Population-based study of rare epilepsy incidence in a US urban population.

OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

Creating rare epilepsy cohorts using keyword search in electronic health records.

OBJECTIVE: Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an alternative method for rare epilepsy cohort creation using electronic health records data. METHODS: Data included clinical notes from encounters with International Classification of Diseases, Ninth Revision (ICD-9) codes for seizures, epilepsy, and/or convulsions during 2010-2014, across six health care systems in New York City. We identified cases with rare epilepsies by searching clinical notes for keywords associated with 33 rare epilepsies. We validated cases via manual chart review. We compared the performance of keyword search to manual chart review using positive predictive value (PPV), sensitivity, and F-score. We selected an initial combination of keywords using the highest F-scores. RESULTS: Data included clinical notes from 77 924 cases with ICD-9 codes for seizures, epilepsy, and/or convulsions. The all-keyword search method identified 6095 candidates, and manual chart review confirmed that 2068 (34%) had a rare epilepsy. The initial combination method identified 1862 cases with a rare epilepsy, and this method performed as follows: PPV median = .64 (interquartile range [IQR] = .50-.81, range = .20-1.00), sensitivity median = .93 (IQR = .76-1.00, range = .10-1.00), and F-score median = .71 (IQR = .63-.85, range = .18-1.00). Using this method, we identified four cohorts of rare epilepsies with over 100 individuals, including infantile spasms, Lennox-Gastaut syndrome, Rett syndrome, and tuberous sclerosis complex. We identified over 50 individuals with two rare epilepsies that do not have specific ICD-10 codes for cohort creation (epilepsy with myoclonic atonic seizures, Sturge-Weber syndrome). SIGNIFICANCE: Keyword search is an effective method for cohort creation. These findings can improve identification and surveillance of individuals with rare epilepsies and promote their referral to specialty clinics, clinical research, and support groups.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Decreased Electroencephalographic Alpha Power During Anesthesia Induction Is Associated With EEG Discontinuity in Human Infants.

BACKGROUND: Electroencephalogram (EEG) discontinuity can occur at high concentrations of anesthetic drugs, reflecting suppression of electrocortical activity. This EEG pattern has been reported in children and reflects a deep state of anesthesia. Isoelectric events on the EEG, a more extreme degree of voltage suppression, have been shown to be associated with worse long-term neurologic outcomes in neonates undergoing cardiac surgery. However, the clinical significance of EEG discontinuities during pediatric anesthesia for noncardiac surgery is not yet known and merits further research. In this study, we assessed the incidence of EEG discontinuity during anesthesia induction in neurologically normal infants and the clinical factors associated with its development. We hypothesized that EEG discontinuity would be associated with sevoflurane-induced alpha (8-12 Hz) power during the period of anesthesia induction in infants. METHODS: We prospectively recorded 26 channels of EEG during anesthesia induction in an observational cohort of 54 infants (median age, 7.6 months; interquartile range [IQR] [4.9-9.8 months]). We identified EEG discontinuity, defined as voltage amplitude <25 microvolts for >2 seconds, and assessed its association with sevoflurane-induced alpha power using spectral analysis and multivariable logistic regression adjusting for clinically important variables. RESULTS: EEG discontinuity was observed in 20 of 54 subjects (37%), with a total of 25 discrete events. Sevoflurane-induced alpha power in the posterior regions of the head (eg, parietal or occipital regions) was significantly lower in the EEG discontinuity group (midline parietal channel on the electroencephalogram, International 10-20 System [Pz]; 8.3 vs 11.2 decibels [dBs]; P = .004), and this association remained after multivariable adjustment (adjusted odds ratio [aOR] = 0.51 per dB increase in alpha power [95% CI, 0.30-0.89]; P = .02). There were no differences in the baseline (unanesthetized) EEG between groups in alpha power or power in any other frequency band. CONCLUSIONS: We demonstrate that EEG discontinuity is common during anesthesia induction and is related to the level of sevoflurane-induced posterior alpha power, a putative marker of cortical-thalamic circuit development in the first year of life. This association persisted even after adjusting for age and propofol coadministration. The fact that this difference was only observed during anesthesia and not in the baseline EEG suggests that otherwise hidden brain circuit properties are unmasked by general anesthesia. These neurophysiologic markers observed during anesthesia may be useful in identifying patients who may have a greater chance of developing discontinuity.

Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

OBJECTIVE: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. METHODS: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. RESULTS: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. SIGNIFICANCE: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.

Predictors of SUDEP counseling and implications for designing interventions.

OBJECTIVE: We aimed to describe how often and why clinicians counsel people with epilepsy about sudden unexpected death in epilepsy (SUDEP). Understanding counseling gaps can help design interventions. METHODS: We searched clinical notes of 77,924 patients from 2010 to 2014 from six hospitals to find examples of SUDEP counseling and seizure safety counseling. Visits were coded for patient, clinician, and visit factors, and documented reasons for counseling. We evaluated factors associated with SUDEP vs. seizure safety counseling, and reasons for counseling using bivariate and multivariable statistics. Reasons for counseling included: poor medication adherence, lifestyle factors (e.g., poor sleep, drinking alcohol), patient/family reluctance to make recommended medication adjustment, epilepsy surgery considerations, and patient education only. RESULTS: Analysis was restricted to two of six hospitals where 91% of counseling occurred. Documentation of SUDEP counseling was rare (332 of 33,821 patients, 1.0%), almost exclusively by epileptologists (98.5% of counseling), and stable over time, X2 (4, n = 996) = 3.81, p = 0.43. Adult neurologists were more likely to document SUDEP counseling than pediatric (OR = 1.65, 95% CI = 1.12-2.44). Most SUDEP counseling was documented with a goal of seizure reduction (214 of 332, 64.5%), though some was for patient education only (118 of 332, 35.5%). By the time SUDEP counseling was documented, the majority of patients had refractory epilepsy (187 of 332, 56.3%) and/or a potentially modifiable risk factor (214 of 332, 64.5%). Neurologists with more years of clinical experience (OR = 2.18, 95% CI = 1.12-4.25) and more senior academic titles (OR = 2.25, 95% CI = 1.27-3.99) were more likely to document SUDEP counseling for patient education only. People with ≥2 anti-seizure medications (ASM) were more likely to receive counseling for patient education (OR = 2.72, 95% CI = 1.49-4.97). CONCLUSIONS: Documentation of SUDEP is rare, and varies by clinician, hospital, and patient factors. Efforts to increase SUDEP counseling should focus on junior clinicians, and emphasize starting the conversation soon after onset of epilepsy.

Electroencephalographic assessment of infant spinal anesthesia: A pilot prospective observational study.

INTRODUCTION: Spinal anesthesia is utilized as an alternative to general anesthesia in infants for some surgeries. After spinal anesthesia, infants often become less conscious without administration of sedative medications. The aim of this study was to assess electroencephalographic (EEG) correlates after spinal anesthesia in a cohort of infants. PATIENTS AND METHODS: This pilot study included 12 infants who underwent spinal anesthesia. Unprocessed electroencephalography was recorded. The electroencephalogram was interpreted by four neurologists. Processed analyses compared electroencephalogram changes 30 min after spinal anesthesia to baseline. RESULTS: Following spinal anesthesia, all 12 infants became sedated. Electroencephalography in all 12 demonstrated Stage 2 sleep with the appearance of sleep spindles (12-14 Hz) in the frontal and central leads in 8/12 (67%) of subjects. The median time to onset of sleep spindles was 24.7 interquartile range (21.2, 29.9) min. The duration of sleep spindles was 25.1 interquartile range (5.8, 99.8) min. Voltage attenuation and background slowing were the most common initial changes. Compared to baseline, the electroencephalogram 30 min after spinal anesthesia showed significantly increased absolute delta power (p = 0.02) and gamma power (p < 0.0001); decreases in beta (p = 0.0006) and higher beta (p < 0.0001) were also observed. The Fast Fourier Transform power ratio difference for delta/beta was increased (p = 0.03). Increased coherence was noted in the delta (p = 0.02) and theta (p = 0.04) bandwidths. DISCUSSION: Spinal anesthesia in infants is associated with increased electroencephalographic slow wave activity and decreased beta activity compared to the awake state, with appearance of sleep spindles suggestive of normal sleep. The etiology and significance of the observed voltage attenuation and background slowing remains unclear. CONCLUSIONS: The EEG signature of infant spinal anesthesia is distinct from that seen with general anesthesia and is consistent with normal sleep. Further investigation is required to better understand the etiology of these findings. Our preliminary findings contribute to the understanding of the brain effects of spinal anesthesia in early development.

Electroencephalographic Findings and Clinical Behavior During Induction of Anesthesia With Sevoflurane in Human Infants: A Prospective Observational Study.

Seizures and interictal epileptiform discharges (IEDs) have been described during sevoflurane. We prospectively estimated their incidence in 54 otherwise neurologically healthy infants by obtaining the full-head video electroencephalogram (EEG). No infants had clinical seizures, but 1 had an electrographic seizure; 3 others had focal IEDs (7.4%; 95% confidence interval [CI], 2.1%-17.9%). We detected no differences in demographic or clinical characteristics between normal and abnormal EEG groups. Diffuse slowing was the most common initial EEG change followed by fast (α, ß) activity in all head leads. Larger studies with more statistical power are needed to further investigate the hypotheses generated with this research.

Automated detection of sudden unexpected death in epilepsy risk factors in electronic medical records using natural language processing.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). We evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability. METHODS: Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, we identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, we identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, we removed three "boilerplate" standard text phrases from away notes and repeated performance. RESULTS: We observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data. SIGNIFICANCE: Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. Our methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling.

Multicenter Assessment of Sturge-Weber Syndrome: A Retrospective Study of Variations in Care and Use of Natural History Data.

BACKGROUND: We summarize the history of individuals with Sturge-Weber syndrome (SWS) to inform clinical trial design and identify variations in care. METHODS: We performed retrospective chart review of individuals with SWS from centers in New York City. We characterized data quality using a novel scoring system. For 13 clinical concepts, we evaluated if data were present and if they were of high quality. RESULTS: We included 26 individuals with SWS (58% female; median age at initial visit 7 years; absolute range 1 month to 56 years]). Twenty-two had nevus flammeus, 13 glaucoma, four homonymous hemianopia, and 15 hemiparesis. Nineteen of 21 had at least one confirmed seizure with a known first seizure date, all before 24 months. Most (18 of 26, 69%) epilepsy was controlled. A plurality (10 of 23, 43%) had either normal cognitive function or mild cognitive delays. Aspirin use varied by site (P = 0.02)-at four sites, use was 0% (zero of three), 0% (zero of four), 80% (four of five), and 64% (nine of 14). Data were present for more than 75% of cases for 11 of 13 clinical concepts (missing: age of diagnosis, age of glaucoma onset). There were gaps in level of detail for motor impairments, glaucoma severity, seizure history, cognition, and medication history. CONCLUSIONS: Clinical charts have important gaps in the level of detail around core SWS clinical features, limiting value for some natural history studies. Any clinical trial in SWS designed to prevent epilepsy should begin in the first year of life. Variations in use of aspirin suggest de facto clinical equipoise and warrant a comparative effectiveness study.

Application of the International League Against Epilepsy Neonatal Seizure Framework to an international panel of medical personnel.

OBJECTIVE: The International League Against Epilepsy (ILAE) Neonatal Seizure Framework was tested by medical personnel. METHODS: Attendees at the 2016 ILAE European Congress on Epileptology in Prague, the International Video-EEG Course in Pediatric Epilepsies in Madrid 2017, and a local meeting in Utrecht 2018, were introduced to the proposed ILAE neonatal classification system with teaching videos covering the seven types of clinical seizures in the proposed neonatal classification system. Five test digital video recordings of electroencephalography (EEG)-confirmed motor neonatal seizures were then shown and classified by the rater based on their knowledge of the proposed ILAE Neonatal Seizure Framework. A multi-rater Kappa statistic was used to assess the agreement between observers and the true diagnosis. RESULTS: The responses of 194 raters were obtained. There was no single predominant classification system that was currently used by the raters. Using the ILAE framework, 78%-93% of raters correctly identified the clinical seizure type for each neonate; the overall inter-rater agreement (Kappa statistic) was 0.67. The clonic motor seizure type was most frequently accurately identified (93% of the time; κ = 0.870). EEG technicians correctly identified all presented motor seizure types more frequently than any other group (accuracy = 0.9). SIGNIFICANCE: The ILAE Neonatal Seizure Framework was judged by most raters to be better than other systems for the classification of clinical seizures. Among all seizure types presented, clonic seizures appeared to be the easiest to accurately identify. Average accuracy across the five seizure types was 84.5%. These data suggest that the ILAE neonatal seizure classification may be used by all healthcare professionals to correctly identify the predominant clinical seizure type.

Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

BACKGROUND AND OBJECTIVES: Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response. METHODS: The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response. RESULTS: Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy. DISCUSSION: Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.

Recurrence of childhood absence epilepsy as pyknolepsy in adolescence.

A developmentally normal adolescent boy with a history of childhood absence epilepsy presented with recurrence of pyknolepsy after a seven-year period of remission. The characteristics of his EEG showed the same 3-Hz generalised spike-wave discharge as in his previous EEG in childhood. To our knowledge, this is the first case report describing recurrence of childhood absence epilepsy as pyknolepsy in an adolescent. [Published with video sequences].

Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort.

OBJECTIVE: Compare the effectiveness of initial treatment for infantile spasms. METHODS: The National Infantile Spasms Consortium prospectively followed children with new onset infantile spasms that began at age 2-24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations. RESULTS: Freedom from treatment failure rates were: ACTH 88/190 (46%), oral steroids 42/95 (44%), vigabatrin 32/87 (37%), and non-standard therapy 4/51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% CI 34-54]). Changing from non-standard therapy to ACTH would improve response from 8% to 39 [17-67]%, and to oral steroids from 8% to 38 [15-68]%. There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42 [15-75]%), vigabatrin to oral steroids (29% to 42 [28-57]%), and non-standard therapy to vigabatrin (8% to 20 [6-50]%). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p<0.05) CONCLUSION: Compared to non-standard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between ACTH / oral steroids and non-standard therapy, though the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children with new onset infantile spasms, ACTH or oral steroids were superior to non-standard therapies.

Management of Infantile Spasms During the COVID-19 Pandemic.

Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.

Neonatal seizures: Is there a relationship between ictal electroclinical features and etiology? A critical appraisal based on a systematic literature review.

The aim of this study was to evaluate whether specific etiologies of neonatal seizures have distinct ictal electroclinical features. A systematic review of English articles using the PubMed database since 2004 (last update 9/26/16). Search terms included text words and Medical Subject Headings (MeSH) terms related to neonatal seizures. Eligible articles included reports of neonates with seizures with a full description of seizure semiology and electroclinical findings. Independent extraction of data was performed by 2 authors using predefined data fields, including study quality indicators. Data were collected for every individual patient described in the articles. The dataset was analyzed with the Fisher exact test. The initial search led to 8507 titles; using filters, 2910 titles and abstracts were identified, with 177 full texts selected to be read. Fifty-seven studies were included in the analysis with 151 neonates (37.7 male and 62.9% term). Genetic etiologies (51%) and sequential seizures (41.1%) predominated in this sample and hypoxic-ischemic encephalopathy (HIE) accounted for only 4%. The low prevalence of HIE observed was probably due to a publication bias. A significant association was found between etiology and seizure type: hemorrhage with autonomic seizures (P = 0.003), central nervous system (CNS) infection and stroke with clonic seizures (P = 0.042, P < 0.001, respectively), metabolic/vitamin-related disorders, and inborn errors of metabolism with myoclonic seizures (P < 0.001). There were also specific electroencephalography (EEG) patterns seen with certain etiologies: vascular disorders and electrolyte imbalance with focal ictal discharges (P < 0.001, P = 0.049 respectively), vitamin-related disorders with multifocal (P = 0.003), and all categories of genetic disorders with burst-suppression (P < 0.001). Clonic and autonomic seizures were more frequently present with focal EEG abnormalities (P = 0.001 and P < 0.001), whereas tonic and myoclonic seizures present with burst-suppression (P = 0.001, P = 0.005). In conclusion, our data suggest that specific associations of etiologies of neonatal seizures with distinct clinical features and EEG patterns might help in the decision to establish appropriate treatment.