Etiology Of Seizures Research Articles

Seizures in dogs under primary veterinary care in the United Kingdom: Etiology, diagnostic testing, and clinical management.

BackgroundAlthough seizures are common in dogs, limited published information is available on the classifications of seizures, diagnostic approaches, or clinical management of seizure‐affected patients in the veterinary primary care setting.ObjectivesExplore seizure etiology, diagnostic testing, and clinical management of seizure‐affected dogs in the primary care veterinary setting.AnimalsA total of 455 553 dogs in VetCompass.MethodsCross‐sectional analysis by cohort clinical data.ResultsFrom 2834 incident seizure cases, we identified 579 (20.5%) dogs with epilepsy based on the International Veterinary Epilepsy Task Force (IVETF) classification system, including 484 (17.1%) with idiopathic epilepsy, 95 (3.4%) with structural epilepsy, and 179 dogs (6.3%) with reactive seizures. In their clinical first opinion records, 245 (8.6%) cases were recorded with epilepsy. Overall, 1415 (49.9%) cases received diagnostic evaluation equivalent to or higher than IVETF Tier 1 diagnostic testing.Being <12 years of age and being insured were risk factors for receiving IVETF Tier 1 or higher diagnostic evaluation among seizure cases. Anti‐seizure drug (ASD) treatment was not prescribed for 1960/2834 (69.2%) dogs in association with the incident seizure event. Of the remainder, 719 (25.3%) dogs received 1 ASD, whereas 155 (5.5%) an ASD combination.Conclusion and clinical importanceThe differences between seizure classifications in the clinical records and those retrospectively assigned by the researchers support the need for clearer diagnostic guidelines in clinical practice. Insured dogs and dogs <12 years of age were more likely to receive advanced diagnostic evaluation, suggesting that financial and perceived prognostic factors influence case management.

Optimizing data collection in dietary therapy clinics for epilepsy: A recommendation for standardized data collection forms

ObjectiveThe objectives of this study were to 1) examine medical records from one medium-sized dietary clinic as an example of data being collected clinically, 2) identify data limitations, and then 3) create standardized data collection forms with the long-term goals of improving clinical care and facilitating multicenter data analysis. MethodsA retrospective chart review was conducted at the Dietary Therapies for Epilepsy Clinic at Children’s National Medical Center (CNMC) in Washington, D.C. Patients who initiated dietary therapy between 2015 and 2018 were assessed. Categorical variables were examined via Chi Square or Fisher’s Exact tests and continuous variables were assessed via an independent t-test or Mann-Whitney U test, depending on normality. ResultsForty-two patients underwent dietary therapy initiation during this time period, but only 26 had follow-up visit data. Of these patients, 54% reported non-seizure symptom improvement(s), and only 16 had quantitative seizure frequency information available, with 63% being clinical responders. No significant associations were observed between patient or diet characteristics and seizure or non-seizure improvement. Some variables, such as seizure duration, seizure severity, beta-hydroxybutyrate, and dietary compliance were not typically included in the records and therefore could not be evaluated statistically. Variations in seizure type(s), etiology, and clinical diagnoses/syndromes also made it unfeasible to evaluate differences in improvement based on these variables. Standardized data collection forms were created to address these limitations and are included as appendices. SignificanceThe results suggest limitations with the clinical data currently being collected. Medium-sized clinics may not see enough patients to study specific epilepsy populations. Standardized patient forms could target these issues, thereby improving clinical care and expanding research opportunities. Future research can test these forms for clinical use and as a collection tool for larger scale research across clinics.

Catastrophising and repetitive negative thinking tendencies in patients with psychogenic non-epileptic seizures or epilepsy

PurposePrevious research suggests that catastrophisation and perseverative, or repetitive negative thinking (RNT) could play an important role in the aetiology of Psychogenic Nonepileptic Seizures (PNES). This study was designed to explore whether these cognitive tendencies are more prevalent in patients with PNES than those with epilepsy and to examine the relationship between these cognitions, depression, anxiety, seizure frequency and diagnosis. Methods26 patients with PNES (PWPNES) and 29 with epilepsy (PWE) self-reported RNT (Perseverative Thinking Questionnaire), catastrophisation tendencies (modified Safety Behaviors and Catastrophizing Scale), symptoms of anxiety (Generalised Anxiety Disorder Assessment 7) and depression (Primary Health Questionnaire 9) as well as seizure frequency. ResultsRNT and catastrophic thinking were highly correlated with each other and more prevalent in PWPNES than PWE. Positive correlations were also found between all other self-report measures and seizure frequency. The PNES diagnosis predicted RNT (perseverative thinking) independently of catastrophic thinking, anxiety, depression and seizure frequency. ConclusionPWPNES exhibit greater negative perseverative and catastrophising cognitive tendencies than PWE. PNES as a diagnosis independently predicted RNT. Hence, RNT and catastrophisation should be considered as possible specific targets for psychological interventions in patients with PNES.

Prevalence of Biochemical Abnormalities in Neonatal Seizures in Term and Preterm Neonates

Background: The most vulnerable period of life to develop seizures is the neonatal period. These events very often signify serious damage or malfunction of the immature developing central nervous system. Neonatal seizures may arise as a result of diverse etiologies and can have varied presentations. Biochemical abnormalities are commonly observed in neonates who are admitted in neonatal intensive care unit with seizures. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long-term outcome.&#x0D; Objective: To assess clinical types and importance of biochemical abnormalities in neonatal seizures and to evaluate clinical type &amp; time of onset of seizures in term and preterm neonates.&#x0D; Methods: A prospective observational study, where 100 neonates presenting with seizures admitted to neonatal intensive care unit of Jagadguru Jayadeva Murugarajendra Medical College, Davangere, from September 2015 to August 2017 were enrolled in the study. The detailed history along with clinical examination, baseline characteristics of convulsing neonate were recorded at admission. Clinical details of each seizure episode reported by the mother and subsequently observed by the resident doctors on duty were recorded. The relevant biochemical investigations were done immediately after baby had seizures and before instituting any specific treatment. The descriptive statistics such as mean and standard deviation (SD) for continuous variables, frequencies and percentages were calculated for categorical variables. The association between gestational age and other categorical variables were analyzed using chi-square test of independence. The comparison of mean of various quantitative variables was analyzed using ANOVA test. Etiology of neonatal seizures and associated biochemical abnormalities were diagnosed.&#x0D; Results: In the present study, out of 100 neonates studied, 64 were full term of which 49(76.5%) were appropriate for gestational age and 15(23.5%) were small gestational age, whereas 36 cases were preterm. Most neonatal seizures occur in first 3 days of life, i.e. 59%. Most of them occurred on first day of life (34%). Birth asphyxia was the cause of neonatal seizures in 82.35% neonates who developed seizures on day-1 of life. Birth asphyxia and septicemia are common cause of neonatal seizures in our study (38 cases each), followed by pure metabolic disturbances 19%. In pure metabolic seizures, hypoglycemia (47.8%) is most common more in preterm babies (55%) followed by hypocalcemia. In cases of non- metabolic seizures, which showed associated biochemical abnormalities, hypoglycemia was most common abnormality 23 of 52 cases (44.2%). 12 cases (52.1%) are associated with birth asphyxia and 11 cases (47.9%) are associated with septicemia. Subtle seizures were most common type of seizures in our study, followed by focal clonic, multifocal clonic, generalized tonic, subtle with GTC and subtle with clonic.&#x0D; Conclusion: Biochemical abnormalities are common in neonatal seizures and often go unorganized. These abnormalities may significantly contribute to seizure activity correction of these abnormalities work up is necessary for all cases of neonatal seizures.

Glioma-induced peritumoral hyperexcitability in a pediatric glioma model.

Epileptic seizures are among the most common presenting symptom in patients with glioma. The etiology of glioma‐related seizures is complex and not completely understood. Studies using adult glioma patient tissue and adult glioma mouse models, show that neurons adjacent to the tumor mass, peritumoral neurons, are hyperexcitable and contribute to seizures. Although it is established that there are phenotypic and genotypic distinctions in gliomas from adult and pediatric patients, it is unknown whether these established differences in pediatric glioma biology and the microenvironment in which these glioma cells harbor, the developing brain, differentially impacts surrounding neurons. In the present study, we examine the effect of patient‐derived pediatric glioma cells on the function of peritumoral neurons using two pediatric glioma models. Pediatric glioma cells were intracranially injected into the cerebrum of postnatal days 2 and 3 (p2/3) mouse pups for 7 days. Electrophysiological recordings showed that cortical layer 2/3 peritumoral neurons exhibited significant differences in their intrinsic properties compared to those of sham control neurons. Peritumoral neurons fired significantly more action potentials in response to smaller current injection and exhibited a depolarization block in response to higher current injection. The threshold for eliciting an action potential and pharmacologically induced epileptiform activity was lower in peritumoral neurons compared to sham. Our findings suggest that pediatric glioma cells increase excitability in the developing peritumoral neurons by exhibiting early onset of depolarization block, which was not previously observed in adult glioma peritumoral neurons.

Levetiracetam as the First-line Antiepileptic in Neonatal Seizures

Background: The quest persists for an ideal newer antiepileptic drug (AED) with better efficacy and tolerability. Levetiracetam (LEV) is one of these AEDs with a novel mechanism of action, good pharmacokinetic profile, acceptable tolerability, and side-effect profile. The present study assessed the safety and efficacy of intravenous levetiracetam as a first-line AED in neonatal seizures.Methods: This prospective observational study was conducted on all term neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary care center. Neonates with hypoglycemia, hypocalcemia, hypomagnesemia, inborn errors of metabolism, or those who received other AEDs prior to admission were excluded from the study. 20mg/kg Intravenous LEV was administered as first-line AED and graded up to 40mg/kg if seizures were not controlled in 2 h; thereafter, second-line AED was added.Results: Only 36.2% (21/58) of the cases responded to LEV as first-line AED. Hypoxic Ischaemic Encephalopathy(HIE) was the most common etiology of seizures (55.2%). Subtle seizures were most responsive to LEV (60%), while multifocal clonic seizures (22.3%) responded the least. No adverse effect of LEV was observed during the study period.Conclusion: Only 36.2% of the cases responded to LEV as first-line AED, and subtle seizures were the most responsive seizures. Therefore, the efficacy of LEV as first-line AED in neonatal seizures is yet to be proven by a larger study. There were no adverse effects of LEV during the study period indicating the relative safety of this drug.

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program

IntroductionAn intermediate-sized, multicenter, expanded-access study was opened in 2015 through the support of the State of Georgia. This study provided children with treatment-resistant epilepsy (TRE) access to plant-derived highly purified cannabidiol (CBD; Epidiolex® in the US; Epidyolex® in the EU; 100 mg/mL oral solution). These children had failed to achieve seizure freedom with available treatment options and were ineligible to participate in randomized controlled trials that only included patients with Lennox–Gastaut and Dravet syndromes. MethodsCannabidiol safety, changes in seizure type, frequency, and seizure-free days were evaluated for children aged 1–18 years (at time of consent) as an adjunctive treatment for 36 months. The study consisted of a two-month baseline period, a titration period, treatment period, and optional titration period, which occurred after ≥26 weeks of treatment. Cannabidiol treatment was administered up to a targeted dose of 25 mg/kg/day, with an optional secondary treatment up to 50 mg/kg/day. Daily seizure type, seizure frequency, and seizure-free days were recorded in a Web-based diary, and changes in these outcomes were recorded and analyzed for the duration of the study. The occurrence of adverse events (AEs) was also recorded. ResultsThe median percentage change in seizures for 45 patients in Months 3, 6, 12, 18, 24, and 36 showed a statistically significant (p < 0.001) reduction in major seizures (ranging from 54 to 72% at various time points) and all seizures (61–70%) compared with baseline. A mean increase in seizure-free days per 28 days was >5 in all treatment periods after Month 2, and an average increase of 7.52 (p < 0.001) seizure-free days per 28 days was observed at the end of follow-up compared with baseline. All patients experienced ≥1 AE. Children who transitioned to the optional secondary treatment (high-dose group) reported more AEs before increasing their dose to >25.0 mg/kg/day compared with the low-dose group. However, the average rate of AEs was significantly lower after moving to a high-dose regimen (p = 0.004). Twelve children reported 20 serious AEs, none of which were considered related to CBD. ConclusionsThis study supports CBD as an adjunctive treatment for children with TRE. Treatment was well tolerated in doses up to 50 mg/kg/day. Patients who did not achieve desired results at a dose of ≤25.0 mg/kg/day reported more AEs when CBD dose increased to >25.0 mg/kg/day. Decreases in major seizure frequency and an increase in seizure-free days compared with baseline were reported during treatment. This supports the efficacy and tolerability of CBD for mixed seizure etiologies.

Utility of invasive electroencephalography in children 3 years old and younger with refractory epilepsy.

Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger. The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher's exact test was used to compare proportions. Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23). While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.

Efficacy of vagus nerve stimulation for drug-resistant epilepsy in children age six and younger

ObjectivesThe objective of the study were to examine the safety and efficacy of vagus nerve stimulation (VNS) for reducing seizure frequency and antiepileptic drugs (AEDs) in children younger than six years and to examine long-term VNS efficacy for children who receive the device at ages 1–3 and at ages 4–6. MethodsWe conducted a 10-year retrospective analysis of VNS implantations at UPMC Children's Hospital of Pittsburgh. Relevant data were collected within 12 months of VNS implantation and at six months, one, two, and four years after VNS implantation. ResultsThis analysis included 99 patients ages 0–3 (n = 40) and 4–6 (n = 59) at first VNS implantation. Eighty-six patients followed up for ≥4 years. There were no significant differences between age at VNS implant (0–3 vs. 4–6) and seizure etiology or most seizure semiologies. Patients took an average of 3.01 ± 1.29 AEDs prior to VNS and 3.84 ± 1.68 AEDs at their latest follow-up. The overall response to VNS therapy (≥50% seizure reduction) at one year, two years, and four years after VNS implantation was 55%, 60%, and 52%, respectively. At two years, 59% of 0- to 3-year-old patients responded to VNS and 52% of 4- to 6-year-old patients responded to VNS. The overall major complication rate was 5.6%, consistent with VNS use for older age groups. SignificanceThis study demonstrates the safety and efficacy of VNS for children with drug-resistant epilepsy (DRE) younger than six. One, two, and four years after VNS implantation, 55%, 60%, and 52% of these patients, respectively, achieved ≥50% reduction in seizure frequency. The safety of VNS is also comparable with older, better studied, age groups. Based on these data, VNS therapy should be considered for children younger than six.

Pluralistic and singular causal attributions for epilepsy in Uganda

ObjectiveIn Uganda, causal attributions for epilepsy reflect a variety of beliefs and impact care-seeking behavior, perpetuate stigma, and undermine the effectiveness of interventions to narrow the epilepsy treatment gap. The objective of this study was to characterize beliefs about seizure etiology to gain a better understanding of how epilepsy is conceptualized in the community in order to inform culturally appropriate educational policies and interventions. MethodsIn a community-based study, 15,383 participants were surveyed about beliefs related to 15 potential causes for epilepsy. Principal axis factor analysis (PFA) was performed to identify causative factors and then utilized to classify singular versus pluralistic belief systems related to epilepsy etiology. Analysis of variance (ANOVA) and Mann–Whitney U-tests were conducted to examine the differences in background characteristics across the etiology belief groups. ResultsThree main causative factors emerged from the PFA: biological, sociospiritual, and biospiritual. Among those endorsing at least one factor (n = 13,036), the biological factor was endorsed most frequently as a potential cause for epilepsy (88.0%), followed by the sociospiritual (63.4%), then biospiritual (47.6%). Review of the patterns of endorsement found that only 22.2% endorsed the biological factor alone, 6.7% the sociospiritual factor alone, and 2.8% the biospiritual factor alone (total 31.7%). The remainder endorsed a combination of two or all three factors as being potentially causal, and most (65.7%) endorsed a pluralistic combination inclusive of a biological etiology. Group comparisons showed that endorsing only the biological factor was associated with the highest levels of education (p < 0.01), the pluralistic group had the highest ratio of people in the household who needed assistance to those that could provide aid (p < 0.01), and there were significant differences in income across specific groups (p < 0.01). ConclusionsPluralistic attributions for epilepsy are common in Uganda, with the majority of community members drawing from biomedical and traditional concepts to construct complex explanations for seizures that transcend discrete belief categories traditionally depicted in the literature. These findings emphasize the need to understand cultural beliefs about epilepsy in order to design contextually specific interventions and education programs, which respect the fundamental beliefs and values of the community.This article is part of the Special Issue “The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda"

Telomere shortening in patients with drug-resistant epilepsy

Epilepsy affects about 1 % of the world population. Mesial temporal lobe epilepsy (mTLE) presents with seizures initiated in hippocampus and is the most frequent form of epilepsy. About 30 % of individuals with mTLE do not respond to conventional medications maintaining seizures and consequently new lesions on a daily basis. Treatment-resistant epilepsy has a huge social and individual burden due to impaired quality of life and increased mortality rate.There are many reasons for telomere shortening in individuals with mTLE, such as a chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators. In the past 10 years, there was a boom of studies establishing association between telomere length and chronic/complex disorders. Telomeres are essential for the maintenance of genomic integrity. Telomere length has been assumed as a biological marker for stress and cellular ageing. Here we hypothesized that individuals affected with treatment-resistant mTLE would course with a shorter telomere than controls. So, we measured leucocytes telomere length in a sample of 89 individuals, 48 treatment-resistant mTLE compared to 41 healthy controls. As expected, we observed a significant shorter telomere in the peripheral cell leukocytes of treatment-resitant mTLE group. Telomere length was not associated with sex, side of hippocampal sclerosis, family history, etiology of seizures, duration of disease or the Engel score. Our results points towards the need of further investigation to shed light on the relation of telomeres shortening and the outcomes and impacts of epilepsy.

Language representation and presurgical language mapping in pediatric epilepsy: A narrative review.

As one of the most common neurological diseases in children, epilepsy affects 0.9-2% of children. Complex interactions among the etiologies of epilepsy, interictal discharges, seizures, and antiepileptic drugs lead to cognitive impairments in children with epilepsy. Since epilepsy is considered as a network disorder, in which seizures have a widespread impact on many parts of the brain, childhood epilepsy can even affect the normal development of language. About 25% of children with epilepsy do not respond to medications; therefore, brain surgery is considered as a treatment option for some of them. Presurgical neuropsychological evaluations including language mapping are recommended to preserve cognitive and language abilities of patients after surgery. Functional magnetic resonance imaging as a non-invasive technique for presurgical language mapping has been widely recommended in many epileptic centers. The present study reviewed language representation and presurgical language mapping in children with epilepsy. Mapping language in children with epilepsy helps to localize the epileptogenic zone, and also, to predict the cognitive outcome of epilepsy surgery and possible cognitive rehabilitation. This review collected information about language representation and language mapping in pediatric epilepsy settings.

Etiology and Types of Seizures in Patients Presenting to a Tertiary Care Hospital in Karachi: A Cross-Sectional Study.

IntroductionEpilepsy is a burdensome disorder for affected individuals and community. There is limited data available on the epidemiological aspects of seizures in Pakistan and further research is necessary. We aimed to fill this gap by studying this information in epilepsy patients presenting to our neurology department. The purpose of this study is to evaluate the causes and types of seizures among the target population.MethodThis is a cross-sectional study conducted at the Department of Neurology, Dr. Ruth K.M. Pfau Civil Hospital Karachi. In this study we evaluated the causes and types of seizures among patients presenting to our department during the two-year study duration (January 2018-December 2019). Informed consent was taken. Detailed history was taken including features of seizure episodes, age at first seizure, family history and comorbid conditions. Relevant investigations were carried out. The data was compiled to deduce the relevant information using SPSS v20.0. T-test and Chi-square were used for analyzing the data.ResultsA total of 996 patients presented during the study duration. Primary seizures were found in 58% cases while secondary seizures were found in 42% cases. This distribution was more equal in children with 49.6% primary seizures and 50.4% secondary seizures; the gap widened in adults with 64.3% primary seizures and 35.7% secondary seizures. The most common cause of secondary seizures was neonatal encephalopathy which was present in 18.7% patients, followed by traumatic head injury in 18.2% patients. Central nervous system (CNS) infection was the cause in 17.9% patients, cerebral tumors in 14.1% patients, stroke in 11.5%, metabolic encephalopathy in 7.4%, febrile seizures in 6.5% and CNS malformations in 5.7% patients. The top three causes in children were neonatal encephalopathy (28.3%), CNS infections (19.3%) and febrile seizures (12.7%). Adults with secondary seizures were diagnosed most often with head trauma (25.2%), cerebral tumors (19.9%) and stroke (18.4%) as causative factors. The most common type of seizures was generalized onset tonic-clonic seizures which was found in 73.0% patients followed by focal to bilateral tonic-clonic seizures in 8.9% patients. Other types of seizures included focal aware seizures in 5.0%, mixed seizure types in 4.2%, focal impaired awareness seizures in 3.1%, absence seizures in 2.7%, myoclonic seizures in 2.0% and atonic seizures in 1.0% patients. Seizures in children were mostly generalized onset tonic-clonic seizures (75.4%), mixed seizure types (5.7%) and focal to bilateral tonic-clonic seizures (5.2%). In adults the three most common types corresponded to the overall result: generalized onset tonic-clonic seizures (71.2%), focal to bilateral tonic-clonic seizures (11.6%) and focal aware seizures (6.6%).ConclusionWe found that the most common cause of seizures overall in our study population was primary seizures, though primary and secondary seizures were more evenly present in children. Among secondary causes neonatal encephalopathy stood out as the most common cause in children; head trauma was the predominant cause in adults. Most common type of seizures overall and in adults was generalized onset tonic-clonic seizures, followed by focal to bilateral tonic-clonic and focal aware seizure types. Pediatric patients presented most often with generalized onset tonic-clonic seizures, followed by mixed seizure types and focal to bilateral tonic-clonic seizures.

Quantifying the burden of generalized tonic-clonic seizures in patients with drug-resistant epilepsy.

Compared to other seizure types, generalized tonic-clonic (GTC) seizures may be disproportionately related to increased morbidity, and reducing seizure frequency could translate into improvements across measures of morbidity in medically treated patients with drug-resistant epilepsy (DRE). The primary objective of this analysis was to quantify the burden of patients with DRE who experience GTC seizures (GTC+) compared to patients with DRE who do not experience GTC seizures (GTC-). Adult patients from the Cleveland Clinic Epilepsy Center-Neurological Institute from 2012-2016 with DRE with epilepsy for at least 1year were eligible for inclusion and were divided into GTC ±groups based on whether the patient had experienced a GTC seizure in the year preceding the first visit. Epilepsy duration, comorbidities, antiepileptic drug use, patient-reported outcomes (PROs) and seizure type, frequency, and etiology were captured. Generalized linear models, negative binomial regression, logistic regression, and linear regression were used as appropriate for multivariate analyses. A total of 379 patients met inclusion criteria and had data at 1-year follow-up after their baseline visit (192 GTC+and 187 GTC-). Although DRE patients experiencing GTC seizures had fewer seizures per day over the preceding 6 months than those not experiencing GTC seizures, seizure severity and levels of depression and anxiety were greater. GTC+patients who reported five or more seizures in the preceding 4 weeks had 82% lower odds (1-0.18=0.82) of working than patients with no seizures. Patients with DRE experience a significant burden and decreased quality of life. Multivariate analysis is necessary to understand the complex relationship between seizure type, frequency, and impact on health-related quality of life (HRQoL) and changes over time. Effective treatments to reduce the burden for DRE patients who experience GTC seizures continue to be needed.

Etiology and type of neonatal seizures

Background: Neonatal seizure is the most common disorder in neonate and the etiology varies among neonates. Materials and Methods: In total of 100 neonates less than 28 days with seizures are take into consideration and compared. Results: Among the 100 neonates Hypoxic Ischemic Encephalopathy was the most common cause followed by sepsis and metabolic causes. Subtle Seizures was the most common type followed by clonic and focal and myoclonic seizures. Discussion: The initial evaluation based on examination and etiology of seizures is important for pediatrician to assess for the treatment given. Conclusion: HIE is the most common cause of neonatal seizures. Subtle seizures are the most common type of neonatal seizures.

Evaluation of the Neonate with Seizures.

Neonatal seizures are common, occurring in 2 to 5 of 1,000 live births in the United States. The neonatal brain is thought to be predisposed toward seizures due to a combination of excessive excitatory and deficient inhibitory neuronal activity. The seizures tend to be focal or multifocal without secondary generalization, resulting in subtle seizure appearance. There are five main categories of neonatal seizures: focal clonic, focal tonic, myoclonic, subtle, and generalized tonic. An electroencephalogram is recommended to diagnose and treat neonatal seizures due to poor reliability of the clinical examination. Causes of neonatal seizures are broad, including trauma, structural brain anomalies, infections, metabolic disorders, drug withdrawal or intoxication, and neonatal epilepsy syndromes. Treatment of neonatal seizures involves management of cardiorespiratory status, correction of metabolic derangements, and antiepileptics as needed. The most common antiepileptics used in neonates are phenobarbital, levetiracetam, and fosphenytoin. The long-term risk of neurodevelopmental disability varies depending upon the etiology of neonatal seizures. Close attention to developmental milestones and neurology follow-up is recommended for all neonates with seizures. [Pediatr Ann. 2020;49(7):e292-e298.].

CLINICO-ETIOLOGICAL PATTERN OF NEONATAL SEIZURES

Background: Incidence of seizures is highest during the neonatal period, and it is considered a medical emergency that necessitate proper clinical and etiological assessment. Aim: This study aimed to focus on the etiological, clinical classification of neonatal seizures and proper assessment for appropriate diagnosis. Patients and methods: This prospective study was performed on 50 neonatal patients who developed neonatal seizures either prior or after admission to the NICU of Al-Hussein University Hospital and Sayed Galal University Hospital below the age of 28 days after an informed written consent from parents in the period between December 2018 and September 2019 Results: In this study, neonatal seizures were more common in males 27 (54%) than females 23(46%); their mean birth weight was 2748 grams. 40% of patients of the study were complaining of perinatal asphyxia evidenced by history of prolonged or instrumental labor, 11 babies (22%) with sepsis,6 babies (12%) with hypocalcemia, 6 babies (12%)with intraventricular hemorrhage, 3 babies (6%)with intracranial hemorrhage, 3 babies(6%) with kernicterus, one baby (2%) with metabolic disorder (Non ketotic hyperglycinemia ) . Many types of seizures are represented in our study with different ratios; out of which 18 (36%) had myoclonic seizures, 14(28%) had mixed, 8 (16%) babies had subtle, 4(8%) had clonic and 5(10%) had tonic types), and only 1(2%) baby had multifocal clonic fit. Conclusion: This study confirms that Hypoxic ischemic encephalopathy was most important etiology of neonatal seizures and most important risk factor for poor neurological outcome followed by sepsis, intraventricular hemorrhage, intracranial hemorrhage, kernicterus and metabolic respectively and most important risk factor for poor neurological outcome and myoclonic seizures being most common clinical type of seizure observed.

Genes Bound by ΔFosB in Different Conditions With Recurrent Seizures Regulate Similar Neuronal Functions.

Seizure incidence is increased in Alzheimer’s disease (AD) patients and mouse models, and treatment with the antiseizure drug levetiracetam improves cognition. We reported that one mechanism by which seizures can exert persistent effects on cognition is through accumulation of ΔFosB, a transcription factor with a long half-life. Even the infrequent seizures that spontaneously occur in transgenic mice expressing human amyloid precursor protein (APP) lead to persistent increases in ΔFosB in the hippocampus, similar to what we observed in patients with AD or temporal lobe epilepsy. ΔFosB epigenetically regulates expression of target genes, however, whether ΔFosB targets the same genes when induced by seizures in different neurological conditions is not clear. We performed ChIP-sequencing to assess the repertoire of ΔFosB target genes in APP mice and in pilocarpine-treated wildtype mice (Pilo mice), a pharmacological model of epilepsy. These mouse models allowed us to compare AD, in which seizures occur in the context of high levels of amyloid beta, and epilepsy, in which recurrent seizures occur without AD-specific pathophysiology. Network profiling of genes bound by ΔFosB in APP mice, Pilo mice, and respective control mice revealed that functional domains modulated by ΔFosB in the hippocampus are expanded and diversified in APP and Pilo mice (vs. respective controls). Domains of interest in both disease contexts involved neuronal excitability and neurotransmission, neurogenesis, chromatin remodeling, and cellular stress and neuroinflammation. To assess the gene targets bound by ΔFosB regardless of seizure etiology, we focused on 442 genes with significant ΔFosB binding in both APP and Pilo mice (vs. respective controls). Functional analyses identified pathways that regulate membrane potential, glutamatergic signaling, calcium homeostasis, complement activation, neuron-glia population maintenance, and chromatin dynamics. RNA-sequencing and qPCR measurements in independent mice detected altered expression of several ΔFosB targets shared in APP and Pilo mice. Our findings indicate that seizure-induced ΔFosB can bind genes in patterns that depend on seizure etiology, but can bind other genes regardless of seizure etiology. Understanding the factors that underlie these differences, such as chromatin accessibility and/or abundance of co-factors, could reveal novel insights into the control of gene expression in disorders with recurrent seizures.

Clinico-etiological profile of children admitted with seizures to a tertiary care hospital – A cross-sectional study

Background: Seizures are one of the common causes of hospitalization in children causing significant morbidity and mortality. Objective: The objective of the study was to study the clinico-etiological profile of children admitted with seizures. Materials and Methods: This cross-sectional study included 120 children admitted with seizures to the pediatric ward and pediatric intensive care unit of a teaching hospital over a period of 12 months. Clinically relevant history, demographic data, and laboratory investigations were obtained. Electroencephalogram (EEG) and magnetic resonance imaging (MRI) were done based on the clinical situation. Results: The sex-wise distribution of children showed an overall male predominance (male:female=1.3:1). The occurrence of convulsions was highest (60%) in the age group of 1–5 years. The majority of children had (81.7%) generalized tonic-clonic seizures. Febrile seizures (46.7%) were found to be the most common cause of seizures in children. This was followed by a seizure disorder in 19.2% and cerebral palsy in 15% of them. Conclusion: The etiology of seizures was identified in almost 94% of the cases through a detailed history, physical examination, laboratory workup, and with EEG and MRI studies as indicated. Thus, a thorough evaluation is recommended in every child presenting with seizures to understand the clinico-demographic profile and the etiology of seizures in children.

Intractable convulsion in critically ill children

Introduction: To determine the etiology of intractable convulsion, the outcome of intractable convulsions in pediatric patients and risk factors related to poor outcome. Material and methods: This case-control study conducted on 100 children where 50 patients who fulfilled the criteria for intractability admitted into pediatric intensive care unit (PICU) and 50 epileptic children on appropriately chosen antiepileptic drug (AED) with no seizures for more than 1 year who attending to the pediatric neurology clinic for follow up. Full history taking, examination, investigations performed for patients groups on admission and then followed up to six months for an outcome. Results: This study showed no significant difference between studied groups as regard age, sex, consanguinity and positive family history but noticed a highly statistically significant increase in prenatal problems (n; 20 patients), neonatal seizure (n; 15 patients), and postnatal problem (n; 10 patients) in intractable groups compared to controlled groups (p value 0.001).Delayed developmental history (n; 40 patients) was significantly higher among intractable groups compared to controlled groups (p value 0.001).Intractable groups had significantly increased in abnormal neurological examination than controlled groups (p value 0.001).History of prenatal problems, neonatal seizures, delayed developmental milestones, presence of underlying etiology of seizures, and abnormality findings in EEG and neuroimaging are risk factors for the intractability of convulsion. There was a significant relation between poor outcome and other studied variables including being female, presence of consanguinity, delayed developmental milestones, disturbed level of consciousness and secondary etiology of seizures (p value; 0.04, 0.003, 0.001, 0.001 0.001 respectively). Conclusion: The most common etiology of intractability in epileptic children is a secondary etiology of seizures. Early detection of risk factors for intractable epilepsy is important to decrease intractability complications. Proper perinatal care is important for decreasing prevalence of intractable epilepsy.