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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.

Background: Coronavirus disease 2019 (COVID-19) has been associated with many neurological complications affecting the central nervous system. Purpose: Our aim was to describe a case of COVID-19 associated with a probable variant of acute necrotizing encephalopathy (ANE). Results: A 60-year-old man who presented with a 3-day history of dyspnea, fever, and cough tested positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Five days following his admission, the patient was intubated secondary to respiratory failure. Following his extubation 16 days later, he was found to have a left-sided weakness. Magnetic resonance imaging (MRI) of the brain showed hemorrhagic rim-enhancing lesions involving the right thalamus, left hippocampus, and left parahippocampal gyrus. These lesions showed decreased relative cerebral blood flow on MR perfusion and restricted on diffusion-weighted imaging. These neuroimaging findings were consistent with ANE. The left-sided weakness gradually improved over the subsequent weeks. Conclusions: We concluded that COVID-19 can be associated with ANE, a condition believed to be the result of an immune-mediated process with activation of the innate immune system. Future studies must address whether biological drugs targeting the pro-inflammatory cytokines could prevent the development of this condition.

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, free trough 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.

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.

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.

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.

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.

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.

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.

Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.

FARS2, a nuclear gene, encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS). Previous reports have described two distinct phenotypes linked to FARS2 gene mutation: an early onset epileptic encephalopathy and spastic paraplegia. This report describes a distinctive phenotype of FARS2-linked, juvenile onset refractory epilepsy, caused by a hemizygous mutation in a compound heterozygous state (p.V197M and exon 2 microdeletion). A 17-year- old woman with normal development presented with a super refractory focal motor status epilepticus. Only an emergency life-saving surgery aborted her status after all therapeutic interventions, including anesthesia, failed to control her seizures. Pathological and biochemical activities on muscle biopsy showed mitochondrial proliferation with enhanced isolated activities of complexes II and IV, suggestive of a compensatory mechanism for the bioenergetic deficiency. Postoperatively, the patient started experiencing focal aware motor seizures originating from the contralateral hemisphere after being seizure free for a few months. This report suggests a third phenotypic manifestation of FARS2 gene mutation.

Baclofen, a muscle relaxant prescribed for the alleviation of symptoms of spasticity acts primarily at the spinal level but with high doses, it penetrates the blood-brain barrier and can result in prominent central nervous depression. Baclofen toxicity has been associated with a variety of symptoms ranging from dizziness to deep coma. We report the clinical course, management, and outcome of a case of baclofen overdose who presented in deep coma with loss of brainstem reflexes and a burst suppression (BS) pattern on his electroencephalogram (EEG). In addition, we reviewed the presentation and outcomes of all reported cases of baclofen toxicity with a BS pattern on EEG to evaluate if those cases share a common clinical presentation and for the presence of signs and symptoms that would help the clinician to consider this diagnosis. There appears to be a common clinical picture associated with severe baclofen toxicity consisting of deep coma associated with loss of all brainstem reflexes including pupillary reactivity, frequent association with seizures/myoclonic jerks, and a BS pattern on EEG. The outcome is generally good, and serial EEGs are recommended to document a reversal of the abnormal electrographic features.

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.

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.

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.

PURPOSE The purpose of this study was to assess the frequency of occurrence of a unilateral mu rhythm and the associated neuroimaging findings on dedicated epilepsy protocol brain MRI. METHODS We retrospectively reviewed the EEG reports database at the American University of Beirut Medical Center between 2011 and 2014 searching for the presence of a unilateral mu rhythm. For patients with a unilateral mu rhythm, we recorded the patients' demographics, number of EEGs performed, characteristics of the mu activity, and the findings on the epilepsy protocol brain MRIs. RESULTS A total of 7986 patients underwent 9,509 EEG between 2011 and 2014. Four patients (0.05%) aged between 19 and 55 years had evidence of a unilateral mu rhythm. Three patients were diagnosed with localization-related epilepsy and one with syncope. The brain MRIs showed cortical lesions involving the parietal cortex, ipsilateral to the unilateral mu rhythm in the three patients with epilepsy. CONCLUSIONS A unilateral mu rhythm is a rare phenomenon on the scalp EEG that should prompt a search for an ipsilateral lesion, even in the absence of additional EEG abnormalities.

Thrombolysis is the standard of care in acute ischemic stroke. It is usually contraindicated in patients with aortic dissection.We report a case of Marfan syndrome and chronic aortic dissection presenting with acute ischemic stroke treated with thrombolysis.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.

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.

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.

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.

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. Valproate is a broad-spectrum antiepileptic drug approved as monotherapy and adjunctive therapy for the treatment of simple and complex partial seizures in adults and children 10 years or older; as adjunctive therapy for the treatment of multiple seizure types, including absence seizures; for the treatment of acute manic episodes in those with bipolar disorder older than 18 years of age; and as a prophylactic agent for migraine headaches in adults and children older than 16 years. 1 Adverse events associated with valproate include idiosyncratic reactions, such as hepatotoxicity and pancreatitis, and dose-related adverse events including weight gain, hair thinning, tremor, drowsiness, nausea, vomiting, ataxia, and thrombocytopenia. 2–4 Primary and secondary nocturnal enuresis is common in children, with a peak prevalence of 15% to 25% at age 5 years. 5 Although enuresis typically disappears as the child matures, it can be distressing for children and their families and can prompt treatment with desmopressin or imipramine, or behavioural interventions. 5,6

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.

Early myoclonic encephalopathy (EME) is an epileptic encephalopathy characterized by highly refractory seizures and an overall bad prognosis. In this report, we present an infant who developed EME secondary to nonketotic hyperglycinemia. A vagus nerve stimulator inserted when the infant was 6 months and 3-weeks-old resulted in mild psychomotor improvement and in a dramatic reduction in seizure frequency documented by closed-circuit television-electroencephalography monitoring. This is the youngest infant in the literature reported so far inserted with a vagus nerve stimulator, and the results suggest that this treatment modality is safe and can be of benefit in reducing seizures associated with EME.

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A small number of molecular and clinical studies found an association between increases in fetal hemoglobin concentration and valproate (VPA) use. However, the effect of VPA on total hemoglobin (Hb) level has not been studied. We herein review a randomized, double-blind, parallel group, multicenter, concentration-response design trial that compared the safety and efficacy of target trough plasma VPA concentrations in patients with complex partial seizures treated with divalproex sodium as monotherapy. Trough VPA concentrations and concomitant Hb levels that were drawn at baseline and intermittently throughout a 24-week period were analyzed. A total of 549 trough plasma VPA levels and concomitant total Hb levels were analyzed. Correlation between all study variables (gender, age, trough plasma VPA level, duration of exposure, baseline Hb level) and change in total Hb level showed that only baseline Hb level was a significant factor (inverse relationship). Hb increase was evident in 47.0% of values. A clinically relevant increase in Hb (>0.5 g/dL) occurred in 23.9% of values. VPA is associated with a change in total Hb level that correlates inversely with baseline Hb levels.

Neuropathic pain is a frequent condition that can result from a variety of underlying conditions and is frequently chronic and difficult to treat. A number of drugs are used to treat neuropathic pain, including anticonvulsants and antidepressants. Oxcarbazepine, a recently introduced antiepileptic drug, was found to possess antineuralgic properties in animal models of neuropathic pain. Several double-blind, placebo-controlled trials have evaluated oxcarbazepine in painful diabetic neuropathy and trigeminal neuralgia. There is good evidence that oxcarbazepine is effective in relieving the pain associated with trigeminal neuralgia. Its efficacy in treating painful diabetic neuropathy is less clear; however, it seems to be useful when tolerated at doses of 1800 mg/day.

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.

To determine the effect of intermittent photic stimulation (IPS) and frequency of asymmetric driving responses in patients with occipital spikes.The amplitude of the driving response at 4 flash frequencies was measured from a referential montage in 60 patients with occipital spikes and in 60 normal EEG records from age-matched patients. Responses were classified as asymmetric if the amplitude at one occipital area was less than 50% of the amplitude at the other.A measurable photic response occurred significantly less frequently in patients with occipital spikes (48%) compared to the control group (70%; Fisher's test P0.05). The driving response was asymmetric in 7/36 patients (37%) with unilateral spike foci versus none in the control group (Fisher's test, P0.001). The amplitude was suppressed ipsilateral to the focus in 5 patients, all of whom had an ipsilateral structural lesion or focal slowing. In two cases the amplitude was higher ipsilateral to the focus, neither having slowing or a structural lesion.Patients with occipital spikes have an increased frequency of asymmetric driving response. An attenuated response ipsilateral to the focus seems to be related to an underlying lesion while the presence of an epileptiform focus in some cases with no slowing on EEG and normal imaging studies may lead to an accentuation of this response.

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.

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.

Regular consumption of licorice based beverages can provoke pseudohyperaldosteronism with hypokalemia but can rarely lead to severe muscle weakness.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.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.

Hypercoagulability and venous thromboembolism are common in patients with β-thalassemia intermedia (TI), especially in the splenectomized adult. Although arterial involvement is not commonly reported, we have recently observed a high prevalence (60%) of silent brain infarction on brain MRI in 30 splenectomized adults with TI. The pathophysiology of these white matter lesions remains unknown.In this prospective work, we evaluated magnetic resonance angiography (MRA) scans of the same cohort of 30 patients. Data collected were the presence or absence of vascular lesions, their locations, and severity. Correlations between MRA abnormality and patients/disease characteristics were evaluated. Comparisons between MRA and previous MRI findings were made.Of 29 evaluable patients, 8 (27.6%) had evidence of arterial stenosis on MRA. The majority of lesions had mild narrowing and mostly involved the internal carotid artery. Five patients (17.2%) had evidence of aneurysms. Low total hemoglobin and high non-transferrin-bound iron levels independently characterized patients with evidence of stenosis on MRA. Among the 18 patients with silent brain infarction on MRI, three had evidence of stenosis on MRA with only one patient having lesions that could explain the silent infarcts.Cerebral vasculopathy is common in splenectomized adults with TI. However, large-vessel disease does not explain the occurrence of silent brain infarction. The combined use of MRA and MRI better identifies splenectomized TI adults with neuroimaging abnormalities.

Covert brain infarction is an emerging concern in patients with β-thalassemia intermedia (TI). We have recently observed a high prevalence (60%) of silent brain infarction on brain magnetic resonance imaging (MRI) in 30 splenectomized adults with TI. In this work, we further evaluate cerebral involvement in the same 30 patients using fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) scanning. The median age was 32 years (range, 18–54 years) with a male to female ratio of 13:17. Nineteen patients (63.3%) had evidence of decreased neuronal function on PET-CT. Involvement was mostly left sided, multiple, and most commonly in the temporal and parietal lobes. Elevated liver iron concentration, beyond 15 mg Fe/g dry weight, characterized patients with decreased neuronal function. The concordance rate between brain MRI and PET-CT for the detection of brain abnormality was only 36.7% (Kappa 0.056, P = 0.757), highlighting that both modalities reveal different types of brain pathology. Decreased neuronal function is a common finding in patients with TI and is associated with iron overload. Moreover, the addition of PET-CT to MRI identifies a greater proportion of TI patients with silent neuroimaging abnormalities.

Patients with epilepsy have recurrent unproved seizures. Epilepsy is common, with a prevalence range that centers at around 1%. Patients with epilepsy can have a poor quality of life and suffer significant social stigma. Despite the availability of a large number of antiepileptic drugs (AEDs) including standard and newer ones, a significant percentage of patients with epilepsy remain poorly controlled.In this review, we briefly summarize data on the available AEDs, then present current information on the emerging AEDs, including their chemical structure, pharmacology, mechanism of action, and efficacy and adverse event profile in clinical trials. The AEDs included are rufinamide, lacosamide, eslicarbazepine, retigabine, brivaracetam, ganaxolone, stiripentol and carisbamate. Most of the literature related to these AEDs was published in the past 5 years.The reader will become familiar with the pharmacology of emerging AEDs and the results of clinical trials with these AEDs. The reader will also be able to assess the advantages of AEDs and their potential respective places in the treatment of epilepsy.The emerging AEDs offer predominantly improved pharmacokinetics and tolerability and occasionally new mechanisms of action. They will probably have a modest impact on drug-resistant epilepsy.

We describe a patient with Kleine-Levin syndrome who was initially misdiagnosed as having epilepsy and who achieved complete remission on carbamazepine treatment. A drug effect was established when symptoms recurred after carbamazepine taper and disappeared after reintroduction of the drug. Carbamazepine, a safer drug than lithium, can be a highly effective treatment in some patients with Kleine-Levin syndrome. This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants.

Pregabalin, the most recently approved antiepileptic drug, is a structural analog of GABA with a favorable pharmacokinetic profile. Pregabalin binds to the alpha2-delta subunit of a neuronal voltage-gated calcium channel and is believed to exert its anticonvulsant effect by modulating the release of specific neurotransmitters from hyperexcited presynaptic neurons. Animal models of epilepsy have suggested that this drug will be efficacious against partial-onset and generalized tonic-clonic seizures. Four pivotal, add-on clinical trials conducted in patients with partial-onset seizures demonstrated that pregabalin at daily doses of 150-600 mg is efficacious and associated with dose-dependent adverse events. Meta-analyses of efficacy and tolerability indicated that pregabalin is an efficacious and relatively well-tolerated antiepileptic drug.

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