Niemann-Pick disease type C (NPC) is a neurovisceral lysosomal storage disorder with a great variation in clinical spectrum and age at presentation. Clinical features of 10 NPC patients who presented in the newborn period between 1993 and 2015 at our center were retrospectively analyzed. Males and females were equally distributed; there was a history of parental consanguinity (n = 8) and first-degree relative with NPC (n = 3). Patients were symptomatic between 1 and 10 days (mean 3.6 ± 2.6 days). Age at diagnosis was between 1 and 30 days (mean 14.6 ± 13.3 days). Laboratory work-up included bone marrow aspiration (n = 8) and/or filipin staining (n = 4). Confirmation was done by molecular analysis, indicating NPC1 (n = 8) and NPC2 (n = 2) mutations. All patients had neonatal cholestasis and hepatosplenomegaly. Pulmonary involvement (n = 9) and fetal ascites (n = 2) were additional accompanying features. All but one died due to pulmonary complications (n = 6) and liver insufficiency (n = 3) between 1.5 and 36 months of age (mean 8.1 ± 10.8 months). Currently, one patient is alive at the age of 11 months without any neurological deficit.
CONCLUSIONS: Neonatal presentation is a rare form of NPC with exclusively visceral involvement in the newborn period and poor prognosis leading to premature death due to pulmonary complications and liver failure. What is known: • Neonatal presentation is a rare form of NPC with exclusively visceral involvement in the newborn period and poor prognosis leading to premature death. • Progressive liver disease is the most common cause of death among neonatal-onset NPC patients. What is new: • Natural course of neonatal-onset NPC may show variations. • Pulmonary involvement should be considered as an important cause of death in neonatal-onset cases, and appropriate precautions should be taken to prevent complications of respiratory insufficiency and airway infections.
Pick Disease of the Brain (2), Hepatic Insufficiency (1), Respiratory Insufficiency (1), more mentions
AIM: This study examined cross-sectional population-based rates in reported need and unmet need for occupational, physical, and speech therapy services in children with autism spectrum disorder (ASD) compared with children with attention-deficit-hyperactivity disorder (ADHD) and cerebral palsy (CP).
METHOD: The 2005-2006 and 2009-2010 (USA) National Survey of Children with Special Health Care data sets were used to compare therapy need and unmet need among children younger than 18 years with ASD (n=5178), ADHD (n=20 566), and CP (n=1183). Bivariate approaches and multivariate logistic regression using imputed data were used to identify associations between child and family characteristics, and access to therapy services.
RESULTS: After adjusting for other variables, children with ASD had a significantly greater likelihood of having an unmet therapy need compared with children with ADHD (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.36-2.03), but a similar unmet need as children with CP (OR 1.30, 95% CI 0.97-1.74). Factors associated with unmet need included survey year, younger child age, no health insurance, and increased functional and behavioral difficulties.
INTERPRETATION: Children in our sample had greater unmet therapy needs in 2009 than in 2005. Caregiver-reported reasons for unmet need included cost and school resources. Research examining future trends in therapy access are warranted for children with ASD and CP.
Neuroscience (9) Cerebral Palsy (6), Attention Deficit Disorder with Hyperactivity (3), Autism Spectrum Disorders (2), more mentions
OBJECTIVE: To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age.
METHODS: From 2006-2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs. Brain magnetic resonance imaging (MRI) was assessed using a 0-11 severity score. Postneonatal seizures, epilepsy rates, and AED treatments were documented. One hundred thirty-four survivors were assessed at 18-24 months; adverse outcome was defined as death or Bayley III composite Cognition/Language or Motor scores <85 and/or severe cerebral palsy or severely reduced vision/hearing. Epilepsy rates in 103 children age 4-8 years were also documented.
RESULTS: aEEG confirmed seizures occurred precooling in 77 (57%) 151 of neonates; 48% had seizures during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18-24 months, one third of infants had an adverse outcome including 11% mortality. At 2 years, 8 (6%) infants had an epilepsy diagnosis (ILAE definition), of whom 3 (2%) received AEDs. Of the 103 4- to 8-year-olds, 14 (13%) had developed epilepsy, with 7 (7%) receiving AEDs. Infants/children on AEDs had higher MRI scores than those not on AEDs (median [interquartile range] 9 [8-11] vs. 2 [0-4]) and poorer outcomes. Nine (64%) of 14 children with epilepsy had cerebral palsy compared to 13 (11%) of 120 without epilepsy, and 10 (71%) of 14 children with epilepsy had adverse outcomes versus 23 (19%) of 120 survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity precooling, and MRI scores predicted childhood epilepsy.
SIGNIFICANCE: We report, in a regional cohort of infants cooled for perinatal asphyxia, 6% with epilepsy at 2 years (2% on AEDs) increasing to 13% (7% on AEDs) at early school age. These AED rates are much lower than those reported in the cooling trials, even with adjusting for our cohort's milder asphyxia. Long-term follow-up is needed to document final epilepsy rates.
Neurological and Central Nervous System Diseases (16), Neuroscience (1) Epilepsy (16), Seizures (6), Asphyxia (3), more mentions
OBJECTIVE: This study examined services used by young children with autism spectrum disorder (ASD) and factors associated with use.
METHODS: A retrospective observational study was conducted with baseline data for toddlers (under age three) and preschoolers (three to less than six years) with ASD enrolled in the Autism Speaks Autism Treatment Network registry from 2008 to 2013 (N=2,804). Parents' reports at enrollment of services received by children were documented. Factors associated with service use and with hours per week of services used were identified by multiple regression analyses.
RESULTS: At baseline, 79% of children had received at least one service; 28% had received behavioral services. In the sample, less than 30% of children who received at least one service spent more than ten hours per week in any service use. Children who received services were more likely to be of white race and to have had an ASD diagnosis prior to registry enrollment. Age, previous ASD diagnosis, maternal education, and child's IQ were significantly associated with the use of behavioral services; IQ was negatively associated with use. A consistent trend toward greater use of behavioral services was found over the study period. Factors associated with hours of any services used per week included age, gender, race, maternal education, and clinical characteristics. The predicted average weekly service hours for children with ASD across registry sites ranged from 3.1±1.0 to 9.5±2.1.
CONCLUSIONS: Service use varied according to child, family, and system characteristics. More efforts should be focused on early intervention and on children with ASD who have low socioeconomic status and cognitive disability.
OBJECTIVE: To evaluate whether frontal-lobe magnetic resonance spectroscopy measures of γ-aminobutyric acid (GABA) would be altered in a sample of adolescents scanned after sport concussion because mild traumatic brain injury is often associated with working memory problems.
METHODS: Eleven adolescents (age 14-17 years) who had sustained a first-time sport concussion were studied with MRI/magnetic resonance spectroscopy within 23 to 44 days after injury (mean 30.4 ± 6.1 days). Age- and sex-matched healthy controls, being seen for sports-related injuries not involving the head and with no history of concussion, were also examined. GABA/creatine + phosphocreatine (Cre) was measured in left-sided frontal lobe and central posterior cingulate regions. The frontal voxel was positioned to overlap with patient-specific activation on a 1-back working memory task.
RESULTS: Increased GABA/Cre was shown in the frontal lobe for the concussed group. A decreased relationship was observed in the parietal region. High correlations between GABA/Cre and task activation were observed for the control group in the frontal lobe, a relationship not shown in the concussed participants.
CONCLUSIONS: GABA/Cre appears increased in a region colocalized with working memory task activation after sport concussion. Further work extending these results in larger samples and at time points across the injury episode will aid in refining the clinical significance of these observations.
BACKGROUND: Age is a frequent consideration for surgical timing in pediatric craniofacial surgery for optimal psychosocial development. However, systematic evaluations of the effects of age in children under active treatment have not been thoroughly evaluated.
METHODS: Ninety-nine patients (age, 8 to 17 years; 46.5 percent male) from the University of California, Los Angeles, Craniofacial Clinic were prospectively evaluated using the Pediatric Patient-Reported Outcomes Measurement Information System to assess anger, anxiety, depression, and quality of peer relationships. Patients were stratified into three age groups by years: group A, 8 to 10 years, n = 30; group B, 11 to 13 years, n = 41; and group C, 14 to 17 years, n = 28. Analyses of variance and logistic regression analyses were performed.
RESULTS: Significant differences in anxiety (F2,96 = 5.1; p = 0.008), depression (F2,96 = 9.7; p < 0.001), peer relationships (F2,96 = 3.5; p = 0.03), and anger (F2,96 = 4.9; p = 0.009) were found among the age groups. Group A demonstrated the highest anxiety, highest depression, and lowest peer relationship scores overall. Although there were no differences in anger between groups A and C, group B had the lowest anger scores. Children with poor scores of higher severity, defined as greater than 1 SD worse than the national mean, were compared. Group A contributed the highest percentages of more severely affected children in all categories. A logistic regression analysis demonstrated that group A was a statistically significant predictor for scores of higher severity in both anxiety (OR, 3.8; 95 percent CI, 1.3 to 11.5; p = 0.02) and peer relationships (OR, 3.4; 95 percent CI, 1.3 to 9.3; p = 0.02).
CONCLUSIONS: Children between 8 and 10 years of age with craniofacial anomalies constitute a high-risk subset for psychosocial dysfunction. The authors' work suggests that tight surveillance with family and school awareness may be necessary for this age group.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
BACKGROUND: Findings are mixed on the relationship between attention-deficit hyperactivity disorder (ADHD) and younger relative age in the school year. We aimed to investigate whether relative age is associated with ADHD diagnosis in a country where prescribing rates are low and whether any such association has changed over time or relates to comorbid disorders (eg, conduct disorder [CD], oppositional defiant disorder [ODD], or learning disorder [LD]).
METHODS: We used nationwide population-based registers to identify all Finnish children born between Jan 1, 1991, and Dec 31, 2004, who were diagnosed with ADHD from age 7 years onwards (age of starting school). We calculated incidence ratios to assess the inter-relations between relative age within the school year, age at ADHD diagnosis, and year of diagnosis (1998-2003 vs 2004-11).
FINDINGS: Between Jan 1, 1998, and Dec 31, 2011, 6136 children with ADHD were identified. Compared with the oldest children in the school year (ie, those born between January and April), the cumulative incidence of an ADHD diagnosis was greatest for the youngest children (ie, those born between September and December); for boys the incidence ratio was 1·26 (95% CI 1·18-1·35; p<0·0001) and for girls it was 1·31 (1·12-1·54; p=0·0007). The association between relative age and age at ADHD diagnosis reflected children diagnosed before age 10 years, and the strength of this association increased during recent years (2004-11). Thus, compared with children born between January and April, for those born between May and August, the ADHD incidence ratio was 1·37 (95% CI 1·24-1·53; p<0·0001) and for those born between September and December, the incidence ratio was 1·64 (1·48-1·81; p<0·0001). The relative age effect was not accounted for by comorbid disorders such as CD, ODD, or LD.
INTERPRETATION: In a health service system with low prescribing rates for ADHD, a younger relative age is associated with an increased likelihood of receiving a clinical diagnosis of ADHD. This effect has increased in recent years. Teachers, parents, and clinicians should take relative age into account when considering the possibility of ADHD in a child or encountering a child with a pre-existing diagnosis.
FUNDING: Academy of Finland, Finnish Medical Foundation, Orion Pharma Foundation, Finnish Cultural Foundation.
Neuroscience (11) Attention Deficit Disorder with Hyperactivity (11), Oppositional Defiant Disorder (1), Learning Disorders (1), more mentions
BACKGROUND: Children with central nervous system (CNS) tumours may present with a multitude of symptoms, ranging from elevated intracranial pressure to focal neurological deficit. In everyday practice, some signs may be misleading, thereby causing prolonged prediagnostic symptomatic intervals. Prediagnostic symptomatic intervals are longer for pediatric brain tumors than for other childhood malignancies. This study evaluated prediagnostic symptomatic intervals and parental and diagnostic intervals for pediatric patients with CNS tumours in Austria. It also considered socioeconomic factors.
METHODS: Patients ≤ 19 years of age treated at the Medical University of Vienna and diagnosed during the years 2008 to 2013 were included. Patients diagnosed incidentally or by screening were excluded.
RESULTS: Two hundred twelve consecutive patients were included in the study. They reflected the expected spectrum of CNS tumors. Patients presented with a median of five symptoms at diagnosis, most frequently with signs of elevated intracranial pressure. The median prediagnostic symptomatic interval was 60 days (0 days to seven years), the median parental interval was 30 days (0 days to 6.7 years), and the median diagnostic interval was three days (0 days to 6.5 years). In spinal tumors alone (n = 7), the median prediagnostic symptomatic interval was 70 days (ten days to seven years), and three of seven patients had a prediagnostic symptomatic interval longer than 320 days. Young age, higher tumor grade, and ataxia were associated with a shorter prediagnostic symptomatic interval. Localization in the supratentorial midline, histology of craniopharyngioma, and endocrine symptoms prolonged the prediagnostic symptomatic interval. There was a clear trend for longer prediagnostic symptomatic interval in non-native speakers.
CONCLUSIONS: Results are comparable to other industrialized countries. However, long delays in diagnosis of central nervous system tumors still occur, urging increased awareness.
Oncology (1) Neoplasms (3), Intracranial Hypertension (2), Central Nervous System Neoplasms (2), more mentions
OBJECTIVE: Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents.
METHOD: A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction.
RESULTS: Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use.
CONCLUSIONS: Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.
Neuroscience (6) Depressive Disorder (10), Attention Deficit Disorder with Hyperactivity (1), more mentions
Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations. We sought to further delineate this spectrum, study levels of mosaicism and identify genotype-phenotype correlations of AKT3-related disorders. We performed targeted sequencing of AKT3 on individuals with these phenotypes by molecular inversion probes and/or Sanger sequencing to determine the type and level of mosaicism of mutations. We analysed all clinical and brain imaging data of mutation-positive individuals including neuropathological analysis in one instance. We performed ex vivo kinase assays on AKT3 engineered with the patient mutations and examined the phospholipid binding profile of pleckstrin homology domain localizing mutations. We identified 14 new individuals with AKT3 mutations with several phenotypes dependent on the type of mutation and level of mosaicism. Our comprehensive clinical characterization, and review of all previously published patients, broadly segregates individuals with AKT3 mutations into two groups: patients with highly asymmetric cortical dysplasia caused by the common p.E17K mutation, and patients with constitutional AKT3 mutations exhibiting more variable phenotypes including bilateral cortical malformations, polymicrogyria, periventricular nodular heterotopia and diffuse megalencephaly without cortical dysplasia. All mutations increased kinase activity, and pleckstrin homology domain mutants exhibited enhanced phospholipid binding. Overall, our study shows that activating mutations of the critical AKT3 gene are associated with a wide spectrum of brain involvement ranging from focal or segmental brain malformations (such as hemimegalencephaly and polymicrogyria) predominantly due to mosaic AKT3 mutations, to diffuse bilateral cortical malformations, megalencephaly and heterotopia due to constitutional AKT3 mutations. We also provide the first detailed neuropathological examination of a child with extreme megalencephaly due to a constitutional AKT3 mutation. This child has one of the largest documented paediatric brain sizes, to our knowledge. Finally, our data show that constitutional AKT3 mutations are associated with megalencephaly, with or without autism, similar to PTEN-related disorders. Recognition of this broad clinical and molecular spectrum of AKT3 mutations is important for providing early diagnosis and appropriate management of affected individuals, and will facilitate targeted design of future human clinical trials using PI3K-AKT pathway inhibitors.
Research into emotional responsiveness in Autism Spectrum Disorder (ASD) has yielded mixed findings. Some studies report uniform, flat and emotionless expressions in ASD; others describe highly variable expressions that are as or even more intense than those of typically developing (TD) individuals. Variability in findings is likely due to differences in study design: some studies have examined posed (i.e., not spontaneous expressions) and others have examined spontaneous expressions in social contexts, during which individuals with ASD-by nature of the disorder-are likely to behave differently than their TD peers. To determine whether (and how) spontaneous facial expressions and other emotional responses are different from TD individuals, we video-recorded the spontaneous responses of children and adolescents with and without ASD (between the ages of 10 and 17 years) as they watched emotionally evocative videos in a non-social context. Researchers coded facial expressions for intensity, and noted the presence of laughter and other responsive vocalizations. Adolescents with ASD displayed more intense, frequent and varied spontaneous facial expressions than their TD peers. They also produced significantly more emotional vocalizations, including laughter. Individuals with ASD may display their emotions more frequently and more intensely than TD individuals when they are unencumbered by social pressure. Differences in the interpretation of the social setting and/or understanding of emotional display rules may also contribute to differences in emotional behaviors between groups.
Objectives: The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes.
Methods: Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores, and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving subjects were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition.
Results: Twenty-nine subjects completed the Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2=0.22, p=0.007, and 0.27, 0.004, respectively). Decreased 0.5-2 Hz EEG power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2=0.25, p=0.0005, and 0.33, 0.001, respectively). Predictive value remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p<0.05).
Conclusions: These prospective, longitudinal data suggest that inefficient neonatal sleep - as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness - may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.
BACKGROUND: Cerebral palsy is the most common physical disability in childhood, and is mostly diagnosed after age 2 years. Delays in diagnosis can have negative long-term consequences for children and parents. New guidelines for early cerebral palsy diagnosis and intervention were recently published, after systematic review of the evidence by international multidisciplinary experts aiming to decrease age at diagnosis. The current study tested the feasibility of implementing these guidelines in an American clinical setting.
METHODS: We designed a stepwise implementation process in a neonatal intensive care follow-up clinic. Efficacy was tested by comparing 10-month pre- and post-implementation periods. Clinic visit types, cerebral palsy diagnosis, provider competencies and perspectives, and balancing measures were analyzed.
RESULTS: Changes to infrastructure, assessments, scheduling algorithms, documentation and supports in diagnosis or counseling were successfully implemented. Number of three- to four-month screening visits increased (255 to 499, P < 0.001); mean age at diagnosis decreased (18 to 13 months, P < 0.001). Clinic team awareness of early diagnosis and interventions increased (P < 0.001). There was no decrease in family satisfaction with overall clinic function. Opportunities for improvements included documentation for transitioning patients, generalizabilty across hospital clinics, systematic identification of high-risk status during hospitalization, and need for cerebral palsy care guidelines for infants under age 2 years.
CONCLUSIONS: We demonstrated for the first time in a US clinical setting the feasibility of implementation of international early diagnosis and treatment guidelines for cerebral palsy. This process is adaptable to other settings and underscores the necessity of future research on cerebral palsy treatments in infancy.
OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5'-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5'-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5'-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5'-phosphate oxidase deficiency.
METHODS: A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5'-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations.
RESULTS: Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674 G>T, c.686 G>A and c.352G>A).
CONCLUSION: In addition to the well-described epileptic encephalopathy, pyridox(am)ine 5'-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.
Neurological and Central Nervous System Diseases (3), Blood Disorders and Hematology (2) Epilepsy (3), Movement Disorders (2), Anemia (2), more mentions
OBJECTIVE: The study provides updated information about the distribution of seizures, epilepsies, and etiologies of epilepsy in the general child population, and compares the old and new classification systems from the International League Against Epilepsy (ILAE).
METHODS: The study platform was the Norwegian Mother and Child Cohort Study. Cases of epilepsy were identified through registry linkages and sequential parental questionnaires. Epilepsy diagnoses were validated using a standardized protocol, and seizures, epilepsies, and etiologies were classified according to the old (ILAE 1981/1989) and new (ILAE 2017) classifications. Information was collected through medical record reviews and/or parental telephone interviews.
RESULTS: The study population included 112,744 children aged 3-13 years at the end of follow-up on December 31, 2012. Of these, there were 606 children with epilepsy (CWE). Distribution of seizure types varied by age of onset. Multiple seizure types were common with early onset. Focal epilepsies were the most common, occurring in 317 per 100,000 children in the study population and in 59% of CWE. Generalized epilepsies were found in 190 per 100,000 (35% of CWE). CWE with onset during the first 2 years of life had an even distribution of focal and generalized epilepsies, whereas focal epilepsies became dominant at later ages of onset. A definite cause of epilepsy had been demonstrated in 33% of CWE. The ILAE 1989 classification allowed for a broad syndrome category in 93% of CWE and a defined epileptic syndrome in 37%. With the ILAE 2017 classification, 41% of CWE had a defined epileptic syndrome and 63% had either a defined syndrome or structural-metabolic etiology.
SIGNIFICANCE: The distribution of seizures and epilepsies is strongly dependent on age of onset. Despite diagnostic advances, the causes of epilepsy are still unknown in two-thirds of CWE. The ILAE 2017 classifications allow for a higher precision of diagnoses, but at the expense of leaving more epilepsies classifiable only at the mode of onset level.
Neurological and Central Nervous System Diseases (9) Epilepsy (9), Seizures (6), more mentions
BACKGROUND: The risk of febrile seizure is temporarily increased for a few days after the administration of certain vaccines in children aged six to 23 months. Our objective was to determine the febrile seizure risk following vaccination in children aged one to five months, when six different vaccines are typically administered.
METHODS: We identified emergency department visits and inpatient admissions with International Classification of Diseases, Ninth Revision, febrile seizure codes among children enrolled in nine Vaccine Safety Datalink participating health care organizations from 2006 through 2011. Febrile seizures were confirmed by medical record abstraction. We used the self-controlled risk-interval method to compare the incidence of febrile seizure during postvaccination days 0 to 1 (risk interval) versus days 14 to 20 (control interval).
RESULTS: We identified 15 febrile seizure cases that occurred after 585,342 vaccination visits. The case patients were aged three to five months. The patients had received a median of four (range two to six) vaccines simultaneously. The incidence rate ratio of febrile seizure after vaccination was 23 (95% confidence interval 5.13 to 100.8), and the attributable risk was 3.92 (95% confidence interval 1.68 to 6.17) febrile seizure cases per 100,000 persons vaccinated.
CONCLUSIONS: Vaccination in children aged three to five months was associated with a large relative risk of febrile seizure on the day of and the day after vaccination, but the risk was small in absolute terms. Postvaccination febrile seizure should not be a concern for the vast majority of children receiving vaccines, but clinicians might take this risk into consideration when evaluating and treating children susceptible to seizures precipitated by fever.
AIM: The aim is to analyze the sleep architecture using polysomnography (PSG) in patients with Juvenile Myoclonic Epilepsy (JME): (newly diagnosed and those on valproate drug) attending epilepsy clinic at Alexandria University Hospitals.
METHODS: This study involved 20 patients with JME on valproate (age: 22.40 ± 5.80 years; M:F = 6:14), 20 newly diagnosed patients (age: 18.55 ± 6.0 years; M:F = 6:14), and 20 matched healthy controls (age: 22.10 ± 5.0 years; M:F = 6:14). Clinical assessment, electroencephalogram (EEG), evaluation with comprehensive sleep questionnaire, and PSG were done for all patients.
RESULTS: PSG showed significant alterations in sleep architecture in the total JME group in the form of reduced mean sleep efficiency (p = 0.001(∗)), increased mean Rapid eye movement (REM) onset latency (p = 0.046(∗)), decrease mean REM percentage (p = 0.011(∗)), increased mean wakefulness after sleep onset (p = 0.018(∗)), increase the index of total arousal (p = 0.005(∗)), increased mean periodic limb movement index (P = 0.001(∗)), and reduced apnea hypopnea index (P = <0.001) in comparison to control group. Valproate treated group showed increased sleep efficiency (p = 0.040(∗)), decreased REM arousal index (P = 0.012), longer stage 3 (P = 0.038), and prolonged stage 2 (P = 0.049(∗)) than the newly diagnosed group.
CONCLUSIONS: Sleep architecture was significantly disturbed in JME, with improvement in sleep efficiency in valproate treated patients.
Neurological and Central Nervous System Diseases (4), Sleep Disorders (1) Juvenile Myoclonic Epilepsy (7), Apnea (1), Epilepsy (1), more mentions
OBJECTIVE: The aim of this study was to explore the perspectives of families regarding their expectations and experience of visiting the emergency department (ED) for migraine.
METHODS: This was a qualitative study involving the families of 25 patients aged 10 to 18 years receiving ED care for acute migraine. Following their visit, independent semistructured telephone interviews were conducted with both the patient and parent or guardian. Questions were designed to explore factors pertaining to the family's perspective regarding their visit to the ED and expectations for the ED visit.
RESULTS: Families reported a variety of reasons for visiting the ED. The majority of participants reported that they were worried about their headaches. Families more commonly had expectations for treatment than they did for investigations. As compared with patients, parents more commonly reported specific expectations for investigations and less commonly expressed concerns about intravenous treatments. Expectations for treatment efficacy varied: whereas some parents expected complete pain relief, for others, lesser degrees of relief were considered satisfactory. The experience of treatment efficacy was related to willingness to receive the same treatment again.
CONCLUSIONS: Given that a high frequency of families endorsed that they were worried about the headache when presenting to the ED, clinicians should strive to make a diagnosis of migraine in the ED setting and to educate families about this diagnosis. Because of divergent parent and patient perspectives, health care providers should inquire about family expectations, especially in relation to expectations for investigations and concerns surrounding intravenous interventions, and ensure that both the patient's and parent's perspectives are considered when developing a management plan for pediatric migraine.
Men's Health (7), Pain Management (5) Migraine Disorders (5), Headache (2), more mentions
BACKGROUND: Febrile seizures can be classified as simple or complex. Complex febrile seizures are associated with fever that lasts longer than 15 minutes, occur more than once within 24 hours, and are confined to one side of the child's body. It is common in some countries for doctors to recommend an electroencephalograph (EEG) for children with complex febrile seizures. A limited evidence base is available to support the use of EEG and its timing after complex febrile seizures among children.
OBJECTIVES: To assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age.
SEARCH METHODS: For the latest update of this review, we searched the Cochrane Epilepsy Group Specialized Register (23 January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 January 2017), MEDLINE (Ovid, 23 January 2017), and ClinicalTrials.gov (23 January 2017). We applied no language restrictions.
SELECTION CRITERIA: All randomised controlled trials (RCTs) that examined the utility of an EEG and its timing after complex febrile seizures in children.
DATA COLLECTION AND ANALYSIS: The review authors selected and retrieved the articles and independently assessed which articles should be included. Any disagreements were resolved by discussion and by consultation with the Cochrane Epilepsy Group. We applied standard methodological procedures expected by Cochrane.
MAIN RESULTS: Of 41 potentially eligible studies, no RCTs met the inclusion criteria.
AUTHORS' CONCLUSIONS: We found no RCTs as evidence to support or refute the use of EEG and its timing after complex febrile seizures among children. An RCT can be planned in such a way that participants are randomly assigned to the EEG group and to the non-EEG group with sufficient sample size. Since the last version of this review, we have found no new studies.
Neurological and Central Nervous System Diseases (2) Febrile Seizures (8), Epilepsy (2), more mentions