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Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored. [ABSTRACT FROM AUTHOR]

AbstractCymbopogon martinii essential oil (Palmarosa essential oil, PRO) has a wide range of applications in food, medicine, and cosmetics. Because of its hydrophobicity, instability, and volatility, the best option to safeguard this oil is to encapsulate it using nanoemulsion technology. In this work, we synthesize O/W (oil/water) nanoemulsions from C. martini essential oil and analyze their biological activity. The study uses co-surfactants like ethanol and surfactants like tween 80 and sodium dodecyl sulfate to create O/W nanoemulsions. The nanoemulsions were investigated using UV, fluorescence, and FT-IR fingerprinting techniques in addition to parameters such as pH and conductivity. Additionally, the study explored the biological effects of the nanoemulsions, including their antibacterial, anti-inflammatory, anticancer, and anti-diabetic capabilities. The pharmacokinetics of drug release was also examined. By using GC-FID analysis, it has been determined that geraniol is the primary component of PRO. The concentrations of total phenolic, total flavonoid, and total condensed tannin were found to be 2.91 mg/g GAE, 9.29 mg/g RE, and 3.78 mg/g VAE, respectively. Palmarosa essential oil nanoemulsions (PNE) were discovered to have 93.24% encapsulation efficiency. The nanoemulsions remained stable and spherical even after 50 days of storage. PNE was synthesized with a mean diameter of 460.55 ± 98.65 nm, a polydispersity index (PDI) value of 0.45 ± 0.04, and a zeta potential measurement of 0.1711 ± 0.05 mV. According to a drug kinetic analysis, PNE displayed a first-order model with an R2 value of 0.930. PNE revealed a dose-dependent 92% inhibition of α-amylase. Additionally, PNE demonstrated potent anti-bacterial activity against the investigated pathogens that varied from 38% to 94%. In the same way, PNE demonstrated potent anti-fungal efficacy against the studied fungal infections, with a range of 50–95%. Anticancer research showed that the PNE-containing cells had a percent viability of 21.29% after 24 hours and 14.92% after 48 hours, respectively. The article explores the possible applications of nanoemulsions made from palmarosa essential oil in the cosmetic, food, and medicinal sectors. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia plays a significant role in the formation of gallstones more important being the cholesterol gallstones. Lipid parameters including total cholesterol, triglycerides, high density lipoproteins and low-density lipoproteins show a significant relation with cholesterol gallstones. Patients with cholesterol type of gallstones have lipid profile parameters towards undesirable ranges as compared to other stones. [ABSTRACT FROM AUTHOR]

Gallbladder disease is a common health problem throughout the world. The commonest reason is gallstones accounting for over 90% of cases. Gallstones can occur in any age group of both the sexes. Incidence of gallstones increases with age and is more common in female population including both symptomatic and asymptomatic cases. The present study was conducted to assess the age and sex distribution of cholelithiasis cases in tertiary hospital of northern india. [ABSTRACT FROM AUTHOR]

Cerium oxide (CeO2) is a material with unique dielectric properties that make it a promising candidate for various applications. High electrical resistance and a wide bandgap of pristine CeO2 limit its applicability in photovoltaics and photo‐electrocatalysis. CeO2 is co‐doped with transition metals (Fe+2/Fe+3 and Cu+2), which reduces its optical bandgap energy and electrical resistance. This study aims to investigate the dielectric relaxation behavior and charge‐carrier dynamics of Fe, Cu–CeO2. The enhanced charge‐carrier dynamics in the Fe, Cu–doped CeO2 compared to pristine CeO2 are reported. Using temperature‐dependent electrochemical impedance spectroscopy (TD‐EIS), the dielectric relaxation and carrier dynamics in pristine CeO2 and Fe, Cu–doped CeO2 in the temperature range 313–473 K along with the modulus spectroscopy are investigated. It is observed that Z′ values reduced with the temperature, thus showing the negative temperature coefficient of resistance in the frequency range 6.28–1.005 × 105 radians s−1. Furthermore, a correlated study of –Z″ and M″ shows the charge‐carrier relaxation behavior changes from ideal Debye type to non‐Debye type with temperature rise in Fe, Cu–doped CeO2. [ABSTRACT FROM AUTHOR]

Aim: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.Method: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.Results: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'.Interpretation: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.What This Paper Adds: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag. [ABSTRACT FROM AUTHOR]

This scientific commentary refers to 'Randomized placebo-controlled crossover trial of memantine in children with epileptic encephalopathy' by Schiller I et al. i (https://doi.org/10.1093/brain/awac380). Nine patients (33%) in the memantine group achieved the primary outcome compared to only two patients (7%) in the placebo group ( I P i < 0.04).[4] Of the nine responders, six had >50% seizure reduction. Trend reductions in autism probability were seen, but with both memantine and placebo, while measures of functional impairment trended lower with memantine but not placebo. [Extracted from the article]

The contamination of environmental sully with antibiotics is regarded as a major problem today and predictable to attain more recognition in near future. However, human intervention resulting in antibiotic consumption is being enhancing all around the world. Our review of literature revealed the role of microbiome in sully and how antibiotic resistant genes raised. The structure of antibiotics basically influenced by natural components such as biotic and abiotic push which shifts based on different soils. Therefore, management of microbiome in soil and their expression studies were distinctively revealed. The assessment of antibiotic resistance genes with help of next generation sequencing provided a clear comprehension on genome and transcriptome of the bacterial genes. Thus, interaction of microbiome with soil can also be well understood. The current findings in our study will guide every researcher to follow logical protocol in analyzing microbiota composition is covered as well and also to understand its metagenomic and sequenced with next-generation sequencer which helps to comprehend the diverse micro-flora present in soil and its operation. Finally, later progresses in bioinformatics computer program, flow of work, and applications for analyzing metagenomic information are put in a nutshell. [ABSTRACT FROM AUTHOR]

In the present work, fluorescence anisotropy studies of BODIPY (pyrromethene 546 or C14H17BF2N2) dye have been performed and found that it has a potential to be used as a thermal probe to measure the temperature of microfluid. It is well-known that a dye rotates in its excited state, so to control the molecular rotation of the dye in the excited state, sorbitol is used in the solution. It has been found that adding sorbitol, fluorescence anisotropy increases, fluorescence lifetime decreases. It has been found that adding sorbitol, temperature sensitivity increases. To study the effect of -CH2 groups on fluorescence properties, another BODIPY (pyrromethene 597 or C22H33BF2N2) dye is also used, as C14H17BF2N2 and C22H33BF2N2 have similar structures with a difference of only -8CH2 groups. It has been found that C22H33BF2N2 has superior properties over C14H17BF2N2, i.e., pyrromethene 597 shows larger temperature sensitivity as compared to pyrromethene 546, even without the addition of sorbitol. [ABSTRACT FROM AUTHOR]

Background: Infantile apneic seizures (IASs) are unexpected life-threatening events. We aimed to determine the utility of prolonged video-electroencephalography (vEEG) and heart rate variability (HRV) in IAS.Methods: The study included seven infants with apneic seizures captured by vEEG, percutaneous oxygen saturation (SpO2), and electrocardiography (ECG). Interictal, preictal, and postictal HRV of patients and N2 sleep HRV of 10 age-matched controls were determined.Results: We analyzed seven vEEGs (duration = 17 to 87 hours) of seven patients aged three to 13 months (mean onset age of apneic event = 6.3 months). Fifteen apneic seizures (one to five per infant) were captured. The initial apneic seizure was captured at 7.5 to 76 hours (mean = 36.6 hours) after vEEG initiation. Ictal rhythmic delta/theta/fast waves were seen over temporal (five patients), central (one), and diffuse areas (one). Ictal SpO2 decreased between 1.5% and 90% (mean = 47.9%). Ictal decreased heart rate (HR) (six seizures) and ictal increased HR (14) was detected. Both decreased and increased HR was observed (five). The preictal low-frequency (LF)/high-frequency (HF) ratio was significantly higher than the interictal LF/HF ratio (P = 0.048). Preictal (P = 0.048), and postictal (P = 0.019) root mean square of successive differences (RMSSDs) of patients were lower than the sleep RMSSD of controls. These results indicated dominant sympathetic activity. RMSSD from interictal to preictal periods tended to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.066). The postictal RMSSD showed tendency to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.088). The decreased HR and increased RMSSD suggested not only sympathetic activity but also escalated parasympathetic activity in IAS.Conclusions: Infants with unexpected apneic events should be monitored with prolonged vEEG, SpO2, and ECG. Abnormal HRV in infants with apneic seizures might indicate additional autonomic dysregulation in IAS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Users with Severe Speech and Motor Impairment (SSMI) often use a communication chart through their eye gaze or limited hand movement and care takers interpret their communication intent. There is already significant research conducted to automate this communication through electronic means. Developing electronic user interface and interaction techniques for users with SSMI poses significant challenges as research on their ocular parameters found that such users suffer from Nystagmus and Strabismus limiting number of elements in a computer screen. This paper presents an optimized eye gaze controlled virtual keyboard for English language with an adaptive dwell time feature for users with SSMI. OBJECTIVE: Present an optimized eye gaze controlled English virtual keyboard that follows both static and dynamic adaptation process. The virtual keyboard can automatically adapt to reduce eye gaze movement distance and dwell time for selection and help users with SSMI type better without any intervention of an assistant. METHODS: Before designing the virtual keyboard, we undertook a pilot study to optimize screen region which would be most comfortable for SSMI users to operate. We then proposed an optimized two-level English virtual keyboard layout through Genetic algorithm using static adaptation process; followed by dynamic adaptation process which tracks users' interaction and reduces dwell time based on a Markov model-based algorithm. Further, we integrated the virtual keyboard for a web-based interactive dashboard that visualizes real-time Covid data. RESULTS: Using our proposed virtual keyboard layout for English language, the average task completion time for users with SSMI was 39.44 seconds in adaptive condition and 29.52 seconds in non-adaptive condition. Overall typing speed was 16.9 lpm (letters per minute) for able-bodied users and 6.6 lpm for users with SSMI without using any word completion or prediction features. A case study with an elderly participant with SSMI found a typing speed of 2.70 wpm (words per minute) and 14.88 lpm (letters per minute) after 6 months of practice. CONCLUSIONS: With the proposed layout for English virtual keyboard, the adaptive system increased typing speed statistically significantly for able bodied users than a non-adaptive version while for 6 users with SSMI, task completion time reduced by 8.8% in adaptive version than nonadaptive one. Additionally, the proposed layout was successfully integrated to a web-based interactive visualization dashboard thereby making it accessible for users with SSMI. [ABSTRACT FROM AUTHOR]

Essential oil from Melaleuca alternifolia (also known as Tea tree essential oil, TTO) is used as traditional medicine and used as therapeutic in medicine, food and cosmetic sectors. However, this oil is highly unstable, volatile and prone to oxidation which limits its practical use. The objective of this study was synthesis of tea tree oil based O/W (oil/water) nanoemulsions (tea tree essential oil nanoemulsions, TNE) and evaluation of its biological potential. Physiological characterization was carried out using UV, fluorescent, and FT-IR techniques. Various biological activities such as anticancerous, antidiabetic and anti-inflammatory were also estimated. Pharmacokinetics study on TNE was carried out. Encapsulation efficiency of nanoemulsions was found to be 83%. Nanoemulsions were spherical in shape with globule size 308nm, zeta potential -9.42 and polydispersity index was 0.31. Nanoemulsions were stable even after 50days of storage at different temperatures. Anti-oxidant potential of TNE was conducted by various assays and IC50 were: Nitric oxide radical scavenging activity:225.1, DPPH radical scavenging activity:30.66, Iron chelating assay:38.73, and Iron reducing assay:39.36. Notable anticancer activity was observed with the percent cell viability of HeLa cells after treatment with 1, 2 and 5µl of TNE was 82%, 41% and 24%, respectively. Antidiabetic study revealed that TNE inhibited -amylase in a dose-dependent manner, with 88% inhibition at its higher volume of 250µl. Drug kinetic study revealed that nanoemulsions exhibited first-order model. Based on this, the possible role of M. alternifolia oil-based nanoemulsions in cosmetic, food, and pharma sectors has been discussed. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Infantile spasms syndrome (ISS) being a severe epileptic encephalopathy characterized by epileptic spasms, developmental stagnation and/or regression. Topics include treatment of ISS showing the use of anti‑seizure medications and hormonal therapy in the form of prednisolone or adrenocorticotropic hormone; and determining other forms of steroid therapy being used for the treatment of ISS.

Titanium dioxide (TiO2) is a highly stable, photosensitive, and nontoxic metal oxide. The physical and chemical properties of TiO2 electrodes have been explored extensively for the last few decades. However, a detailed and comparative study of the dielectric relaxation and carrier kinetics with the dopants is still lacking. Herein, the crystallinity of TiO2 electrodes decreased with the dopants is reported. The doping of copper (Cu) in TiO2 reduces its bandgap to 2.98 eV from 3.22 eV. The improved charge carrier conduction at high frequencies (ω = 103–106 radians s−1) with the doping is noticed. The charge transfer resistance (Rct) for the electrons is minimum for Cu–TiO2 (Rct = 34.11 Ω) and Cu, Zn, and N–TiO2 (Rct = 27.44 Ω) compared to pristine and Cu and Zn–TiO2. Further, the high electrical permittivity is associated with the polar nature of electrodes. The correlation analysis of impedance and modulus spectroscopy data provides a prodigious picture of the charge carrier relaxation and conduction mechanism. A shift in the dielectric relaxation process from Debye type to non‐Debye type is observed after doping due to defect‐mediated fast relaxation of polarization. [ABSTRACT FROM AUTHOR]

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug‐resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non‐blinded, randomized patient preference trial of 18 children (aged 8–17 years) who did not respond to VNS after at least 1 year, add‐on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add‐on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non‐response to VNS. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a rare autosomal dominant condition that affects multiple body systems. Disruption of the mammalian target of rapamycin (mTOR) pathway results in abnormal cell growth, proliferation, protein synthesis, and cell differentiation and migration in TSC. In the central nervous system, mTOR disruption is also believed to influence neuronal excitability and promote epileptogenesis. Epilepsy is the most common neurological manifestation of TSC and affects 80% to 90% of individuals with high rates of treatment resistance (up to 75%). The onset of epilepsy in the majority of individuals with TSC occurs before the age of two years, which is a critical time in neurodevelopment. Both medically refractory epilepsy and early-onset epilepsy are associated with intellectual disability in TSC, while seizure control and remission are associated with lower rates of cognitive impairment. Our current knowledge of the treatment of epilepsy in TSC has expanded immensely over the last decade. Several new therapies such as preemptive vigabatrin therapy in infants, cannabidiol, and mTOR inhibitors have emerged in recent years for the treatment of epilepsy in TSC. This review will provide clinicians with a comprehensive overview of the pharmacological and nonpharmacological therapies available for the treatment of epilepsy related to TSC. [ABSTRACT FROM AUTHOR]

KBG syndrome is a genetic disorder characterized by short stature, dysmorphic features, macrodontia, cognitive impairment, and limb anomalies. Epilepsy is an important comorbidity associated with KBG syndrome, although the entire phenotypic spectrum may not be fully appreciated. We identified five new patients with KBG syndrome-related epilepsy and compared their phenotype to previously reported cases in the literature. Five patients with KBG syndrome-related epilepsy were identified. Three patients (60%) were male. Median age of seizure onset was 18 months (interquartile range 5, 32). The epilepsy type was generalized in three patients (60%); in two, the epilepsy type was combined (40%), with focal and generalized seizures. In one patient (20%), the epilepsy syndrome was classifiable and the child was diagnosed with myoclonic-atonic epilepsy. All five patients had pathogenic variants in the ANKRD11 gene. Epilepsy was refractory in two patients (40%). No specific antiseizure medication (ASM) was found to be superior. Literature review yielded 134 cases, median age of seizure onset was 4 years, and seizures were generalized (n = 60, 44%), focal (n = 26, 19%), or combined (n = 13, 10%). An epilepsy syndrome was diagnosed in 12 patients (8.8%). In those with documented response to ASM (n = 49), 22.4% were refractory (n = 11). Our study confirms that few patients with epilepsy and KBG syndrome have an identifiable epilepsy syndrome and generalized seizures are most common. We highlight that epilepsy associated with KBG syndrome may occur before age one year and should be an important diagnostic consideration in this age group. [ABSTRACT FROM AUTHOR]

CNKSR2 variants have been associated with X linked intellectual disability and epilepsy including developmental and epileptic encephalopathy with spike wave activation in sleep (D/EE SWAS) in males. We aimed to describe a sibling pair with a novel pathogenic variant in CNKSR2 with D/EE SWAS and review published cases of D/EE SWAS. A retrospective chart review and a comprehensive review of the literature were conducted. Two brothers with a novel pathogenic variant in the CNKSR2 gene (c. 114delG, p.Ile39SerfsX14) were identified. The epilepsy phenotype was similar to previous cases and was characterized by early onset seizures, nocturnal seizures (focal motor with/without impaired awareness), global developmental delay and language impairment, frontal central temporal predominant epileptiform discharges with a spike wave index >95%, and treatment resistance. However, phenotypic variability was observed and the younger brother had milder neuro developmental impairment, and the diagnosis of D/EE SWAS was made by surveillance electro encephalogram (EEG). Literature search yielded 23 cases, and their clinical/neuro physiological features are discussed. To conclude, CNKSR2 related D/EE SWAS may be early onset and occur before the age of 5 years in some. Early surveillance EEG may aid in diagnosis. Phenotypic variability was observed in our cases as well as sibling pairs in the literature, which may impact genetic counseling. [ABSTRACT FROM AUTHOR]

Cognitive flexibility encompasses the ability to efficiently shift focus and forms a critical component of goal-directed attention. The neural substrates of this process are incompletely understood in part due to difficulties in sampling the involved circuitry. We leverage stereotactic intracranial recordings to directly resolve local-field potentials from otherwise inaccessible structures to study moment-to-moment attentional activity in children with epilepsy performing a flexible attentional task. On an individual subject level, we employed deep learning to decode neural features predictive of task performance indexed by single-trial reaction time. These models were subsequently aggregated across participants to identify predictive brain regions based on AAL atlas and FIND functional network parcellations. Through this approach, we show that fluctuations in beta (12–30 Hz) and gamma (30–80 Hz) power reflective of increased top-down attentional control and local neuronal processing within relevant large-scale networks can accurately predict single-trial task performance. We next performed connectomic profiling of these highly predictive nodes to examine task-related engagement of distributed functional networks, revealing exclusive recruitment of the dorsal default mode network during shifts in attention. The identification of distinct substreams within the default mode system supports a key role for this network in cognitive flexibility and attention in children. Furthermore, convergence of our results onto consistent functional networks despite significant inter-subject variability in electrode implantations supports a broader role for deep learning applied to intracranial electrodes in the study of human attention. [ABSTRACT FROM AUTHOR]

In article number 2200807 by Manish Kumar Vishwakarma, Monojit Bag, and Puneet Jain, the correlation analysis of impedance and modulus spectroscopy data paints a detailed picture of the charge carrier relaxation and conduction mechanism. B TiO SB 2 sb -Based Materials b The incorporation of both metallic and non-metallic ions into TiO SB 2 sb has emerged as a promising area of research, as it has the potential to enhance the charge carrier kinetics. [Extracted from the article]

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well‐being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti‐seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed‐effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β ± SE = 49.91 ± 16.55 ms, p =.003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p <.001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p =.009) and improved task performance (β ± SE = −107.43 ± 39.54 ms, p =.007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function. [ABSTRACT FROM AUTHOR]

Background: Infantile epileptic spasms syndrome is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. Appropriately selected patients with infantile epileptic spasms syndrome may be candidates for epilepsy surgery. Methods: This is a single-center retrospective case series of children 0-18 years with a current or previous diagnosis of infantile epileptic spasms syndrome with a lesion on magnetic resonance imaging (MRI) and/or positron emission tomography scan who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. The records of 223 patients seen in the infantile epileptic spasms syndrome clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of infantile epileptic spasms syndrome was encephalomalacia in 6 patients (32%), malformations of cortical development in 12 patients (63%), and atypical hypoglycemic injury in 1 patient (5%). Nine patients (47%) underwent hemispherectomy, and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE seizure outcome class 1 (completely seizure free; no auras) at their most recent follow-up visit. The percentage of patients who were ILAE class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome after surgery was improved in 14 of 19 (74%) and stable in 5 of 19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of infantile epileptic spasms syndrome with a structural lesion detected on MRI brain. Patients who undergo surgery earlier have improved seizure freedom rates and improved developmental outcomes. [ABSTRACT FROM AUTHOR]

Objective: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye‐tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. Methods: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization‐related epilepsy performed an attentional set‐shifting task while tandem intracranial electroencephalographic signals and eye‐tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial‐by‐trial basis. Hierarchical mixed‐effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. Results: Hierarchical mixed‐effects modeling revealed that both the presence of an IED (β ± SE = 72.74 ± 24.21 ms, p =.003) and the frequency of epileptiform events (β ± SE = 67.54 ± 17.30 ms, p <.001) were associated with prolonged RT on the attentional set‐shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p =.017). Significance: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target‐directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior. [ABSTRACT FROM AUTHOR]

Objective: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. Methods: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory‐related networks of children with drug‐resistant epilepsy during a 1‐back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. Results: Twelve children (mean age = 14.3 ± 2.8 years) with drug‐resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z‐score = 9, Rayleigh z‐score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p =.01, p =.03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory‐related networks were enhanced (phase difference derivative [PDD] z‐scores = 6–11). During retrieval trials with pre‐encoding or pre‐retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z‐score = 5, Rayleigh z‐score = 1), interregional connectivity was altered (PDD z‐scores = 1–3), and reaction times were prolonged (p =.01, p =.03). Significance: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a serious public health concern across the world. Gram-negative resistance has propagated over the globe via various methods, the most challenging of which include extendedspectrum ß-lactamases, carbapenemases, and AmpC enzymes. Gram-negative bacterial infections are difficult to treat in critically extremely sick persons. Resistance to different antibiotic treatments nearly always lowers the probability of proper empirical coverage, sometimes resulting in severe outcomes. Multidrug resistance can be combated with varying degrees of success using a combination of older drugs with high toxicity levels and novel therapeutics. The current therapies for multidrug-resistant Gram-negative bacteria are discussed in this review, which includes innovative medications, older pharmaceuticals, creative combinations of the two, and therapeutic targets. [ABSTRACT FROM AUTHOR]

Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis. • Subtle anterior temporal signal changes were noted in 38.9% children with hippocampal sclerosis (HS). • 77.8% children became seizure free after anterior temporal lobectomy with amygdalohippocampectomy. • Overall, 30.6% cases had additional pathological abnormalities. • Seizure freedom rates of children with additional pathological abnormalities similar to those with isolated HS. [ABSTRACT FROM AUTHOR]

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child’s neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function. [ABSTRACT FROM AUTHOR]

To investigate the utility of Low Density (LD) Electrical Source Imaging (ESI) to model the ictal onset zone (IOZ) for the surgical work up of children with medically refractory epilepsy. This was a retrospective review of 12 patients from a district and regional pediatric epilepsy center, who underwent focal resections between 2014 and 2019. ESI was generated using the Curry 8 software , incorporating T1 Magnetic Resonance Imaging (MRI) scans and scalp electroencephalogram (EEG) recordings. Concordance of the ictal LD-ESI localizations to the epileptogenic zone was assessed by comparing the location of the ictal LD-ESI to the focal resection margins on neuroimaging and noting the post-operative outcomes at one year. Localizations determined by ictal LD-ESI were also compared to interictal LD-ESI, positron emission tomography (FDG-PET) and interictal magnetoencephalography (MEG). Ictal ESI correctly localized the ictal onset zone in 4/6 patients, with all four being seizure free at one year. Similarly, interictal ESI localized the irritative zone in 7/9 patients with focal resections, with 6/7 being seizure free at one year. Additionally, we observed ictal ESI to be concordant to interictal ESI in 5/6 patients. Ictal ESI and interictal ESI were concordant to interictal MEG in 3/6 patients. Ictal ESI was concordant with FDG-PET in 6/7 cases. IOZ source localization through LD-ESI is a promising complementary method of assessing the epileptogenic focus in children. These findings may support the inclusion of ictal LD-ESI within the pre-surgical evaluation of children to supplement current diagnostic tools. • Ictal LD-ESI is a complementary tool to assess the epileptogenic focus in children. • Post-operative seizure freedom is likely when the presurgical data is concordant. • Ictal LD-ESI can be included in the pediatric epilepsy surgical evaluation. [ABSTRACT FROM AUTHOR]