Tatum, William O.

AbstractTemporal lobe epilepsy is the most common form of focal epilepsy and is frequently resistant to antiseizure medication. Non‐invasive biomarkers are crucial when resective epilepsy surgery is considered in order to guide diagnostic work‐up and management. Interictal epileptiform discharges, when concordant with ictal EEG recording and a focal abnormality on functional imaging or anatomic MRI in patients with temporal lobe epilepsy, portend a favorable outcome with resective or ablative surgery. An interictal nonepileptiform feature on EEG believed to have the same localizing potential as epileptiform discharges is temporal intermittent rhythmic delta activity (TIRDA). The precise localization of TIRDA has been a subject of debate, but has been associated with seizures that arise from the temporal region. We report a 64‐year‐old female who underwent unsuccessful right anterior temporal lobectomy for drug‐resistant focal epilepsy, suspected to originate from the right temporal lobe. Subsequent video‐EEG monitoring revealed right, greater than left, TIRDA and interictal epileptiform discharges arising from the temporal regions bilaterally, despite a generous temporal lobectomy demonstrated by brain MRI. Further, using EEG source localization, we identified TIRDA using scalp EEG in sensor space, localized to the ipsilateral orbitofrontal region. We discuss the proposed localization of TIRDA in this case and address the importance of characterizing TIRDA in the presurgical evaluation of patients with epilepsy.

Abstract This educational topical review and Task Force report aims to address learning objectives of the International League Against Epilepsy (ILAE) curriculum. We sought to extract detailed features involving semiology from video recordings and interpret semiological signs and symptoms that reflect the likely localization for focal seizures in patients with epilepsy. This glossary was developed by a working group of the ILAE Commission on Diagnostic Methods incorporating the EEG Task Force. This paper identifies commonly used terms to describe seizure semiology, provides definitions, signs and symptoms, and summarizes their clinical value in localizing and lateralizing focal seizures based on consensus in the published literature. Video‐EEG examples are included to illustrate important features of semiology in patients with epilepsy.

Summary: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.

Coronavirus 19 (COVID-19) has infected over 400 million people worldwide. Although COVID-19 causes predominantly respiratory symptoms, it can affect other organs including the brain, producing neurological symptoms. People with epilepsy (PWE) have been particularly impacted during the pandemic with decreased access to care, increased stress, and worsening seizures in up to 22% of them probably due to multiple factors. COVID-19 vaccines were produced in a record short time and have yielded outstanding protection with very rare serious side effects. Studies have found that COVID-19 vaccination does not increase seizures in the majority of PWE. COVID-19 does not produce a pathognomonic EEG or seizure phenotype, but rather 1 that can be seen in other types of encephalopathy. COVID-19 infection and its complications can lead to seizures, status epilepticus and post-COVID inflammatory syndrome with potential multi-organ damage in people without pre-existing epilepsy. The lack of access to care during the pandemic has forced patients and doctors to rapidly implement telemedicine. The use of phone videos and smart telemedicine are helping to treat patients during this pandemic and are becoming standard of care. Investment in infrastructure is important to make sure patients can have access to care even during a pandemic.

AbstractDrug‐resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: ((“mesenchymal”) AND (“stem cell”)) AND ((“epilepsy”) OR (“convulsion”) OR (“seizures”)). This review followed Preferred Reporting Items for Systemic Reviews and Meta‐Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ‐aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

While abnormalities of the hippocampus have been well characterized in temporal lobe epilepsy, various additional temporal lobe abnormalities have also been described. One poorly understood entity, the so-called temporal pole blurring (TPB), is one of the more frequently described neocortical abnormalities in TLE and is thought to represent dysmyelination and axonal loss due to chronic electrical perturbations in early age-onset temporal lobe epilepsy. In this study, we describe the first reported cases of TPB diagnosed by a recently described MRI sequence known as 3D Edge-Enhancing Gradient Echo (3D-EDGE), which has an effective “myelin weighting” making it exquisitely sensitive to this temporal pole dysmyelination. The value of detection of TPB lies in lateralizing seizure onset, as well as predicting a lower baseline neuropsychological performance compared to temporal lobe epilepsy without TPB. Additionally, it is critical to not mistake TPB for alternative diagnoses, such as focal cortical dysplasia or neoplasm.

Summary The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long‐term video‐electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using the PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis) statement. We found limited high‐level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events. For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long‐term outcome effects of LTVEM and to establish its clinical utility.

Purpose Exploration of the effect of chronic recurrent seizures in focal epilepsy on brain volumes has produced many conflicting reports. To determine differences in brain structure in temporal lobe epilepsy (TLE) and extratemporal epilepsy (using frontal lobe epilepsy (FLE) a surrogate) further, we performed a retrospective analysis of a large cohort of patients with seizure-onset zone proven by intracranial monitoring. Methods A total of 120 TLE patients, 86 FLE patients, and 54 healthy controls were enrolled in this study. An analysis of variance of voxel-based morphometry (VBM) was used to seek morphometric brain differences among TLE patients, FLE patients, and healthy controls. Additionally, a vertex-based surface analysis was utilized to analyze the hippocampus and thalamus. Significant side-specific differences in hippocampal gray matter volume were present between the left TLE (LTLE), right TLE RTLE (RTLE), and control groups ( p<0.05, family-wise error (FWE) corrected). Results Vertex analyses revealed significant volume reduction in inferior parts of the left hippocampus in the LTLE group and lateral parts of the right hippocampus in the RTLE group compared to controls ( p<0.05, FWE corrected). Significant differences were also detected between the LTLE and control group in the bilateral medial and inferior thalamus ( p<0.05, FWE corrected). FLE patients did not exhibit focal atrophy of gray matter across the brain. Conclusion Our results highlight the variation in morphometric lateralized changes in the brain between different epilepsy onset zones, providing critical insight into the natural history of people with drug-resistant focal epilepsies.

Abstract BACKGROUND Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an increasingly utilized treatment of drug-resistant epilepsy. To date, the effect of high-frequency stimulation (HFS) vs low-frequency stimulation (LFS) in ANT DBS is poorly understood. OBJECTIVE To assess differences in the acute effect of LFS vs HFS in ANT DBS utilizing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS In this prospective study of 5 patients with ANT DBS for epilepsy, BOLD activation and deactivation were modeled for 145-Hz and 30-Hz ANT stimulation using an fMRI block design. Data were analyzed with a general linear model and combined via 2-stage mixed-effects analysis. Z-score difference maps were nonparametrically thresholded using cluster threshold of z > 3.1 and a (corrected) cluster significance threshold of P = .05. RESULTS HFS produced significantly greater activation within multiple regions, in particular the limbic and default mode network (DMN). LFS produced minimal activation and failed to produce significant activation within these same networks. HFS produced widespread cortical and subcortical deactivation sparing most of the limbic and DMN regions. Meanwhile, LFS produced deactivation in most DMN and limbic structures. CONCLUSION Our results show that HFS and LFS produce substantial variability in both local and downstream network effects. In particular, largely opposing effects were identified within the limbic network and DMN. These findings may serve as a mechanistic basis for understanding the potential of HFS vs LFS in various epilepsy syndromes.