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Epilepsia Dec 2023A lot of mileage has been made recently on the long and winding road toward seizure forecasting. Here we briefly review some selected milestones passed along the way,...
A lot of mileage has been made recently on the long and winding road toward seizure forecasting. Here we briefly review some selected milestones passed along the way, which were discussed at the International Conference for Technology and Analysis of Seizures-ICTALS 2022-convened at the University of Bern, Switzerland. Major impetus was gained recently from wearable and implantable devices that record not only electroencephalography, but also data on motor behavior, acoustic signals, and various signals of the autonomic nervous system. This multimodal monitoring can be performed for ultralong timescales covering months or years. Accordingly, features and metrics extracted from these data now assess seizure dynamics with a greater degree of completeness. Most prominently, this has allowed the confirmation of the long-suspected cyclical nature of interictal epileptiform activity, seizure risk, and seizures. The timescales cover daily, multi-day, and yearly cycles. Progress has also been fueled by approaches originating from the interdisciplinary field of network science. Considering epilepsy as a large-scale network disorder yielded novel perspectives on the pre-ictal dynamics of the evolving epileptic brain. In addition to discrete predictions that a seizure will take place in a specified prediction horizon, the community broadened the scope to probabilistic forecasts of a seizure risk evolving continuously in time. This shift of gears triggered the incorporation of additional metrics to quantify the performance of forecasting algorithms, which should be compared to the chance performance of constrained stochastic null models. An imminent task of utmost importance is to find optimal ways to communicate the output of seizure-forecasting algorithms to patients, caretakers, and clinicians, so that they can have socioeconomic impact and improve patients' well-being.
Topics: Humans; Seizures; Epilepsy; Brain; Forecasting; Electroencephalography
PubMed: 36780237
DOI: 10.1111/epi.17546 -
Ugeskrift For Laeger Apr 2024Non-traumatic fractures due to seizures are an overlooked diagnostic group. It is well known that patients with generalized tonic-clonic seizures have an increased...
Non-traumatic fractures due to seizures are an overlooked diagnostic group. It is well known that patients with generalized tonic-clonic seizures have an increased trauma risk. However, the cause of fracture is rarely due to the violent forces of muscle contractions. Usually, the primary patient examination focuses on the aetiology of the seizure, which sometimes delays the diagnosis of fractures. This is a case report of a 19-year-old woman who sustained three compression fractures of the thoracic spine due to a generalized tonic-clonic seizure, and a discussion of the diagnostic challenges in such a rare case.
Topics: Humans; Female; Spinal Fractures; Young Adult; Fractures, Compression; Thoracic Vertebrae; Seizures; Fractures, Multiple; Tomography, X-Ray Computed; Epilepsy, Tonic-Clonic
PubMed: 38704711
DOI: 10.61409/V05230296 -
Mitochondrion Sep 2023Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging.... (Review)
Review
Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.
Topics: Animals; Mice; Selenium; Mitochondria; Epilepsy; Seizures; Iron
PubMed: 37582467
DOI: 10.1016/j.mito.2023.08.002 -
Frontiers in Immunology 2023Epilepsy is a group of enduring neurological disorder characterized by spontaneous and recurrent seizures with heterogeneous etiology, clinical expression, severity, and... (Review)
Review
Epilepsy is a group of enduring neurological disorder characterized by spontaneous and recurrent seizures with heterogeneous etiology, clinical expression, severity, and prognosis. Growing body of research investigates that epileptic seizures are originated from neuronal synchronized and excessive electrical activity. However, the underlying molecular mechanisms of epileptogenesis have not yet been fully elucidated and 30% of epileptic patients still are resistant to the currently available pharmacological treatments with recurrent seizures throughout life. Over the past two decades years accumulated evidences provide strong support to the hypothesis that neuroinflammation, including microglia and astrocytes activation, a cascade of inflammatory mediator releasing, and peripheral immune cells infiltration from blood into brain, is associated with epileptogenesis. Meanwhile, an increasing body of preclinical researches reveal that the anti-inflammatory therapeutics targeting crucial inflammatory components are effective and promising in the treatment of epilepsy. The aim of the present study is to highlight the current understanding of the potential neuroinflammatory mechanisms in epileptogenesis and the potential therapeutic targets against epileptic seizures.
Topics: Humans; Neuroinflammatory Diseases; Brain; Electricity; Epilepsy; Seizures
PubMed: 38187384
DOI: 10.3389/fimmu.2023.1269241 -
Pediatric Annals Oct 2023
Topics: Humans; Child; Seizures
PubMed: 37820702
DOI: 10.3928/19382359-20230829-07 -
Epilepsy Research Jul 2023Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or... (Review)
Review
Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy. Recently, specific genetic mutations have been recognized in a minority patients, including in SYNGAP1, NEXMIF, RORB, and CHD2 genes. There are no randomized controlled trials in EEM, and the management literature is largely restricted to small retrospective studies. Broad-spectrum antiseizure medications such as valproate, levetiracetam, lamotrigine, and benzodiazepines are typically used. Seizures typically persist into adulthood, and drug-resistant epilepsy is reported in over 50%.
Topics: Humans; Female; Child; Male; Retrospective Studies; Anticonvulsants; Epilepsy, Generalized; Seizures; Myoclonus; Epilepsy, Absence; Eyelids; Electroencephalography
PubMed: 37121024
DOI: 10.1016/j.eplepsyres.2023.107147 -
Frontiers in Endocrinology 2023
Topics: Humans; Epilepsy; Seizures
PubMed: 37842313
DOI: 10.3389/fendo.2023.1288784 -
International Journal of Molecular... Sep 2023Epilepsy is a highly prevalent neurological disorder, affecting between 5-8 per 1000 individuals and is associated with a lifetime risk of up to 3%. In addition to high... (Review)
Review
Epilepsy is a highly prevalent neurological disorder, affecting between 5-8 per 1000 individuals and is associated with a lifetime risk of up to 3%. In addition to high incidence, epilepsy is a highly heterogeneous disorder, with variation including, but not limited to the following: severity, age of onset, type of seizure, developmental delay, drug responsiveness, and other comorbidities. Variable phenotypes are reflected in a range of etiologies including genetic, infectious, metabolic, immune, acquired/structural (resulting from, for example, a severe head injury or stroke), or idiopathic. This review will focus specifically on epilepsies with a genetic cause, genetic testing, and biomarkers in epilepsy.
Topics: Humans; Epilepsy; Seizures; Genetic Testing; Comorbidity; Stroke
PubMed: 37834053
DOI: 10.3390/ijms241914606 -
International Journal of Molecular... Nov 2023Advanced identification of the gene mutations causing epilepsy syndromes is expected to translate into faster diagnosis and more effective treatment of these conditions.... (Review)
Review
Advanced identification of the gene mutations causing epilepsy syndromes is expected to translate into faster diagnosis and more effective treatment of these conditions. Over the last 5 years, approximately 40 clinical trials on the treatment of genetic epilepsies have been conducted. As a result, some medications that are not regular antiseizure drugs (e.g., soticlestat, fenfluramine, or ganaxolone) have been introduced to the treatment of drug-resistant seizures in Dravet, Lennox-Gastaut, maternally inherited chromosome 15q11.2-q13.1 duplication (Dup 15q) syndromes, and protocadherin 19 (PCDH 19)-clusterig epilepsy. And although the effects of soticlestat, fenfluramine, and ganaxolone are described as promising, they do not significantly affect the course of the mentioned epilepsy syndromes. Importantly, each of these syndromes is related to mutations in several genes. On the other hand, several mutations can occur within one gene, and different gene variants may be manifested in different disease phenotypes. This complex pattern of inheritance contributes to rather poor genotype-phenotype correlations. Hence, the detection of a specific mutation is not synonymous with a precise diagnosis of a specific syndrome. Bearing in mind that seizures develop as a consequence of the predominance of excitatory over inhibitory processes, it seems reasonable that mutations in genes encoding sodium and potassium channels, as well as glutamatergic and gamma-aminobutyric (GABA) receptors, play a role in the pathogenesis of epilepsy. In some cases, different pathogenic variants of the same gene can result in opposite functional effects, determining the effectiveness of therapy with certain medications. For instance, seizures related to gain-of-function (GoF) mutations in genes encoding sodium channels can be successfully treated with sodium channel blockers. On the contrary, the same drugs may aggravate seizures related to loss-of-function (LoF) variants of the same genes. Hence, knowledge of gene mutation-treatment response relationships facilitates more favorable selection of drugs for anticonvulsant therapy.
Topics: Humans; Anticonvulsants; Epilepsy; Seizures; Epileptic Syndromes; Genetic Background; Fenfluramine
PubMed: 38003469
DOI: 10.3390/ijms242216280 -
Journal of Neurology Oct 2023Vagus nerve stimulation (VNS) is an effective, non-pharmacological therapy for epileptic seizures. Until now, favorable combinations of different groups of antiseizure... (Observational Study)
Observational Study
INTRODUCTION
Vagus nerve stimulation (VNS) is an effective, non-pharmacological therapy for epileptic seizures. Until now, favorable combinations of different groups of antiseizure medication (ASM) and VNS have not been sufficiently addressed. The aim of this study was to identify the synergistic effects between VNS and different ASMs.
METHODS
We performed an observational study of patients with epilepsy who were implanted with VNS and had a stable ASM therapy during the first 2 years after the VNS implantation. Data were collected from the Mainz Epilepsy Registry. The efficacy of VNS depending on the concomitantly used ASM group/individual ASMs was assessed by quantifying the responder rate (≥ 50% seizure reduction compared to the time of VNS implantation) and seizure freedom (absence of seizures during the last 6 months of the observation period).
RESULTS
One hundred fifty one patients (mean age 45.2 ± 17.0 years, 78 females) were included in the study. Regardless of the used ASM, the responder rate in the whole cohort was 50.3% and the seizure freedom was 13.9%. Multiple regression analysis showed that combination of VNS with synaptic vesicle glycoprotein (SV2A) modulators (responder rate 64.0%, seizure freedom 19.8%) or slow sodium channel inhibitors (responder rate 61.8%, seizure freedom 19.7%) was associated with a statistically significant better responder rate and seizure freedom than combinations of VNS and ASM with other mechanism of action. Within these ASM groups, brivaracetam showed a more favorable effect than levetiracetam, whereas lacosamide and eslicarbazepine were comparable in their effects.
CONCLUSION
Our data suggest that the combination of VNS with ASMs belonging to either SV2A modulators or slow sodium channel inhibitors could be optimal to achieve a better seizure control following VNS. However, these preliminary data require further validation under controlled conditions.
Topics: Female; Humans; Adult; Middle Aged; Vagus Nerve Stimulation; Treatment Outcome; Epilepsy; Seizures; Registries; Drug Resistant Epilepsy; Retrospective Studies
PubMed: 37368131
DOI: 10.1007/s00415-023-11825-9