Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons.

Robust compression and detection of epileptiform patterns in ECoG using a real-time spiking neural network hardware framework.

Interictal Epileptiform Discharges (IED) and High Frequency Oscillations (HFO) in intraoperative electrocorticography (ECoG) may guide the surgeon by delineating the epileptogenic zone. We designed a modular spiking neural network (SNN) in a mixed-signal neuromorphic device to process the ECoG in real-time. We exploit the variability of the inhomogeneous silicon neurons to achieve efficient sparse and decorrelated temporal signal encoding.

COVID-19 response in a long-term care facility for people with epilepsy.

Objective: To assess asymptomatic rates and severity of SARS-CoV-2 infection in people with epilepsy and their healthcare workers in a long-term care facility which had implemented weekly surveillance testing between April 2020 and June 2022.

Methods: Questionnaires focused on objective and subjective COVID-19 symptoms for people with epilepsy residing in and their healthcare workers at the Chalfont Centre for Epilepsy in June 2022. Demographic information, comorbidities, and seizure frequency were gathered from medical records.

Spatial omics reveals molecular changes in focal cortical dysplasia type II.

Focal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinical mouse model of FCD type II (Rheb), focusing on spatial omics techniques to define the proteomic and lipidomic changes.

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?

Introduction: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT).

Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

Background And Objectives: High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups.

Methods: We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022.

Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.

Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABA receptors.

mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.

Epilepsy remains a major health concern as anti-seizure medications frequently fail, and there is currently no treatment to stop or prevent epileptogenesis, the process underlying the onset and progression of epilepsy. The identification of the pathological processes underlying epileptogenesis is instrumental to the development of drugs that may prevent the generation of seizures or control pharmaco-resistant seizures, which affect about 30% of patients. mTOR signalling and neuroinflammation have been recognized as critical pathways that are activated in brain cells in epilepsy.

Shock and Temperature Monitoring During Transport of Immunoglobulins from a Hospital to Patients' Homes: A Pilot Study.

Transport of biopharmaceuticals from a hospital to a patient's home is scarcely researched but it is essential to investigate the effects of such transport on the stability of the drug, before home-based care can take place. In this study, transport of biopharmaceuticals in vials that are marketed as ready-to-administer from a hospital pharmacy to patients' homes was investigated. Immunoglobulin packages were tracked with 10 G and 25 G shock indicators and temperature data loggers.

SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment.

SorLA, encoded by the gene SORL1, is an intracellular sorting receptor of the VPS10P domain receptor gene family. Although SorLA is best recognized for its ability to shuttle target proteins between intracellular compartments in neurons, recent data suggest that also its microglial expression can be of high relevance for the pathogenesis of brain diseases, including glioblastoma (GBM). Here, we interrogated the impact of SorLA on the functional properties of glioma-associated microglia and macrophages (GAMs).

Identification of gene regulatory networks affected across drug-resistant epilepsies.

Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies).

Mood disorders in adults with epilepsy: a review of unrecognized facts and common misconceptions.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy.

Astroglial calcium signaling and homeostasis in tuberous sclerosis complex.

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by the development of benign tumors in various organs, including the brain, and is often accompanied by epilepsy, neurodevelopmental comorbidities including intellectual disability and autism. A key hallmark of TSC is the hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway, which induces alterations in cortical development and metabolic processes in astrocytes, among other cellular functions. These changes could modulate seizure susceptibility, contributing to the progression of epilepsy and its associated comorbidities.

Effectiveness of Seizure Dogs for People With Severe Refractory Epilepsy: Results From the EPISODE Study.

Background And Objectives: The aim of this study was to evaluate whether people living with severe medically refractory epilepsy (PSRE) benefit from a seizure dog.

Methods: An individual-level stepped-wedge randomized controlled trial was conducted. The study was conducted in the Netherlands among adults with daily to weekly seizures.

[Hitting and yelling during sleep: diagnosis and implications of REM sleep behavior disorder].

Rapid eye movement (REM) sleep behavior disorder is characterized by dream enactment during REM sleep. Due to different treatment requirements, it is important to distinguish REM sleep behavior disorder from other causes of nocturnal restlessness, including sleep apnea, non-REM parasomnia and sleep-related hypermotor epilepsy. In addition, a diagnosis of isolated REM sleep behavior disorder is impactful, because it carries a greatly increased risk for the later development of Parkinson's disease and related synucleinopathies.

Clinical outcome assessment in patients with epilepsy: The value of health-related quality of life measurements.

This narrative review provides an overview of the current knowledge on health-related quality of life (HRQOL), a relevant clinical outcome in patients with epilepsy. It shows that the most important factor determining HRQOL in this patient group is seizure frequency. In particular, seizure-freedom is associated with better HRQOL scores.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

Background And Objective: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied.

Quality indicators for epilepsy management in China: The development of a tool to assess care and first three-year report.

Objectives: Epilepsy care in China has expanded considerably in the last decade but still remains largely unknown; we developed an easy-to-use tool to assess its quality.

Methods: We adapted the Epilepsy Update Quality Measurement, produced by the American Academy of Neurology (AAN) for use in China: The Quality Indicator for Epilepsy Treatment-China National Action (QUIET-CHINA). This tool incorporates a standardized case report form initially for logging quality indicators for people with epilepsy during in-patient stays.

Computer-assisted analysis of routine EEG to identify hidden biomarkers of epilepsy: A systematic review.

Background: Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic performances of computed biomarkers for epilepsy in individuals undergoing rEEG.

Methods: We searched MEDLINE, EMBASE, EBM reviews, IEEE Explore and the grey literature for studies published between January 1961 and December 2022.