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The present study used a qualitative approach to explore 1) how sports students manage their commitments towards both academics and sports and 2) what kinds of stressors do these sports students experience during this process. A sample of 93 sports students enrolled in various undergraduate programmes of Delhi University (DU) selected through purposive sampling. A semi structured interview was developed for the study. A thematic analysis was used to explore how the students manage the various commitments towards academics and sports as well as to examine the various stressors arising from combining academics and sports. With respect to commitment to academics and sports, four higher order categories or themes emerged: prioritizing academics over sports, prioritizing sports over academics, want to manage both academics and sports but unable to do so, and able to manage both academics and sports equally. Five themes that emerged with respect to the various stressors that sports students experienced while they negotiated their commitment between academics and sports included: lack of support for sports from college administration and teachers, lack of support from non-sports students, lack of support for academics from team-mates, lack of support for academics from coach and lack of support for academics from family. A model has been proposed which tries to integrate and refine the major themes which emerged from the study to form a larger theory. [ABSTRACT FROM AUTHOR]

Diphtheria, a dreaded disease of childhood which had undergone a dramatic decline in incidence and mortality in the twentieth century as a result of immunisation and effective treatment, has recently been enjoying a minor resurgence especially amongst older children and adolescents, mainly due to waning immunity. Caused by toxigenic Corynebacteria, it is spread by droplet infection from acute cases as well as asymptomatic carriers. The clinical manifestations result from the local infection especially in the upper airways as well as the potent exotoxin which can have long term effect on the heart and nervous system. Management of diphtheria requires administration of antibiotics and anti-toxin as well as effective supportive care for the airway management, myocarditis and neuropathy. Universal immunisation with the fve doses of Diphtheria, Pertussis, Tetanus toxoid (DPT) vaccine needs to be augmented by Tetanus, diphtheria, acellular Pertussis (TdaP) at the of 10-12 years for controlling the rising incidence of diphtheria, especially in India. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of addition of melatonin or triclofos to sleep deprivation as compared with sleep deprivation with placebo for conduct of successful sleep electroencephalogram (EEG) among children between 6 months and 12 years of age., Design, Setting and Patients: 486 children aged between 6 months and 12 years who were uncooperative or referred for sleep EEG were enrolled for this double-blind, placebo-controlled randomised trial between 30 June 2022 and 31 March 2023., Intervention: On the day of sleep EEG, participants were sleep deprived by 25% of their regular sleep duration and then randomly assigned to receive either triclofos (50 mg/kg), melatonin (weight ≤15 kg=3 mg; weight >15 kg=6 mg) or placebo., Outcome: Primary outcome was the conduct of a successful sleep EEG., Results: 486 children were randomly assigned to intervention with triclofos (n=165), melatonin (n=161) or placebo (n=160). Sleep EEG success (p<0.001) with different interventions was: triclofos=145/165(88%); melatonin=123/161 (76%) and placebo=65/160 (41%). Sleep EEG's success rate was better with triclofos than melatonin (OR=2.2; 95% CI 1.2 to 4.1) or placebo (OR=10.6; 95% CI 6.1 to 19.0). Melatonin was better than placebo in the rate of successful sleep EEG (OR=4.7; 95% CI 2.9 to 7.7). Beta artefacts were significantly more with triclofos (51/145) than melatonin (19/123) and placebo (12/65), but the readability of EEG was not impacted. Movement/unwanted arousal artefacts were significantly more with placebo (37/65) than with triclofos (37/145) and melatonin (34/123). Drug-related adverse events were comparable between triclofos and melatonin. Neither of the drugs was associated with any serious adverse events., Conclusions: Both triclofos and melatonin are individually better than sleep deprivation alone for conducting successful sleep EEGs. Triclofos is significantly better than melatonin for conducting sleep EEGs, with no significant increase in adverse events., Trial Registration Number: CTRI/2022/05/042479; Clinical Trials Registry of India., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The childhood central nervous system (CNS) acquired demyelinating syndromes (ADS) can be monophasic or recurrent, with both having considerable overlap in the first decade of life., Objectives: The objective of the study was to describe clinical and radiological features, immunological characteristics, response to therapy and difference between monophasic and first episode of recurrent disorders of pediatric-onset CNS ADS., Methods: Case records of all patients presenting with CNS ADS to the Department of Pediatrics between January 2009 to December 2018 were retrospectively reviewed. Those with complete records and at least 12 months follow up were included for analysis., Results: Overall 95 case records were reviewed (66 monophasic: 20 ADEM and 46 CIS, 29 recurrent: 18 MS, 9 NMOSD, and 2 multiphasic ADEM). The median age of the cohort was 7 years (range: 1-12) and nearly two-thirds (62/95) were males. All acute cases were treated with intravenous pulse followed by tapering oral steroid therapy. All the recurrent entities received azathioprine with rituximab in few. Certain clinical and radiological features of CIS and immune and inflammatory characteristics in CSF were found to be significantly different in monophasic cases compared to first episode of recurrent cases., Conclusions: The CNS ADS show favourable response to immunotherapy. Azathioprine may be an effective long term immunomodulator, particularly in resource limited settings. Certain clinical, radiological and immunological features may differentiate monophasic illness from first episode of recurrent disorder., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Most kidney cancers are metabolically dysfunctional 1-4 , but how this dysfunction affects cancer progression in humans is unknown. We infused 13 C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U- 13 C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2- 13 C]acetate and [U- 13 C]glutamine infusions in patients, coupled with measurements of respiration in isolated human kidney and tumour mitochondria, reveal lower electron transport chain activity in ccRCCs that contributes to decreased oxidative and enhanced reductive TCA cycle labelling. However, ccRCC metastases unexpectedly have enhanced TCA cycle labelling compared with that of primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, whereas inhibiting electron transport chain complex I decreases metastasis. These findings in humans and mice indicate that metabolic properties and liabilities evolve during kidney cancer progression, and that mitochondrial function is limiting for metastasis but not growth at the original site., (© 2024. The Author(s).)

Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration., Competing Interests: Declaration of interests R.J.D. is a founder at Atavistik Bio and serves on the Scientific Advisory Boards of Atavistik Bio, Agios Pharmaceuticals, Faeth Therapeutics, General Metabolics, and Vida Ventures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to understand the experiences of primary caretakers (PCTs) with a child diagnosed with celiac disease (CeD). There is paucity of research in understanding the experiences of PCTs of children with CeD in India., Methods: Purposive sampling was used to select PCTs of CeD-affected children from a tertiary hospital in New Delhi. Ten PCTs took part in the investigation. To gather the data, semi-structured interviews were held with participants. Hindi was used to administer the interviews., Results: The current study focused on the difficulties and worries PCTs experience in managing CeD. The main themes and sub-themes that emerged from the data were diagnosis of CeD (misdiagnosis of CeD, late diagnosis of CeD, feelings at the time of diagnosis, help from a doctor/nutritionist at the time of diagnosis); characteristics of CeD (CeD as a new disease, CeD as an allergy); attitude towards wheat (wheat as a poison, ignorance regarding negative effect of wheat); influence of significant others (making fun of the child, queries from others are a source of worry, non-acceptance of celiac disease by others and pressure to give gluten to the child); issues in following gluten-free diet (GFD) (fear of cross-contamination, distrust on GFD available outside home, GFD is expensive, making GFD is difficult, joint family, non-adherence to GFD, making non-GFD along with GFD); effect of CeD (financial effect of CeD, effect on physical and mental health of the child and PCT, effect on social life, change in family dynamics, eating restrictions); management of CeD (GFD for the whole family to manage CeD, family support to manage CeD, adhering to GFD, early diagnosis); and concerns (future marital concern for the child, cure of CeD, proper physical growth)., Conclusion: The current study gave an understanding of how PCTs dealt with a child's CeD. The difficulties and worries of caretakers should be taken into consideration and appropriate recommendations made to lessen the strain of managing the child's CeD and the daily obstacles associated with it., (© 2023. Indian Society of Gastroenterology.)

Objective: To describe the comorbidities in children with cerebral palsy (CP) and determine the characteristics associated with different impairments., Design: Cross-sectional study., Setting: Tertiary care referral centre in India., Patients: Between April 2018 and May 2022, all children aged 2-18 years with a confirmed diagnosis of CP were enrolled by systematic random sampling. Data on antenatal, birth and postnatal risk factors, clinical evaluation and investigations (neuroimaging and genetic/metabolic workup) were recorded., Main Outcome Measures: Prevalence of the co-occurring impairments was determined using clinical evaluation or investigations as indicated., Results: Of the 436 children screened, 384 participated (spastic CP=214 (55.7%) (spastic hemiplegic=52 (13.5%); spastic diplegia=70 (18.2%); spastic quadriplegia=92 (24%)), dyskinetic CP=58 (15.1%) and mixed CP=110 (28.6%)). A primary antenatal/perinatal/neonatal and postneonatal risk factor was identified in 32 (8.3%), 320 (83.3%) and 26 (6.8%) patients, respectively. Prevalent comorbidities (the test used) included visual impairment (clinical assessment and visual evoked potential)=357/383(93.2%), hearing impairment (brainstem-evoked response audiometry)=113 (30%), no understanding of any communication (MacArthur Communicative Development Inventory)=137 (36%), cognitive impairment (Vineland scale of social maturity)=341 (88.8%), severe gastrointestinal dysfunction (clinical evaluation/interview)=90 (23%), significant pain (non-communicating children's pain checklist)=230 (60%), epilepsy=245 (64%), drug-resistant epilepsy=163 (42.4%), sleep impairment (Children's Sleep Habits Questionnaire)=176/290(60.7%) and behavioural abnormalities (Childhood behaviour checklist)=165 (43%). Overall, hemiparetic and diplegic CP and Gross Motor Function Classification System ≤3 were predictive of lesser co-occurring impairment., Conclusion: CP children have a high burden of comorbidities, which increase with increasing functional impairment. This calls for urgent actions to prioritise opportunities to prevent risk factors associated with CP and organise existing resources to identify and manage co-occurring impairments., Trial Registration Number: CTRI/2018/07/014819., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: We aimed to determine the rate of 30-day hospital readmissions of uncomplicated choledocholithiasis and its impact on mortality and health care use in the United States., Methods: Nonelective admissions for adults with uncomplicated choledocholithiasis were selected from the Nationwide Readmission Database 2016-2018. The primary outcome was the all-cause 30-day readmission rate. Secondary outcomes were reasons for readmission, readmission mortality rate, procedures, and resource use (length of stay and total hospitalization costs and charges). Independent risk factors for readmission were identified using Cox regression analysis., Results: The 30-day rate of readmission was 9.3%. Biliary and pancreatic disorders and postprocedural complications accounted for 36.6% and 10.3% of readmission, respectively. The mortality rate among patients readmitted to the hospital was higher than that for index admissions (2.0% vs. 0.4%, P <0.01). Readmitted patients were less likely to receive endoscopic retrograde cholangiopancreatography (61% vs. 69%, P <0.01) and laparoscopic cholecystectomy (12.5% vs. 26%, P <0.01) during the index admissions. A total of 42,150 hospital days was associated with readmission, and the total health care in-hospital economic burden was $112 million (in costs) and $470 million (in charges). Independent predictors of readmission were male sex, Medicare (compared with private) insurance, higher Elixhauser Comorbidity Index score, no endoscopic retrograde cholangiopancreatography or laparoscopic cholecystectomy, postprocedural complications of the digestive system, hemodynamic or respiratory support, urban hospitals, and lower hospital volume of uncomplicated choledocholithiasis., Conclusions: The uncomplicated choledocholithiasis 30-day readmission rate is 9.3%. Readmission was associated with higher mortality, morbidity, and resource use. Multiple independent predictors of readmission were identified., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited., Methods: This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events., Results: Of 1 304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85-3.20]) and portal vein thrombosis (PVT) (18.46 [14.86-22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75-.89])., Conclusions: Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Literature search forms the foundation of most clinical decisions about patient management and is the starting point for all bedside/bench-side research. Despite being an essential tool in the armamentarium of all medical professionals and researchers, literature search remains a challenge, often resulting in frustration and waste of time (and resources). This article aims to provide a beginner's guide to information seekers for a step-wise approach to literature search on web-based databases., (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background: Coronavirus disease 2019 (COVID 19) usually causes a mild illness among children. However, in a minority of children, it may be associated with the life-threatening multisystem inflammatory syndrome (MIS-C), or thrombotic microangiopathy, or sequelae like type-1 diabetes mellitus (T1DM). We describe a previously healthy, 12-year-old boy with new-onset T1DM with diabetic ketoacidosis (DKA) in the setting of MIS-C, with a course complicated by thrombotic microangiopathy., Case Presentation: The patient presented with four days history of fever, non-bilious vomiting, polyuria and polydipsia. On evaluation, he was noted to have diabetic ketoacidosis. Although Diabetic ketoacidosis with insulin and intravenous fluids, his hospital course was notable for shock requiring vasopressor, purpura fulminans with eschar formation, neurological manifestations (left hemiparesis due to right middle cerebral artery territory infarct, mononeuritis multiplex) and thrombotic microangiopathy. MIS-C-like illness secondary to COVID-19 was suspected due to diabetic ketoacidosis, thrombotic microangiopathy, elevated inflammatory markers, history of contact with COVID-19-infected individual and detectable COVID-19 IgG antibodies. He improved following management with methylprednisolone, intravenous immunoglobulin, low-molecular-weight heparin and aspirin, and was discharged on hospital day 48., Conclusion: MIS-C-like illness should be considered in children and adolescents presenting with complex multisystem involvement in this era of COVID 19. Management with immunomodulatory agents can be lifesaving.

Justification: Febrile seizures are quite common in children but there are controversies in many aspects of their diagnosis and management., Methods: An expert group consisting of pediatric neurologists and pediatricians was constituted. The modified Delphi method was used to develop consensus on the issues of definitions and investigations. The writing group members reviewed the literature and identified the contentious issues under these subheadings. The questions were framed, pruned, and discussed among the writing group members. The final questions were circulated to all experts during the first round of Delphi consensus. The results of the first round were considered to have arrived at a consensus if more than 75% experts agreed. Contentious issues that reached a 50-75% agreement was discussed further in online meetings and subsequently voting was done over an online platform to arrive at a consensus. Three rounds of Delphi were conducted to arrive at final statements., Results: The expert group arrived at a consensus on 52 statements. These statements pertain to definitions of febrile seizures, role of blood investigations, urine investigations, neuroimaging, electroencephalography (EEG), cerebrospinal fluid analysis and screening for micronutrient deficiency. In addition, role of rescue medications, intermittent anti-seizure medication and continuous prophylaxis, antipyretic medication and micronutrient supplementation have been covered., Conclusions: This consensus statement addresses various contentious issues pertaining to the diagnosis and management of febrile seizures. Adoption of these statements in office practice will improve and standardize the care of children with this disorder.

Objectives: The risk of developing new-onset seizure following ascent to high-altitude areas is currently unknown. We undertook a prospective study to quantify this risk., Methods: The study was conducted at a tertiary care hospital in India between July 2015 and December 2017. It included apparently healthy males of age ≥18 years who ascended to an altitude of ≥ 2500 m and stayed there for > 30 continuous days. Individuals with a history of seizure in the past two years, those who had not undergone acclimatization protocol, and those who had a history of any chronic systemic illness were excluded., Results: The 39,213 individuals included in the study together had 39,848.6 person-years of high-altitude exposure. New-onset seizure after ascent occurred in 41 of them, indicating a seizure incidence rate of 102.9 per 100,000 person-years (95% CI = 75.8-139.7). The incidence per 100,000 person-years (95% CI) at altitudes of 2,500-3,500 m, 3,500-5,800 m, and > 5,800 m was 82.3 (53.6-126.1), 134.6 (84.9-213.6), and 210.8 (52.8-841.4), respectively. Seizure was secondary to cerebral venous thrombosis in 12 (29.3%) individuals. No etiology could be determined in the remaining 29 (70.7%) individuals., Conclusions: Our findings suggest that when subjects living at sea level are exposed to high altitudes, they will be at a higher risk for new-onset seizure in the immediate few months of exposure, and that this risk increases with increasing altitude., (Copyright © 2022. Published by Elsevier Ltd.)

Background: POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG -related disorders are sparse. This study maps the clinicogenetic spectrum of POLG -related disorders in the pediatric population., Methods: Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia., Results: A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain., Conclusions: We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Introduction/aims: Corticosteroids prolong ambulation and improve muscle power among boys with Duchenne muscular dystrophy (DMD). However, the optimal steroid regimen remains unclear. Hence, this study was undertaken to compare the efficacy of daily- versus intermittent-steroid regimens in ambulatory boys with DMD., Methods: In this single-center, open-label randomized trial, 72 children were randomized to receive either daily prednisolone (0.75 mg/kg/day) or intermittent prednisolone (0.75 mg/kg/day, for first 10 days of every month). The primary outcome measure was the difference in average score on manual muscle testing (MMT) at baseline and after 6 mo of steroids. A difference of >0.2 was hypothesized to be significant. Secondary outcomes included changes in timed functions, muscular dystrophy-specific functional-rating scale score, peak torque, average power, and pulmonary function., Results: In the intention-to-treat analysis, the mean (SD) change in MMT scores was 0.17 (0.15) and 0.08 (0.10) for the daily and intermittent steroid groups, respectively. The mean difference between the two interventions was 0.10 (95% confidence interval [CI] = 0.04-0.16; P = .003), which although significant was less than the predefined value of 0.2. Statistically significantly improvements were observed with daily-steroid regimen in the Gowers time (P = .01), nine-metre walk test (P = .02) and average power (P = .02) as compared to intermittent-steroid regimen. A total of 19/32 (52.8%) children in the daily-steroid group and 8/29 (27%) children in the intermittent-steroid group experienced some form of adverse effect (P = .02)., Discussion: Over a short-term period, the intermittent-steroid regimen was non-inferior to the daily-steroid regime in preserving muscle strength among children with DMD. However, better improvement of functional measures was observed with daily-steroid administration. The frequency of individual side effects was similar between the two groups., (© 2021 Wiley Periodicals LLC.)

The Developmental Assessment Scale for Indian Infants (DASII) remains the mainstay in India for diagnostic confirmation and validation of upcoming screening tools for development in infants and toddlers. This is an Indian adaptation of Bayley Scales of Infant Development which is the globally accepted gold standard. However, the DASII cutoff points used for categorizing development and distinguishing normal from abnormal development are not in agreement across different studies conducted over the last two decades in India. This is probably due to a lack of mention of cutoff points in the DASII manual and existing literature. The current systematic review summarizes the heterogeneity in literature for interpretation of DASII and its cutoff points. Also, a perspective on the ideal cutoff points is presented., (© 2021. Dr. K C Chaudhuri Foundation.)

The emerging paradigm of childhood autoimmune neurological disorders has exploded in recent times due to reliable diagnostic methods and their ease of availability, well-defined diagnostic criteria, and universal awareness about these disorders. The most important aspect of these disorders is a considerable recovery in response to early targeted immunotherapy. If left untreated and/or ill-treated, these can lead to mortality or lifelong morbidity. Autoantibodies can target any part of the central nervous system (CNS), ranging from superficial structures like myelin to deep intracellular ion channels like voltage-gated potassium channels, resulting in contrasting and at times overlapping symptomatology. Though neuroimaging characteristics and serological tests confirm these disorders' diagnosis, it is essential to suspect them clinically and start management before the reports are available for minimizing morbidity and mortality. In the pediatric age group, several metabolic conditions, like mitochondrial disorders and enzyme deficiencies like HMG-CoA-lyase deficiency, can develop neuroimaging patterns similar to those seen in childhood CNS autoimmune disorders and may also show a favorable response to steroids in acute phases. Hence, the clinician must suspect and work up the index patient appropriately. Here, we briefly discuss the pathophysiology, clinical clues, and potential therapeutic targets related to pediatric CNS autoimmune disorders., Competing Interests: All authors have none to declare., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background: Lockdown due to Corona pandemic is an unprecedented event, which has had a profound impact on the lives of children across all ages. Its effects on children with Neurodevelopmental Disorders (NDD) has not been adequately studied. This study was performed in order to explore the effects of lockdown during the Corona pandemic on children with NDD and their parents., Methods: The survey was conducted in three Indian tertiary-care hospitals wherein parents of children with NDD were requested to respond to an online questionnaire. The questions attempted to elicit various aspects of the children`s therapies and behavioural profiles as well as their parents` experiences during the pandemic related lockdown., Results: 135/188 (71.8%) parents of children with Autism Spectrum Disorder (ASD)(n=104), Attention Deficit Hyperactivity Disorder (ADHD) (n=26) and Learning Disability (LD)(n=5) responded. Pre-lockdown, 133 (99%) children were receiving regular institution-based therapy, which ceased intra-lockdown. Mean cumulative home-based therapy duration significantly increased during lockdown (p=0.03). Parents reported significantly increased temper tantrums in children (p=0.02). They perceived that during lockdown, their children were bored and their interactions and speech worsened. Majority of parents reported worsening of own qualities of life, but felt confident of taking care of their children during lockdown., Conclusions: To conclude, children with NDD and their parents were significantly affected by Corona pandemicrelated lockdown. Institutional therapy discontinuation, behavioural deterioration (especially among ASD and ADHD) and parental stress were prominent challenges whereas parental motivation and reliance on homebased therapy were the positive highlights. The survey points to the role of regular parent-administered homebased therapy in children with NDD, especially to tide over similar unexpected adverse scenarios.

Nearly 20-40% of patients with epilepsy are likely to have drug resistant epilepsy (DRE). Add-on antiseizure drugs do not produce optimal seizure control in these patients. Among the non-pharmacological options, only resective surgery is curative. However, a large majority of patients are not candidates for resective epilepsy surgery. For these children with DRE, non-pharmacological non-surgery "palliative" options should be considered early than late. These include dietary therapies and neuromodulation. While there are numerous clinical trials supporting the efficacy of dietary therapies (viz ketogenic diet, modified Atkins diet and low glycemic index therapy), the evidence for neuromodulation is still evolving. Neuromodulation techniques include vagal nerve stimulation, deep brain stimulation, and transcranial magnetic stimulation. Each of the options, whether diet or neuromodulation, has its own advantages, disadvantages and adverse events profile. These have to be considered and discussed with the family before deciding the modality being chosen.

Importance: The ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet compared with the KD are scarce., Objective: To determine whether the MAD and LGIT diet are noninferior to the KD among children with drug-resistant epilepsy., Design, Setting, and Participants: One hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016, and August 20, 2017, at a tertiary care referral center in India., Exposures: Children were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs., Main Outcomes and Measures: Primary outcome was percentage change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort. The trial was powered to assess noninferiority of the MAD and LGIT diet compared with the KD with a predefined, noninferiority margin of -15 percentage points. Intention-to-treat analysis was used., Results: One hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Intention-to-treat analysis showed that, after 24 weeks of intervention, the median (interquartile range [IQR]) change in seizure frequency (KD: -66%; IQR, -85% to -38%; MAD: -45%; IQR, -91% to -7%; and LGIT diet: -54%; IQR, -92% to -19%) was similar among the 3 arms (P = .39). The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was -21 percentage points (95% CI, -29 to -3 percentage points) and between the KD and LGIT arms was -12 percentage points (95% CI, -21 to 7 percentage points), with both breaching the noninferiority margin of -15 percentage points. Treatment-related adverse events were similar between the KD (31 of 55 [56.4%]) and MAD (33 of 58 [56.9%]) arms but were significantly less in the LGIT diet arm (19 of 57 [33.3%])., Conclusions and Relevance: Neither the MAD nor the LGIT diet met the noninferiority criteria. However, the results of this study for the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision with regard to the 3 diet interventions needs to be individualized., Trial Registration: ClinicalTrials.gov Identifier: NCT02708030.

Movement disorders in childhood comprise a heterogeneous group of conditions that lead to impairment of voluntary movement, abnormal postures, or inserted involuntary movements. Movement disorders in children are frequently caused by metabolic disorders, both inherited and acquired. Many of these respond to vitamin supplementation. Examples include infantile tremor syndrome, biotinidase deficiency, biotin-thiamine-responsive basal ganglia disease, pyruvate dehydrogenase deficiency, aromatic amino acid decarboxylase deficiency, ataxia with vitamin E deficiency, abetalipoproteinemia, cerebral folate deficiency, and cobalamin metabolism defects. Recognition of these disorders by pediatricians and neurologists is imperative as they are easily treated by vitamin supplementation. In this review, we discuss vitamin-responsive movement disorders in children., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2020 Annals of Indian Academy of Neurology.)

Background: Aicardi-Goutières syndrome (AGS) is a genetic inflammatory disorder that presents with early infantile encephalopathy. We report the clinical and molecular details of multiple members of a family with AGS secondary to a novel RNASEH2C mutation, highlighting the evolution of phenotypic abnormalities in AGS., Methods: Between February 2018 and June 2019, a pedigree tree was constructed for 141 members of a family. The clinical and radiological details of 14 symptomatic children were chronicled and compared with the asymptomatic family members. Genetic analysis was performed on 23 individuals (six symptomatic). This involved whole exome sequencing for one patient and confirmation of the identified indel variant in other family members., Results: The symptomatic children were diagnosed as AGS secondary to a novel indel variation in exon 2 of the RNASEH2C gene (chr11:65487843&#95;65487846delinsGCCA). Clinically, between the ages of 2 and 6 months, the symptomatic children developed irritability (14/14), unexplained fever (9/14), chill blains (12/14), sleep irregularities (14/14) and developmental delay (14/14), with deterioration to vegetative state at a median (IQR) age of 10.5 months (9.25-11). In addition, chill blains were observed in 5/17 (29.4%) carrier individuals. Neuroimaging demonstrated a gradual progression of calcification involving basal ganglia, periventricular white matter and dentate nucleus. Three patients also demonstrated presence of subependymal germinolytic cysts., Conclusion: This report highlights a novel founder RNASEH2C mutation and the phenotypic evolution of AGS. In addition, we report chill blains in one-third of RNASEH2C mutation carriers. Neuroradiologically, the report illustrates novel MRI findings and demonstrates a progression pattern of disease. These findings will aid in earlier suspicion and diagnosis of AGS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have declared that no competing interests exist.

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by abnormalities of muscle tone, movement and motor skills, and is attributed to injury to the developing brain. The clinical features of this entity evolve over time and the specific CP syndrome may be recognizable only after 3-5 y of age; although suggestive signs and symptoms may be present at an earlier age. The management involves neurological rehabilitation (addressing muscle tonal abnormalities, and devising physical and occupational therapies) and diagnosis and management of co-morbidities (including epilepsy, impairment of cognition, vision, hearing, and disturbances of growth and gastrointestinal function). The management, therefore, is multidisciplinary involving the treating physician working with a team of rehabilitation-, orthopedic-, psychologic-, and social care- providers.

Alcohol and ketogenic diets increase water consumption. Here, we show that the hormone FGF21 is required for this drinking response in mice. Circulating levels of FGF21 are increased by alcohol consumption in humans and by both alcohol and ketogenic diets in mice. Pharmacologic administration of FGF21 stimulates water drinking behavior in mice within 2 hr. Concordantly, mice lacking FGF21 fail to increase water intake in response to either alcohol or a ketogenic diet. The effect of FGF21 on drinking is mediated in part by SIM1-positive neurons of the hypothalamus and is inhibited by β-adrenergic receptor antagonists. Given that FGF21 also is known to suppress alcohol intake in favor of pure water, this work identifies FGF21 as a fundamental neurotropic hormone that governs water balance in response to specific nutrient stresses that can cause dehydration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ongoing refractory status epilepticus is associated with significant morbidity and mortality. Therapeutic coma induction with midazolam, thiopentone, phenobarbitone or propofol is indicated when conventional antiepileptics fail to abort seizure. Of these, the most extensively studied is midazolam. Amongst the remaining three, phenobarbitone has the most favourable pharmacological profile, but has not been studied adequately, more so in the pediatric age group. The current retrospective case records analysis is an attempt to describe use of phenobarbitone coma in pediatric refractory status epilepticus., Methods: Case records of patients, admitted with status epilepticus to the pediatric inpatient services of a tertiary care teaching hospital of North India between January 2014 and December 2016 were reviewed. Those with refractory status epilepticus who failed to respond to midaolam infusion and phenobarbitone coma was used were included for analysis., Results: Overall, 108 children presented in status, of which 34 developed refractory status epilepticus. Of these 34, 21 responded to midazolam infusion and in 13 high dose phenobarbitone coma following a standardised protocol was used. Amongst these 13 (8 males and 5 females, median age 6 years, IQR: 2.5-9.5), 12 responded and 1 succumbed. The median time to clinical seizure resolution and desired electroencephalographic changes post phenobarbitone initiation were 16 (IQR: 12-25) and 72 h (IQR: 48-120) respectively., Conclusion: High dose phenobarbitone appears to be an effective therapeutic modality in pediatric refractory status epilepticus. The current study provides a protocol for its use which can be validated in future studies with larger sample size., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Acute necrotizing encephalopathy (ANE) is a rare disorder characterized by encephalopathy following a febrile illness, mostly viral. Most cases are sporadic; however, recurrent and familial cases have been linked to RANBP2 mutation., Description of the Case: This is a description of a three and half years old girl with recurrent ANE with RANBP2 mutation (c.1754 C>T (p.T585M)). She had two episodes of encephalopathy, each following a short non-specific febrile illness. Neuroradiologically, she had typical findings involving bilateral thalami during the first episode and involving bilateral temporal and occipital lobes, bilateral cerebellar hemispheres and brainstem during the second episode. She was managed with intravenous gamma globulin and dexamethasone during both the episodes. She recovered significantly with residual deficits in her cognitive and language domains., Conclusions: In relevant clinic-radiological scenarios both isolated and recurrent ANE should be considered because of treatment and long-term outcome related implications., (Copyright © 2016. Published by Elsevier B.V.)

Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5(flox/flox):Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings.

Fibroblast growth factor 15 (FGF15) has been proposed as a postprandial hormone that signals from intestine to liver to regulate bile acid and carbohydrate homeostasis. However, detecting FGF15 in blood using conventional techniques has proven difficult. Here, we describe a stable isotope standards and capture by anti-peptide antibodies (SISCAPA) assay that combines immuno-enrichment with selected reaction monitoring (SRM) mass spectrometry to overcome this issue. Using this assay, we show that FGF15 circulates in plasma in an FXR and circadian rhythm-dependent manner at concentrations that activate its receptor. Consistent with the proposed endocrine role for FGF15 in liver, mice lacking hepatocyte expression of the obligate FGF15 co-receptor, β-Klotho, have increased bile acid synthesis and reduced glycogen storage despite having supraphysiological plasma FGF15 concentrations. Collectively, these data demonstrate that FGF15 functions as a hormone and highlight the utility of SISCAPA-SRM as a sensitive assay for detecting low-abundance proteins in plasma., (Copyright © 2015 Elsevier Inc. All rights reserved.)

An 11-year-old boy presented with complaints of multiple skin-colored hard lumps on the right side of his body and progressive deformity of the right leg of 7-years duration. His parents had also noticed multiple asymptomatic pits over his right arm, palms, and soles since childhood. Examination revealed skin-colored nontender nodules on the right half of his body and shortening of his right leg. The multiple hyperpigmented pits over the right arm, palm, and sole raised diagnostic difficulties, but histopathologic, radiologic, and biochemical investigations confirmed the features of idiopathic calcinosis cutis and porokeratotic eccrine ostial and dermal duct nevus. Unilateral idiopathic calcinosis cutis has not been previously reported in the literature, and the association with ipsilateral porokeratotic eccrine ostial and dermal duct nevus makes this case unique. Diagnostic difficulties and limited options for treatment make this case interesting academically., (© 2015 Wiley Periodicals, Inc.)