Seizure Rate Research Articles

Epileptiform activity index for assessing oxcarbazepin therapy of newly-diagnosed focal epilepsy in adolescents and adults

Introduction. Oxcarbazepine (OXC) is approved for initial and adjunctive therapy of focal epilepsy (FE), being also a drug of choice in case of pediatric FE. Despite that OXC has been used in the Russian Federation (RF) since 2007, studies assessing its efficacy and tolerability are scarce. Aim. To evaluate efficacy and tolerability of OXC therapy in patients with newly-diagnosed epilepsy. Patients and methods . There were enrolled 103 patients (56 (54.4%) into the study: males and 47 (45.6%) females with FE, aged 44.32±19.71 years. Depending on the OXC daily dose, all patients were divided into 3 subgroups: 1200 mg/day (n=16; 15.5%). Video-electroencephalographic (video-EEG) monitoring was performed at each visit (at baseline, 1, 3, 6 and 12 months after then onset of therapy). Treatment efficacy was assessed by using the criteria of retention on treatment, seizure absence, seizure rate decrease by >50%, seizure rate decrease by <50% (insufficient efficacy). Adverse effects (AEs) were assessed in accordance to the Side Effects of Anti-Epileptic Drugs (SIDAED) treatment scale and emerging pharmacodynamics aggravation (increased seizure rate compared to baseline/emergence of new seizure type). Results . It was found that retention on OXC monotherapy during the 12-month follow-up period was achieved in 69.0% (n=71) patients, among which 15.5% (n=16) received less than OXC at dose of 1200 mg/day, 44.7% (n=46) - 1200 mg/ day, and 8.8% (n=9) - more than 1200 mg/day, respectively. Total rate of intolerable AEs during the follow-up period was 13.6% (n=14). Comparing initial vs. 12-month timepoint EAI magnitude after the onset of OXC therapy revealed that it was significantly decreased by 6.9-fold (p<0.05). Conclusions. OXC is an effective drug for the initial treatment of FE in adolescents and adults highlighted with favorable tolerability profile. 12-month follow-up monitoring demonstrated that EAI was reduced almost by 7-fold allowing to consider it as an objective quantitative marker for assessing treatment efficacy.

Escalate and De-Escalate Therapies for Intracranial Pressure Control in Traumatic Brain Injury.

Severe traumatic brain injury (TBI) is frequently associated with an elevation of intracranial pressure (ICP), followed by cerebral perfusion pressure (CPP) reduction. Invasive monitoring of ICP is recommended to guide a step-by-step “staircase approach” which aims to normalize ICP values and reduce the risks of secondary damage. However, if such monitoring is not available clinical examination and radiological criteria should be used. A major concern is how to taper the therapies employed for ICP control. The aim of this manuscript is to review the criteria for escalating and withdrawing therapies in TBI patients. Each step of the staircase approach carries a risk of adverse effects related to the duration of treatment. Tapering of barbiturates should start once ICP control has been achieved for at least 24 h, although a period of 2–12 days is often required. Administration of hyperosmolar fluids should be avoided if ICP is normal. Sedation should be reduced after at least 24 h of controlled ICP to allow neurological examination. Removal of invasive ICP monitoring is suggested after 72 h of normal ICP. For patients who have undergone surgical decompression, cranioplasty represents the final step, and an earlier cranioplasty (15–90 days after decompression) seems to reduce the rate of infection, seizures, and hydrocephalus.

Dynamic Transitions in Neuronal Network Firing Sustained by Abnormal Astrocyte Feedback.

Astrocytes play a crucial role in neuronal firing activity. Their abnormal state may lead to the pathological transition of neuronal firing patterns and even induce seizures. However, there is still little evidence explaining how the astrocyte network modulates seizures caused by structural abnormalities, such as gliosis. To explore the role of gliosis of the astrocyte network in epileptic seizures, we first established a direct astrocyte feedback neuronal network model on the basis of the hippocampal CA3 neuron-astrocyte model to simulate the condition of gliosis when astrocyte processes swell and the feedback to neurons increases in an abnormal state. We analyzed the firing pattern transitions of the neuronal network when astrocyte feedback starts to change via increases in both astrocyte feedback intensity and the connection probability of astrocytes to neurons in the network. The results show that as the connection probability and astrocyte feedback intensity increase, neuronal firing transforms from a nonepileptic synchronous firing state to an asynchronous firing state, and when astrocyte feedback starts to become abnormal, seizure-like firing becomes more severe and synchronized; meanwhile, the synchronization area continues to expand and eventually transforms into long-term seizure-like synchronous firing. Therefore, our results prove that astrocyte feedback can regulate the firing of the neuronal network, and when the astrocyte network develops gliosis, there will be an increase in the induction rate of epileptic seizures.

Meta-analyzing count events over varying durations using the piecewise Poisson model: The case for poststroke seizures.

Meta-analyzing count data can be challenging when follow-up time varies across studies. Simply pooling aggregate data over time-periods would result in biased estimates, which may erroneously inform clinical decision-making. In this study, we exploit the convolution property of the Poisson distribution to develop a likelihood for observed cumulative counts over varying follow-up periods, where different Poisson distributions are used to represent the data generating processes for the latent counts in pre-defined successive intervals of follow-up. We illustrate this approach using an example of poststroke seizures, a case in which risk may change over time, and mimic its survival duration with time-varying hazard. Data were extracted from observational studies (1997-2016) reporting poststroke seizures over a maximum of 10 years of follow-up. Three clinically meaningful follow-up time intervals were considered: 0 to 7 days, 8 to 365 days, and 1 to 10 years poststroke. External validation was performed using claims data. Results suggest the incidence rate of seizures was 0.0452 (95% confidence interval: 0.0429, 0.0475), 0.0001 (0, 0.016), and 0.0647 (0.0441, 0.0941) for the three time intervals, respectively, indicating that the risk of seizures changes over time poststroke. We found that the model performed well against the incidence rate of seizures among actual retrospective cohort from claims data. The piecewise Poisson model presents a flexible way to meta-analyze count data over time and mimic survival curves. The results of the piecewise Poisson model are readily interpretable and may spur meaningful clinical action. The method may also be applied to other diseases. HIGHLIGHTS: It is challenging to perform a meta-analysis when follow-up time varies across studies. Ideally, outcomes over different time-periods should be pooled with individual patient-level data (IPD). A new model was developed to meta-analyze count data over time using aggregate-level data from previous published studies. The piecewise Poisson model could be a useful tool to estimate time-vary hazards given available data, and mimic survival curves over time which would be readily interpretable.

Amygdala Low-Frequency Stimulation Reduces Pathological Phase-Amplitude Coupling in the Pilocarpine Model of Epilepsy.

Temporal-lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and warrants the development of new therapies, such as deep-brain stimulation (DBS). DBS was applied to different brain regions for patients with epilepsy; however, the mechanisms of action are not fully understood. Therefore, we tried to characterize the effect of amygdala DBS on hippocampal electrical activity in the lithium-pilocarpine model in male Wistar rats. After status epilepticus (SE) induction, seizure patterns were determined based on continuous video recordings. Recording electrodes were inserted in the left and right hippocampus and a stimulating electrode in the left basolateral amygdala of both Pilo and age-matched control rats 10 weeks after SE. Daily stimulation protocol consisted of 4 × 50 s stimulation trains (4-Hz, regular interpulse interval) for 10 days. The hippocampal electroencephalogram was analyzed offline: interictal epileptiform discharge (IED) frequency, spectral analysis, and phase-amplitude coupling (PAC) between delta band and higher frequencies were measured. We found that the seizure rate and duration decreased (by 23% and 26.5%) and the decrease in seizure rate correlated negatively with the IED frequency. PAC was elevated in epileptic animals and DBS reduced the pathologically increased PAC and increased the average theta power (25.9% ± 1.1 vs. 30.3% ± 1.1; p < 0.01). Increasing theta power and reducing the PAC could be two possible mechanisms by which DBS may exhibit its antiepileptic effect in TLE; moreover, they could be used to monitor effectiveness of stimulation.

Synthesis and investigation of anti-inflammatory and anticonvulsant activities of novel coumarin-diacylated hydrazide derivatives

A number of novel coumarin derivatives synthesized by the reaction of 3-carbonyl chloride coumarin with some substituted aryl acid hydrazides to investigate their anti-inflammatory and anticonvulsant activities. Carrageenan (0.1 ml of 1%, w/v) was injected subplantarly in the right paw of rats to induce an acute model of inflammation. Anti-inflammatory efficacy was evaluated for 5 hours at 3 different dosages 5, 10, 25 mg/kg. After that, the changes in the level of paw edema volumes and percentage inhibition of all groups were observed and the most effective coumarin derivative was found as N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide. In addition, N’-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N’-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide, and N’-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3-carbohydrazide showed their anti-inflammatory effects in a dose-dependent manner. On the other hand, pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was used to investigate the anticonvulsant activities of six newly synthesized coumarin derivatives in mice. Hybrid compound of salicylic acid hydrazide and 3-carbonyl chloride coumarin (8d) was found the most promising anticonvulsant agent among all treatment groups according to the onset of seizure and survival rate. Moreover, (E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide (8b) and (E)-N'-(3-(4-hyroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide (8c) has potential anticonvulsant efficiency in low doses (30 mg/kg). The anticonvulsant effect of these coumarin derivatives may be through enhanced GABA-mediated inhibition in the brain.

Post Marketing Rate of Seizures During Transcranial Magnetic Stimulation (TMS) Treatment with NeuroStar Advanced Therapy Is Lower Than Previously Estimated

Background: Published reviews and surveys of incident rate of seizures with any TMS device (Wasserman et al. 1998, Rossi et al. 2009, and Lerner 2019) revealed that the rate ranges from 0.003-0.043%. Many subjects that developed seizures during TMS were treated with parameters outside those recommended in TMS guidelines or were predisposed due to seizure threshold-lowering factors, e.g., concurrent use of certain medications or alcohol, sleep deprivation. Additionally, some non-epileptic events may have been misreported. The objective of this research is to determine the rate of seizures reported to Neuronetics, Inc. relative to treatment sessions and review the number of seizures reported in literature naming this device as the means of TMS delivery. Design/Methods: 1. We conducted a review of TMS literature published after Wasserman (1998) and Rossi (2009) that mentioned seizures and that named this system as the device used for TMS treatment through June 30, 2019. These are captured as part of Neuronetics’ post marketing surveillance procedure. We also reviewed articles that identified this device as that used to deliver TMS treatment. Articles that referenced single-pulse TMS and those that reported seizures during TMS treatment delivered to subjects with epilepsy were excluded. 2. We reviewed all seizure events reported to Neuronetics, Inc., directly or through FDA MedWatch, from time of FDA clearance through June 30, 2019. 3. Seizure incidences reported from antidepressant medication trials were reviewed for comparison. Results: The post marketing surveillance seizure rate with this system is 0.001%, or approximately 1 in 89,000 TMS treatments. Our literature review revealed that no seizures have been reported in articles that identified this system as the TMS system used. Additionally, this system was not named in any articles that reported seizures and identified the TMS system used. Conclusions: The rate of seizures reported for individuals receiving TMS with this system (0.001%) is generally lower than the rates reported in clinical trials for widely used antidepressant medications (0.1% to 0.4%).

Neuropathophysiology of preeclampsia and eclampsia: A review of cerebral hemodynamic principles in hypertensive disorders of pregnancy.

Preeclampsia and eclampsia are hypertensive disorders of pregnancy associated with abnormal placental vascular development. The systemic angiogenic imbalance, endothelial dysfunction and proinflammatory state caused by abnormal placental development results in abnormalities in renal, hepatic, pulmonary and neurologic function. Neurosensory symptoms related to pregnancy induced hypertension (PIH), the most devastating of which are intracranial hemorrhage and seizure, are among the leading causes of maternal and perinatal morbidity and mortality globally, yet risk stratification strategies and targeted therapies remain elusive. Current treatment for preeclampsia with severe features is limited to delivery, antihypertensive therapy, and magnesium sulfate seizure prophylaxis. Magnesium sulfate reduces seizure rates among severe preeclamptics, but predisposes patients to weakness, uterine atony, pulmonary edema and respiratory depression. Therefore, this drug should ideally be administered only to the subset of preeclamptics who are at increased risk for neurologic complications. While there are no objective methods validated to predict eclampsia, we hypothesize that measurement of optic nerve sheath diameters, optic disc height and middle cerebral artery transcranial doppler resistance indices may be useful in identifying subclinical cerebral edema, potentially allowing us to recognize those patients at highest risk for seizures. This summary of the current literature provides an initial framework for developing more sophisticated and noninvasive methods for identifying, monitoring and treating parturients who are at highest risk for neurologic complications from preeclampsia.

Environmental Exposures and Seizures Treated by Illinois Emergency Medical Services and Hospitals.

Up to 10% of the population will have at least one seizure in their lifetime, with young children and elderly having the highest risk (WHO 2019). Human epidemiological studies and controlled animal studies have shown that exposure to common environmental pollutants, including carbon monoxide, lead, and nitrogen dioxide may lead to neurotoxicity and alter human susceptibility to seizures. While the biomechanism causing altered human seizure susceptibility is not entirely clear, air pollution has been shown to increase oxidative stress and neuroinflammation in humans and animals. The small number of human studies have included populations exposed to high levels of ambient air pollution, but the results have been inconsistent in regard to an increase in seizure occurrence and sudden deaths among people with epilepsy. There remains no reported data on the presence and strength of an association between chronic low-level environmental exposures to common air pollutants and seizure risk. Using medical billing records from Illinois hospitals and emergency medical services data on ambulance runs from 2011-2019, we evaluated the association between point sources of pollution mixtures (Toxic Release Inventory sites, Superfund sites, highways) and ZIP code level seizure rates.

Preventing epilepsy after traumatic brain injury: A propensity score analysis

Background:Due to the potential consequences of post-traumatic epilepsy (PTE) exacerbating secondary injury following traumatic brain injury (TBI), the use of antiepileptic drugs (AEDs) is an accepted option for seizure prophylaxis. However, there is only a paucity of data that can be found regarding outcomes surrounding the use of AEDs. The purpose of this retrospective study is to evaluate whether the prophylactic administration of AEDs significantly decreased the incidence of PTE, when considering the severity of TBI.Methods:All trauma patients who had been newly diagnosed with TBI from January 1, 2010 to December 31, 2017 were retrospectively analyzed. Statistical comparisons were made using the chi-square test, Mann-Whitney U test, and Cox regression modeling. After excluding any exposed subjects with no appropriate match, patients who had received AED prophylaxis were matched by propensity score with those who did not receive AEDs. All of the TBI populations were followed up until June 30, 2018.Results:We identified 1316 patients who met the inclusion and exclusion criteria in our matched cohort through their propensity scores, where 138 patients had been receiving prophylactic AEDs and 138 patients had not. Baseline characteristics were similar in gender, age, Glasgow Coma Scale (GCS) scores, and risk factors of PTE including skull fracture, chronic alcoholism, subdural hematoma, epidural hematoma, and intracerebral hematoma. After adjusting for those risk factors, the relative incidence of seizure was not statistically significant in either of the groups (p = 0.566).Conclusion:In our cohort analysis, AED prophylaxis was ineffective in preventing seizures, as the rate of seizures was similar whether patients had been receiving the drugs or not. We therefore concluded that the benefits of routine prophylactic anticonvulsant therapy in patients with TBI need to be re-evaluated.

Diagnostic yield of seizure recordings and neuroimaging in patients with focal epilepsy without interictal epileptiform discharges

ObjectiveRepeated routine electroencephalography (EEG) or even long-term video-EEG monitoring (VEM) does not always record interictal epileptiform discharges (IEDs) in some patients with epilepsy. The present study investigated whether focal seizures detected by VEM and focal abnormalities on neuroimaging are useful for the diagnosis of patients with focal epilepsy without IEDs. MethodsWe retrospectively reviewed 409 consecutive patients with focal epilepsy (207 men, aged 9 to 76 years) who underwent 4- or 5-day VEM, magnetic resonance imaging (MRI), and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis to identify patients without IEDs. The occurrence of focal seizures during VEM and the presence of focal abnormalities on neuroimaging were investigated in those patients. The occurrence rate of seizures during VEM was investigated in patients with daily, weekly, monthly, and yearly seizure frequency based on history-taking. ResultsNinety-five (23.2%) of 409 patients with focal epilepsy did not have IEDs. Fifty-five (57.9%) of the 95 patients had focal seizures during VEM. Fifty-four patients (56.8%) showed focal abnormalities compatible with seizure semiology on neuroimaging investigations. Neither seizure recordings nor neuroimaging abnormalities were seen in 16 (16.8%) of the 95 patients. The occurrence rate of seizures during VEM depended on the seizure frequency at history-taking. However, 28 (45.9%) of 61 patients with monthly and yearly seizure frequency had focal seizures during 4- or 5-day VEM with seizure induction. ConclusionsVideo-EEG monitoring can detect focal seizures in patients with focal epilepsy but no IEDs. Comprehensive assessment including VEM and neuroimaging study is important for the diagnosis.

Seizure in patients with COVID-19.

ObjectiveThe purpose of the current study was to collect the data on the occurrence of seizures in patients with COVID-19 and to clarify the circumstances of the occurrence of seizures in these patients.MethodsAll consecutive patients who referred to healthcare facilities anywhere in Fars province (located in South Iran with a population of 4.851 million people) from February 19 until June 2, 2020, and had confirmed COVID-19 by positive result on polymerase chain reaction testing and seizure were included.ResultsDuring the study period, 6,147 people had confirmed COVID-19 in Fars province, Iran; 110 people died from the illness (case fatality rate 1.79%). During this time period, five people had seizures (seizure rate 0.08%). In four patients, seizure was one of the presenting manifestations, and in one person, it happened during the course of hospital admission. Two patients had status epilepticus. All patients experienced hypoxemia and four of them needed respirator. Two patients had related metabolic derangements and one had cerebrospinal fluid (CSF) lymphocytic pleocytosis. Brain imaging was abnormal in three patients. Four patients died.ConclusionNew-onset seizures in critically ill patients with COVID-19 should be considered as acute symptomatic seizures and the treating physician should try to determine the etiology of the seizure and manage the cause immediately and appropriately. Detailed clinical, neurological, imaging, and electrophysiological investigations and attempts to isolate SARS-CoV-2 from CSF may clarify the role played by this virus in causing seizures in these patients.Electronic supplementary materialThe online version of this article (10.1007/s10072-020-04731-9) contains supplementary material, which is available to authorized users.

A Human TSC1 Variant Screening Platform in Gabaergic Cortical Interneurons for Genotype to Phenotype Assessments.

The TSC1 and TSC2 genes are connected to multiple syndromes from Tuberous Sclerosis Complex (TSC) to autism spectrum disorder (ASD), with uncertainty if genetic variants cause all or subsets of phenotypes based on the location and type of change. For TSC1, few have addressed if non-TSC associated genetic variants have direct contributions to changes in neurological genotype-to-phenotype impacts, including elevated rates of ASD and seizures. Dominant variants cause TSC, yet TSC1 has many heritable variants not dominant for TSC that are poorly understood in neurological function, with some associated with ASD. Herein, we examined how missense variants in TSC1, R336W, T360N, T393I, S403L, and H732Y, impacted the development of cortical inhibitory interneurons, cell-types whose molecular, cellular, and physiological properties are altered after the loss of mouse TSC1. We found these variants complemented a known phenotype caused by loss of TSC1, increased cell size. However, distinct variants, particularly S403L showed deficits in complementing an increase in parvalbumin levels and exhibited smaller amplitude after hyperpolarizations. Overall, these data show that subtle phenotypes can be induced by some TSC1 missense variants and provide an in vivo system to assess TSC1 variants’ neurological impact better.

Efficacy assessment of levetiracetam monotherapy in newly-diagnosed epilepsy in adults using epileptiform activity index

Abstract. Levetiracetam (LEV) is one of the most commonly prescribed antiepileptic drugs (AED). However, there were no studies on its efficacy and safety in terms of the correlation with epileptiform activity index (EAI) performed among the Russian population.Aim. To evaluate the efficacy and tolerability of LEV monotherapy in patients with newly-diagnosed epilepsy using epileptiform activity index (EAI) assessment.Materials and methods. The study included 107 patients (46 (43.0%) male and 61 (57.0%) female) with focal epilepsy (FE) (39.3%; n=42) or idiopathic generalized epilepsy (IGE) (60.7%; n=65). At each visit, video-electroencephalographic (video-EEG) monitoring was performed (baseline and in 1, 3, 6, and 12 months of the therapy). Therapeutic drug monitoring was performed at dose titration in 1 month of the therapy or in case of therapy correction. Treatment efficacy was assessed using the criteria of seizure absence (medically induced remission), seizure rate decrease by &gt;50% (responders), seizure rate decrease by &lt;50% – insufficient efficacy, a composite index of efficacy/tolerability (retention on treatment), and seizure rate increase compared to baseline and/or development of a new type of seizures (aggravation). Adverse events (AE) were assessed using the scale for side effects in AED treatment (SIDAED).Results. Total EAI at baseline was 5.2-fold higher in patients with IGE compared to FE patients (23.4±3.0 and 4.5±0.97, respectively). After 1 month of LEV therapy, EAI decreased to 3.4±1.1 and 1.9±0.4 in patients with IGE and FE, respectively (p&lt;0.01). The decrease continued during the whole follow-up period. Retention on monotherapy was achieved in 82.2% (n=88/107) patients; in 87.6% (n=57/65) patients with IGE and in 73.8% (n=31/42) with FE. The rate of serious AEs during the follow-up period was 8.4% (n=9).Conclusions. LEV is an effective drug of choice for the initial treatment of newly-diagnosed FE and IGE in monotherapy along with a significant decrease in EAI. EAI is an objective measure of LEV treatment efficacy.

Predicting Autism Spectrum Disorder in Very Preterm Infants.

Children born preterm are known to be at higher risk for developing autism spectrum disorder (ASD) compared with their term-born counterparts, with an estimated 7% prevalence of ASD based on a recent large prospective study and a meta-analysis.1,2 This high prevalence is in contrast to the currently estimated prevalence of ASD in the United States of 1.8% in the general population.3 ASD has been shown to be associated with a variety of prenatal, perinatal, and neonatal risk factors, including a variety of maternal health risk factors and medications and neonatal risk factors such as seizures, birth asphyxia, and low birth weight.4 Previously identified perinatal risk factors for ASD specific to preterm infants include factors such as low birth gestational age and birth weight, intracranial hemorrhage, and acute and chronic lung disease (CLD).5The article by Chen et al6 in this issue of Pediatrics provides the first prospectively obtained data regarding whether there is an early developmental trajectory of prematurely born children that predicts who will develop ASD. The authors tested 319 preterm children prospectively with Bayley Scales of Infant Development examinations at 6, 12, and 24 months and used group-based trajectory modeling to assess whether early-life developmental trajectory predicted autism at 5 years of age. The approach of looking at developmental trajectory has been used in other high-risk populations, such as infant siblings of children with ASD7 or those with a specific genetic disorder (tuberous sclerosis complex) with a high prevalence of ASD.8The authors provide the first data revealing that although a small percentage of preterm infants who develop ASD have a similar early-life trajectory to that of term-born children, with decline in mental development from age 12 to 24 months,9,10 the highest-risk group was identified as having low cognitive scores at 6 months, with further decline over time, allowing for early identification and intervention. The converse finding that infants with low cognitive scores who improve to >85 and those with stably high cognitive scores are at lower risk of developing ASD enables the clinician to provide reassurance to families.Their analysis also illuminates risk factors for ASD related to preterm birth by comparing the 29 children who developed ASD with the 290 children without ASD. Notably, their study identified both nonmodifiable (eg, male sex, gestational age, and birth weight) and potentially modifiable risk factors (eg, CLD and duration of oxygen therapy) for the development of ASD. As the authors discussed, CLD is known to be a risk factor for developmental delay and cognitive impairment and/or disability, but it is unclear the extent to which the risk associated with CLD is related to brain injury and altered brain development.One acknowledged limitation of the study was the lack of neuroimaging data, so it is unknown whether there was a contribution of identifiable brain injury to the development of ASD in their subjects. It is likely that at least some of the infants in the low cognitive score group had easily detected brain injury, such as large cerebellar injury11 or cerebral injury and/or impaired brain development,12–14 both of which are associated with low IQ and are suspected to increase the risk of ASD. Additionally, there were no data regarding genetic risk factors for ASD, which could contribute a “second hit” to risk factors related to prematurity. Numerous genes have now been identified to be associated with ASD and/or intellectual disability and could have contributed to some cases of ASD in this study. Male sex remains a strong risk factor for ASD in both preterm and term-born children, and particularly in preterm children, male sex may contribute to inherent genetic risks related to sex as well as increased vulnerability to complications of preterm birth that also increase the risk of ASD. The importance of neuroimaging and genetic data relates in part to the observation that preterm and term-born children with ASD have been shown to have important phenotypic differences. In one study, boys with ASD born preterm had higher rates of seizures, attention-deficit/hyperactivity disorder, and sleep apnea,15 suggesting a potentially different neural substrate for ASD than term-born children.Perhaps most importantly, these findings provide an opportunity for initiating interventions in early life to mitigate ASD before the diagnosis of ASD can be definitively established. Identification of a constellation of prenatal and neonatal risk factors could help clinicians target infants at highest risk, while providing reassurance to parents whose infants are at low risk. Identification of high-risk infants with low cognitive scores at 6 months of age or those with declining scores over time could provide another opportunity to intensify early intervention services aimed at mitigating manifestations and/or symptoms of ASD. Importantly, identification of high-risk infants by neonatal discharge and/or 6 months of age could improve research into novel therapies to mitigate the manifestations of ASD, such as communication and social-emotional deficits or impairments.

Intrapartum fetal monitoring and perinatal risk factors of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) in term infants, is a major cause of neonatal mortality and severe neurologic disability. To identify in labor fetal monitoring characteristic patterns and perinatal factors associated with neonatal HIE. Single-center retrospective case-control study between 2010 and 2017. Cases clinically diagnosed with neonatal HIE treated by therapeutic hypothermia according to strict criteria (HIE-TH) were compared to a group of neonates born in the same period, gestational age-matched diagnosed with fetal distress according to fetal monitoring interpretation that was followed by prompt delivery, without subsequent HIE or therapeutic hypothermia (No-HIE). The primary outcome of the study was the electronic fetal monitoring (EFM) pattern during 60min prior to delivery; the secondary outcome was the identification of perinatal associated factors. 54 neonates with HIE were treated by therapeutic hypothermia. EFM parameters most predictive of HIE-TH were indeterminate baseline heart rate OR = 47.297, 95% (8.17-273.76) p < 0.001, bradycardia OR = 15.997 95% (4.18-61.18) p < 0.001, low variability OR = 10.224, 95% (2.71-38.45) p < 0.001, higher baseline of the fetal heart rate calculated for each increment of 1 BPM OR = 1.0547, 95% (1.001-1.116) p = 0.047. Rupture of a previous uterine cesarean scar and placental abruption were characteristic of the HIE-TH group 14.8% vs. 1% p < 0.05; and 16.7% vs. 6% p < 0.05, respectively. Adverse neonatal outcomes also differed significantly: HIE-TH had a higher rate of neonatal seizures 46.2% vs. 0% p < 0.001 and mortality 7.7% vs. 0% p < 0.001. Characteristic fetal monitoring pattern prior to delivery together with acute obstetric emergency events are associated with neonatal HIE, neurological morbidity, and mortality.

Predictors of early, recurrent, and intractable seizures in low-grade glioma.

Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients. We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test. A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase (IDH) mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the IDH mutation was identified (P = .09). Male sex was significantly associated with higher seizure incidence during preoperative (P < .001) and postoperative periods (P < .001); men were also more likely to develop intractable seizures (P = .01). Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with IDH-mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.

Blood Pressure Profiles in Infants With Hypoxic Ischemic Encephalopathy (HIE), Response to Dopamine, and Association With Brain Injury.

Objective: To describe mean arterial blood pressure (MABP), responsiveness to dopamine, and relationship to brain injury in infants with moderate/severe hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). We hypothesized that, when utilized, dopamine would rapidly and effectively increase MABP in treated patients.Methods: Continuous arterial blood pressure measurements were prospectively recorded from infants with moderate/severe HIE undergoing TH in a multi-institutional cohort from 2010 to 2018. Treatment with dopamine was at the discretion of the medical team for hypotension/hypoperfusion. MABP values of treated infants were compared to those obtained at an equivalent time period in control infants receiving TH but not dopamine (24 h after birth). MRI was obtained per unit protocols and included T1/T2/DWI sequences. Injury was classified as no injury/mild injury or moderate/severe injury using a standardized scoring system. Seizures were confirmed with conventional EEG.Results: Eighteen infants were treated with dopamine and were similar to untreated controls (n = 36) with the exception of lower cord gas pH (6.92 ± 0.2 vs. 7.07 ± 0.2, p < 0.05). Dopamine was initiated at a mean of 24 h after birth. MABP was significantly lower in the dopamine group at the start of therapy (39.9 ± 2.0 vs. 49.1 ± 1.3, p < 0.01) and 1 h later (44.3 ± 2.0 vs. 49.8 ± 1.1, p < 0.05). However, after 9 h of treatment, dopamine increased the MABP by an average of 9 mmHg and MABP values were similar to untreated controls for the remainder of the observation period. There were no significant differences in rates of seizures, brain injury, or death.Conclusion: Neonates with moderate/severe HIE treated with dopamine during TH had MABP significantly lower than controls. The majority of infants responded to dopamine monotherapy following adequate volume resuscitation. An association between requirement for dopamine and severity of brain injury was not detected.

Trans-sulcal versus trans-parenchymal approach in supratentorial cavernomas. A multicentric experience

ObjectivesCavernous malformations (CM) are low-flow vascular lesions that can cause significant symptoms and neurological deficits. Different intraoperative surgical approaches have been developed. Aim of the present investigation is the comparison between the trans-sulcal approach (TS) and the trans-parenchymal neuronavigation-assisted approach (TPN) in a surgical series from two neurosurgical centers. The technique and clinical outcomes are discussed, with a specific focus on seizure outcome. Patients and methodsClinical and radiological data from two neurosurgical centers (“A. Gemelli” Hospital in Rome and A.O.U. Città della Salute e della Scienza in Turin) were retrospectively reviewed in order to evaluate the different outcome of TS and TPN approach for cavernous malformation treatment. ResultsA total of 177 patients underwent surgical intervention for supratentorial CM, 130 patients with TPN approach and 47 with TS approach. TS approach was associated with higher rate of seizure in early post-operative period both in epileptic patients (p < 0,001) and in patients without history of seizures before surgery (p = 0,002). Moreover, length of incision (p < 0,001), area of craniotomy (p < 0,001) and corticectomy (p < 0,001) were bigger in TS than in TPN approach. Brain contusion (p < 0,001) and fluid collection (p < 0,001) were more likely to be discovered after TS approach. ConclusionsTPN is a valuable approach for resection of CM. Minor complications are significantly lower in TPN approach when compared with TS approach. In addition, it is associated with lower rate of early post-operative seizure and shorter length of stay.

Efficacy and Tolerability of Lacosamide for Focal Epileptic Patients: Study from Epilepsy Clinic in Makkah.

Lacosamide is characterized by its novel dual mode of action on account of its structural components; its molecule contains a functional amino acid that selectively and slowly promotes the inactivation of voltage-gated sodium channels. This study aims to assess the effectiveness and tolerability of Lacosamide with respect to its use in the treatment of focal epileptic patients. This retrospective cohort study used data collected from the clinical notes or diaries of all epileptic patients who were treated in King Abdullah Medical City during the time period from 2014 to 2019. The multivariate Generalized Estimating Equation (GEE) repeated measure logistic regression analysis was used to assess the odds of having an improvised seizure rate. Majority of the focal epileptic patients (57.9%) were diagnosed with temporal epilepsy, while 26.3% patients had frontal epileptic lesion/diagnoses. Majority of the patients (54.4%) had received a combination of old and new treatment. Out of the seven patients who reported side effects, 57.14% experienced dizziness and headache, tremors (n = 1), loss of balance (n = 1) and increased seizure with abnormal vision acuity and psychosis (n = 1). 84.2% patients experienced reduced median seizure frequency in 12-month period. However, on the basis of clinical characteristics, no significant difference was observed in the seizure control rate. No statistically significant differences were observed between male and female patients with respect to their average improvement rate across the four time points. Lacosamide is an effective and well tolerable drug for patients with focal epilepsy.