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Abstract To conduct a systematic review of the literature regarding rates and predictors of favorable seizure outcome after resective surgery for epileptic spasms (ES) in pediatric patients. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses standards were followed. We searched PubMed, EMBASE, and Cochrane CENTRAL for articles published on the prevalence or incidence of epileptic spasm since 1985. Abstract, full‐text review, and data extraction were conducted by two independent reviewers. Meta‐analysis was performed to assess overall seizure freedom rate. Subject‐level analysis was performed on a subset of studies to identify prognostic indicators. A total of 21 retrospective studies (n = 531) were included. Meta‐analysis of all studies demonstrated a pooled seizure freedom rate of 68.8%. Subject‐level analysis on 18 studies (n = 360) demonstrated a significant association between duration of spasms and recurrence of spasms after surgery, with an estimated increased risk of 7% per additional year of spasms prior to operation. Patients who underwent resective surgery that was not a hemispherectomy (i.e., lobectomy, lesionectomy, etc.) had an increased recurrence risk of 57% compared to patients who had undergone hemispherectomy. Resective surgery results in seizure freedom for the majority of pediatric patients with epileptic spasms. Patients who undergo hemispherectomy have lower risk of recurrence than patients who undergo other types of surgical resection. Increased duration of spasms prior to surgery is associated with increased recurrence risk after surgery. Plain Language Summary Children with epileptic spasms (ES) that do not respond to medications may benefit from surgical treatment. Our study reviewed existing research to understand how effective surgery is in treating ES in children and what factors predict better outcomes. Researchers followed strict guidelines to search for and analyze studies published since 1985, finding 21 studies with a total of 531 patients. They found that, on average, nearly 70% of children became seizure‐free after surgery. Further individual analysis of 360 patients showed that longer duration of spasms before surgery increased the risk of spasms returning by 7% per year. Additionally, children who had less extensive surgeries, such as removal of only a specific part of the brain, had a 57% higher risk of seizure recurrence compared to those who had a hemispherectomy, which removed or disconnected half of the brain. Overall, the study concludes that surgery can often stop seizures, especially when more extensive surgery is performed and when the surgery is done sooner rather than later.

Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data.

Abstract Background CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. Methods We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. Results The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14–48% and sustained 3-month response in 5–36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. Conclusions Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development.

Children with leukemia are at risk for epilepsy due to primary disease or neurotoxic therapies. We describe the phenotypes of drug-resistant epilepsy in 10 children with history of leukemia.Of 10 cases, 6 had features of Lennox-Gastaut syndrome, and 4 had focal epilepsy. Mean age of epilepsy onset was 5 years in Lennox-Gastaut cases and 6.5 years in focal epilepsy cases. Mean latency between leukemia diagnosis and seizure onset was about 3 years. Brain MRI of 2 patients with epileptic encephalopathy had structural abnormalities – unclear if causative for epilepsy, and 4 had no overt structural abnormalities. In focal epilepsy group, 3 had temporal lobe epilepsy and one had fronto-temporal localization. All 10 patients had received intrathecal chemotherapy; 2 also had received whole brain irradiation. Seizures were poorly controlled in the epileptic encephalopathy group. Three underwent corpus callosotomy with variable response. Two patients with temporal lobe epilepsy had temporal lobectomy with Engel 1 outcome at 2 year follow-up in both.Two phenotypes of refractory epilepsy were observed in children with previous history of leukemia, focal epilepsy and epileptic encephalopathy. Children with temporal lobe epilepsy had good response to temporal lobectomy; response to palliative surgery was variable.

To conduct a systematic review of the literature regarding rates and predictors of favorable seizure outcome after resective surgery for epileptic spasms (ES) in pediatric patients. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses standards were followed. We searched PubMed, EMBASE, and Cochrane CENTRAL for articles published on the prevalence or incidence of epileptic spasm since 1985. Abstract, full‐text review, and data extraction were conducted by two independent reviewers. Meta‐analysis was performed to assess overall seizure freedom rate. Subject‐level analysis was performed on a subset of studies to identify prognostic indicators. A total of 21 retrospective studies (n = 531) were included. Meta‐analysis of all studies demonstrated a pooled seizure freedom rate of 68.8%. Subject‐level analysis on 18 studies (n = 360) demonstrated a significant association between duration of spasms and recurrence of spasms after surgery, with an estimated increased risk of 7% per additional year of spasms prior to operation. Patients who underwent resective surgery that was not a hemispherectomy (i.e., lobectomy, lesionectomy, etc.) had an increased recurrence risk of 57% compared to patients who had undergone hemispherectomy. Resective surgery results in seizure freedom for the majority of pediatric patients with epileptic spasms. Patients who undergo hemispherectomy have lower risk of recurrence than patients who undergo other types of surgical resection. Increased duration of spasms prior to surgery is associated with increased recurrence risk after surgery. Plain Language Summary: Children with epileptic spasms (ES) that do not respond to medications may benefit from surgical treatment. Our study reviewed existing research to understand how effective surgery is in treating ES in children and what factors predict better outcomes. Researchers followed strict guidelines to search for and analyze studies published since 1985, finding 21 studies with a total of 531 patients. They found that, on average, nearly 70% of children became seizure‐free after surgery. Further individual analysis of 360 patients showed that longer duration of spasms before surgery increased the risk of spasms returning by 7% per year. Additionally, children who had less extensive surgeries, such as removal of only a specific part of the brain, had a 57% higher risk of seizure recurrence compared to those who had a hemispherectomy, which removed or disconnected half of the brain. Overall, the study concludes that surgery can often stop seizures, especially when more extensive surgery is performed and when the surgery is done sooner rather than later. [ABSTRACT FROM AUTHOR]

Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data. [ABSTRACT FROM AUTHOR]

Aim: To differentiate phenotypic features of individuals with CDKL5 deficiency disorder (CDD) from those of individuals with other infantile‐onset epilepsies. Method: We performed a retrospective cohort study and ascertained individuals with CDD and comparison individuals with infantile‐onset epilepsy who had epilepsy gene panel testing. We reviewed records, updated variant classifications, and compared phenotypic features. Wilcoxon rank‐sum tests and χ2 or Fisher's exact tests were performed for between‐cohort comparisons. Results: We identified 137 individuals with CDD (110 females, 80.3%; median age at last follow‐up 3 year 11 months) and 313 individuals with infantile‐onset epilepsies (156 females, 49.8%; median age at last follow‐up 5 years 2 months; 35% with genetic diagnosis). Features reported significantly more frequently in the CDD group than in the comparison cohort included developmental and epileptic encephalopathy (81% vs 66%), treatment‐resistant epilepsy (95% vs 71%), sequential seizures (46% vs 6%), epileptic spasms (66% vs 42%, with hypsarrhythmia in 30% vs 48%), regression (52% vs 29%), evolution to Lennox–Gastaut syndrome (23% vs 5%), diffuse hypotonia (72% vs 36%), stereotypies (69% vs 11%), paroxysmal movement disorders (29% vs 17%), cerebral visual impairment (94% vs 28%), and failure to thrive (38% vs 22%). Interpretation: CDD, compared with other suspected or confirmed genetic epilepsies presenting in the first year of life, is more often characterized by a combination of treatment‐resistant epilepsy, developmental and epileptic encephalopathy, sequential seizures, spasms without hypsarrhythmia, diffuse hypotonia, paroxysmal movement disorders, cerebral visual impairment, and failure to thrive. Defining core phenotypic characteristics will improve precision diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Abstract Independent control of electromagnetic (EM) waves by metasurfaces for multiple tasks are highly desired and is the recent hot topic of research. In this work we contribute a polarization insensitive frequency multiplexed 2-bit coding metasurface to control the Terahertz (THz) waves in the two operating bands independently. In this regard, as a first step a cascaded meta-atom composed of square rings and/or square metallic patches separated by two polyimide substrates is designed and optimized that provides sixteen independent distinct discrete phases in the reflection geometry. These meta-atoms are then distributed with distinct coding sequences in the two-dimensional spatial plane to realize various bi-functional metasurfaces. As a proof of the concept various full structures are designed and simulated to realize a series of bi-functionalities including anomalous reflection/beam shaping, beam shaping/anomalous reflection, beam deflection/Orbital angular momentum (OAM) beam generation with distinct modes and propagating wave to surface wave (PW–SW) conversion/PW beam manipulation in the lower and higher THz bands, respectively. All the simulation results are in excellent agreement with their theoretical equivalents. We envision that the proposed meta-designs have potential applications for the multi-spectral control of EM waves in THz band. The idea can be further extended to design frequency dependent tri-functional and multi-functional THz meta-devices.

Abstract The continuously reinforced concrete pavement (CRCP) system grapples with challenges such as non-uniform transverse crack patterns and the need for substantial reinforcement. Field research on the Belgian CRCP sections along motorway E313 indicates that active cracking induced by partial surface saw-cuts consistently leads to transverse crack patterns. This study introduces an innovative modification to the CRCP: the actively reinforced concrete pavement design (ARCP). The ARCP leverages partial surface saw-cuts to reduce reinforcement needs by replacing continuous-length steel bars with partial-length counterparts. The main objective of the present study is to develop a 3D finite element (FE) model capturing the active cracking behavior of ARCP under realistic external temperature variations. Comparative analysis with CRCP considers early-age crack patterns, crack strain development, and the distribution of maximum steel stress for different steel ratios (0.67%, 0.75%, and 0.85%). FE simulation results align with field data, indicating that ARCP exhibits similar early-age cracking behavior to CRCP but with a significant 24 to 42% reduction in total reinforcement. This innovation presents a promising avenue for addressing CRCP challenges while optimizing material usage in pavement construction.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy. Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form. Results: Across four clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals. Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.