Discovering EEG biomarkers of Lennox-Gastaut syndrome through unsupervised time-frequency analysis.

Objective: The discovery and validation of electroencephalography (EEG) biomarkers often rely on visual identification of waveforms. However, bias toward visually striking events restricts the search space for new biomarkers, and low interrater reliability can limit rigorous validation. We present a data-driven approach to biomarker discovery called scalp EEG Pattern Identification and Categorization (s-EPIC), which enables automated, unsupervised identification of EEG waveforms.

Symptomatic vigabatrin-associated MRI toxicity is associated with simultaneous hormonal therapy among patients with infantile spasms.

Vigabatrin-associated brain abnormalities on MRI (VABAM) are observed in approximately 20% of children who receive vigabatrin for treatment of infantile epileptic spasms syndrome. Although usually reversible and asymptomatic, VABAM is occasionally symptomatic. Whereas asymptomatic VABAM appears to be dose-dependent, symptomatic VABAM is possibly associated with co-administration of vigabatrin and hormonal therapy (i.

Multi-disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series.

Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi-system disorder associated with germline or mosaic variants within the PI3K-mTOR-GATOR1 signaling pathways. Patients with HME typically develop drug-resistant epilepsy necessitating extensive evaluation, hemispherectomy, and long-term management. We describe the role of a multidisciplinary team (MDT) for the diagnosis and management of recent patients with HME at UCLA who underwent hemispherectomy.

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy.

Background: Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.

Methods: In a phase 2-3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI).

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders.

Objective: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD).

Study Design: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined.

Bilateral centromedian nucleus of thalamus responsive neurostimulation for pediatric-onset drug-resistant epilepsy.

Neuromodulation therapies offer an efficacious treatment alternative for patients with drug-resistant epilepsy (DRE), particularly those unlikely to benefit from surgical resection. Here we present our retrospective single-center case series of patients with pediatric-onset DRE who underwent responsive neurostimulation (RNS) depth electrode implantation targeting the bilateral centromedian nucleus (CM) of the thalamus between October 2020 and October 2022. Sixteen patients were identified; seizure outcomes, programming parameters, and complications at follow-up were reviewed.

PyHFO: lightweight deep learning-powered end-to-end high-frequency oscillations analysis application.

. This study aims to develop and validate an end-to-end software platform, PyHFO, that streamlines the application of deep learning (DL) methodologies in detecting neurophysiological biomarkers for epileptogenic zones from EEG recordings..

Computational EEG attributes predict response to therapy for epileptic spasms.

Objective: We set out to evaluate whether response to treatment for epileptic spasms is associated with specific candidate computational EEG biomarkers, independent of clinical attributes.

Methods: We identified 50 children with epileptic spasms, with pre- and post-treatment overnight video-EEG. After EEG samples were preprocessed in an automated fashion to remove artifacts, we calculated amplitude, power spectrum, functional connectivity, entropy, and long-range temporal correlations (LRTCs).

Epileptic spasms relapse is associated with response latency but not conventional attributes of post-treatment EEG.

Objective: Relapse of epileptic spasms after initial treatment of infantile epileptic spasms syndrome (IESS) is common. However, past studies of small cohorts have inconsistently linked relapse risk to etiology, treatment modality, and EEG features upon response. Using a large single-center IESS cohort, we set out to quantify the risk of epileptic spasms relapse and identify specific risk factors.

Interrater reliability of interictal EEG waveforms in Lennox-Gastaut Syndrome.

Objective: Identification of EEG waveforms is critical for diagnosing Lennox-Gastaut Syndrome (LGS) but is complicated by the progressive nature of the disease. Here, we assess the interrater reliability (IRR) among pediatric epileptologists for classifying EEG waveforms associated with LGS.

Methods: A novel automated algorithm was used to objectively identify epochs of EEG with transient high power, which were termed events of interest (EOIs).

Optimizing detection and deep learning-based classification of pathological high-frequency oscillations in epilepsy.

Objective: This study aimed to explore sensitive detection methods for pathological high-frequency oscillations (HFOs) to improve seizure outcomes in epilepsy surgery.

Methods: We analyzed interictal HFOs (80-500 Hz) in 15 children with medication-resistant focal epilepsy who underwent chronic intracranial electroencephalogram via subdural grids. The HFOs were assessed using the short-term energy (STE) and Montreal Neurological Institute (MNI) detectors and examined for spike association and time-frequency plot characteristics.

Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment-resistant epilepsies in the Expanded Access Program.

The cannabidiol (CBD) Expanded Access Program (EAP), initiated in 2014, provided CBD (Epidiolex) to patients with treatment-resistant epilepsy (TRE). In the final pooled analysis of 892 patients treated through January 2019 (median exposure = 694 days), CBD treatment was associated with a 46%-66% reduction in median monthly total (convulsive plus nonconvulsive) seizure frequency. CBD was well tolerated, and adverse events were consistent with previous findings.

Optimizing Detection and Deep Learning-based Classification of Pathological High-Frequency Oscillations in Epilepsy.

Objective: This study aimed to explore sensitive detection methods and deep learning (DL)-based classification for pathological high-frequency oscillations (HFOs).

Methods: We analyzed interictal HFOs (80-500 Hz) in 15 children with medication-resistant focal epilepsy who underwent resection after chronic intracranial electroencephalogram via subdural grids. The HFOs were assessed using the short-term energy (STE) and Montreal Neurological Institute (MNI) detectors and examined for pathological features based on spike association and time-frequency plot characteristics.

Evolution of Cortical Functional Networks in Healthy Infants.

During normal childhood development, functional brain networks evolve over time in parallel with changes in neuronal oscillations. Previous studies have demonstrated differences in network topology with age, particularly in neonates and in cohorts spanning from birth to early adulthood. Here, we evaluate the developmental changes in EEG functional connectivity with a specific focus on the first 2 years of life.

Characterizing physiological high-frequency oscillations using deep learning.

Intracranially-recorded interictal high-frequency oscillations (HFOs) have been proposed as a promising spatial biomarker of the epileptogenic zone. However, HFOs can also be recorded in the healthy brain regions, which complicates the interpretation of HFOs. The present study aimed to characterize salient features of physiological HFOs using deep learning (DL).

Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

Background And Objectives: Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.

Inequities in Therapy for Infantile Spasms: A Call to Action.

Objective: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity.

Methods: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression.

Refining epileptogenic high-frequency oscillations using deep learning: a reverse engineering approach.

Intracranially recorded interictal high-frequency oscillations have been proposed as a promising spatial biomarker of the epileptogenic zone. However, its visual verification is time-consuming and exhibits poor inter-rater reliability. Furthermore, no method is currently available to distinguish high-frequency oscillations generated from the epileptogenic zone (epileptogenic high-frequency oscillations) from those generated from other areas (non-epileptogenic high-frequency oscillations).

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

Background: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited.

Objective: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients.

Methods: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers.

Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome.

Background: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.

Computational characteristics of interictal EEG as objective markers of epileptic spasms.

Objective: Favorable neurodevelopmental outcomes in epileptic spasms (ES) are tied to early diagnosis and prompt treatment, but uncertainty in the identification of the disease can delay this process. Therefore, we investigated five categories of computational electroencephalographic (EEG) measures as markers of ES.

Methods: We measured 1) amplitude, 2) power spectra, 3) Shannon entropy and permutation entropy, 4) long-range temporal correlations, via detrended fluctuation analysis (DFA) and 5) functional connectivity using cross-correlation and phase lag index (PLI).