Clinico-Etiologic Profile of Children and Adolescents with Drug-Resistant Epilepsy in a low-Resource Setting: 10 Years' Experience.

Purpose: Nearly 25% to 30% of children with epilepsy develop drug-resistant epilepsy. Etiology of epilepsy, including drug-resistant epilepsy, varies with geographical region. Identifying paucity of etiologic data on drug-resistant epilepsy from our region and similar low-resource settings, we aimed to describe the clinical and etiologic profile of children and adolescents with drug-resistant epilepsy, to better inform region-specific concerns. Methods: A chart-based retrospective review covering 10 years (January 2011-December 2020) was conducted. Participants between 1 months and 18 years of age who fulfilled International League Against Epilepsy (ILAE) definition of drug-resistant epilepsy were enrolled. Clinical details, perinatal history, electroencephalography (EEG), magnetic resonance imaging (MRI), and other evaluation-based data were analyzed. Results: Five hundred ninety-three children (52.3% males) were enrolled. The median age at presentation was 63 (interquartile range [IQR] 12-72) months and median age at onset was 12 (IQR 2-18) months. The most frequent seizure type was generalized (76.6%). Of these, epileptic spasms (48.1%) were most frequent. Focal seizures comprised 22.9%. The predominant contributor to etiology was perinatal adverse events, including perinatal asphyxia (37.9%), neonatal hypoglycemic brain injury (15.6%), and neonatal sepsis/meningitis. Electroclinical syndromes were observed in 361 (60.9%) children. Of these, the most frequent were West syndrome (48%) and Lennox-Gastaut syndrome (6.2%). Conclusion: Perinatal brain injury and brain infections were the most common causes of drug-resistant epilepsy identified. These findings indicate an opportunity for reducing the burden of pediatric drug-resistant epilepsy in our region by instituting preventive measures, including improved perinatal care, promotion of institutional deliveries, optimized obstetric and neonatal care, and immunization for vaccine-preventable infections such as bacterial meningitis and Japanese B encephalitis.

Diagnostic Accuracy of the Government of India Mother and Child Protection Card for Developmental Screening of Indian Children Aged 2-36 Months: A Hospital-based Mixed Method Study.

OBJECTIVE: Universal developmental screening is recommen-ded at 9, 18, 24 and 36 months. The Government of India Mother and Child Protection (MCP) card is an immunization record that is used to monitor child development, and identify children requiring further evaluation. OBJECTIVES: To determine the diagnostic accuracy of the MCP card for developmental screening, and perform its item analysis. STUDY DESIGN: Mixed-method study (prospective study of diag-nostic accuracy and qualitative study). PARTICIPANTS: Mother-child dyads of children between 2-36 months of age were recruited from the outpatient department or wards of a tertiary level children's hospital from November, 2019 to October, 2021. Children with confirmed neurodevelopmental disorders/disability, and mothers with less than 6th standard education were excluded. INTERVENTION: Each mother was given a MCP card, and taught how to mark the items. This was followed by the researcher's evaluation (index tool). The reference tool was a comprehensive clinical assessment (CCA) by the researcher and an expert. The CCA included clinical examination of hearing, vision, and neuro-development; and psychometric assessment of development and adaptive function. Each mother underwent an in-depth inter-view. Overall and group wise psychometric properties of diagnostic accuracy were computed. The interview transcripts were analyzed thematically. OUTCOMES: The proportion of children with 'fail' and 'delay' by the evaluation of the researcher with the MCP card and the expert by the CCA, respectively. RESULTS: The study population included 213 children (40.4% females). Fifty-two (24.4%) children were identified as 'Fail' by the MCP card and 43 (20.2%) as 'delay' by the expert's CCA. The overall sensitivity and specificity was 83.7% (95% CI 69.3-93.2) and 90.6% (95% CI 85.2-94.5), respectively. Acceptable diagnostic accuracy was found in the age-group 7-9 months, 13-18 months, and 25-36 months. CONCLUSIONS: The MCP card may be used for developmental screening at 9, 18, and 36 months.

Spectrum of Movement Disorders Among Children With Subacute Sclerosing Panencephalitis: A Cross-Sectional Study.

Background: Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. Methods: In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. Results: We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Conclusions: Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.

Clinical Profile of COVID-19 Illness in Children-Experience from a Tertiary Care Hospital.

OBJECTIVE: To detail clinical profile and outcome in children infected with SARS-CoV-2. METHODS: This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children (< 18 y) with COVID-19 illness from April 2020-October 2020 were reviewed and analyzed. RESULTS: A total of 2919 children with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness were tested for novel COVID-19 virus in the flu emergency (n = 1744), severe acute respiratory infection (SARI) ward (n = 825), and non-COVID area (n = 350) of the hospital. 8.73% (255/2919) children tested positive for SARS-CoV-2 infection. Of the 255 positive cases, 144 (56.47%) were managed on an outpatient basis and 100 (59 boys) required admission in COVID ward. The mortality rate of patients with SARS-CoV-2 was 11.4% (29/255). Majority of children admitted with COVID-19 had severe to critical illness due to the presence of malnutrition and underlying comorbidities. CONCLUSIONS: Children of all age groups were susceptible to COVID-19 illness with a slight male preponderance. Amongst infected, two-third were asymptomatic or had mild symptoms that required outpatient management and home isolation. The adverse outcomes were more commonly seen in infants and children > 10 y of age with malnutrition and comorbid illness.

Emerging Role of the Ketogenic Dietary Therapies beyond Epilepsy in Child Neurology.

Ketogenic dietary therapies (KDTs) have been in use for refractory paediatric epilepsy for a century now. Over time, KDTs themselves have undergone various modifications to improve tolerability and clinical feasibility, including the Modified Atkins diet (MAD), medium chain triglyceride (MCT) diet and the low glycaemic index treatment (LGIT). Animal and observational studies indicate numerous benefits of KDTs in paediatric neurological conditions apart from their evident benefits in childhood intractable epilepsy, including neurodevelopmental disorders such as autism spectrum disorder, rarer neurogenetic conditions such as Rett syndrome, Fragile X syndrome and Kabuki syndrome, neurodegenerative conditions such as Pelizaeus-Merzbacher disease, and other conditions such as stroke and migraine. A large proportion of the evidence is derived from individual case reports, case series and some small clinical trials, emphasising the vast scope for research in this avenue. The term 'neuroketotherapeutics' has been coined recently to encompass the rapid strides in this field. In the 100th year of its use for paediatric epilepsy, this review covers the role of the KDTs in non-epilepsy neurological conditions among children.

Expanding the electro-clinical phenotype of CARS2associated neuroregression.

Biallelic variants in CARS2 (Cysteinyl-tRNA synthetase 2; MIM*612800), are known to cause combined oxidative phosphorylation deficiency 27 (MIM#616672), characterized by severe myoclonic epilepsy, neuroregression and complex movement disorders. To date, six individuals from five families have been reported with variants in CARS2. Herein, we present an 11-year-old boy who presented with neuroregression, dysfluent speech, aggressive behavior and tremors for 2 years. An electroencephalogram (EEG) revealed a highly abnormal background with generalized spike-and-wave discharges suggestive of Electrical Status Epilepticus during Sleep (ESES). A known homozygous c.655G > A(p.Ala219Thr) pathogenic variant in exon 6 of the CARS2(NM_024537.4) was identified on exome sequencing. Our report expands the electro-clinical spectrum of the phenotype with presence of severe behavioral abnormalities, continuous tremors and ESES pattern on EEG, not previously reported.

Intersectoral Action for Early Childhood Development in India: Opportunities, Challenges and the Way Forward.

Nurturing care framework for early childhood development (ECD) focuses on five essential aspects of the holistic development of a child, which are interrelated and inseparable. This multidimensional approach to child development is dependent on contributions from multiple sectors, requiring the 'whole of government' approach. In India, the lack of a single multisectoral framework for ECD, narrow accountability to sector-specific outcomes, overlapping responsibilities of frontline workers, lack of leadership for coordination, and limited supervisory mechanisms result in fragmented service delivery. In recent years, there is high-level political commitment to intersectoral action, which promote holistic health. Better results and developmental outcomes are possible with different sectors working closely by converging their resources under the Sustainable Development Goals strategic action plans, POSHAN Abhiyaan, and the Aspirational districts program. Leveraging opportunities for intersectoral action requires a deliberate and consistent effort towards alignment of goals, favorable conditions of partnerships, leadership and governance, and capacity at every level.

Early Childhood Development: A Paradigm Shift From Developmental Screening and Surveillance to Parent Intervention Programs.

A large proportion of children under the age of five years who do not attain their expected developmental potential belong to low- and middle-income countries (LMICs). The strategies used for identifying children with high risk for developmental delay/disorders include developmental screening, surveillance, and monitoring. Suitability criteria for developmental screening tools in LMICs have been established, but few tools meet all the benchmarks. Based on these, the authors identified two tools that may be considered suitable in the Indian context; the International guide for monitoring child development and the Monitoring child development in the integrated management of childhood illnesses context. However, implementing and sustaining a universal developmental screening program using these is not feasible in the present circumstances. There is emerging evidence that parent intervention programs have significant impact on outcomes related to early childhood development (ECD). The nurturing care framework encompasses five strategies known to enhance ECD in young children even in the presence of adversities; good health, adequate nutrition, responsive caregiving, opportunities for early learning and safety and security. This article discusses the paradigm shift to incorporation of nurturing care-based preventive, supportive and promotive health care services in office practice with active parental involvement. This may prove to be a better option with a more positive, long lasting and quicker impact on ECD.

Utility of the END-IT Score to Predict the outcome of Childhood Status Epilepticus: A Retrospective Cohort Study.

INTRODUCTION: Scoring systems to predict outcomes in pediatric status epilepticus (SE) are limited. We sought to assess usefulness of the END-IT score in pediatric SE. METHODOLOGY: We conducted a retrospective study at a tertiary hospital in New Delhi, India. Children aged 1 month-18 years who presented with seizure for ≥5 min/actively convulsing to emergency were enrolled. END-IT score was calculated and correlated with outcome at discharge using Pediatric Overall Performance Category (POPC) scale, in-hospital mortality, and progression to refractory and super-refractory SE (SRSE). RESULTS: We enrolled 140 children (mean age 5.8 years; 67.1% males). Seven children died and 15 had unfavorable outcomes. The predictive accuracy of END-IT at a cutoff of > 2: for unfavorable outcome (POPC score ≥3) was: sensitivity 0.73 (95% CI: 0.45-0.92), specificity 0.94 (95% CI: 0.89-0.98), PPV 0.61 (95% CI: 0.36-0.83), NPV 0.97 (95% CI: 0.92-0.99), positive likelihood ratio (13.09), F1 score (0.666); for death: sensitivity 0.86 (95% CI: 0.42-0.99), specificity 0.91 (95% CI: 0.85-0.95), PPV 0.33 (95% CI: 0.13-0.59), NPV 0.99 (95% CI: 0.96-1.00), F1 score (0.48); for RSE: sensitivity 0.80 (95%CI: 0.28-0.99), specificity 0.90 (95% CI: 0.83-0.94), PPV 0.22 (95% CI: 0.06-0.48) NPV 0.99 (95% CI: 0.96-1.00), F1 score (0.35); for SRSE: sensitivity 0.67 (95% CI: 0.22-0.96) specificity 0.75 (95% CI: 0.66-0.82), PPV 0.22 (95% CI: 0.06-0.48) NPV 0.98 (95% CI: 0.94-0.99), F1 score (0.33). CONCLUSION: We demonstrate utility of the END-IT score to predict short-term outcomes as well as progression to refractory and SRSE for the first time among children with SE.

Acute Kidney Injury in Hospitalized Children with COVID19.

BACKGROUND: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection. AIM: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting. METHODS: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group. RESULTS: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality. CONCLUSION: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.

Impact of Comorbidities on Outcome in Children With COVID-19 at a Tertiary Care Pediatric Hospital.

OBJECTIVE: To study the various comorbidities and their impact on outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children. METHODOLOGY: Review of medical records of 120 children (58.4% males), aged 1 month to 18 years, admitted between 1 March and 31 December, 2020 with at least one positive RT-PCR test for SARS-CoV-2. Clinical and demographic variables were compared between children with and without co-morbidities. RESULTS: 62 (51.7%) children had comorbidities. The most common comorbidity was tuberculosis (32.3%) followed by other infections (27.4%) and hematological (19.4%) conditions. Fever (89.2%) was the most common clinical feature followed by respiratory (52.5%) and gastrointestinal (32.5%) manifestations. There was no significant difference in the severity of COVID illness, length of hospital stay and adverse outcomes (ventilation and mortality) among children with and without comorbidities. CONCLUSIONS: The presence of a comorbid illness in pediatric inpatients with COVID-19 did not impact the illness severity, length of hospitalization, ventilation requirement and mortality.

Inherited Manganese Disorders and the Brain: What Neurologists Need to Know.

Although acquired manganese neurotoxicity has been widely reported since its first description in 1837 and is popularly referred to as "manganism," inherited disorders of manganese homeostasis have received the first genetic signature as recently as 2012. These disorders, predominantly described in children and adolescents, involve mutations in three manganese transporter genes, i.e., SLC30A10 and SLC39A14 which lead to manganese overload, and SLC39A8, which leads to manganese deficiency. Both disorders of inherited hypermanganesemia typically exhibit dystonia and parkinsonism with relatively preserved cognition and are differentiated by the occurrence of polycythemia and liver involvement in the SLC30A10-associated condition. Mutations in SLC39A8 lead to a congenital disorder of glycosylation which presents with developmental delay, failure to thrive, intellectual impairment, and seizures due to manganese deficiency. Chelation with iron supplementation is the treatment of choice in inherited hypermanganesemia. In this review, we highlight the pathognomonic clinical, laboratory, imaging features and treatment modalities for these rare disorders.

Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial.

OBJECTIVES: We aimed to evaluate the efficacy of the modified Atkins diet in children with epileptic spasms who had failed hormonal therapy. METHODS: Children aged 9 months to 3 years having daily epileptic spasms despite a trial of ACTH or oral prednisolone and 1 additional anticonvulsant medication were enrolled. Children were randomly assigned to receive the modified Atkins diet either immediately or after a delay of 4 weeks. The ongoing anticonvulsant medications were continued unchanged. The primary outcome variable was the proportion of children who achieved spasm freedom as per parental reports at 4 weeks. Secondary outcomes included time to spasm cessation, proportion of children with electroclinical remission, the proportion of children with >50% reduction of spasms at 4 weeks, and adverse effects of the diet. (ClinicalTrials.gov Identifier: NCT03807141). RESULTS: A total of 91 children were enrolled in the study; 46 in the diet group and 45 in the control group. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤ .001). The median time to achieve spasm cessation was 10 days (interquartile range 9-20). Nine of these had resolution of hypsarrhythmia on electroencephalography (EEG). Thirty (65.2%) in the diet group had >50% reduction in spasms, compared with none in the control group (P < .001). The most common side effect was constipation, noted in 34.8% of the children. CONCLUSIONS: The modified Atkins diet was found to be effective and well tolerated in children with epileptic spasms refractory to hormonal therapy.

Intravenous Methylprednisolone Versus Oral Prednisolone for West Syndrome: A Randomized Open-Label Trial.

OBJECTIVE: To compare intravenous methylprednisolone (IVMP) with oral prednisolone (OP) for the treatment of West syndrome. METHODS: In this randomized, open-label trial, children aged 2 to 30 mo presenting with epileptic spasms with hypsarrhythmia or its variants on EEG were randomized to receive either IVMP (30 mg/kg/d for 3 d followed by oral prednisolone taper) or OP (4 mg/kg/d for two weeks followed by taper). The primary outcome measure was spasms cessation on day 14. Secondary outcomes included time to response, electroclinical remission at 2 and 6 wk, and frequency of adverse effects. ( ClinicalTrials.gov Identifier: NCT03876444). RESULTS: Sixty children were enrolled; 31 in the IVMP and 29 in the OP arm. Proportion of children achieving spasms cessation at day 14 was similar in both groups (54.8% versus 68.9%, p = 0.26). Time to achieve remission was lower in the IVMP group (mean 5.4 ± 0.9 versus 9.5 ± 2.6 d, p < 0.0001). Electroclinical remission at 2 wk was similar in both groups (51.6% versus 44.8%, p = 0.59) but lower at 6 wk in the IVMP group (45.2% versus 75.9%, p < 0.015). Adverse effects like sleep disturbance, irritability and hypertension were more common in IVMP group whereas weight gain was more common in the OP group. CONCLUSIONS: There was no significant difference in spasms cessation between the groups on day 14 although remission was higher at 6 wk in OP group. Our study suggests that OP was better than IVMP in efficacy and sustained remission with fewer adverse effects.

Electroclinical spectrum of childhood epilepsy secondary to neonatal hypoglycemic brain injury in a low resource setting: A 10-year experience.

PURPOSE: Neonatal hypoglycemic brain injury (NHBI) is being increasingly recognized as an important cause of drug resistant childhood epilepsy in low resource settings. We report the electro-clinical spectrum of children with epilepsy secondary to NHBI. METHODS: This was a retrospective study of children enrolled in the Epilepsy Clinic from January 2009 to August 2019. Data of children who had developed epilepsy after documented symptomatic neonatal hypoglycemia was collected. Details of clinical profile, seizure types, neurodevelopmental co-morbidities, EEG, neuroimaging findings and seizure outcomes were noted. RESULTS: One hundred and seventy children were enrolled. The mean age at seizure onset was 10.3 months (SD 0.5 months). The seizures types were epileptic spasms (76.5%), focal with visual auras (11.2%), bilateral tonic clonic (7.1%), myoclonic (3.5%) and atonic seizures (1.8%). The EEG findings included classical hypsarrhythmia (49.4%), hypsarrhythmia variant (27.1%), focal occipital or temporo-occipital spike wave discharges (10.6%), multifocal discharges (4.7%), diffuse slow spike and wave with bursts of fast rhythms (2.4%), continuous spike waves during sleep (1.2%) and normal EEG (4.7%). MRI showed gliosis with or without encephalomalacia in the occipital lobe with or without parietal lobe in 96.5% of the patients. Co-morbidities included global developmental delay (91.2%), cerebral palsy (48.7%), vision impairment (48.2%), microcephaly (38.2%), hearing impairment (19.4%), and behavioural problems (16.5%). Drug resistant childhood epilepsy was seen in 116 (68.2%) patients. CONCLUSIONS: Our study highlights the varied electroclinical and radiological spectrum and the adverse epilepsy and neurodevelopmental outcomes associated with NHBI.

Providing Expressed Breast Milk to Preterm Neonates Admitted in an Extramural Neonatal Intensive Care Unit: Where do we stand?

Provision of expressed breast milk (EBM) to premature neonates poses a great challenge in extramural Neonatal Intensive Care Units (NICUs). We conducted a questionnaire-based survey to identify the various challenges faced by the parents to provide EBM to their hospitalized premature infant. 40 preterm neonates (<34 wk gestation and <1500 g weight) planned to be started on EBM were included in the study. The median (range) duration after which EBM was received in NICU after the time it was asked for was 34.5 (13 to 40) hours, and it was received in a clean, sterile and covered container in only 8 (20%) cases. There were multiple hurdles in ensuring early availability of EBM in optimal condition. Sensitization and motivation of families regarding the importance of ensuring early administration of EBM to their prematurely delivered neonate may lead to substantial improvement in outcome of these neonates.