Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Association of fetal ultrasound anthropometric parameters with neurodevelopmental outcomes at 24 months of age.

BACKGROUND: There is a paucity of studies which have examined associations between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants. We examined the association between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants through a secondary analysis of data collected in a large community based randomized controlled trial. METHODS: A total of 1465 mother-child dyads were included. Ultrasound based fetal anthropometric parameters which included the head circumference (HC), abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and transcerebellar diameter (TCD) were collected at 26-28 weeks of gestation and their association with neurodevelopment at 24 months of age was examined. RESULTS: Only the transcerebellar diameter z score was positively associated +0.54 units (95% CI: 0.15, 0.93) with motor composite score. When the neurodevelopment outcomes were analyzed as categorical, none of the fetal variables were associated with risk of moderate to severe neurodevelopment impairment. CONCLUSION: The findings suggest that transcerebellar diameter could be useful for early prediction of neurodevelopmental outcomes in childhood. CLINICAL TRIAL REGISTRATION: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Safety, Efficacy, and Tolerability of Modified Atkins Diet in Persons With Drug-Resistant Epilepsy: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Modified Atkins diet (MAD) has emerged as an adjuvant therapy in drug-resistant epilepsy (DRE). Most studies are in children; there is limited evidence for DRE in adults. This study aimed to investigate whether MAD along with standard drug therapy (SDT) was indeed more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE (nonsurgical). METHODS: A prospective randomized controlled trial was conducted at tertiary care referral center in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than 2 seizures per month despite using at least 3 appropriate antiseizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past 1 year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm). The primary outcome was >50% reduction in seizure frequency, and the secondary outcomes were quality of life (QOL), behavior, adverse events, and rate of withdrawal at 6 months. Intention-to-treat analysis was performed. RESULTS: A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5-33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea. DISCUSSION: The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies. TRIAL REGISTRATION INFORMATION: The clinical trial registry of India: CTRI/2015/07/006048. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.

The spectrum of neurological manifestations and genotype-phenotype correlation in Indian children with Gaucher disease.

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype-phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.

Short-term neurodevelopment and growth outcomes of very and moderate preterm Indian infants.

OBJECTIVE: To study the growth and neurodevelopmental outcome of very and moderate preterm infants (VMPT) compared to term appropriate-for-age (term AGA) infants at 18-months corrected age. METHODS: This prospective cohort study enrolled consecutively born 212 VMPT infants and 250 term AGA controls delivered during study period. OUTCOME MEASURES: Major neurodevelopmental impairment (NDI) defined as any one of cerebral palsy, motor (MoDQ) or mental developmental quotient (MoDQ) <70 on Developmental Assessment Scale for Indian infants, visual or hearing impairment, or epilepsy, and growth outcomes. RESULTS: Among 195 VMPT and 240 term AGA infants who completed follow-up, the frequency of major NDI was 12.8% and 2.5% respectively (RR 5.1; 95% CI [2.13-12.19]). Major NDI was higher among infants <28 weeks gestation (39%) and birthweight <1000 grams (27%). A quarter of VMPT infants exhibited wasting and 18% stunting than 7% each among controls. CONCLUSION: VMPT infants had a higher frequency of major NDI and growth failure at 18-months.

Neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia: Experience from a tertiary care center in India.

BACKGROUND: Data of neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL) is scarce from low middle-income countries (LMICs), and is influenced by biological and cultural variations. The objective of this study was to assess the prevalence and spectrum of neurocognitive deficits in a cohort of survivors from India. PROCEDURE: Seventy survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IVINDIA ). The prevalence of neurocognitive deficits was calculated based on the full-scale intelligence quotient (FSIQ), and scores in discrete domains like verbal comprehension, perceptual reasoning, working memory, and processing speed were calculated and compared to demographics, treatment, and sociocultural factors. RESULTS: The mean (SD) current age and time since diagnosis was 10.5 (±3.2) years and 5 (±2.8) years, respectively. The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit (FSIQ <90) being prevalent in 50% (95% CI: 38%-62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory, and processing speed were 49%, 50%, 47%, and 44%, respectively. The odds of having neurocognitive deficits were higher when a child belonged to lower socioeconomic strata (OR 5.7, p = .004), parents with lower education attainment (OR 4.3, p = .041), and whose birth order was higher (OR 20.1, p = .005). Age at diagnosis/assessment, chemotherapy received, or dose of radiotherapy did not have a direct impact on neurocognition. CONCLUSIONS AND RELEVANCE: Rates of neurocognitive deficits are higher in survivors in LMICs, with socioeconomic variables contributing more than the direct neurotoxic effects of treatment.

Mutation Spectrum of Tuberous Sclerosis Complex Patients in Indian Population.

Tuberous sclerosis complex (TSC) is a multiorgan disorder characterized by formation of hamartomas and broad phenotypic spectrum including seizures, mental retardation, renal dysfunction, skin manifestations and brain tubers. It is inherited in an autosomal dominant pattern, caused due to mutation in either TSC1 or TSC2 genes. Seizures are one of the major presenting symptoms of TSC that helps in early diagnosis. The present study describes the mutation spectrum in TSC1 and TSC2 genes in TSC patients and their association with neurocognitive-behavioral phenotypes. Ninety-eight TSC patients were enrolled for TSC genetic testing after detailed clinical and neurobehavioral assessment. Large genomic rearrangement testing was performed by multiplex ligation-dependent probe amplification (MLPA) technique for all cases and Sanger sequencing was performed for MLPA negative cases. Large rearrangements were identified in approximately 1% in TSC1 and 14.3% in TSC2 genes. The present study observed the presence of duplications in two (2%) cases, both involving TSC2/PKD1 contiguous genes which to the best of our knowledge is reported for the first time. 8.1% of small variants were identified in the TSC1 gene and 85.7% in TSC2 gene, out of which 23 were novel variations and no variants were found in six (6.1%) cases. This study provides a representative picture of the distribution of variants in the TSC1 and TSC2 genes in Indian population along with the detailed assessment of neurological symptoms. This is the largest cohort study from India providing an overview of comprehensive clinical and molecular spectrum.

A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome.

Van Esch-O'Driscoll syndrome (VEODS) is a rare cause of syndromic X-linked intellectual disability characterised by short stature, microcephaly, variable degree of intellectual disability, and hypogonadotropic hypogonadism. To date, heterozygous hypomorphic variants in the gene encoding the DNA Polymerase α subunit, POLA1, have been observed in nine patients from five unrelated families with VEODS. We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression.

Association of Sleep Apnea With Development and Behavior in Down Syndrome: A Prospective Clinical and Polysomnographic Study.

BACKGROUND: The prevalence of sleep-disordered breathing is high in children with Down syndrome. Although the association between sleep-disordered breathing and developmental delay and behavioral abnormalities are proven among typically developing children, there are few such studies of children with Down syndrome. This study assesses the relationship between the severity of sleep apnea and development and behavioral abnormalities in individuals with Down syndrome. METHODS: In a cross-sectional prospective study, 53 children with Down syndrome were assessed for sleep-disordered breathing by overnight polysomnography. Behavior was assessed using Child Behavior Checklist (CBCL) and developmental quotient (DQ) using Developmental Profile 3. The association between various domains of behavior and development with the Apnea-Hypopnea Index (AHI) was assessed using Spearman rank correlation. Multiple linear regression assessed the independent effects of various factors on development and behavior. RESULTS: Of 53 subjects (three to 11.8 years), 51 (96%) were found to have obstructive sleep apnea (OSA). In both three to five year and six to 12 year age groups, there was a statistically significant positive correlation between the CBCL scores and the AHI (rho = 0.77 and 0.83, respectively). There was a statistically significant negative correlation between the DQ and the AHI (rho = -0.62). In multiple linear regression, AHI was the only independent variable that was associated with CBCL and DQ. CONCLUSIONS: This study provides robust evidence that OSA can negatively influence the development and behavior in children with Down syndrome as in typically developing children. Moreover, with increasing severity of OSA, children with Down syndrome have more behavioral abnormalities, especially attention deficit and hyperactivity, and also have poorer development scores.

Development and Evaluation of a Working Memory Intervention Kit in Children with Epilepsy in Low-Resource Settings.

OBJECTIVES: In this pilot study, the authors developed and evaluated a working memory intervention (WMI) using a combination of mobile phone-based application and an activity booklet, among children with idiopathic generalized epilepsy. METHODS: Pre- and post-intervention cognitive evaluation at 8 wk included: subtests comprising working memory index from Wechsler Intelligence Scale-IV, color cancellation task for sustained attention, and parent's rating from the Conners' ADHD/DSM-IV Scales of the Conners' Rating Scales-Revised. RESULTS: Fourteen children completed the intervention; one was lost to follow-up. Significant improvement in most working memory parameters occurred at 8 wk: digit span [scaled scores: median 7 (IQR 4-9) to 12 (IQR 9-14.25); p = 0.001]; letter-number sequencing [scaled scores: median 9 (IQR 5-10) to 11.5 (IQR 6.75-13); p = 0.03]; WMI [median 14 (IQR 9-18) to 22 (IQR 16.75-27); p = 0.001] and sustained attention [time for cancellation test improved from 95 (72-117) to 85 (63-98) s; p = 0.001]. CONCLUSION: This indigenous WMI was feasible and efficacious in improving working memory deficits in CWE in low-resource settings.

The Development and Validation of DSM 5-Based AIIMS-Modified INDT ADHD Tool for Diagnosis of ADHD: A Diagnostic Test Evaluation Study.

BACKGROUND: The current study was planned at a tertiary centre in northern India to develop and validate a Diagnostic and Statistical Manual-5 (DSM-5)-based diagnostic tool and design a severity score for attention deficit hyperactivity disorder (ADHD) in children aged 6-18 years. An existing DSM-IV-based tool, INDT (International Clinical Epidemiology Network [INCLEN] diagnostic tool) for ADHD has been modified and named All India Institute of Medical Sciences (AIIMS)-modified INDT ADHD tool. METHOD: The first phase was development of the tool and the second phase was validation of the same against the gold standard of diagnosis by the DSM-5. A severity score was developed for ADHD in concordance with the Conners rating scale. RESULTS: The tool was validated in 66 children with a sensitivity and specificity of 100 per cent and 90 per cent, respectively. A cut-off score of 12 was decided for labelling severity of ADHD, which corresponded to 63 in the Conners rating scale. CONCLUSION: This diagnostic tool for ADHD based on DSM-5 has acceptable psychometric properties. The severity score will be useful for prognostication, monitoring treatment response, and designing intervention trials.

Decoding of novel missense TSC2 gene variants using in-silico methods.

BACKGROUND: Mutations in TSC1 or TSC2 gene cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by the formation of non-malignant hamartomas in multiple vital organs. TSC1 and TSC2 gene products form TSC heterodimer that senses specific cell growth conditions to control mTORC1 signalling. METHODS: In the present study 98 TSC patients were tested for variants in TSC1 and TSC2 genes and 14 novel missense variations were identified. The pathogenecity of these novel variations was determined by applying different bioinformatics tools involving computer aided protein modeling. RESULTS: Protein modelling could be done only for ten variants which were within the functional part of the protein. Homology modeling is the most reliable method for structure prediction of a protein. Since no sequence homology structure was available for the tuberin protein, three dimensional structure was modeled by a combination of homology modeling and the predictive fold recognition and threading method using Phyre2 threading server. The best template structures for model building of the TSC1 interacting domain, tuberin domain and GAP domain are the crystal structures of clathrin adaptor core protein, Rap1GAP catalytic domain and Ser/Thr kinase Tor protein respectively. CONCLUSIONS: In this study, an attempt has been made to assess the impact of each novel missense variant based on their TSC1-TSC2 hydrophobic interactions and its effect on protein function.

Development, Cognition, Adaptive Function and Maladaptive Behavior in HIV-infected and HIV-exposed Uninfected Children Aged 2-9 Years.

OBJECTIVE: To compare development/cognition, adaptive function and maladaptive behavior of HIV-infected and HIV-exposed uninfected children between 2 to 9 years with HIV-uninfected controls. METHODS: This hospital-based cross-sectional study was conducted from November, 2013 to March, 2015. 50 seropositive HIV-infected, 25 HIV-exposed uninfected and 25 HIV-uninfected children between 2 to 9 years were administered Developmental Profile 3, Vineland Adaptive Behavior Scale 2, and Child Behavior Checklist for assessing development, adaptive function and maladaptive behaviour, respectively. Additional data were obtained by history, examination and review of records. RESULTS: Significant developmental/cognitive impairment was observed in 38 (76%), 16 (64%) and 6 (24%) HIV-infected, HIV-exposed uninfected, and HIV-uninfected children, respectively. Significant impairment in adaptive function was found in 12 (24%) and 2 (8%) HIV-infected and HIV-exposed uninfected children, respectively. Maladaptive behavior was not seen in any group. CONCLUSIONS: High magnitude of impaired development/cognition and adaptive function in HIV-exposed and HIV-infected children warrants assessment of these domains during follow-up of these children, and incorporation of interventions for these deficits in standard care for this group.

Development and validation of DSM-5 based diagnostic tool for children with Autism Spectrum Disorder.

Diagnostic and Statistical Manual of mental disorder-IV (DSM-IV) TR based INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD) is an established instrument for the diagnosis of ASD in Indian subcontinent and low-middle income countries (LMIC). The introduction of DSM-5 necessitated revision of existing INDT-ASD tool to incorporate the DSM-5 related changes. This study was undertaken to develop and validate the DSM-5 based All India Institute of Medical Sciences (AIIMS)-Modified-INDT-ASD Tool. The modifications were done using Delphi method and included: (a) rearrangement of questions from the previous tool; and (b) addition of new questions on sensory symptoms. The modified tool was validated against DSM-5 diagnostic criteria. In addition, receiver operating characteristic (ROC) curves were used to determine the cut-off for total score as compared to Childhood Autism Rating Scale (CARS) score to grade the severity of ASD. Two-hundred-twenty-five children (159 boys, median age = 47months) were enrolled. The modified tool demonstrated sensitivity of 98.4% and specificity of 91.7% to diagnose ASD. A score ≥14 on the tool was suggestive of severe ASD (CARS>36.5) with a sensitivity and specificity of 80% and 80.7% respectively [Area under the curve = 0.89]. AIIMS-Modified-INDT-ASD Tool is a simple and structured instrument based on DSM-5 criteria which can facilitate diagnosis of ASD with acceptable diagnostic accuracy.

Developmental Status of Children Operated for Esophageal Atresia with or without Tracheoesophageal Fistula Along with Maternal Stress, Their Quality of life, and Coping Abilities at AIIMS, New Delhi.

INTRODUCTION: Esophageal atresia with or without tracheoesophageal fistula (EA with or without TEF) is one of the neonatal surgical emergencies requiring surgical intervention in the early neonatal period, influencing the developmental outcome in the operated children. This study was aimed to assess the developmental status of children operated for EA with or without TEF along with maternal stress, their quality of life (QOL), and coping abilities. MATERIALS AND METHODS: A descriptive cross-sectional survey was conducted on 51 children aged up to 5 years after EA with or without TEF repair and their mothers' in a tertiary care facility. The tools used were, namely, demographic datasheet of child and mother, anthropometry assessment, Developmental Assessment Scale for Indian Infants, and modified Vineland Social Maturity Scale for the developmental evaluation, Child Behavior Checklist (1.5-5 years) caregiver report form, Parental Stress Scale, WHOQOL BREF, and Coping Strategies Checklist. RESULTS: The majority of children had low weight (47.1%) and height (31.4%), for reference age. The overall and social developmental delay was observed in 40.7 and 37.5% of children, respectively, and few children (7.4%) had behavioral problems in the borderline range. Among the mothers, 47% had moderate stress and relatively poor QOL in environmental (60.1 ± 18.9) and psychological (60.8 ± 18.8) domains. The most commonly used coping strategy by the mothers was an emotional outlet (29.4%). CONCLUSION: Developmental delay was present in children operated for EA with or without TEF caused significant stress among mothers, affecting their QOL for which the emotional outlet was the most commonly used coping strategy.

Hospital Based Psychosocial Support Program for Children with ALL and their Families: A Comprehensive Triad's Perspective.

OBJECTIVES: To elucidate potential target areas of intervention and mechanisms for implementation of intervention for children with cancer during the treatment phase. METHODS: Focused group discussion (FGDs) served as a primary source of providing phenomenal perspectives to explore the key objective. Eight focus groups of 45-60 min each were held with 5-9 members in each discussion. The participants were either patients, their caregivers or health care providers. The focus group audio recordings were professionally transcribed after all identifiers were removed. Employing a constructivist paradigm with a phenomenological approach, also known as emergent-systematic focus group design the study reported on families' experiences of childhood cancer as construction of objective reality. Investigator triangulation method was adopted to ensure trustworthiness. RESULTS: Using constant comparison analysis, multistage process analysis was done which resulted in 849 codes, 32 subthemes, 20 themes and 5 domains. A total of 64 participants participated: 4 FGDs with parents of children with ALL (n = 31); 1 FGD with professionals working in the field of cancer (n = 10) and 3 FGDs with children with ALL (n = 23). Participant's mean age at the time of study was 10 y (+3.3) for children; 37 y (+4.93) for caregivers and 35 y (+3.5) for professionals. The number of participants and their age range at study varied slightly between the eight focus groups. CONCLUSIONS: Caregivers presented care burden and compromised aspects of Quality of life (QOL). An effective and culturally sensitive psychosocial support for patients and their families during and post treatment, in addition to medical therapy, is strongly recommended.

Endoscope-assisted (with robotic guidance and using a hybrid technique) interhemispheric transcallosal hemispherotomy: a comparative study with open hemispherotomy to evaluate efficacy, complications, and outcome.

OBJECTIVEEndoscope-assisted hemispherotomy (EH) has emerged as a good alternative option for hemispheric pathologies with drug-resistant epilepsy.METHODSThis was a prospective observational study. Parameters measured included primary outcome measures (frequency, severity of seizures) and secondary outcomes (cognition, behavior, and quality of life). Blood loss, operating time, complications, and hospital stay were also taken into account. A comparison was made between the open hemispherotomy (OH) and endoscopic techniques performed by the senior author.RESULTSOf 59 cases (42 males), 27 underwent OH (8 periinsular, the rest vertical) and 32 received EH. The mean age was 8.65 ± 5.41 years (EH: 8.6 ± 5.3 years; OH: 8.6 ± 5.7 years). Seizure frequency per day was 7 ± 5.9 (EH: 7.3 ± 4.6; OH: 15.0 ± 6.2). Duration of disease (years since first episode) was 3.92 ± 1.24 years (EH: 5.2 ± 4.3; OH: 5.8 ± 4.5 years). Number of antiepileptic drugs per patient was 3.9 ± 1.2 (EH: 4.2 ± 1.2; OH: 3.8 ± 0.98). Values for the foregoing variables are expressed as the mean ± SD. Pathologies included the following: postinfarct encephalomalacia in 19 (EH: 11); Rasmussen's syndrome in 14 (EH: 7); hemimegalencephaly in 12 (EH: 7); hemispheric cortical dysplasia in 7 (EH: 4); postencephalitis sequelae in 6 (EH: 2); and Sturge-Weber syndrome in 1 (EH: 1). The mean follow-up was 40.16 ± 17.3 months. Thirty-nine of 49 (79.6%) had favorable outcomes (International League Against Epilepsy class I and II): in EH the total was 19/23 (82.6%) and in OH it was 20/26 (76.9%). There was no difference in the primary outcome between EH and OH (p = 0.15). Significant improvement was seen in the behavioral/quality of life performance, but not in IQ scores in both EH and OH (p < 0.01, no intergroup difference). Blood loss (p = 0.02) and hospital stay (p = 0.049) were less in EH.CONCLUSIONSEH was as effective as the open procedure in terms of primary and secondary outcomes. It also resulted in less blood loss and a shorter postoperative hospital stay.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Clinical spectrum of psychogenic non epileptic seizures in children; an observational study.

PURPOSE: The current study was designed to analyze the clinical spectrum of Psychogenic non-epileptic seizures (PNES) in children. METHODS: Children aged 6-16years with clinically suspected PNES, confirmed by short-term VEEG (STVEEG{video electroencephalogram}) and induction were classified as per Seneviratne classification. Stressors, associated co morbidities, Verbal IQ (Intelligence Quotient) and behavioral abnormalities were assessed using HTP(House tree person) test, DSM IV (Diagnostic and statistical manual of mental disorders) TR criteria, MISIC (Malin intelligence scale for Indian children) and CBCL (Child behaviour checklist). RESULTS: Eighty children with PNES {45 boys; mean age: 10.5 (±1.6) years} were enrolled. Median delay in diagnosis was 5 months {IQR(interquartile range)- 0.5 to 48 months}) and 45% patients were already on AEDs (antiepileptic drugs). Commonest semiology was dialeptic (42.5%), followed by mixed (28.8%), motor (15%) and nonepileptic aura (13.8%). Family stressors were the commonest followed by school related issues. The most common psychiatric comorbidity was adjustment disorder. Somatic complaints were observed in 50% children. CONCLUSIONS: Dialeptic PNES is commonest in children. In resource constrained settings, STVEEG along with induction is a reliable method to diagnose PNES. A comprehensive assessment protocol (including assessment of stressors) is needed for holistic management of pediatric PNES.

Does surgery help in reducing stigma associated with drug refractory epilepsy in children?

INTRODUCTION: Epilepsy has several comorbidities and associated stigma. Stigma associated with epilepsy is well known and prevalent worldwide. Surgical treatment is an established treatment for drug refractory epilepsy. Following surgery in children, it is possible that the stigma may reduce, but such an effect has not been studied earlier. MATERIALS AND METHODS: Analysis of prospectively collected data was performed for pediatric patients at a single tertiary center for treating epilepsy. Child stigma scale, as described by Austin et al., was used to evaluate stigma both pre- and postoperatively. Analysis was done using Paired t test. RESULTS: In this study, following surgery, there was significant reduction of stigma (P<0.001). This was proportional to the reduction in seizures, though there were 9 (30%) patients, who due to persistent neurodisability did not have any reduction of stigma despite having good seizure outcome. CONCLUSION: Surgery in drug-resistant epilepsy helps in reducing stigma. Seizure reduction is probably not the only factor responsible for a change in stigma outcome.