Neurodevelopmental outcomes in a cohort of Australian families with self-limited familial epilepsy of neonatal/infantile onset.

OBJECTIVES: To determine: i) seizure recurrence; ii) developmental disability; iii) co-morbidities and risk factors in self-limited familial neonatal and/or infantile epilepsy (SeLFE) in a multigenerational study. METHODS: Families were retrospectively recruited from epilepsy databases (2021-2022) in 2 paediatric hospitals, Sydney, Australia. Eligible families had 2 first degree relatives with seizures and underwent genetic testing. Demographics/clinical data were collected from interviews and medical records. Vineland Adaptive Behaviour Scales-Third Edition measured adaptive function. RESULTS: Fifteen families participated. Fourteen had a genetic diagnosis (93%): 11 pathogenic; PRRT2 (n=4), KCNQ2 (n=3), SCN2A (n=4), 3 likely pathogenic; KCNQ2 (n=1), SCN8A (n=2). Seizures affected 73 individuals (ages 1-76 years); 30 children and 20 adults had in-depth phenotyping. Ten of 50 individuals (20%) had seizure recurrence, aged 8-65 years. Median time from last neonatal/infantile seizure was 11.8/12.8 years. Predictors of recurrence were high seizure number (p=0.05) and longer treatment duration (p=0.03). Seven children had global developmental delay (GDD): mild (n=4), moderate (n=1) and severe (n=2). Vineland-3 identified 3 had low-average and 3 had mild-moderately impaired functioning. The majority (82%) were average. GDD was associated with older age at last seizure (p=0.03), longer epilepsy duration (p=0.02), and higher number of anti-seizure medications (p=0.05). Four children had speech delay, 5 (10%) had Autism Spectrum Disorder. Paroxysmal kinesiogenic dyskinesia (n=5) occurred in 4 families and hemiplegic migraine (n=8) in 3 families. CONCLUSIONS: Individuals with SeLFE have a small risk of recurrent seizures (20%) and neurodevelopmental disability. Significant predictors are higher seizure number and longer epilepsy duration. Developmental surveillance is imperative.

Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.

OBJECTIVE: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. METHODS: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. RESULTS: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. CONCLUSIONS: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

EpApp: Development and evaluation of a smartphone/tablet app for adolescents with epilepsy.

The study aimed to comprehensively evaluate a mobile application (EpApp), designed with stakeholder input, to educate and facilitate management of adolescents with epilepsy. A prospective cohort of adolescents with epilepsy (13-19 years) and their parent/carer participated between June 2015 and December 2016. Primary outcome measure was knowledge acquisition. Secondary outcomes were psychosocial variables (attitude towards illness and seizure self-efficacy) and clinical parameters (medication adherence, seizure burden). Functionality, design, content and app utility were appraised via survey and open-ended questions. 51 adolescents completed baseline surveys (mean age 14.49 years), 36 follow-up surveys. Both self and general epilepsy knowledge increased following intervention (p ≤ 0.005). Significantly fewer medication reminders were required during intervention (M = 2.93, p = .002) and follow-up (M = 3.54, p = .030) compared to baseline (M = 6.64). Measures of app design, content, functionality and utility were very favourable. There was no significant improvement in seizure burden, or psychosocial parameters. Educational page-visits reflected interests and concerns. This study demonstrates that EpApp increases knowledge and is engaging. The app is available free, internationally via Android/Apple platforms.

Exploring carer perceptions of training in out-of-hospital use of buccal midazolam for emergency management of seizures (2008-2012).

AIM: This study aims to explore carer perceptions of training in out-of-hospital use of buccal midazolam for emergency management of seizures. METHODS: A random sample of 100 families (from n = 198) who underwent training at the Sydney Children's Hospitals Network, Randwick campus (2008-2012) were invited to participate in a telephone questionnaire. RESULTS: Sixty-three carers participated. Thirty-three children were female, median age at training was 4 years and seizure onset 2.75 years. Seizures were generalised in 26 children and focal in 37. Common reasons for prescription included history of prolonged seizures (38%), recent diagnosis of epilepsy (33%) and overseas travel (11%). Ninety-eight per cent of carers reported that training instructions were clear, and 94% reported the risks of using benzodiazepines were satisfactorily explained. Ninety per cent felt confident to administer the drug following training and 62% completed first aid training as recommended. Suggestions for improvement included follow-up/review and additional demonstration/practice. Twenty-one carers (33%) reported giving buccal midazolam a median five times, 67% reported it was effective in terminating the seizure and 71% called an ambulance as instructed. Problems reported in administration included excessive secretions and difficulties drawing up the solution. One child experienced breathing difficulties requiring oxygen by the paramedics. Four children were admitted to children's intensive care unit with status epilepticus requiring intubation. CONCLUSIONS: Training for out-of-hospital use of buccal midazolam was considered valuable by carers. Only a third of the sample subsequently used midazolam. Half of these carers reported problems in administration and one reported respiratory difficulty. These results highlight the importance of drug safety and efficacious training programmes.

Caring for children and adolescents with epilepsy: creating an innovative electronic educational resource.

The majority of children and adolescents with epilepsy are managed in the community setting by general paediatricians. However, there is a paucity of practical, relevant information and standardised management documents assisting paediatricians. In the era of sub-specialisation, an electronic educational resource developed by specialists in epilepsy and paediatrics enhances the interface between tertiary and secondary/primary care. We aimed to create a website (www.pennsw.com.au) designed to optimise the care of all children and adolescents living with epilepsy and to assess its clinical usefulness. The site provides clinicians and families an aligned resource, including key information on epilepsy syndromes, medication usage and adverse effects, safety (sleep deprivation, water sports), driving, pregnancy, psychosocial impact of epilepsy and coping skills. General paediatricians and carers completed a questionnaire, utilising rating scales and open ended questions, to evaluate design, content and clinical usefulness. Forty-nine general paediatricians with a median 12 years of paediatric practice participated. Thirty-two carers participated. Epilepsy syndrome was focal in 59% of the children and generalised in 41%. The majority of participants (paediatricians: 84-100%, families: 69-100%) rated the website as well designed, practical, informative and clinically useful. General paediatricians considered the "Medication" pages and "Epilepsy Management Documents" as practically useful. Carers recorded the "Family Resources", seizure recording documents, the support information on mental health, and the "Coping with Epilepsy" segment as most informative. General paediatricians and carers highly valued the website, reflected by 120,000 page views in 12 months since its launch.

'Beyond Milestones': a randomised controlled trial evaluating an innovative digital resource teaching quality observation of normal child development.

AIMS: The study aimed to create and evaluate the educational effectiveness of a digital resource instructing paediatric trainees in a systematic approach to critical and quality observation of normal child development. METHODS: A digital educational resource was developed utilising the skills of an expert developmental paediatrician who was videoed assessing normal early child development at a series of critical stages. Videos illustrated aspects of language, sophistication of play and socialisation, cognition, and motor progress. Expert commentary, teaching text and summaries were used. A randomised controlled trial evaluated the resource. Paediatric trainees were recruited from The Sydney Children's Hospitals Network. Outcome measures were repeated at three time points (pre-teaching, immediate-post and 1 month) and included self-rated attitudes, knowledge of markers of development and observational expertise. Qualitative data on teaching usefulness were obtained through open-ended questions. RESULTS: Fifty-six paediatric trainees (registrar 79%, women 82%; mean age 31 years) completed the pre-assessment, 46 the immediate-post and 45 the 1-month follow-up (20% attrition). Compared with the Control group, the Teaching group scored higher over time on markers of development (P = 0.006), observational expertise (P < 0.0001), confidence (P = 0.035) and satisfaction (P < 0.0001). Teaching participants valued the video and expert commentary and reported improvement in confidence and understanding and acquiring a more structured approach. CONCLUSIONS: The 'Beyond Milestones' free online resource for medical professionals improves knowledge, increases confidence and is useful, providing a structured approach to developmental assessment. The techniques taught can be applied to every paediatric consultation.

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood.

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.

Personalised epilepsy education intervention for adolescents and impact on knowledge acquisition and psychosocial function.

AIM: Patients frequently have poor knowledge of epilepsy, and this is associated with low self-esteem in adolescence. There is a paucity of data determining whether education alone can improve psychosocial outcome. The study investigated whether an educational intervention in adolescence: 1 Increased understanding of epilepsy syndrome and general epilepsy knowledge. 2 Improved self-esteem, seizure self-efficacy and attitudes towards epilepsy. METHODS: In session 1, adolescents were educated about their epilepsy syndrome in a one-on-one session, producing a personalised epilepsy medical record. In session 2, the impact of epilepsy on life-style was discussed. Pre- and post-intervention measures of knowledge, self-esteem, seizure self-efficacy and attitudes towards epilepsy were completed using validated scales. Focus groups explored the intervention's value. RESULTS: Thirty adolescents with epilepsy participated (female: 24, male: 6; median age: 16 years; partial symptomatic epilepsy: 15, generalised idiopathic epilepsy: 15). Self-knowledge of syndrome (P < 0.0001), general knowledge of epilepsy (P < 0.0001), attitudes towards epilepsy (P= 0.008) and seizure self-efficacy (P= 0.049) improved. Focus group data indicated that sessions were enjoyable and valuable, and the medical record was helpful. CONCLUSIONS: The intervention significantly improved self-knowledge and general knowledge of epilepsy, attitudes towards epilepsy and seizure self-efficacy. This is the first study to demonstrate a positive impact on psychosocial outcomes following an educational intervention without a psychological component. The model has widespread application.

Teaching paediatric epilepsy to medical students: A randomised crossover trial.

AIM: Research has shown computerised tutorial to be as effective as face-to-face teaching in promoting knowledge acquisition. Subsequently, the clinician must synthesise and interpret data (clinical reasoning). This study extends previous research and compares the effectiveness of interactive lecture and computerised tutorial in promoting observational skills and clinical reasoning in the evaluation of paroxysmal events. METHODS: The modalities were compared through a randomised crossover trial teaching epilepsy to third and fourth year medical students. The content matter (history and video clip) and format were identical for each topic (Topic 1: altered awareness, Topic 2: movement and posturing) in both modalities (interactive lecture and computerised tutorial). Structured worksheets promoted and evaluated skills of observation and clinical reasoning. Responses in both domains were compared with gold standard qualitative scores. Participants rated modality preference and perceptions of teaching. RESULTS: One-hundred and fifty-seven medical students participated. Interactive lecture and computerised tutorial were both effective in promoting observational skills and clinical reasoning with no differences between modalities. Participants preferred the interactive lecture and rated it more enjoyable and effective. Twenty-five participants randomised to the computerised tutorial for Topic 1, elected to withdraw participation. Both modalities promoted interest and willingness to further learn. CONCLUSION: This is the first randomised crossover trial evaluating the teaching of clinical reasoning in comparative medical education research. Interactive lecturing and computerised tutorial were both effective in teaching observational skills and clinical reasoning. Interactive lecture is the preferred method, and may influence initial engagement in learning.

Voxel-based morphometry in the detection of dysplasia and neoplasia in childhood epilepsy: limitations of grey matter analysis.

The purpose of this exploratory investigation was to evaluate voxel-based morphometry (VBM) in detecting lesions underlying childhood epilepsy, and to establish the optimal image processing and statistical parameters in this context. The patients were 16 children (10 boys) aged 5.9 to 15.2 years (mean 11.3 years) with epilepsy and focal cortical dysplasia (FCD) or neoplasia. The control group comprised 24 normal children (12 boys), age matched to the patients. MRI volumes were spatially normalised to a custom template and segmented into grey matter (GM) and white matter. Using statistical parametric mapping, the GM segment from each patient was then contrasted with the mean GM segment of the control group utilising different VBM post-processing methods. Maps showing increased/decreased areas of GM concentration or volume were generated and compared with visually identified lesions. The results indicated that conservative VBM parameters of linear normalisation with no modulation produced the highest rates of lesion detection, which were identical for FCD and neoplasia at 5/8 lesions. These preliminary data suggest that VBM analysis of GM using conservative parameters can usually detect FCD and neoplasia in the MRI of children with epilepsy, but sensitivity may be inadequate for routine clinical application. Further refinement of the technique may be necessary.

Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

Teaching doctors how to diagnose paroxysmal events: a comparison of two educational methods.

OBJECTIVES: Two educational methods, facilitated case discussion and a computerised tutorial, were compared for teaching about childhood epilepsy. We used a comprehensive and clinically relevant assessment method to evaluate the hypothesis that a computerised tutorial more effectively increases knowledge acquisition than a facilitated case discussion. METHODS: Paediatric trainees (n = 66) were arbitrarily allocated to facilitated case discussion or computerised tutorial. The analysis of paroxysmal events was taught by the same teacher, using a standardised protocol and principles of active learning. Outcome measures included knowledge acquisition, clinical confidence and usefulness pre- and post-teaching, and at 3 months follow-up. RESULTS: Computerised tutorial participants scored significantly higher on knowledge acquisition post-teaching. There was gain in clinical confidence in both modalities post-teaching which did not differ between the groups. Confidence and knowledge were not related post-teaching. Both groups found the teaching relevant to clinical practice. However, facilitated case discussion participants rated the session as more enjoyable, and more useful in reinforcing and acquiring knowledge, and felt more motivated for further learning. At 3 months follow-up, participants in both modalities showed significant increases in knowledge acquisition, with no difference between modalities. CONCLUSIONS: The computerised tutorial more effectively imparted knowledge immediately post-teaching. However, facilitated case discussion is the preferred modality in terms of participant enjoyment and perceived usefulness.

Voxel-based morphometry in the detection of dysplasia and neoplasia in childhood epilepsy: combined grey/white matter analysis augments detection.

PURPOSE: Analysis of grey matter on MRI utilising voxel-based morphometry (VBM) may have insufficient sensitivity for routine clinical application. The aim of this exploratory study was to evaluate combined analysis of grey and white matter using VBM for detecting focal lesions underlying childhood epilepsy, and to establish the optimal statistical parameters in this context. METHODS: The patients were 16 children (10 boys) aged 5.9-15.2 years (11.3+/-2.8 years; mean+/-S.D.) with epilepsy and focal cortical dysplasia (FCD) or neoplasia. The control group comprised 24 normal children (12 boys), age matched to the patients. VBM was used to spatially normalise MRI volumes to a custom template and segment them into grey matter (GM) and white matter (WM). The combined GM/WM segments from each patient were contrasted with the control group. Three different VBM post-processing techniques of combined GM/WM were evaluated along with GM-only analysis. Maps showing increased/decreased GM or GM/WM concentration were generated and compared with visually identified lesions. Rates of detection and true/false positives voxels were calculated. RESULTS: The GM-only lesion detection rate was equal for FCD and neoplasia at 5/8, whereas the best combined GM/WM technique detected 8/8 FCD and 6/8 neoplasia. The combined technique also produced a higher overall rate of true positives (87%) than GM-only (44%) with a similar low rate of false positives. CONCLUSIONS: These preliminary data suggest that VBM is ineffective for precise delineation of lesion margins, but could potentially be used to detect subtle dysplasia in MRI negative and equivocal cases.

A triangulated approach to the assessment of teaching in childhood epilepsy.

BACKGROUND: A comprehensive methodology is needed to assess student teaching. The present study employed a triangulated approach evaluating participant perceptions of learning, critical reflection by the lecturer and peer observation to measure confidence, interest and usefulness of the subject matter. METHODS: Using an interactive lecturing style, seven teaching sessions were delivered to medical students and junior doctors. Rating scales, open-ended questions and focus group discussions evaluated participant perceptions. Critical reflections and observations were made by the lecturer and independent learning consultants. RESULTS: Seventy per cent of participants rated the lecture on the highest scale for usefulness and interest. There was a significant post-lecture increase in clinical confidence in seizure identification (p < 0.0005). Open-ended questions showed that videos were most useful (81/149) and interesting (109/149), and that the presentation of the syndromal classification provided a useful approach (114/149). Focus group discussion, lecturer and peer observation cross-validated these findings and highlighted the importance of expert commentary to the videos and the clinical relevance of material.

Memory and phonological awareness in children with Benign Rolandic Epilepsy compared to a matched control group.

PURPOSE: In a previous study we demonstrated children with Benign Rolandic Epilepsy have normal intelligence and language ability. However, difficulties in verbal and visual memory and aspects of phonological awareness were found compared to normative data. To address the methodological limitations related to the use of normative data, we compared the same cohort of children with Benign Rolandic Epilepsy to a matched control group. METHOD: Controls (n=40) matched on age and gender to the Benign Rolandic Epilepsy cohort underwent neuropsychological assessment. The life functioning of the control group was assessed using a modified version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). RESULTS: The study confirmed the previous findings of memory and phonological awareness difficulties. In addition, the children with Benign Rolandic Epilepsy had significantly lower IQ scores than the matched control group. Paired sample t-tests showed that on 8 of 11 QOLCE scales, children with Benign Rolandic Epilepsy were rated by parents as having poorer life functioning compared to matched controls, including lower parental ratings on the subscales of memory and language. DISCUSSION: Benign Rolandic Epilepsy has an excellent seizure prognosis, but this study further emphasizes potential cognitive difficulties. Using an age and gender matched control group, the previous findings of memory and phonological awareness difficulties were validated. These problems in cognition were also identified by parents of children with Benign Rolandic Epilepsy as problematic and impacting upon the child's quality of life.

Longitudinal assessment of neuropsychologic and language function in children with benign rolandic epilepsy.

Previous studies of benign rolandic epilepsy have reported improvement in cognitive functioning over time. Their focus was the impact of paroxysmal electroencephalographic (EEG) activity on neuropsychologic function. Comprehensive longitudinal language assessment has not previously been undertaken. In a cross-sectional study, we demonstrated that some children with benign rolandic epilepsy have difficulties in verbal and visual memory and phonologic awareness. The current study evaluated a subgroup longitudinally to determine if difficulties improved. Twenty-eight patients underwent comprehensive longitudinal neuropsychologic and language assessments. The clinical features evaluated included seizure frequency, absolute age, medications, and a follow-up EEG. Differences in performance were analyzed using t-tests. Improvement in cognitive functioning, particularly in the areas of verbal memory, receptive language ability, and phonemic manipulation, was demonstrated. Visual memory and aspects of phonologic awareness showed no change. The improvements were not related to the clinical variables. It is important to recognize cognitive difficulties in children with benign rolandic epilepsy. Some difficulties can resolve; however, continued monitoring, particularly in areas of visual memory and phonologic awareness, is required.

Quality of life of children with benign rolandic epilepsy.

The first objective of this study was to determine the quality of life of children with benign rolandic epilepsy. Secondly, this investigation aimed to predict the influence of cognition on quality of life, controlling for the emotional impact of the epilepsy on the parent. Initial recruitment was through the major electroencephalography laboratories of metropolitan Sydney. The syndrome was defined using the International League Against Epilepsy classification. Patients underwent a comprehensive cognitive assessment, and parents completed the Child Health Questionnaire, Child Behavior Checklist, and Quality of Life in Childhood Epilepsy Questionnaire. Parental emotional impact was assessed using a subscale from the Child Health Questionnaire. The cohort included 30 patients (22 males, 8 females), mean age 9.67 years. There was a higher incidence of competence problems compared with normative data. The average psychosocial score was significantly lower than normative data. Controlling for parental emotional impact, general intellectual ability predicted quality of life in the areas of self-esteem and language. Clinical variables had minimal impact and were not included in the regression models. Parental emotional impact, however, was a major independent predictor of quality of life. Quality of life may be compromised in children with benign rolandic epilepsy and is related to cognitive variables and emotional impact of the epilepsy on the parent.

The neuropsychological and language profile of children with benign rolandic epilepsy.

PURPOSE: Benign rolandic epilepsy (BRE) has an excellent prognosis for seizures, but recent research has raised concerns using cognition as an outcome measure. Methodologic problems related to recruitment bias and assessment processes are evident in previous studies. With well-defined criteria for inclusion and comprehensive assessment, the aim of this study was to define the cognitive profile of children with BRE and to assess the effect of interictal EEG activity. METHODS: Patients (n=42) were recruited from six EEG laboratories. The EEG features analyzed were spike frequency, trains, and laterality. Comprehensive neuropsychological and language assessments were conducted. Group means on cognitive measures were compared with normative means. Tests were correlated with EEG features. RESULTS: The study demonstrated that children with BRE have normal intelligence and language ability. However, a specific pattern of difficulties in memory and phonologic awareness was found. Furthermore, a large proportion of children had disproportionate scores in these areas compared with intellectual and language ability. EEG features were minimally associated with cognitive difficulties, and no correlation was found with memory indices and tests of phonologic awareness. CONCLUSIONS: Some children with BRE have specific difficulties in memory and phonologic processing skills, not explained by interictal activity. We recommend that pediatricians ask about academic performance specifically in areas of prereading, reading, spelling, and memory. If difficulties are suspected, assessment targeting phonologic awareness and memory are recommended, as they may not be reflected in overall intellectual and language ability. Difficulties in phonologic awareness affect literacy, and memory problems affect academic performance.

Spike morphology, location, and frequency in benign epilepsy with centrotemporal spikes.

The literature on benign epilepsy with centrotemporal spikes reports a constellation of neurophysiologic features in selected populations with heterogeneous methodologies. The aim of this study was to determine the specific electroencephalographic (EEG) features (spike morphology, location, and frequency and associated background slowing) in a broad population-based cohort identified through EEG laboratories. The mean spike frequency in the awake state was 9.3 per minute (95% confidence interval 6.5-12.0), in drowsiness, 21.2 per minute (16.7-25.6); and in sleep, 45.6 per minute (38.3-52.8), where 60% of patients had > 40 discharges per minute. In five patients, spike train rates occupied > 80% of the sleep record, and in nine patients, they occupied 61% to 80%. An ambulatory overnight record did not add new information comparing early-onset sleep with a mean spike frequency of 37.1 per minute (27.3-46.9) with slow-wave sleep, 36.0 per minute (27.3-44.7). Patients with benign epilepsy with centrotemporal spikes have a high spike burden, which can impact on cognitive function.