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BACKGROUND: Safinamide (SAF), an α-aminoamide derivative and a selective, reversible monoamine oxidase (MAO)-B inhibitor, has both dopaminergic and nondopaminergic (glutamatergic) properties. Several studies have explored the potential of SAF against various neurological disorders; however, to what extent SAF modulates the magnitude, gating, and voltage-dependent hysteresis [Hys(V)] of ionic currents remains unknown. METHODS: With the aid of patch-clamp technology, we investigated the effects of SAF on voltage-gated sodium ion (NaV) channels in pituitary GH3 cells. RESULTS: SAF concentration-dependently stimulated the transient (peak) and late (sustained) components of voltage-gated sodium ion current (INa) in pituitary GH3 cells. The conductance-voltage relationship of transient INa [INa(T)] was shifted to more negative potentials with the SAF presence; however, the steady-state inactivation curve of INa(T) was shifted in a rightward direction in its existence. SAF increased the decaying time constant of INa(T) induced by a train of depolarizing stimuli. Notably, subsequent addition of ranolazine or mirogabalin reversed the SAF-induced increase in the decaying time constant. SAF also increased the magnitude of window INa induced by an ascending ramp voltage Vramp. Furthermore, SAF enhanced the Hys(V) behavior of persistent INa induced by an upright isosceles-triangular Vramp. Single-channel cell-attached recordings indicated SAF effectively increased the open-state probability of NaV channels. Molecular docking revealed SAF interacts with both MAO and NaV channels. CONCLUSION: SAF may interact directly with NaV channels in pituitary neuroendocrine cells, modulating membrane excitability.
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Alanina/análogos & derivados , Bencilaminas , Monoaminooxidasa , Simulación del Acoplamiento Molecular , Bencilaminas/farmacología , SodioAsunto(s)
Errores Diagnósticos , Imagen por Resonancia Magnética , Meningioma , Meningitis , Humanos , Meningitis/diagnóstico , Meningitis/sangre , Meningitis/inmunología , Meningioma/diagnóstico , Meningioma/diagnóstico por imagen , Inmunoglobulina G/sangre , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , HipertrofiaRESUMEN
BACKGROUND: Poststroke epilepsy poses a significant clinical challenge for individuals recovering from strokes, leading to a less favorable long-term outlook and increased mortality rates. Existing studies have primarily concentrated on administering antiseizure or anticonvulsant treatments only after the onset of late-onset seizures, without intervening during the epileptogenesis phase following a stroke. OBJECTIVE: This research protocol is designed to conduct a randomized controlled trial to assess whether the early, preventive introduction of low-dose antiepileptic drug therapy (levetiracetam [LEV] or perampanel [PER]) in patients who have experienced middle cerebral artery (MCA) infarction can reduce the risk of developing poststroke epilepsy (primary prevention). METHODS: Participants with MCA infarction, either with or without reperfusion treatments, will be recruited and promptly receive preventive intervention within 72 hours of the stroke occurrence. These participants will be randomly assigned to receive either PER (4 mg per day), LEV (1000 mg per day), or a placebo that matches the active drugs. This treatment will continue for 12 weeks after allocation. Brain magnetic resonance imaging will be used to confirm the presence of MCA territory infarction, and an electroencephalography will be used to ensure the absence of epileptiform discharges or electrographic seizures at the time of the stroke. All participants will undergo follow-up assessments for 72 weeks after allocation. RESULTS: The primary outcome under evaluation will be the incidence of poststroke epilepsy in the 3 groups following the 18-month study period. Secondary outcomes will encompass the time to the occurrence of the first seizure, the severity of seizures, any treatment-related adverse events, and the modified Rankin scale score at 3 and 18 months. Exploratory outcomes will involve comparing the effectiveness and safety of PER and LEV. CONCLUSIONS: We anticipate that the intervention groups will experience a lower incidence and reduced severity of poststroke epilepsy compared to the control group after 18 months. We aim to establish evidence supporting the potential preventive effects of LEV and PER on poststroke seizures and epilepsy in patients with MCA infarction, as well as to explore the antiepileptogenic potential of both LEV and PER in patients with major ischemic strokes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04858841; https://clinicaltrials.gov/study/NCT04858841. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49412.
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PURPOSE: To evaluate and compare the performance of the status epilepticus severity score (STESS), modified STESS (mSTESS), and the newly modified STESS (nSTESS) in predicting mortality in patients with status epilepticus (SE) at a regional hospital in Taiwan. METHODS: Data were collected from 81 patients with SE, aged over 18 years at a regional medical hospital in Tainan from January 2012 to December 2022. SE were treated following the standard treatment protocol. Exclusion criteria included missing data, lack of adherence to the treatment protocol, and transfer to tertiary medical centers. Outcome measures included differences in characteristics between survivor and non-survivor groups, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of STESS, nSTESS, mSTESS. Receiver operating characteristic (ROC) curve and area under curve (AUC) of scales were generated. Calibration with Hosmer-Lemeshow test was built as well. RESULTS: The study found significant differences in seizure types (p = 0.015) and undergoing intubation (p = 0.017) between survivor and non-survivor groups. No significant differences were observed in age, gender, underlying diseases, or the category of antiseizure medications (ASMs) usage. The ROC curve for STESS, nSTESS and mSTESS showed similar predictive values of around 0.75, indicating moderate performance of prediction. The Hosmer-Lemeshow test showed no significant difference between real-world predictions and these three clinical scales. In the aspect of accuracy, sensitivity and specificity, nSTESS has similar overall accuracy as in STESS and mSTESS. CONCLUSION: This external validation study demonstrates the moderate performance of nSTESS in predicting mortality in SE patients at a regional hospital in Taiwan. These outcomes underscore the practical utility of these scales in clinical practice, with nSTESS demonstrating accuracy on par with the others. Further validation in larger, multicenter cohorts and other healthcare settings is necessary to fully confirm its predictive value.
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Estado Epiléptico , Humanos , Adulto , Persona de Mediana Edad , Pronóstico , Taiwán/epidemiología , Índice de Severidad de la Enfermedad , Mortalidad Hospitalaria , Estado Epiléptico/tratamiento farmacológico , Hospitales , Estudios RetrospectivosRESUMEN
Coarse-grained (CG) molecular dynamics enables the study of biological processes at temporal and spatial scales that would be intractable at an atomistic resolution. However, accurately learning a CG force field remains a challenge. In this work, we leverage connections between score-based generative models, force fields, and molecular dynamics to learn a CG force field without requiring any force inputs during training. Specifically, we train a diffusion generative model on protein structures from molecular dynamics simulations, and we show that its score function approximates a force field that can directly be used to simulate CG molecular dynamics. While having a vastly simplified training setup compared to previous work, we demonstrate that our approach leads to improved performance across several protein simulations for systems up to 56 amino acids, reproducing the CG equilibrium distribution and preserving the dynamics of all-atom simulations such as protein folding events.
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Epilepsy is a multifactorial neurologic disease that often leads to many devastating disabilities and an enormous burden on the healthcare system. Until now, drug-resistant epilepsy has presented a major challenge for approximately 30% of the epileptic population. The present article summarizes the validated rodent models of seizures employed in pharmacological researches and comprehensively reviews updated advances of novel antiseizure candidates in the preclinical phase. Newly discovered compounds that demonstrate antiseizure efficacy in preclinical trials will be discussed in the review. It is inspiring that several candidates exert promising antiseizure activities in drug-resistant seizure models. The representative compounds consist of derivatives of hybrid compounds that integrate multiple approved antiseizure medications, novel positive allosteric modulators targeting subtype-selective γ-Aminobutyric acid type A receptors, and a derivative of cinnamamide. Although the precise molecular mechanism, pharmacokinetic properties, and safety are not yet fully clear in every novel antiseizure candidate, the adapted approaches to design novel antiseizure medications provide new insights to overcome drug-resistant epilepsy.
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Epilepsia Refractaria , Convulsiones , Animales , Convulsiones/tratamiento farmacológicoRESUMEN
Temporal lobe epilepsy is the most common focal epilepsy syndrome and has a broad spectrum of presentations. Nevertheless, isolated vestibular symptoms without other symptoms typical of temporal lobe seizures are relatively rare. Here, we report one female patient who suffered from chronic refractory vertigo and had inappropriate pharmacotherapy for several years. Eventually, epileptic vertigo and dizziness (ictal vertigo) were accurately diagnosed by detailed history taking and serial examinations assisted by sphenoid electroencephalography. Awareness of this unique syndrome is important in the diagnosis of patients with epileptic vertigo and dizziness.
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Epilepsia del Lóbulo Temporal , Humanos , Femenino , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico , Mareo , Vértigo/complicaciones , Vértigo/diagnóstico , Convulsiones/complicaciones , Convulsiones/diagnóstico , ElectroencefalografíaRESUMEN
Advances in stroke treatment have resulted in a dramatic reduction in stroke mortality. Nevertheless, poststroke seizures and epilepsy are issues of clinical importance affecting survivors. Additionally, stroke is the most common cause of epilepsy in older adults. Although numerous antiseizure medications exist, studies are needed to provide robust evidence of the efficacy and tolerability of these medicines for treating poststroke seizures and epilepsy. Crucially, the newer generations of antiseizure medications require testing. Lacosamide, a third-generation antiseizure medication approved for treating localization-related epilepsy, has a novel mechanism of selectively enhancing the slow inactivation of sodium channels. This literature review evaluated whether lacosamide is effective and safe for the treatment of poststroke seizures and epilepsy. This review critically analyzed studies published in major academic databases (Pubmed, Embase, and Cochrane Library) from inception through June 2022 regarding the interaction of lacosamide with poststroke seizures and epilepsy. We included clinical prospective, retrospective, and case studies on patients with poststroke seizure and epilepsy, lacosamide as a treatment for seizures, neuroprotection in animal models of seizures, and the safety of lacosamide when coadministering anticoagulants. Clinical studies revealed lacosamide to be an effective antiseizure medication with high efficacy and tolerability in patients with poststroke seizures and epilepsy. In animal models, lacosamide proved effective at seizure reduction and neuroprotection. Pharmacokinetic studies demonstrated the safety of lacosamide when coadministering conventional and new anticoagulants. The literature suggests that Lacosamide is a promising candidate antiseizure medication for patients with poststroke seizures and epilepsy.
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Epilepsia , Accidente Cerebrovascular , Animales , Lacosamida/uso terapéutico , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Resultado del Tratamiento , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Anticoagulantes/uso terapéuticoRESUMEN
Carisbamate (CRS, RWJ-333369) is a new anti-seizure medication. It remains unclear whether and how CRS can perturb the magnitude and/or gating kinetics of membrane ionic currents, despite a few reports demonstrating its ability to suppress voltage-gated Na+ currents. In this study, we observed a set of whole-cell current recordings and found that CRS effectively suppressed the voltage-gated Na+ (INa) and hyperpolarization-activated cation currents (Ih) intrinsically in electrically excitable cells (GH3 cells). The effective IC50 values of CRS for the differential suppression of transient (INa(T)) and late INa (INa(L)) were 56.4 and 11.4 µM, respectively. However, CRS strongly decreased the strength (i.e., Δarea) of the nonlinear window component of INa (INa(W)), which was activated by a short ascending ramp voltage (Vramp); the subsequent addition of deltamethrin (DLT, 10 µM) counteracted the ability of CRS (100 µM, continuous exposure) to suppress INa(W). CRS strikingly decreased the decay time constant of INa(T) evoked during pulse train stimulation; however, the addition of telmisartan (10 µM) effectively attenuated the CRS (30 µM, continuous exposure)-mediated decrease in the decay time constant of the current. During continued exposure to deltamethrin (10 µM), known to be a pyrethroid insecticide, the addition of CRS resulted in differential suppression of the amplitudes of INa(T) and INa(L). The amplitude of Ih activated by a 2-s membrane hyperpolarization was diminished by CRS in a concentration-dependent manner, with an IC50 value of 38 µM. For Ih, CRS altered the steady-state I-V relationship and attenuated the strength of voltage-dependent hysteresis (Hys(V)) activated by an inverted isosceles-triangular Vramp. Moreover, the addition of oxaliplatin effectively reversed the CRS-mediated suppression of Hys(V). The predicted docking interaction between CRS and with a model of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel or between CRS and the hNaV1.7 channel reflects the ability of CRS to bind to amino acid residues in HCN or hNaV1.7 channel via hydrogen bonds and hydrophobic interactions. These findings reveal the propensity of CRS to modify INa(T) and INa(L) differentially and to effectively suppress the magnitude of Ih. INa and Ih are thus potential targets of the actions of CRS in terms of modulating cellular excitability.
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Posterior ischemic optic neuropathy (PION), a relatively rare condition, is diagnosed primarily based on the clinical presentation of sudden visual impairment, an optic nerve-related visual field defect, and an initial normal optic disc that corresponds to its pathology of acute ischemia. Among its etiologies, nonarteritic PION is one of the most common causes. Studies on cases of PION associated with herpes zoster ophthalmicus (HZO) are limited, and the diagnosis was made based on the appearance of visual symptoms shortly following rashes. We describe a 64-year-old Asian woman with sudden painless visual loss in the upper half visual field of the left eye 6 weeks after ipsilateral HZO. Within a week, her left vision progressed to total visual loss. Initial examination revealed a near-total visual defect and a normal appearance of the optic disc in the left eye. Laboratory and imaging studies excluded the compressive, infiltrative, or inflammatory etiologies of the left optic nerve. Considering the temporal relationship between the skin rash and visual loss, HZO was the most likely cause of the nonarteritic PION. The patient was given a short course of oral valaciclovir and aspirin. At 6 weeks after the visual loss, an examination revealed stationary visual acuity and visual field defect in the left eye with a pale optic disc, and a retinal nerve fiber loss in the left eye. Compared with previous studies, our case demonstrated a delayed presentation of nonarteritic PION following HZO and broadened the scope of herpes zoster optic neuropathy.
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Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.
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Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing.
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Rufinamide (RFM) is a clinically utilized antiepileptic drug that, as a triazole derivative, has a unique structure. The extent to which this drug affects membrane ionic currents remains incompletely understood. With the aid of patch clamp technology, we investigated the effects of RFM on the amplitude, gating, and hysteresis of ionic currents from pituitary GH3 lactotrophs. RFM increased the amplitude of Ca2+-activated K+ currents (IK(Ca)) in pituitary GH3 lactotrophs, and the increase was attenuated by the further addition of iberiotoxin or paxilline. The addition of RFM to the cytosolic surface of the detached patch of membrane resulted in the enhanced activity of large-conductance Ca2+-activated K+ channels (BKCa channels), and paxilline reversed this activity. RFM increased the strength of the hysteresis exhibited by the BKCa channels and induced by an inverted isosceles-triangular ramp pulse. The peak and late voltage-gated Na+ current (INa) evoked by rapid step depolarizations were differentially suppressed by RFM. The molecular docking approach suggested that RFM bound to the intracellular domain of KCa1.1 channels with amino acid residues, thereby functionally affecting BKCa channels' activity. This study is the first to present evidence that, in addition to inhibiting the INa, RFM effectively modifies the IK(Ca), which suggests that it has an impact on neuronal function and excitability.
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Anticonvulsivantes , Triazoles , Anticonvulsivantes/farmacología , Simulación del Acoplamiento Molecular , Triazoles/farmacología , IonesRESUMEN
Epilepsy is a common neurological disorder; 1% of people worldwide have epilepsy. Differentiating epileptic seizures from other acute neurological disorders in a clinical setting can be challenging. Approximately one-third of patients have drug-resistant epilepsy that is not well controlled by current antiepileptic drug therapy. Surgical treatment is potentially curative if the epileptogenic focus is accurately localized. Diffusion-weighted imaging (DWI) is an advanced magnetic resonance imaging technique that is sensitive to the diffusion of water molecules and provides additional information on the microstructure of tissue. Qualitative and quantitative analysis of peri-ictal, postictal, and interictal diffusion images can aid the differential diagnosis of seizures and seizure foci localization. This review focused on the fundamentals of DWI and its associated techniques, such as apparent diffusion coefficient, diffusion tensor imaging, and tractography, as well as their impact on epilepsy in terms of differential diagnosis, epileptic foci determination, and prognosis prediction.
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Ubiquinone, composed of a 1,4-benzoquinone and naturally produced in the body, actively participates in the mitochondrial redox reaction and functions as an endogenous lipid antioxidant, protecting against peroxidation in the pituitary-dependent hormonal system. However, the questions of if and how ubiquinone directly affects neuronal ionic currents remain largely unsettled. We investigated its effects on ionic currents in pituitary neurons (GH3 and MMQ cells) with the aid of patch-clamp technology. Ubiquinone decreased the peak amplitude of the voltage-gated Na+ current (INa) with a slowing of the inactivation rate. Neither menadione nor superoxide dismutase modified the ubiquinone-induced INa inhibition. In response to an isosceles-triangular ramp pulse, the persistent INa (INa(P)) at high- and low- threshold potentials occurred concurrently with a figure-eight hysteresis loop. With ubiquinone, the INa(P) increased with no change in the intersection voltage, and the magnitude of the voltage-dependent hysteresis of the current was enhanced. Ubiquinone was ineffective in modifying the gating of hyperpolarization-activated cation currents. In MMQ lactotrophs, ubiquinone effectively decreased the amplitude of the INa and the current inactivation rate. In sum, the effects of ubiquinone demonstrated herein occur upstream of its effects on mitochondrial redox processes, involved in its modulation of sodium channels and neuronal excitability.
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Antioxidantes , Sodio , Antioxidantes/farmacología , Lípidos/farmacología , Neuronas , Sodio/farmacología , Ubiquinona/farmacologíaRESUMEN
Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts' opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.
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Super-refractory status epilepticus (SRSE) is a critical condition in which seizures persist despite anesthetic use for 24 h or longer. High mortality has been reported in patients with SRSE, but the cause of death remains unclear. We investigated the factors associated with mortality, including clinical characteristics, SE etiologies and severities, treatments, and responses in patients with SRSE in a 13-year tertiary hospital-based retrospective cohort study comparing these parameters between deceased and surviving patients. SRSE accounted for 14.2% of patients with status epilepticus, and 28.6% of SRSE patients died. Deceased patients were mostly young or middle-aged without known systemic diseases or epilepsy. All deceased patients experienced generalized convulsive status epilepticus and failure of anesthetic tapering-off, significantly higher than survivors. An increased number of second-line anesthetics besides midazolam was observed in the deceased (median, 3, interquartile range 2-3) compared to surviving (1, 1-1; p = 0.0006) patients with prolonged use durations (p = 0.047). For mortality, the cut-off number of second-line anesthetics was 1.5 (AUC = 0.906, p = 0.004). Deceased patients had significantly higher renal and cardiac complications and metabolic acidosis than survivors. In SRSE management, multi-anesthetic use should be carefully controlled to avoid systemic complications and mortality.
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Cardiopatías , Estado Epiléptico , Anticonvulsivantes/uso terapéutico , Cardiopatías/tratamiento farmacológico , Humanos , Midazolam/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Estado Epiléptico/tratamiento farmacológicoRESUMEN
Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise.
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Encefalitis , Epilepsia , Enfermedad de Hashimoto , Encefalitis/complicaciones , Epilepsia/diagnóstico , Epilepsia/etiología , Epilepsia/terapia , Humanos , Canales IónicosRESUMEN
BACKGROUND: Patients with epilepsy have an increased risk of stroke. However, the detailed risk and characteristics of postepilepsy stroke have not been investigated. METHODS: This study utilized the National Health Insurance Research Database in Taiwan. We classified adult patients with newly diagnosed epilepsy from 2003 to 2016 as the epilepsy cohort. Patients in the nonepilepsy cohort were selected with propensity score matching at a case-control ratio of 1:5. The incidence, hazard ratio (HR), period-specific HR, recurrent HR in the Wei-Lin-Weissfeld model, stroke severity index, complications, and mortality of all stroke, ischemic stroke (IS) and hemorrhagic stroke events in the two cohorts were analyzed. RESULTS: We enrolled 23,810 patients in the epilepsy cohort and 119,050 persons in the nonepilepsy cohort. The period-specific HRs of all stroke, IS and hemorrhagic stroke peaked immediately after epilepsy diagnosis and trended downward [Adjusted HRs of all stroke: 4.88 (3.88-6.14), 4.47 (3.50-5.70), 3.17 (2.62-3.84), 2.81 (2.27-3.48), 2.81 (2.36-3.34) and 2.33 (2.07-2.62) in 0-0.5, 0.5-1, 1-2, 2-3, 3-5 and ≥5 years after epilepsy diagnosis, respectively]. The recurrent stroke HRs in the epilepsy cohort were >1 from the first [3.06 (2.71-3.34)] to the fourth events [6.33 (1.08-37.03)]. IS events in the epilepsy cohort were associated with a younger onset age, a higher IS severity index, a higher rate of urinary tract infection, a lower in-hospital mortality, while 90-day stroke mortality was similar between the 2 cohorts. CONCLUSION: Since the increased risk of stroke in epilepsy cohort peaked immediately after epilepsy diagnosis, early implementation of prevention strategies is considered.
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Epilepsia , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Estudios de Cohortes , Epilepsia/complicaciones , Epilepsia/epidemiología , Accidente Cerebrovascular Hemorrágico/epidemiología , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/etiología , Taiwán/epidemiologíaRESUMEN
Background: Among poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct. Methods: A population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan-Meier method. Results: In total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33-3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development. Conclusions: This study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.