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Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for a third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, and oligodendrocytes, are emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, and synaptic plasticity, playing key roles in maintaining the blood–brain barrier (BBB) and mediating neuroinflammatory responses. Dysregulated astrocyte functions, such as reactive astrogliosis, can lead to abnormal neuronal activity and seizure generation. They release gliotransmitters, cytokines, and chemokines that may exacerbate or mitigate seizures. Microglia, the innate immune cells of the CNS, contribute to neuroinflammation, glutamate excitotoxicity, and the balance between excitatory and inhibitory neurotransmission, underscoring their dual role in seizure promotion and protection. Meanwhile, oligodendrocytes, primarily involved in myelination, also modulate axonal excitability and contribute to the neuron–glia network underlying seizure pathogenesis. Understanding the dynamic interactions of glial cells with neurons provides promising avenues for novel epilepsy therapies. Targeting these cells may lead to improved seizure control and better clinical outcomes, offering hope for patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Background: Purulent meningitis (PM) is a commonly encountered infectious condition in newborns, which unfortunately can result in infant mortality. Newborns with PM often present nonspecific symptoms. The success of lumbar puncture, an invasive test, relies on the operator's expertise. Preterm infants pose diagnostic challenges compared to full-term babies. The objective of this study is to establish a convenient and effective clinical prediction model based on perinatal factors to assess the risk of PM in very preterm infants, thereby assisting clinicians in developing new diagnostic and treatment strategies. Methods: This study involved very preterm infants (gestational age < 32 weeks) admitted to the Qilu Hospital of Shandong University from January 2020 to December 2023. All included infants underwent lumbar puncture. We gathered comprehensive data that included information on maternal health conditions and the clinical features of very preterm infants. The PM was diagnosed according to the diagnostic criteria. This study conducted data analysis and processing using R version 4.1.2. A stepwise regression method was applied for multivariate Logistic regression analysis to select the best predictors for PM and to develop a predictive model. Differences were considered statistically significant at P < 0.05. Results: This study enrolled a total of 201 preterm infants, including 117 boys and 84 girls. The gestational age was 28.7 ± 1.7 weeks, and the weight was 1166.2 ± 302.7 g. Ninety infants were diagnosed with PM, while 111 did not have PM. The influencing factors include birth weight, PCT within 24 h after birth, cesarean delivery, and premature rupture of membranes. These were used to construct a risk prediction nomogram and verified its accuracy. The Brier score was 0.157, the calibration slope was 1.0, and the concordance index was 0.849. Conclusions: We developed and validated a personalized nomogram to identify high-risk individuals for early prediction of purulent meningitis in very preterm infants. This practical predictive model may help reduce unnecessary lumbar puncture procedures. [ABSTRACT FROM AUTHOR]

Neurological disorders are characterized by high mortality and disability rates. Furthermore, the burden associated with disability and mortality resulting from neurological disorders has been increasing at an alarming rate. Botanical drugs and their bioactive components have emerged as a prominent area of research, offering a promising avenue for developing novel alternatives for treating neurological diseases. Gastrodin is the principal active component derived from the traditional Chinese medicinal plant Gastrodia elata Blume (GEB). Existing literature reveals that gastrodin exerts various pharmacological protective actions against neurological disorders. This review aimed to collate novel literature on gastrodin for treating neurological disorders from Web of Science, PubMed, Embase and CNKI. The pharmacokinetics of gastrodin, its therapeutic role in neurological disorders, the main mechanisms of action and clinical application were addressed. Furthermore, a detailed overview of gastrodin drug delivery systems and physical enhancement methods was presented, offering invaluable insights into potential research and the extensive applications of gastrodin. [ABSTRACT FROM AUTHOR]

Neonatal sepsis remains a significant cause of neonatal morbidity and mortality globally. At present, no clear consensus definition for sepsis in neonates exists, even though a positive blood culture is considered as the gold standard for definitive diagnosis. The accurate and timely diagnosis of sepsis in neonates presents significant difficulties, since "culture negative" or "suspected" sepsis varies widely worldwide. Antibiotic overuse and resistance are emerging problems, but on the other hand, under-recognition of sepsis and delayed antibiotic treatment could have serious or even fatal adverse outcomes in this vulnerable population. In the context of rapid recognition of sepsis and timely initiation of appropriate antibiotic therapy, various sepsis risk assessment tools have been developed, a variety of biomarkers are in clinical use or under research for future use, and new diagnostic techniques are under evaluation. In this review, we summarize the most recent data on neonatal sepsis, the utility of sepsis risk assessment tools for term and preterm infants with sepsis, and current diagnostic and preventive tools. [ABSTRACT FROM AUTHOR]

Epilepsy is a prevalent chronic neurological disorder that can significantly impact patients' lives. The incidence and risk of psychosis in individuals with epilepsy are notably higher than in the general population, adversely affecting both the management and rehabilitation of epilepsy and further diminishing patients' quality of life. This review provides an overview of the classification and clinical features of psychosis of epilepsy, with the aim of offering insights and references for the clinical diagnosis and treatment of various types of psychosis of epilepsy. Additionally, we examine the potential pathophysiological mechanisms underlying the psychosis of epilepsy from three perspectives: neuroimaging, neurobiology, and genetics. The alterations in brain structure and function, neurotransmitters, neuroinflammatory mediators, and genetic factors discussed in this review may offer insights into the onset and progression of psychotic symptoms in epilepsy patients and are anticipated to inform the identification of novel therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Second-person neuroscience focuses on studying the behavioral and neuronal mechanisms of real-time social interactions within single and across interacting brains. In this review article, we describe the developments that have been undertaken to study socially interactive phenomena and the behavioral and neurobiological processes that extend across interaction partners. More specifically, we focus on the role that synchrony across brains plays in enabling and facilitating social interaction and communication and in shaping social coordination and learning, and we consider how reduced synchrony across brains may constitute a core feature of psychopathology. [ABSTRACT FROM AUTHOR]

Intracranial potentials are used as functional biomarkers of neural networks. As potentials spread away from the source populations, they become mixed in the recordings. In humans, interindividual differences in the gyral architecture of the cortex pose an additional challenge, as functional areas vary in location and extent. We used source separation techniques to disentangle mixing potentials obtained by exploratory deep arrays implanted in epileptic patients of either sex to gain access to the number, location, relative contribution, and dynamics of coactive sources. The unique spatial profiles of separated generators made it possible to discern dozens of independent cortical areas for each patient, whose stability maintained even during seizure, enabling the follow up of activity for days and across states. Through matching these profiles to MRI, we associated each with limited portions of sulci and gyri and determined the local or remote origin of the corresponding sources. We also plotted source-specific 3D coverage across arrays. In average, individual recording sites are contributed to by 3–5 local and distant generators from areas up to several centimeters apart. During seizure, 13–85% of generators were involved, and a few appeared anew. Significant bias in location assignment using raw potentials is revealed, including numerous false positives when determining the site of origin of a seizure. This is not amended by bipolar montage, which introduce additional errors of its own. In this way, source disentangling reveals the multisource nature and far intracranial spread of potentials in humans, while efficiently addressing patient-specific anatomofunctional cortical divergence. [ABSTRACT FROM AUTHOR]

We adapt non-linear optimal control theory (OCT) to control oscillations and network synchrony and apply it to models of neural population dynamics. OCT is a mathematical framework to compute an efficient stimulation for dynamical systems. In its standard formulation, it requires a well-defined reference trajectory as target state. This requirement, however, may be overly restrictive for oscillatory targets, where the exact trajectory shape might not be relevant. To overcome this limitation, we introduce three alternative cost functionals to target oscillations and synchrony without specification of a reference trajectory. We successfully apply these cost functionals to single-node and network models of neural populations, in which each node is described by either the Wilson-Cowan model or a biophysically realistic high-dimensional mean-field model of exponential integrate-and-fire neurons. We compute efficient control strategies for four different control tasks. First, we drive oscillations from a stable stationary state at a particular frequency. Second, we switch between stationary and oscillatory stable states and find a translational invariance of the state-switching control signals. Third, we switch between in-phase and out-of-phase oscillations in a two-node network, where all cost functionals lead to identical OC signals in the minimum-energy limit. Finally, we (de-) synchronize an (a-) synchronously oscillating six-node network. In this setup, for the desynchronization task, we find very different control strategies for the three cost functionals. The suggested methods represent a toolbox that enables to include oscillatory phenomena into the framework of non-linear OCT without specification of an exact reference trajectory. However, task-specific adjustments of the optimization parameters have to be performed to obtain informative results. [ABSTRACT FROM AUTHOR]

The piriform cortex (PC) plays a pivotal role in the onset and propagation of temporal lobe epilepsy (TLE), making it a potential target for therapeutic interventions. This review delves into the anatomy and epileptogenic connections of the PC, highlighting its significance in seizure initiation and resistance to pharmacological treatments. Despite its importance, the PC remains underexplored in surgical approaches for TLE. We examine the specific neuroanatomy of the PC as well as the limitations of current imaging techniques and surgical interventions, emphasizing the need for improved imaging protocols to safely target the PC, especially in minimally invasive procedures. Furthermore, the PC's proximity to vital structures, such as the lenticulostriate arteries, presents challenges that must be addressed in future research. By developing multimodal imaging techniques and refining surgical strategies, the PC could emerge as a crucial node in improving seizure freedom outcomes for TLE patients. [ABSTRACT FROM AUTHOR]

Objective: The study aims to assess the relationship between epilepsy and circadian rhythms. Method: This study included a cohort of 7,410 participants sourced from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) database. The investigation focused on the comparative analysis of seven nonparametric indices associated with circadian rhythms (Interdaily Stability (IS), Intradaily Variability (IV), Relative Amplitude (RA), L5, M10, L5 start time, and M10 start time) between the overall population and patients with epilepsy. Logistic regression analysis was utilized to assess the potential correlation between the rest-activity circadian rhythm patterns and the presence of epilepsy within the cohort. Results: Compared to the general population, individuals with epilepsy exhibited lower values of IS and M10. Multivariable logistic regression analysis, when IS, RA, and M10 were categorized into four groups based on quartiles, revealed that the odds ratio (IS: OR = 0.36, 95% CI: 0.13, 0.89; RA: OR = 0.25, 95% CI: 0.06, 0.77; M10: OR = 0.24, 95% CI: 0.06, 0.73) for the highest quartile was lower than that for the lowest quartile. Furthermore, after adjustment for confounding factors, participants in the highest quartile compared to those in the lowest quartile of IV and M10 start time demonstrated a higher prevalence of epilepsy. Conclusion: Individuals with epilepsy demonstrate significant alterations in circadian rhythms. [ABSTRACT FROM AUTHOR]

In real-world vision, objects may appear for a short period, such as in conjunction with visual search. Presumably, this puts a premium on rapid categorization. We designed a visual categorization task cued by briefly presented images to study how visual categorization is processed in an ethologically relevant context. We compared the performance of monkeys with bilateral area TE lesions, and those with bilateral rhinal cortex lesions, to control animals. TE lesions impaired the accuracy but not the speed of visual categorization. In contrast, rhinal cortex lesions did not affect the accuracy but reduced the speed of visual categorization. A generalized drift-diffusion model (GDDM) with collapsing bounds was fitted to the data. The drift rate was equivalent across all groups, but the decision bounds collapsed more slowly in the rhinal group than in the other two groups. This suggests that, although evidence is accumulated at the same rate in all groups, the rhinal lesion results in slower decision-making. [ABSTRACT FROM AUTHOR]

In this work the effect of changing extracellular potassium concentration ([K+]o) on spontaneous and evoked burst activity of glutamatergic neurons in the mouse hippocampus was investigated using the whole-cell patch clamp technique. It was shown that the increase of [K+]o from 3 to 8.5 mM (potassium load): (1) induced spontaneous tonic and pacemaker burst activity in CA1 pyramidal cells (20% and 10% of total cells, respectively) but did not result in the emergence of pacemaker granule cells in the dentate gyrus (DG). (2) Similarly, potassium load increased the evoked burst activity of CA1 pyramidal cells and, paradoxically, suppressed the burst activity of DG granule cells over the entire range of current steps from 10 to 200 pA. (3) Potassium load caused a rightward shift of the current–voltage (I/V) curves in both cell types, decreasing the reversal potential Erev and increasing the slope of the I/V curves (amplitudes of inward currents at voltages from –100 mV to –70 mV) in the CA1 and DG neurons 2–3- and 4–5-fold, respectively. (4) Potassium load produced an opposite effect on outward currents, causing a significant increase in current amplitude in pyramidal cells and a decrease in granule cells (at membrane voltages above 0 mV). The inward and outward currents of DG neurons were 4–4.5 times higher than those of CA1 neurons. The possible involvement of potassium-activated and other potassium-conducting channels in different excitability responses of glutamatergic CA1 and DG neurons under potassium load is discussed. The high sensitivity of CA1 pyramidal cells to potassium load compared to DG granule cells may play an important role in hyperexcitation of neuronal networks during epileptogenesis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Noncontact forehead thermometers have become increasingly widespread because of their advantages, such as rapid measurement of temperature, noninvasiveness, ease of use, and portability. The aim of the study was to compare the body temperature values measured using a noncontact forehead thermometer and a tympanic thermometer. Methods: A cross-sectional, comparative, and quasi-experimental research design was used in this study. The research population was composed of 200 adult individuals older than 18 years who were being treated at the hospital between January 2015 and March 2015. The temperature and humidity of the environment were measured with an electronic thermo-hygrometer thermometer. The body temperature of the patient was measured with both a noncontact forehead thermometer and a tympanic thermometer by the same researcher. The data were recorded in the patient information form and the patient observation form. Results: Mean body temperature values measured with a noncontact forehead thermometer and a tympanic thermometer were 36.17°C ± 0.47°C and 36.89°C ± 0.44°C, respectively. Results showed that there was no clear relationship between differences and averages, and there was conformity between the two methods. Conclusions: The mean forehead temperature is lower than the tympanic temperature, and there is conformity between the two methods. [ABSTRACT FROM AUTHOR]

Objective: Perampanel (PER), a noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, has been approved as adjunctive therapy for focal and generalized epilepsy. Limited information is available regarding the measurable impact of anti-seizure medications (ASM). In this study, we aimed to investigate the effects of PER on electroencephalography (EEG) background activity and interictal epileptic discharge. Methods: This study included all patients with a clinical diagnosis of epilepsy who underwent routine EEG before and after PER treatment between 2018 and 2023. EEG findings were examined according to their background activity and clinical features such as risk factors of epilepsy, the occurrence of sleep-related seizures, sleep disorders, intellectual disability, abnormality of magnetic resonance imaging and EEG, multifocal features on EEG, the duration between EEG and initiation of PER treatment, frequency of seizures before and after PER treatment (seizure freedom or >50% reduction in seizures), previous epilepsy surgery, the number of current and previous ASM, and dosage of PER. Results: In a total of 11 patients, epilepsy type was focal in 8 (73%), all of the patients were on polytherapy, and 4 of them had undergone epilepsy surgery. PER treatment resulted in seizure freedom in 36% of patients and a >50% decrease in seizures in 55% of patients. There was no statistically significant relationship between background activity, phase reversal, and equipotential in EEG before and after PER treatment. In addition, pre- and posttreatment responses to activation procedures and disruption in sleep structure did not differ significantly. The relationship between seizure freedom and phase reversal decrease after PER treatment was statistically significant. The relationship between a >50% decrease in the frequency of seizures and epileptic discharges also reached statistical significance. Conclusion: To summarize, seizure freedom following PER treatment appears to be associated with reduced epileptic discharge, and EEG monitoring might help determine prognosis. [ABSTRACT FROM AUTHOR]

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile. [ABSTRACT FROM AUTHOR]

Gastroesophageal refluxes (GERs) are universal in newborns and may induce deleterious consequences, especially in preemies. We have previously shown that nasal continuous positive airway pressure (nCPAP) inhibits GERs in full-term lambs, complementing similar results in adult humans. The effect of high-flow nasal cannula (HFNC) on GERs, however, remains unknown. This study aimed to assess the effects of nCPAP and HFNC on GERs in our preterm lamb model. Eleven preterm lambs born 14 days before full-term (∼34 wk of human gestation) were studied. Esophageal pH-impedancemetry and polysomnography recordings were performed simultaneously for 6 h under three randomly ordered conditions: nCPAP 6 cmH2O, HFNC 7 L/min, and no respiratory support (control). The indexes (/h) of GERs and air-containing swallows were analyzed during each condition. The states of alertness and cardiorespiratory events were also analyzed during the identified GERs. nCPAP significantly decreased the GER index compared with control and HFNC during both quiet wakefulness and nonrapid eye movement sleep, whereas HFNC did not alter the GER index. In addition, nCPAP significantly increased the air-containing swallow index compared with control and HFNC. No significant differences were observed between the tested conditions for GER-related cardiorespiratory events, which were nevertheless rarely observed. Similar to full-term lambs, nCPAP strongly inhibited GERs in the preterm lamb, despite an increase in air-containing swallows. In contrast, HFNC did not impact GERs. Our results are clinically relevant when discussing the use of CPAP in preemies with GERs. NEW & NOTEWORTHY: Nasal CPAP inhibited gastroesophageal refluxes in preterm lambs, despite increasing air-containing swallows. High-flow nasal cannula did not impact GERs. Nasal respiratory support did not alter the rare cardiorespiratory events observed during GERs. [ABSTRACT FROM AUTHOR]

Purpose: Restless Legs Syndrome (RLS) is a widespread condition that affects sleep leading to daytime sleepiness, depression, and reduced quality of life. This study aims to determine and describe how patients with RLS experience their everyday life, with a focus on facilitators and barriers related to Maslow's hierarchical theory of human needs. Method: Semi-structured interviews were analysed with qualitative content analysis resulting in facilitators and barriers affecting the fulfilment of the five human needs. Results: Addressing RLS symptoms through medications and a quiet sleep environment fulfils psychological needs. Control over RLS symptoms, engagement in activities, trust in treatments, and social support meet safety and security needs. Social inclusion, close relationships, and meaningful interactions fulfil a sense of belongingness and love needs despite RLS. Competence in managing RLS, effective self-care strategies, confident communication, and trust-building support esteem needs. Finally, comprehensive understanding through person-centred interventions and coping fulfils the self-actualization needs in managing RLS. Conclusion: Holistic and person-centred interventions, including facilitators for the fulfilment of physiological, psychological, and social needs could help healthcare professionals to provide holistic care. [ABSTRACT FROM AUTHOR]

Simple Summary: Numerous findings demonstrate that the central nervous system and the peripheral organs and tissues communicate in physiological and pathological conditions thanks to the exchange of signaling molecules transported via blood, cerebrospinal fluid, and lymph. Extracellular vesicles, which can cross tissue barriers, including the blood–brain barrier, play a key role in this bidirectional communication by safely delivering these molecules, including proteins, lipids, and nucleic acids such as microRNAs (miRNAs). In particular, the latter involved in the post-transcriptional regulation of gene expression can alter recipient cells' functions and orchestrate their behavior in response to different biological events. Thus, elucidating the role played by EVs-delivered miRNAs in brain–periphery communication could offer valuable insights for advancing the treatment and management of neurological and systemic diseases. Bidirectional communication between the central nervous system (CNS) and peripheral organs and tissue has been widely documented in physiological and pathological conditions. This communication relies on the bilateral transmission of signaling molecules and substances that circulate throughout the body and reach their target site(s) via the blood and other biological fluids (e.g., the cerebrospinal fluid, the lymph). One of the mechanisms by which these molecular messengers are exchanged is through the secretion of extracellular vesicles (EVs). EVs are known to mediate cell-to-cell communication by delivering biological molecules, including nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood–brain barrier (BBB), enabling direct communication between the periphery and the brain. In particular, the delivery of microRNAs (miRNAs) can modulate the expression profiles of recipient cells, thereby influencing their functions. This review synthesizes current findings about the brain–periphery cross-talk mediated by EVs-delivered miRNAs. Although this mechanism has been definitively shown in a few cases, much evidence indirectly indicates that it could mediate brain–peripherical organs/tissue communication, especially in pathological conditions. Therefore, understanding this process could provide valuable insights for the treatment and management of neurological and systemic diseases. [ABSTRACT FROM AUTHOR]

Objective: Epileptogenesis is linked to neuroinflammation. We hypothesized that local heat production caused by neuroinflammation can be visualized non‐invasively in vivo via brain magnetic resonance spectroscopic imaging (MRSI) and MRSI‐thermometry (MRSI‐t) and that there is a relationship in patients with temporal lobe epilepsy (TLE) between MRSI‐t and brain metabolites choline and myo‐inositol and between neuroimaging and cellular and serum biomarkers of inflammation. Methods: Thirty‐six (36) participants, 18 with temporal lobe epilepsy (13 females) and 18 age‐matched healthy controls (nine females), were enrolled prospectively and underwent MRSI/MRSI‐t; TLE participants also provided blood samples. Temperature was measured using creatine as a reference metabolite. Analysis of Functional NeuroImages 3dttest++ tool was used to analyze voxel‐level group differences in temperature, choline, and myo‐inositol. Associations with immune cell subsets, cytokines, and chemokines related to inflammation were quantified using correlation coefficients with significant relationships as noted. Results: Patients with TLE showed elevated temperature, choline, and myo‐inositol in the temporal lobes. Higher brain temperature was associated with higher levels of cytokines and chemokines, including GM‐CSF, TNF, IL‐1β, and IL − 12p70, and lower frequency of immune cells including CD3+ T‐cells, CD4+ T‐cells, CD8+ T‐cells, and classical monocytes. Higher choline was associated with higher levels of the cytokines including LT‐α, IL‐13, and IL‐4, and higher myo‐inositol was associated with a higher frequency of CD4+ T‐cell and CD19+ B‐cell subsets and higher levels of cytokines and chemokines including LT‐α, IL‐13, and CCL3. Significance: This study, for the first time, showed that in temporal lobes of patients with TLE temperature and metabolite changes correlate with cellular and serum biomarkers of inflammation. Our results provide support for further development of MRSI‐t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool. Plain Language Summary: Neuroinflammation is associated with excessive heat production which can be visualized with magnetic resonance spectroscopic imaging and thermometry (MRSI‐t). We prospectively investigated the relationship between MRSI‐t and cellular and serum measures of peripheral inflammation in patients with temporal lobe epilepsy (TLE); we compared the results of MRSI‐t in patients with TLE to healthy controls. We showed a relationship between the temperature elevations in TLE and elevations of various measures of peripheral inflammation. Our results support further development of MRSI‐t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool. [ABSTRACT FROM AUTHOR]

For centuries, epileptic seizures have been noticed to recur with temporal regularity, suggesting that an underlying biological rhythm may play a crucial role in their timing. In this review, we propose to adopt the framework of chronobiology to study the circadian timing of seizures. We first review observations made on seizure timing in patients with epilepsy and animal models of the disorder. We then present the existing chronobiology paradigm to disentangle intertwined circadian and sleep–wake timing mechanisms. In the light of this framework, we review the existing evidence for specific timing mechanisms in specific epilepsy syndromes and highlight that current knowledge is far from sufficient. We propose that individual seizure chronotypes may result from an interplay between independent timing mechanisms. We conclude with a research agenda to help solve the urgency of ticking seizures. [ABSTRACT FROM AUTHOR]

Background/Objectives: Ongoing challenges in epilepsy therapy warrant research on alternative treatments that offer improved efficacy and reduced side effects. Designed to enhance mitochondrial targeting and increase bioavailability, mitocurcumin (MitoCur) was evaluated for the first time as an antiepileptic agent, with curcumin (Cur) and sodium valproate (VPA), a standard antiepileptic drug, included for comparison. This study investigated the effects on seizure onset, severity, and progression in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures and measured the concentrations of the compounds in brain tissue. Methods: Zebrafish were pre-treated with MitoCur and Cur (both at 0.25 and 0.5 µM doses) and VPA (0.25 and 0.5 mM) and observed for four minutes to establish baseline locomotor behavior. Subsequently, the animals were exposed to a 5 mM PTZ solution for 10 min, during which seizure progression was observed and scored as follows: 1—increased swimming; 2—burst swimming, left and right movements; 3—circular movements; 4—clonic seizure-like behavior; 5—loss of body posture. The studied compounds were quantified in brain tissue through HPLC and LC-MS. Results: Compared to the control group, all treatments reduced the distance moved and the average velocity, without significant differences between compounds or doses. During PTZ exposure, seizure latencies revealed that all treatments effectively delayed seizure onset up to score 4, demonstrating efficacy in managing moderate seizure activity. Notably, MitoCur also provided significant protection against the most severe seizure score (score 5). Brain tissue uptake analysis indicated that MitoCur achieved higher concentrations in the brain compared to Cur, at both doses. Conclusions: These results highlight the potential of MitoCur as a candidate for seizure management. [ABSTRACT FROM AUTHOR]

Background/Objectives: During the pre-conceptional period, addressing social determinants of health (SDOH) is essential for reducing maternal health disparities, particularly among disadvantaged groups. Key SDOH factors such as income, education, and healthcare access significantly influence maternal and infant outcomes, increasing risks like miscarriage, preterm birth, and pregnancy complications. Here, we aimed to explore maternal and neonatal characteristics according to socio-economic status. Thus, we identified clusters of pregnant women with similar social and behavioral characteristics and explored their variability in terms of neonatal outcomes. Methods: Data from 1512 pregnant women in the "MAMI-MED" cohort at ARNAS Garibaldi Nesima in Catania were analyzed. A two-step cluster analysis grouped the women based on education level, employment status, pre-pregnancy nutritional status, and Mediterranean diet score (MDS). Results: Two clusters of pregnant women were identified. Cluster 1 (n = 739) consisted of women with lower educational attainment who were unemployed, overweight and/or obese, and had a lower mean MDS. Instead, cluster 2 (n = 773) was mostly characterized by women with a medium–high level of education who were employed, had normal weight, and had a higher average MDS. Women in cluster 1 had significantly higher proportions of preterm births (p = 0.004), low-birth weight newborns (p = 0.002), and large-for-gestational-age newborns. Differences in gestational week (p < 0.001), birth weight (p < 0.001), and newborn length (p = 0.004) were also noted between the two clusters. Conclusions: Cluster analysis can help identify high-risk groups who may benefit from personalized public health interventions. Our results highlight the need to examine the complex interactions between socio-demographic, behavioral, and genetic factors that contribute to maternal–infant health. [ABSTRACT FROM AUTHOR]

Energy and nitrogen balances were performed in 12 very low birthweight infants fed on either human milk or on a preterm formula. Energy and nitrogen retention were significantly higher in those given the formula feed (p less than 0.05). Highly significant correlations were found between nitrogen intake and nitrogen retention and between energy retention and nitrogen retention (p less than 0.001). Multiple regression analysis failed to show any effect of energy retention on the correlation between nitrogen intake and nitrogen retention in babies fed on human milk. Protein deficiency seems to be the most likely explanation of poor growth in infants fed on human milk. [ABSTRACT FROM AUTHOR]

Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure., (Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.)

Objective: Nonconvulsive status epilepticus (ncSE) is a severe condition that may result in neurologic sequelae and epilepsy resistant to pharmacologic treatment. We analyze here seizure and electroencephalography (EEG) patterns and their correlation to the development of a chronic epileptic condition in a guinea pig model of focal ncSE induced by intrahippocampal injection of kainic acid (KA)., Methods: Electrobehavioral patterns during ncSE induced by unilateral injection of 1 μg of KA in the CA1 region of the hippocampus were characterized by continuous video-EEG monitoring in 13 guinea pigs bilaterally implanted with recording electrodes in the hippocampus and neocortex., Results: Video-EEG analysis demonstrates a high variability of seizure type and duration during KA-induced ncSE. Seizures showed focal signs correlated with diverse epileptiform EEG discharge distributions, either diffuse or localized. Nonfocal (bilateral motor) signs during seizures most likely correlated with a diffuse EEG pattern. The evolution into a chronic epileptic condition correlated neither with the severity of seizure pattern nor with the diffusion of the EEG discharges observed during the ncSE., Significance: Video-EEG monitoring in a guinea pig model of ncSE induced by unilateral hippocampal injection of KA demonstrates a high variability of electrobehavioral patterns. We demonstrate that the seizure severity score during focal ncSE is not a predictor of the evolution into a chronic epileptic condition of mesial temporal lobe epilepsy., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Objective: Comprehension of the events that lead to seizure termination contributes to the development of strategies to confine propagation of ictal discharges. It is commonly assumed that the inhibitory control fails during seizures and recovers after the end of the ictal event. We examine the possibility that a progressive increase of inhibition that counters an increase in the strength of excitation contributes to terminating a focal seizure., Methods: We analyzed seizures acutely induced by pharmacological manipulations (bicuculline and 4-aminopyridine) in the entorhinal cortex and in the hippocampus of the in vitro isolated guinea pig brain., Results: As seizures ended, extracellular and intracellular recordings showed periodic bursting that progressively decreased in frequency. During the late bursting phase, the duration, number, and rate of occurrence of spikes within single bursts remained constant, whereas cumulative spike amplitude (index of excitation during a burst) and interburst interval (index of inhibition between bursts) progressively increased. The increment of average/cumulative burst excitation and interburst interval toward seizure end was confirmed in human focal seizures recorded with intracerebral electrodes in patients with drug-resistant partial epilepsies. A postburst refractory period of circa 2 seconds that increases with time toward the end of the seizure was confirmed in the experimental model by probing interburst epochs in the CA1 region with local dentate gyrus stimulation just suprathreshold for burst generation., Interpretation: Our findings support the concept that focal seizures are terminated by the simultaneous and opposing enhancement of excitation (burst activity) in addition to postburst inhibition. We hypothesize that a seizure stops when postburst inhibition becomes large enough to prevent reactivation of excitation., (© 2014 American Neurological Association.)

Presurgical monitoring with intracerebral electrodes in patients with drug-resistant focal epilepsy represents a standard invasive procedure to localize the sites of seizures origin, defined as the epileptogenic zone (EZ). During presurgical evaluation, intracerebral single-pulse electrical stimulation (SPES) is performed to define the boundaries of eloquent areas and to evoke seizure-associated symptoms. Extensive intracranial exploration and stimulation generate a large dataset on brain connectivity that can be used to improve EZ detection and to understand the organization of the human epileptic brain. We developed a protocol to analyse field responses evoked by intracranial stimulation. Intracerebral recordings were performed with 105-162 recording sites positioned in fronto-temporal regions in 12 patients with pharmacoresistant focal epilepsy. Recording sites were used for bipolar SPES at 1 Hz. Reproducible early and late phases (<60 ms and 60-500 ms from stimulus artefact, respectively) were identified on averaged evoked responses. Phase 1 and 2 responses recorded at all and each recording sites were plotted on a 3D brain reconstructions. Based on connectivity properties, electrode contacts were primarily identified as receivers, mainly activators or bidirectional. We used connectivity patterns to construct networks and applied cluster partitioning to study the proprieties between potentials evoked/stimulated in different regions. We demonstrate that bidirectional connectivity during phase 1 is a prevalent feature that characterize contacts included in the EZ. This study shows that the application of an analytical protocol on intracerebral stimulus-evoked recordings provides useful information that may contribute to EZ detection and to the management of surgical-remediable epilepsies., (Copyright © 2014 Wiley Periodicals, Inc.)

Purpose: To optimize signal-to-noise ratio (SNR) in fast spin echo (rapid acquisition with relaxation enhancement [RARE]) sequences and to improve sensitivity in ¹⁹F magnetic resonance imaging (MRI) on a 7T preclinical MRI system, based on a previous experimental evaluation of T₁ and T₂ actual relaxation times., Materials and Methods: Relative SNR changes were theoretically calculated at given relaxation times (T₁, T₂) and mapped in RARE parameter space (TR, number of echoes, flip back pulse), at fixed acquisition times. T₁ and T₂ of KPF₆ phantom samples (solution, agar mixtures, ex vivo perfused brain) were measured and experimental SNR values were compared with simulations, at optimal and suboptimal RARE parameter values., Results: The optimized setting largely depended on T₁, T₂ times and the use of flip back pulse improved SNR up to 30% in case of low T₁/T₂ ratios. Relaxation times in different conditions showed negligible changes in T₁ (below 14%) and more evident changes in T₂ (-95% from water solution to ex vivo brain). Experimental data confirmed theoretical forecasts, within an error margin always below 4.1% at SNR losses of ~20% and below 8.8% at SNR losses of ~40%. The optimized settings permitted a detection threshold at a concentration of 0.5 mM, corresponding to 6.22 × 10¹⁶ fluorine atoms per voxel., Conclusion: Optimal settings according to measured relaxation times can significantly improve the sensitivity threshold in ¹⁹F MRI studies. They were provided in a wide range of (T₁, T₂) values and experimentally validated showing good agreement.

In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis. [ABSTRACT FROM AUTHOR]

We performed metabolic balance studies in 77 preterm infants fed on human milk or adapted formulas, to determine the renal solute load and compared it with the potential renal solute load estimated by the composition of the diet or the urine according to Ziegler's, Bergman's, and Shaw's calculations. The renal solute load found in preterm infants was lower than that observed in young full term infants. Although all calculations predicted the renal solute load well, the equation proposed by Ziegler and Fomon from dietary protein and electrolyte load appears to be the simplest to calculate renal solute load accurately in preterm infants. [ABSTRACT FROM AUTHOR]

Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy. [ABSTRACT FROM PUBLISHER]

Dendritic Pathology, Spine Loss and Synaptic Reorganization in Human Cortex From Epilepsy Patients Rossini L, De Santis D, Mauceri RR, Tesoriero C, Bentivoglio M, Maderna E, Maiorana A, Deleo F, de Curtis M, Tringali G, Cossu M, Tumminelli G, Bramerio M, Spreafico R, Tassi L, Garbelli R. Brain. 2021;144(1):251-265. doi:10.1093/brain/awaa387 Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analyzed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined etiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hippocampal sclerosis. Autoptic tissues were used for comparison. Three-dimensional reconstructions of Golgi-impregnated neurons revealed severe dendritic reshaping and spine alteration in the core of the type II focal cortical dysplasia. Dysmorphic neurons showed increased dendritic complexity, reduction of dendritic spines, and occasional filopodia-like protrusions emerging from the soma. Surprisingly, the intermingled normal-looking pyramidal neurons also showed severe spine loss and simplified dendritic arborization. No changes were observed outside the dysplasia (perilesional tissue) or in neocortical postsurgical tissue obtained in the other patient groups. Immunoreactivities of vGLUT1 and vGAT showed synaptic reorganization in the core of type II dysplasia characterized by the presence of abnormal perisomatic baskets around dysmorphic neurons, in particular those with filopodia-like protrusions, and changes in vGLUT1/vGAT expression. Ultrastructural data in type II dysplasia highlighted the presence of altered neuropil engulfed by glial processes. Our data indicate that the fine morphological aspect of neurons and dendritic spines are normal in epileptogenic neocortex, with the exception of type II dysplastic lesions. The findings suggest that the mechanisms leading to this severe form of cortical malformation interfere with the normal dendritic arborization and synaptic network organization. The data argue against the concept that long-lasting epilepsy and seizure recurrence per se unavoidably produce a dendritic pathology. [ABSTRACT FROM AUTHOR]

Inhibitors of the cyclo-oxygenase component of prostaglandin-H2 synthetase, namely indomethacin and ibuprofen, are commonly used in the treatment of hemodynamically significant patent ductus arteriosus. These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol, an inhibitor of the peroxidase component of prostaglandin-H2 synthetase, has been proposed for the treatment of patent ductus arteriosus. We report a series of 8 neonates (birth weight: 724 ± 173 g; gestational age: 26 ± 2 weeks) treated with paracetamol for a hemodynamically significant patent ductus arteriosus, because of contraindications to ibuprofen or indomethacin. Successful closure was achieved in 6 out of 8 babies (75%). Median ductal diameter was significantly reduced after treatment (from 1.2 mm, range 1.0-2.5 mm to 0.6 mm, range 0.0-2.5 mm, p = 0.038). No adverse or side effects were observed during treatment. On the basis of these results, paracetamol could be considered a promising and safe therapy for the treatment of patent ductus arteriosus in neonates.

Objective: In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone (EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography (EEG)., Methods: Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo-EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists., Results: In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80-120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ., Significance: Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Seizure patterns in temporal lobe epilepsies have been described both in humans and in animal models. The involvement of specific hippocampal-parahippocampal subregions in the initiation and progression of temporal lobe seizures is not defined yet. We analyzed limbic network dynamics during seizures induced by 3-min arterial perfusion of 50 µM bicuculline in the in vitro isolated guinea pig brain preparation. As for human and animal temporal lobe epilepsies, 2 seizure types characterized at onset by either fast activity (FA) or hypersynchronous activity (HSA) were observed in our acute model. Simultaneous extracellular recordings were performed from ventral hippocampal-parahippocampal subregions with multichannel electrodes, and laminar analysis and propagation directions were computed to define reciprocal interactions during seizures. FA seizures started with fast oscillations generated in CA1-subiculum and entorhinal cortex, followed by irregular spikes and progressively regular bursts well defined in all subfields, with the exception of pre- and parasubiculum that do not participate in seizure activity. Dentate gyrus was not involved at FA seizure onset and became prominent during the transition to bursting in both FA and HSA patterns. HSA seizures were similar to FA events, but lacked initial FA. During seizures, reliable and steady propagation within the intra-hippocampal re-entrant loop was observed.

Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives.

Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this process.

Background: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements., Objective: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth., Design: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth., Results: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478)., Conclusion: Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)