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Background: The need for stationary phases with unique selectivity in reversed-phase liquid chromatography has been of utmost importance to chromatographers for advancing the analysis of complex samples. Macrocyclic glycopeptide based stationary phases have been widely used for chiral separations with different chromatographic modes such as normal phase, reversed phase, and supercritical fluid chromatography. Given the multimodal retention mechanisms namely π-π complex interaction, hydrogen bonding, dipole-dipole interaction, and strong Coulombic interactions by which analytes are separated using the macrocyclic glycopeptides, these stationary phases are expected to provide novel selectivity when used under the reversed phase for achiral separations., Results: Herein, for the first time we have conducted a systematic study using the improved hydrophobic subtraction model (HSM) which incoporates dipole-dipole interactions to demonstrate the novel selectivity offered by four different macrocyclic glycopeptide based stationary phases, namely NicoShell, TeicoShell, TagShell, and VancoShell. A comparison of the HSM parameters for these columns has been made with 551 commercially available reversed phase stationary phases and the differences in the values point to the importance of adding these columns to the already existing arsenal. These stationary phases offer separations over a wide range of pH and show variability in selectivity depending on the pH of the mobile phase which make them versatile for method development in the reversed phase mode. Additionally, we have provided an actual example of a separation from an Amgen discovery project using the VancoShell column aided by computer-assisted modelling., Significance: This is the first report characterizing macrocyclic glycopeptides for achiral RPLC applications. The selectivity of these stationary phases were found to be unique when compared to other commercially available stationary phases thereby acting as their own class of columns. The unusual selectivity of the columns enabled separation of complex pharmaceutical samples., Competing Interests: Declaration of competing interest DWA is president of AZYP, LLC. All other authors declare no competing financial or personal interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies., Competing Interests: Competing Interests B.M.N is a member of the scientific advisory board at Deep Genomics and Neumora. No other authors have competing interests to declare

Objective: This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic-clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse., Methods: The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new-onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3-h sleep-deprived video-EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow-up. Cumulative time-dependent probabilities of seizure recurrence were calculated using Kaplan-Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper., Results: Eighty-nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike-wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient-initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post-ASM discontinuation., Significance: Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure-free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician-initiated tapering., Plain Language Summary: Seizures in individuals diagnosed with "epilepsy with generalized tonic-clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: This study aims to identify predictive factors of a two-year remission (2YR) in a cohort of children and adolescents with new-onset seizures based on baseline clinical characteristics, initial EEG and brain MRI findings., Methods: A prospective cohort of 688 patients with new onset seizures, initiated on treatment with antiseizure medication was evaluated. 2YR was defined as achieving at least two years of seizure freedom during the follow-up period. Multivariable analysis was performed and recursive partition analysis was utilized to develop a decision tree., Results: The median age at seizure onset was 6.7 years, and the median follow-up was 7.4 years. 548 (79.7%) patients achieved a 2YR during the follow up period. Multivariable analysis found that presence and degree of intellectual and developmental delay (IDD), epileptogenic lesion on brain MRI and a higher number of pretreatment seizures were significantly associated with a lower probability of achieving a 2YR. Recursive partition analysis showed that the absence of IDD was the most important predictor of remission. An epileptogenic lesion was a significant predictor of non-remission only in patients without evidence of IDD, and a high number of pretreatment seizures was a predictive factor in children without IDD and in the absence of an epileptogenic lesion., Conclusion: Our results indicate that it is possible to identify patients at risk of not achieving a 2YR based on variables obtained at the initial evaluation. This could allow for a timely selection of patients who require close follow-up, consideration for neurosurgical intervention, or investigational treatments trials., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: The decision to initiate treatment in patients with a first unprovoked seizure remains controversial. Studies have reported a recurrence rate ranging from 21%-50%, but most have included patients with different etiologies, electroencephalography (EEG) findings, and seizure types. This study aimed to determine the risk of recurrence in patients with a first unprovoked generalized tonic-clonic (GTC) seizure with evidence of generalized spike-wave discharges (GSWDs) on EEG and compare the efficacy of antiseizure medications (ASMs) in preventing recurrence., Methods: This prospective study included consecutive patients who presented with a single GTC seizure, evidence of GSWDs on EEG, and a follow-up period of at least 1 year. All patients underwent extensive evaluation, including a 3-hour sleep-deprived video-EEG recording and an epilepsy protocol brain magnetic resonance imaging (MRI). Treatment with ASMs was recommended for all patients. The decision regarding the specific ASM to be used was left to the treating physician's discretion., Results: A total of 57 patients with a median age of 19 years were included. A total of 41 patients agreed to be started on an ASM while 16 declined. Seizure recurred in 6 of 41 patients (14.6%) in the treated group compared to 11 of 16 (68.8%) in the untreated group (p = .00006). Valproate was significantly more efficacious than levetiracetam or lamotrigine (p = .04). Of the 15 patients who discontinued ASM treatment after remaining seizure-free for an average of 30 months, 6 (40%) experienced a seizure recurrence., Significance: Patients with a first unprovoked GTC seizure and evidence of GSWDs on EEG have a high risk of recurrence if left untreated. Valproate is the most efficacious ASM for preventing recurrence in this population. A sizeable proportion of patients can be successfully tapered off medication after a period of seizure freedom. This study provides valuable information for guiding treatment decisions in this patient population., (© 2023 International League Against Epilepsy.)

Background: Several studies with a small sample size have investigated the relationship between structural and functional changes on MRI and the clinical and natural history of BRE. We aim to assess the frequency of incidental epileptogenic lesions on brain MRI in a large cohort of patients diagnosed with BRE and to assess the difference in volumetric brain measurements in BRE patients compared to healthy controls., Methods: The case-control study includes 214 typical BRE cases and 197 control children with non-epileptic spells. Brain MRIs were evaluated for abnormalities which were classified into normal and abnormal with or without epileptogenic lesions with categorization of epileptogenic lesions. Brain segmentation was also performed for a smaller group of BRE patients and another healthy control group. Pearson's chi-squared test and two-tailed independent samples t-test were used., Results: In patients with BRE, 7% had an epileptogenic lesion on their MRI. The frequency of epileptogenic lesion in the control group was 10.2% and not significantly different from those with BRE ( p= 0.2 ). Significantly higher intracranial and white matter volumes were found in BRE patients compared to the healthy group while lower gray matter volume was found in BRE patients. Cortical and subcortical regions showed either higher or lower volumes with BRE. Interestingly, altered subcallosal cortex development which has a known association with depression was also found in BRE., Conclusions: Our findings confirm the absence of any association between specific brain MRI abnormalities and BRE. However, the altered cortical and subcortical development in BRE patients suggests a microstructural-functional correlation.

Purpose: The likelihood of valproate (VPA) induced thrombocytopenia increases with higher VPA levels. In critically ill patients, the biological active free VPA level cannot be predicted from the total serum level. In this study, we evaluated the relationship between trough free VPA serum levels and concomitant platelet counts and assessed risk factors for the development of thrombocytopenia with the aim of generating a formula specifying the probabilities of developing thrombocytopenia based on trough free serum VPA levels., Methods: Trough free VPA levels and concomitant platelet counts were collected from a large cohort of patients who participated in a prospective VPA monotherapy trial. Significant variables associated with thrombocytopenia in a univariate analysis were evaluated in a multivariate model. A receiver operator curve was performed to compute the trough free VPA levels with the greatest discriminating power in predicting thrombocytopenia., Results: 844 trough free VPA levels and concomitant platelet counts obtained from 264 patients were analyzed. In a multivariate analysis, trough free VPA levels, gender, and baseline platelet counts were significantly associated with thrombocytopenia. Using stepwise regression and multivariate logistic regression analyses, we generated gender-specific formulas for predicting platelet counts and probabilities of developing thrombocytopenia. The trough free VPA with the greatest discriminating power to predict platelet values ≤ 100,000/μL was 16.65 µg/mL., Conclusions: The generated model was based on trough free VPA levels and achieved high sensitivity and specificity. Our results are therefore generalizable and can be applied to estimate the probability of developing thrombocytopenia in critically ill patients., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The aims of this study were to evaluate the frequency of paroxysmal spells of indeterminate nature (PSIN) in a large cohort of children and adults with suspected new-onset seizures, to evaluate the reasons for including patients in this category, and to calculate the rate of erroneous diagnoses if the epileptologists were compelled to label those events as epileptic seizures or nonepileptic paroxysmal spells., Methods: Patients identified for this study participated in a prospective study evaluating patients with suspected new-onset unprovoked seizures. The workup included a detailed history and a thorough description of the spells, a 3-hour video EEG recording, and an epilepsy protocol brain MRI. Based exclusively on a detailed description of the ictal events, two epileptologists were asked to independently classify each patient into those with a definite diagnosis of unprovoked seizures or a definite diagnosis of a nonepileptic paroxysmal spells (group 1) and those with PSIN (group 2)., Results: A total of 1880 consecutive patients were enrolled with 255 (13.6%) included in the PSIN group. Patients with PSIN were significantly younger than those with a definite diagnosis, and PSIN were significantly more frequent in children with developmental delay. The most common reason for including patients in the PSIN group was the inability to categorically discriminate between a seizure and a nonepileptic mimicker. When the raters were compelled to classify the spells in the PSIN group, the frequencies of erroneous diagnoses ranged between 32% and 38%. The final diagnoses on those patients were made based on the results of the EEG, MRI, and follow-up visits., Significance: Our data indicate that a diagnostic category of PSIN should be recognized and ought to be used in clinical practice. Acknowledging this uncertainty will result in lower frequencies of erroneous diagnoses, possible stigma, and potential exposure to unnecessary antiseizure medications., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Purpose: There is a paucity of data regarding the incidence of structural brain lesions in children with new-onset unprovoked seizures. Our aim was to determine the frequencies and types of epileptogenic lesions detected on a dedicated epilepsy protocol MR imaging according to age group, the presence of developmental delay, and the number and types of seizures., Materials and Methods: Consecutive children between 6 months and 18 years of age with new-onset unprovoked seizures were included. The frequencies and types of epileptogenic lesions were determined and then stratified according to sex, age groups, the presence of developmental delay, and the number and types of seizures at presentation. Multivariate analysis was used to identify variables significantly associated with the presence of epileptogenic lesions., Results: One thousand children were included. An epileptogenic lesion was identified in 26%, with malformations of cortical development being the most common lesion (32%), followed by hypoxic-ischemic injury (20%) and vascular etiologies (16%). Univariate analysis showed a significant increase in the frequency of epileptogenic lesions with decreasing age, the presence of developmental delay, and the number and types of seizures at presentation. The presence of developmental delay and seizure type at presentation remained significant in a multivariate analysis., Conclusions: We documented a relatively high rate of epileptogenic lesions in children with new-onset seizures, with the presence of developmental delay and specific seizure types being associated with a higher likelihood of detecting an epileptogenic lesion on neuroimaging. This study fulfills the requirements of the study design recommended by the Practice Committee of the American Academy of Neurology, and we hope that our results will assist the relevant societies and committees in formulating neuroimaging guidelines for children with new-onset seizures., (© 2021 by American Journal of Neuroradiology.)

Objectives: To prospectively compare the frequencies of depression and anxiety in patients with new onset functional seizures versus two age and gender-matched control groups consisting of patients with new onset epileptic seizures and normal individuals., Methods: Consecutive patients, 16 years and older, enrolled in a prospective study for suspected new onset epileptic seizures and diagnosed with documented functional seizures were included. We compared the depression and state and trait anxiety scores using the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) between patients with functional seizures and the other two control groups., Results: The 33 patients with functional seizures had significantly higher depression and anxiety scores compared to those with epileptic seizures and normal controls. Twenty patients (60.6%) in the functional seizures group scored in the "depression" range compared to 5/33 (15.2%) in the epileptic seizures and 1/33 (3%) in the control groups. In the functional seizures group, 14/33 (42.4%) had scores in the "state anxiety" range compared to 6/33 (18.2%) and 2/33 (6.1%) in the epileptic seizures and normal control groups, respectively. Similarly, 15/33 (51.5%) of patients in the functional seizures group had scores in the "trait anxiety" range compared to 4/33 (12.1%) and 1/33 (3%) in the epileptic seizures and normal control groups, respectively., Conclusions: Our results indicate that patients with new onset functional seizures frequently suffer from depression and anxiety at the time of their initial evaluation. These findings underscore the importance of screening for depression and anxiety in that patient population., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Seizure threshold-2 (SZT2) gene variants have been associated with a decrease in seizure threshold resulting in variable phenotypic expressions ranging from mild-moderate intellectual disabilities without seizures, to an early-onset epileptic encephalopathy with severe cognitive impairment. In addition, hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down-slanting palpebral fissures, were present in the majority. We herein report a novel SZT2 variant in one of two siblings both diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). This report is the fourth to document a possible familial case in EIMFS, a condition that was not previously associated with SZT2 variant. This report expands the phenotypic expression of SZT2, corroborates the importance of genetic counseling in some cases of EIMFS, and highlights the efficacy of potassium bromide in controlling the seizures associated with this condition., Competing Interests: None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: The aim of this study was to evaluate the tolerability and efficacy of lacosamide (LCM) in Lebanese children with focal-onset seizures and to determine if specific variables are predictive of better effectiveness., Methods: This is a retrospective analysis from three medical centers on consecutive children diagnosed with focal onset seizures and initiated on LCM. The seizure frequencies following the introduction of LCM were recorded and compared to the baseline monthly frequency at 3, 6, 12, 18, and 24 months. The primary efficacy variables were the 50% responder and seizure-free rates. The secondary outcome variables included the terminal 6-month seizure remission and percentages of discontinuation due to lack of efficacy or tolerability., Results: 58 patients with a mean age of 10 years experiencing a mean of 36.2 seizures per month during baseline were included. The seizure-free rates were 32.8%, 29.7%, and 12.5% at 6, 12 and 24 months follow up, respectively. Patients concomitantly treated with a sodium channel blocker were less likely to achieve a terminal 6-month seizure remission while the early introduction of LCM resulted in a significantly higher likelihood of attaining such a remission. 74.1% of patients were still maintained on LCM at the last follow-up. The most common adverse events consisted of dizziness, somnolence, nausea, vomiting, and rarely double vision., Conclusions: LCM is efficacious and overall well tolerated in children with focal-onset seizures and exhibits higher efficacy with early introduction and when added to a non-sodium channel blocker., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Three Chapters of the Commission of the East Mediterranean Affairs (CEMA) of the ILAE conducted a survey to assess the availability of drugs used for the treatment of generalized convulsive status epilepticus (GCSE) across the CEMA countries and to evaluate the treatment choices of adult and pediatric neurologists for the treatment of this condition., Method: The web-based survey consisted of two similar vignettes of GCSE in a child and an adult. The questions evaluated the sequential drugs of choice based on drug availability and with the assumption that all drugs were at the disposition of the neurologists. The neurologists were also asked about the timing of introduction of anesthetic drugs and how they monitor patients in drug induced coma., Results: Our data showed that the availability of drugs differ substantially across CEMA countries. A benzodiazepine and phenytoin/phenobarbital were the initial drugs of choice for the majority of adults and pediatric neurologists. In cases of refractory status, most neurologists would use a third agent before proceeding to treatment with an anesthetic agent. Although the vast majority would prefer to monitor patients in drug-induced coma with continuous EEG, only 38% are using this modality because of its unavailability at their institutions., Conclusions: Our data emphasize that an algorithm for the treatment of GCSE in the CEMA countries should be flexible and should propose different treatment options at each step of the protocol that are based on the best available data while taking into consideration the drug availability across the CEMA countries., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Hyperventilation (HV) in children can lead to HV-induced high-amplitude rhythmic slowing (HIHARS) on the EEG (electroencephalogram) which is sometimes associated with altered awareness (AA) and concomitant semiological features. Our aims were to determine the frequency of HIHARS in children, to assess if the associated semiological features were temporally related to HV, and to evaluate if specific semiological features can differentiate HIHARS with AA from absence seizures., Methods: Consecutive children with suspected new onset seizure(s) underwent HV and awareness testing during video-EEG acquisition. Hyperventilation-induced high-amplitude rhythmic slowing was defined as 2.5- to 5-Hz generalized rhythmic slowing with amplitude ≥100 μv lasting for ≥3 s. The associated semiological features were compared between the group of children with HIHARS and AA, an age- and gender-matched control group without HIHARS, and in children who experienced absence seizures during HV., Results: One hundred sixteen children with a mean age of 9.8 years were included. Hyperventilation-induced high-amplitude rhythmic slowing occurred in 39 children (33.6%) with AA documented in 30 (76.9%). The probability of developing AA during HIHARS was significantly and positively correlated with the HIHARS duration. The frequencies of HIHARS were not significantly different between children diagnosed with seizure(s) and those with nonepileptic spells. Hyperventilation cessation and staring did not occur in any child of the control group. Fidgeting and yawning were significantly more common in the group with HIHARS with AA while staring and blinking were significantly more frequent in the group of children with absence seizures., Conclusions: We ascertained that HIHARS with AA is a relatively common occurrence in children and most likely represents an age-related nonepileptic phenomenon. When associated with fidgeting or yawning, it can help differentiate this phenomenon from absence seizures. However, recording the concomitant presence of generalized spike wave discharges on the EEG remains essential to confirm the diagnosis of absence seizures., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To observe the incidence of congenital malformations occurring in foetuses exposed to antiseizure drugs (ASDs) during the first trimester and to identify individual drug associations in a population cohort from the United Arab Emirates (UAE)., Methods: Pregnancy outcomes were observed and reported from women with epilepsy (WWE), attending the Obstetric Medicine Neurology Clinic at Corniche Hospital in Abu Dhabi, United Arab Emirates (UAE) from February 2008 to December 2015., Results: Outcome data were available for 179 pregnancies in 112 WWE. There were 139 pregnancies who received ASD treatment during the first trimester, of these 124 were on monotherapy. Thirteen (7.26 %) congenital malformations (CMs) were observed in this cohort, seven were major ones and six were minor. Thirteen of the CMs were from the group with ASDs while one had no ASD-exposure. From the ASD-group, we identified 32 (23.0 %) with poor pregnancy outcomes, including 13 (9.3 %) with CMs and 19 (13.7 %) miscarriages. These figures were significantly higher than that of the no ASD-exposure group (7.9 %) (p = 0.04, Fisher test). The most commonly used ASDs in monotherapy were levetiracetam (25.6 %), carbamazepine (16.2 %), valproate (13.4 %), and lamotrigine (7.3 %). There were 57 (31.8 %) consanguineous marriages in this cohort; there was no statistically significant difference in the CM rate within the consanguineous group between those with and without exposure to ASD., Conclusion: This study was the first to report pregnancy outcomes in a WWE cohort from the Middle East and North Africa (MENA) region. It is the first step towards establishing a national / regional pregnancy registry to create a database on ASD use and pregnancy outcomes among the WWE., (Copyright © 2019. Published by Elsevier B.V.)

Background: Focal cortical dysplasias (FCDs) are highly epileptogenic and frequently associated with medically refractory focal epilepsy. FCDs are frequently located in the frontal lobe, making its complete resection highly challenging when in proximity to the motor cortex., Case Description: We report a case of a 25-year-old woman with medically refractory epilepsy secondary to a focal cortical dysplasia in the motor cortex and extending deeply into the subcortical white matter. A detailed presurgical evaluation and invasive electroencephalographic monitoring performed at our epilepsy monitoring unit, along with the use of motor mapping, functional magnetic resonance imaging, diffusion tensor imaging, and the Stealth navigation system resulted in the complete resection of the lesion without a permanent postoperative motor deficit. The patient remained seizure-free at a 63-month follow-up while being maintained on a single antiepileptic drug., Conclusion: A detailed presurgical evaluation, accurate mapping of the functional and dysplastic cortex, and a well-planned tailored and complete surgical resection of the cortical dysplasia can result in a favorable outcome with relatively little risk of postoperative neurologic deficit., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Thrombolysis is the standard of care in acute ischemic stroke. It is usually contraindicated in patients with aortic dissection., Case Report: We report a case of Marfan syndrome and chronic aortic dissection presenting with acute ischemic stroke treated with thrombolysis., Conclusion: To our knowledge, this is the first case of Marfan syndrome with chronic aortic dissection undergoing thrombolysis for acute ischemic stroke with a near-complete recovery of neurological deficit and favorable long-term outcome.

Objective: To evaluate prospectively the frequency of epileptogenic lesions in a consecutive cohort of elderly patients presenting with new onset unprovoked seizures, and who underwent a complete evaluation including dedicated epilepsy protocol MRI. Methods and materials: We included all consecutive patients 60 years or older who participated in a prospective study on new onset epilepsy. The work-up included the acquisition of a dedicated epilepsy protocol MRI and a 3 h video/EEG recording. We evaluated the frequency and types of epileptogenic lesions in the whole cohort and stratified those variables by age, gender, types and number of seizures at presentation. We also correlated the EEG findings with the clinical characteristics and neuroimaging results. Results: Of the 101 patients enrolled in the study and who underwent an epilepsy protocol MRI, an epileptogenic lesion was identified in 67% of cases. The most common etiologies were vascular events, followed by tumoral causes and traumatic brain injuries. Epileptogenic lesions were more likely to be identified in patients who presented with only focal aware and impaired awareness seizures. In addition, patients with tumoral epilepsy were significantly more likely to only experience those seizure types compared to patients with other pathological substrates. Interictal/ictal discharges were detected in the EEG of 21% of patients. Epileptiform discharges were significantly more frequent in patients with an epileptogenic lesion on brain MRI, especially in those with a brain tumor. Conclusions: Our results stress the importance of obtaining a dedicated epilepsy protocol MRI in elderly patients with new onset seizures. An epileptogenic lesion will be identified in approximately two thirds of patients with important implications regarding initiation of treatment. In addition, the data underscore the value of distinguishing the types of seizures experienced at presentation as this will apprise the treating physician on the likelihood of identifying an epileptogenic lesion and on the probable etiologies.

Purpose: To evaluate variables affecting the valproate (VPA) free fraction and develop an equation for computing free VPA concentration from total VPA concentration., Methods: Trough total and free VPA concentrations were collected from patients who participated in a prospective VPA monotherapy trial. All available paired data of trough total and free VPA concentrations were included. Significant variables from the univariate analysis were evaluated in a multivariate model., Results: A total of 902 concomitant total and free VPA concentrations were available. Multivariate analysis showed that total VPA concentration, age and gender were significantly associated with VPA free fraction. However, the effect size of total VPA concentration was substantially higher than that of gender and age. VPA free fraction remained stable at around 10% for total VPA concentration between 20 and 60 μg/mL with subsequent linear increases for higher concentration. A scatter plot correlating total and free VPA concentrations showed that a quadratic equation best fitted the data, accounting for 88% of the free VPA concentration variance., Conclusions: An increase in the total VPA concentration results in corresponding linear and non-linear rise in the VPA free fraction and free VPA concentration, respectively. The total daily dose of VPA should be increased in smaller increments whenever a total VPA concentration of 60 μg/mL is reached. When drug monitoring is needed, we recommend measuring the free VPA concentration. If this test is unavailable, and for patients with normal albumin levels, it can be predicted from the total VPA concentration using the generated equation., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Lacosamide (LCM) was recently introduced in the Middle East. The aim of this study was to evaluate the safety, tolerability, and efficacy of LCM in patients with focal onset seizures and determine if our results are comparable with those derived from Western countries., Methods: This is a retrospective analysis from two medical centers on consecutive patients diagnosed as having focal onset seizures and treated with add-on LCM. The primary efficacy variables were the 50% responder and seizure-free rates, and the secondary outcome variables included the percentages of patients who achieved seizure remission during the last 6-month follow-up period and the percentages of discontinuation due to lack of efficacy or tolerability., Results: One hundred four patients with a mean age of 30.9 years and experiencing a mean of 9.4 seizures per month during baseline were included. The 50% responder rates were 69% and 70% at 6- and 24-month follow-ups, respectively. Patients concomitantly treated with a sodium channel blocker were less likely to achieve seizure remission during the last 6-month follow-up period while the early introduction of LCM resulted in a significantly higher likelihood of achieving such a remission. Eighty-eight percent of patients were still maintained on LCM at the last follow-up, and the most common adverse events consisted of dizziness and somnolence, double vision, and nausea/vomiting., Conclusions: Our data show similar efficacy and tolerability to those reported from Western countries. Our results also substantiate the early introduction of LCM and support the dose reduction of baseline AED especially that of sodium channel blockers to minimize adverse events., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To study the impact of depression and anxiety on health-related quality of life (HRQOL) in patients with multiple sclerosis (pwMS) in the UAE. All consecutive patients attending the MS clinic over a fourmonth period, October 2014 through February 2015, at Sheikh Khalifa Medical city (SKMC) were asked to complete The World Health Organization quality of life abbreviated scale (WHOQOL-BREF), the Patient Health Questionnaire nine-item (PHQ-9) depression scale, and Generalized Anxiety Disorder seven-item (GAD-7) scale. These last two scales were used to screen for depression and anxiety disorders respectively. The study looked at significant variables associated with HRQOL, using multivariate analysis. Eighty patients were enrolled in the study. Both anxiety and depression had a strong positive correlation with HRQOL in univariate analysis. However, depression was the strongest predictor of HRQOL in the patients using linear multi-regression analysis. Screening and timely treatment of both anxiety and depression in MS patients should be a recommended policy when managing pwMS to improve their optimal care and ensure better quality of life., Competing Interests: Conflict of interest: all authors declare no potential conflict of interest.

Purpose: to investigate potential factors impacting HRQOL among PWE at a medical facility in the UAE., Methods: Depression, anxiety, and health-related quality of life were assessed in 160 adult patients with epilepsy from September 2014 to January 2015 at Sheikh Khalifa Medical City (SKMC). The World Health Organization Quality of Life abbreviated scale (WHOQOL-BREF), the Patient Health Questionnaire nine-item (PHQ-9) depression scale, and Generalized Anxiety Disorder seven-item (GAD-7) scale were administered. Demographic details including psychosocial factors were also obtained. Clinical details including seizure freedom, epilepsy type, epilepsy duration, and magnetic resonance imaging (MRI) results were recorded. Multivariate analysis was used to look at significant variables associated with HRQOL., Results: Depression, anxiety, seizure freedom, and the use of anti-depressants had significant positive correlation with HRQOL in univariate analysis. However, depression, followed by seizure freedom, had the strongest association with HRQOL in a multivariate regression analysis., Conclusion: Depression and seizure freedom, followed by anxiety and anti-depressants use, were significantly correlated with HRQOL. These results underscore the importance of screening for psychiatric comorbidities in patients with epilepsy., Implications: Screening for comorbid psychiatric disorders should be an essential component of the standard of care, and incorporated in the treatment plan for all patients with epilepsy. Factors contributing to psychiatric symptoms among PWE, such as maladaptive illness perceptions, non-adherence to anti-epileptic drugs (AED), and social stigma should be carefully addressed to achieve an optimal health-care plan., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Sedation of children for electroencephalography (EEG) recordings is often required. Chloral hydrate (CH) requires medical clearance and continuous monitoring. To try to reduce personnel and time resources associated with CH administration, a new sedation policy was formulated. This study included all children who underwent an EEG during a consecutive 3-month period following the implementation of the new sedation policy, which consists of the sequential administration of melatonin, hydroxyzine (if needed), and CH (if needed). The comparator group included all children with a recorded EEG during a consecutive 3-month period when the sedation policy consisted of the sole administration of CH. A total of 803 children with a mean age of 7.9 years (SD = 5.1, range = 0.5-17.7 years) were included. Sleep EEG recordings were obtained in 364 of 385 children (94.6%) using the old sedation policy and in 409 of 418 children (97.9%) using the new one. With the new sedation policy, the percentage of children requiring CH dropped from 37.1% to 6.7% (P < .001). Time to sleep onset and duration of sleep were not significantly different between the 2 policies. The new sedation policy was very well tolerated. The new sedation policy is very safe, is highly efficacious in obtaining sleep EEG recordings, and will result in substantial saving of time and personnel resources., (© EEG and Clinical Neuroscience Society (ECNS) 2016.)

This a prospective study comparing 2 interventions, incentive-based and audit-feedback, for measuring compliance to the World Health Organization's My 5 Moments for Hand Hygiene among nursing staff in a Lebanese tertiary care center over 21 weeks. Compliance was not achieved by default. The incentive-driven intervention helped boost compliance, and the audit-feedback intervention helped achieve high sustainability. Analysis of health care workers' behavior toward hand hygiene based on the My 5 Moments for Hand Hygiene concept is necessary to pinpoint difficulties in compliance., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to determine the frequency and characteristics of secondary enuresis in children initiated on valproate treatment., Method: This was a prospective study conducted in children aged 5 to 12 years with suspected newly diagnosed epilepsy and maintained on valproate for at least 1 month. Adverse events spontaneously reported by parents were recorded at each follow-up visit. In addition, we specifically asked about enuresis and other side effects known to occur with valproate treatment. We assessed the frequency of enuresis and its association with a number of variables., Results: Seventy-two children (43 males and 29 females) with a mean age of 8 years 7 months (range 5-12y) were included in this study. Secondary enuresis developed in 17 (24%) of these children after, on average, 19.8 days of exposure to valproate. The data obtained from a multivariate analysis indicate that age was the only significant factor in predicting the development of enuresis. Enuresis ceased in all children after discontinuation of valproate use, and in 10 out of 11 children still on the drug., Interpretation: Secondary enuresis is a common adverse event associated with valproate use in children, which is not usually spontaneously reported and is reversible in most cases., (© 2015 Mac Keith Press.)

Rhythmic midtemporal discharge (RMTD) is one of the benign epileptiform variants, typically consisting of runs of 4-Hz to 7-Hz activity, lasting up to 10 seconds and maximal over the midtemporal area. We report a child who, during an admission for diagnostic closed-circuit television (CCTV) and electroencephalographic (EEG) monitoring, was found to have prolonged rhythmic monomorphic discharges, alternating over both midtemporal areas, with one of the discharges lasting up to 82 minutes. An analysis of the dominant frequency, during the longest discharge, showed that it was monomorphic throughout. On the basis of various features of these discharges, we concluded that they represented RMTD of unusual duration., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Background: Levetiracetam is a broad spectrum antiepileptic drug (AED) with proven efficacy when used as adjunctive therapy against myoclonic seizures. We report two patients suffering from epilepsy with myoclonic-astatic epilepsy (MAE) who experienced a paradoxical worsening of seizures after initiation of treatment with LEV, a finding not previously described., Case Presentation: Patients included were enrolled in an ongoing large prospective study evaluating children and adults with new onset epilepsy in Lebanon conducted at the American University of Beirut Medical Center in association with the Lebanese Chapter of the International League against Epilepsy. Based on an extensive evaluation, these patients were stratified into idiopathic partial, idiopathic generalized, symptomatic partial or symptomatic generalized epilepsies. Whenever possible the electroclinical syndrome was identified according to the ILAE classification of epilepsy syndromes. Patients were subsequently followed up on regular intervals and were assessed for adverse events, and seizure recurrence. MAE was diagnosed in five (1.6%) out of 307 consecutive children enrolled in this study. LEV was used as adjunctive therapy in four of those children with two experiencing a substantial and dose related worsening in the frequency of their myoclonic and atonic seizures., Conclusion: LEV should be used with caution in children with MAE and an exacerbation of seizure frequency temporally related to the introduction of LEV should alert the clinician to the possibility of a paradoxical seizure exacerbation.

Depression and anxiety are highly prevalent in patients with epilepsy (PWE), with prevalence rates ranging from 20% to 55%. The cause of this increased rate is multifactorial. Depression and epilepsy are thought to share the same pathogenic mechanism. Anxiety, on the other hand, seems to have a prevalence rate among PWE comparable to, or even higher than, those reported for depression, and it is closely linked to epilepsy. To test this hypothesis, we screened for depression and anxiety 186 and 160 patients attending the epilepsy and MS clinics, respectively, using standardized screening tools to determine the rates of both depression and anxiety, comparing these rates to 186 age, sex matched controls. Among the three groups, only patients with epilepsy were at increased risk of having depression (OR = 1.9), whereas anxiety was not. This finding could point to the shared pathogenic mechanisms hypothesis between depression and epilepsy.

Introduction: Colonic lipomas are rare subepithelial benign tumors affecting mainly middle-aged women. They are usually asymptomatic and, hence, are discovered incidentally on autopsy, surgery, or colonoscopy. There is a wide range of presentations like abdominal pain, bleeding per rectum, intussusception, etc. The latter picture constitutes the usual presentation of an ileocecal lipoma. Only few cases of ileocecal lipomas presenting as lower GI bleeding have been reported in the literature., Presentation of Case: We present a case of an adult female patient who was admitted to our institution complaining of hematochezia and right lower quadrant pain. She was found to have chronic anemia. She was investigated by CT scan of the abdomen & pelvis and by colonoscopy which showed a fungating, submucosal mass with ulcerated base near the ileocecal valve. She underwent a colonic resection. The pathology came out as a submucosal benign pedunculated ileocecal lipoma., Discussion: Colonic lipomas represent 4% of benign lesions of the gastrointestinal tract. They are usually asymptomatic hence are often discovered incidentally on colonoscopy, surgery or autopsy. The definitive diagnosis is made by pathological evaluation. Colonic lipomas are usually treated if they are symptomatic or there is any suspicion of malignancy. The treatment modalities include endoscopic and surgical resection., Conclusion: We, hereby, describe a case of benign ileocecal lipoma that presented with hematochezia which is an unusual presentation. Also, there is a great controversy regarding the treatment of colonic lipomas. In this article, we tried to answer several questions concerning the management of ileocecal lipomas., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lafora disease is a rare and fatal disease characterized by seizures, progressive cognitive and behavioral deterioration, as well as cerebellar dysfunction. Currently, there is no efficacious treatment that will control the seizures and improve the cognitive decline in this disease. We report a patient with Lafora disease who experienced a dramatic amelioration in her seizure frequency as well as the associated neurological and cognitive dysfunction following initiation of treatment with perampanel administered as monotherapy. Perampanel is the first potentially efficacious treatment for Lafora disease. We discuss a potential mechanism for the efficacy of perampanel in this disease.

Purpose: Troponins are very sensitive biomarkers of myocardial injury. Conflicting data regarding elevation of troponin levels following a generalized tonic-clonic (GTC) seizure have been reported. In this study we hypothesized that troponin elevation after a GTC seizure occurs more frequently in patients with cardiovascular risk factors., Methods: Patients who presented to the ER after a single GTC seizure with troponin levels assessed by cardiac troponin T (cTnT) and drawn within 12h of the GTC seizure were included. Patients with cardiac symptoms, elevated CPK levels or renal insufficiency were excluded. The frequency and risk factors for elevated cTnT levels were analyzed., Results: Fourteen patients with a mean age of 54 years (range: 19-87 years) were included. Four patients (28.6%) had elevated cTnT levels (mean=0.06μg/L; range: 0.035-0.076μg/L). Patients with elevated cTnT levels were significantly older than those with normal levels (77.5 years vs. 45.5 years; P=0.03). Of the eight patients 60 years of age and older, four (50%) had elevated cTnT levels. The coronary heart disease (CHD) score was significantly higher in patients with elevated cTnT levels compared to those with normal levels (13.5 vs. 9.75, P=0.012)., Conclusions: Elevated troponin levels can occur after a GTC seizure. Patients at risk are the elderly and those with cardiovascular risk factors. Our results suggest that elevation of troponin levels after a GTC seizure reflects a minor ischemic cardiac injury related to the demand ischemia during the sympathetic overactivity that accompanies a GTC seizure., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Regular consumption of licorice based beverages can provoke pseudohyperaldosteronism with hypokalemia but can rarely lead to severe muscle weakness., Case Report: A 62-year-old man was admitted for a one-week history of progressive weakness of the four limbs. Blood work revealed severe hypokalemia that was due to primary pseudo-hyperaldosteronism secondary to licorice intoxication. He became normal after correction of the electrolytes disturbances., Discussion & Conclusion: In an area where a liquorice-based beverage (souss), is frequently and sometimes excessively consumed, pseudo-hyperaldosteronism secondary to licorice toxicity should be thought of in front of any muscle weakness accompanied by hypokalemia. A rapid correction of electrolytes disturbances leads to rapid improvement.

Temporal lobectomy can be complicated by somatoform disorders, psychiatric illnesses and non-epileptic psychogenic seizures. We report a woman who developed astasia-abasia and psychogenic tremor following temporal lobectomy for refractory epilepsy. To our knowledge, this type of conversion reaction following temporal lobectomy has not been previously reported., (Copyright © 2012 Elsevier Inc. All rights reserved.)