionsAmong subjects with PO gliosis on MRI, the seizure semiology is unaffected by laterality, radiologic extension beyond the occipital cortex or presence of ulegyria. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. Development of EE is strongly related to the age of onset of seizures, neonatal seizures, prolonged NICU admission, rather than the radiological findings. Subjects with EE and PO gliosis show good response to intravenous pulse methylprednisolone.

Drug-resistant 'Non-Lesional' Visual Sensitive Epilepsies of Childhood - Electroclinical Phenotype-Genotype Associations.

Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy. To study the genetic heterogeneity of drug-resistant visual sensitive epilepsy of childhood. A retrospective chart review was conducted on patients in the pediatric age group between 2016 and 2018, with drug-resistant epilepsy (DRE) and video electro encephalography (VEEG) documented reflex photosensitivity, eye-condition sensitivity. Those patients who underwent genetic testing with targeted next-generation sequencing using an epilepsy gene panel were selected. During the study period, out of 96 patients who underwent genetic testing, 4 patients (4.17%) with sporadic DRE presented with clinical phenotypes ranging from myoclonic-atonic epilepsy, generalized epilepsy with eyelid myoclonia as well as febrile and unprovoked seizures, along with visual sensitivity. Video EEG documented abnormalities ranged from occipital, posterior-cortex and generalized discharges with "eyes-closed state" triggered, self-induced "smart-phone" triggered, photosensitive focal-onset and generalized myoclonic seizures. Accompanying developmental impairment was noted. These patients who were investigated with clinical exome sequencing were detected to have mutations in not only SCN1A genes (pathogenic exonic and intronic variants) but also CHD2 (pathogenic) and CACNA1H genes (a familial febrile-seizure susceptibility variant of unknown significance). The series highlights the complex genetics of drug-resistant visual-sensitive epilepsy of childhood. Such genotype-phenotype associations throw light on the role of ion-channel and non-ion channel genes on reflex epileptogenesis in this group of patients.

High-resolution electric source imaging for presurgical evaluation of tuberous sclerosis complex patients

ObjectiveWe retrospectively assessed the localizing value of patient-history-based semiology (PHS), video-based semiology (VS), long-term monitoring video electroencephalography (LTM-VEEG) and interictal high resolution electric source imaging (HR-ESI) in the presurgical workup of patients with tuberous sclerosis complex (TSC). MethodsData from 24 consecutive TSC surgical candidates who underwent both HR-ESI and LTM-VEEG was retrospectively collected. PHS and VS were analyzed to hypothesize the symptomatogenic zone localization. LTM-VEEG and HR-ESI localization results were extracted from the diagnostic reports. Localizing value was compared between modalities, taken the resected/disconnected area of surgical patients in consideration. HR-ESI’s impact on the epileptogenic zone hypothesis and surgical workup was evaluated. ResultsSemiology, interictal EEG, ictal EEG and HR-ESI were localizing in 25%, 54%, 63% and 79% of patients. Inter-modality concordance ranged between 33–89%. In good surgical outcome patients, PHS, VS, interictal EEG, ictal EEG and HR-ESI showed concordance with resected area in 1/9 (11%), 0/9 (0%), 4/9 (44%), 3/9 (33%) and 6/9 patients (67%). HR-ESI positively impacts clinical management in 50% of patients. ConclusionsIn presurgical evaluation of TSC patients, semiology often has limited localizing value. Presurgical work-up benefits from HR-ESI. SignificanceOur findings may advice future presurgical epilepsy workup of TSC patients with the ultimate aim to improve outcome.

Early initial video-electro-encephalography combined with variant location predict prognosis of KCNQ2-related disorder

BackgroundThe clinical features of KCNQ2-related disorders range from benign familial neonatal seizures 1 to early infantile epileptic encephalopathy 7. The genotype-phenotypic association is difficult to establish.ObjectiveTo explore potential factors in neonatal period that can predict the prognosis of neonates with KCNQ2-related disorder.MethodsInfants with KCNQ2-related disorder were retrospectively enrolled in our study in Children’s Hospital of Fudan University in China from Jan 2015 to Mar 2020. All infants were older than age of 12 months at time of follow-up, and assessed by Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) or Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV), then divided into three groups based on scores of BSID-III or WPPSI-IV: normal group, mild impairment group, encephalopathy group. We collected demographic variables, clinical characteristics, neuroimaging data. Considered variables include gender, gestational age, birth weight, age of the initial seizures, early interictal VEEG, variant location, delivery type. Variables predicting prognosis were identified using multivariate ordinal logistic regression analysis.ResultsA total of 52 infants were selected in this study. Early interictal video-electro-encephalography (VEEG) (β = 2.77, 1.20 to 4.34, P = 0.001), and variant location (β = 2.77, 0.03 to 5.5, P = 0.048) were independent risk factors for prognosis. The worse the early interictal VEEG, the worse the prognosis. Patients with variants located in the pore-lining domain or S4 segment are more likely to have a poor prognosis.ConclusionsThe integration of early initial VEEG and variant location can predict prognosis. An individual whose KCNQ2 variant located in voltage sensor, the pore domain, with worse early initial VEEG background, often had an adverse outcome.

The Comparison Between Neuropsychological Features of Psychogenic Non-epileptic Seizures and Epileptic Seizures

Background: Both epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) are often associated with some degree of cognitive impairment. Video electroencephalography (EEG) monitoring is the gold standard for diagnosing PNES. This diagnostic procedure is costly and available in specific tertiary centers. Neuropsychological assessment can provide clues for the differential diagnosis of PNES and ES and help clarify the nature and etiology of these two disorders. Objectives: Therefore, this study aimed to compare the neuropsychological profiles of PNES and ES patients. Methods: In this analytical cross-sectional study, 30 patients with ES and 31 patients with PNES were compared by neuropsychiatric tests, such as the Wechsler Adult Intelligence scale (WAIS), Addenbrooke’s Cognitive examination (ACE), and California Verbal Learning test (CVLT). Results: There was a female predominance in the PNES group (female-to-male ratio = 4.16/1, P = 0.003). In the PNES group, 77.4% of the patients had a psychiatric disorder versus 66.7% of the patients in the ES group; however, the difference was not statistically significant (P = 0.34). The mean score of total intelligence was higher in the PNES group (84.77 ± 16.94), compared to the ES group (83.63 ± 10.04); however, the difference was not significant (P = 0.75). Based on the mean subscale scores, the digit symbol score (WAIS-IV subscale) and memory score (ACE subscale) were significantly higher in the PNES group compared to the ES group (P = 0.037 and 0.032, respectively). Conclusions: This study showed that neuropsychological assessments might not differentiate ES from non-epileptic seizures.

Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity

Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. The Levetiracetam for Alzheimer's Disease-Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, -0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. ClinicalTrials.gov Identifier: NCT02002819.

Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice.

Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis. In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology. Undercut animals treated with RAGE mAb or TAK242showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p<0.001, when the RAGE mAb or TAK242group is compared with the saline group). The lesioned cortical tissues of RAGE mAb- or TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation. RAGE and TLR4signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.

Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice.

ObjectiveDravet syndrome is a severe developmental and epileptic encephalopathy (DEE) most often caused by de novo pathogenic variants in SCN1A. Individuals with Dravet syndrome rarely achieve seizure control and have significantly elevated risk for sudden unexplained death in epilepsy (SUDEP). Heterozygous deletion of Scn1a in mice (Scn1a +/−) recapitulates several core phenotypes, including temperature‐dependent and spontaneous seizures, SUDEP, and behavioral abnormalities. Furthermore, Scn1a +/− mice exhibit a similar clinical response to standard anticonvulsants. Cholesterol 24‐hydroxlase (CH24H) is a brain‐specific enzyme responsible for cholesterol catabolism. Recent research has indicated the therapeutic potential of CH24H inhibition for diseases associated with neural excitation, including seizures.MethodsIn this study, the novel compound soticlestat, a CH24H inhibitor, was administered to Scn1a +/− mice to investigate its ability to improve Dravet‐like phenotypes in this preclinical model.ResultsSoticlestat treatment reduced seizure burden, protected against hyperthermia‐induced seizures, and completely prevented SUDEP in Scn1a +/− mice. Video–electroencephalography (EEG) analysis confirmed the ability of soticlestat to reduce occurrence of electroclinical seizures.SignificanceThis study demonstrates that soticlestat‐mediated inhibition of CH24H provides therapeutic benefit for the treatment of Dravet syndrome in mice and has the potential for treatment of DEEs.