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Jyotindra Narayan Goswami,1 Suvasini Sharma2 1Department of Pediatrics, Army Hospital (Research & Referral), New Delhi 110010, India; 2Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, IndiaCorrespondence: Suvasini SharmaNeurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, Connaught Place 110001, New Delhi Tel +91-9910234344Email sharma.suvasini@gmail.comAbstract: Drug-refractory epilepsy is a commonly prevalent pediatric neurological illness of global significance. Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has reemerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy. In addition, this modality has been recognized to reduce anti-epileptic exposure, improve cognition and behavioral profile of patients as well as improve the quality-of-life of care-givers. Current indications of KD include refractory epilepsy syndromes, selected metabolic disorders (such as pyruvate dehydrogenase deficiency) and a host of varied neurological entities. KD research has broadened the knowledge-base about its mechanisms of action. Four types of KD are in vogue currently with varying nutritional constitution, palatability, administration protocols and comparable efficacy. KD initiation and maintenance are the result of concerted effort of a team of pediatric neurologist/epileptologist, nutritionist and patient’s primary care-giver. Consensus is being formulated about various practical aspects of KD such as patient-selection, parental counseling, baseline work-up, dietary prescription, nutritional supplementation, concurrent anti-epileptic drug administration, follow-up and treatment-duration. Novel applications of KD include its use in neonatal epilepsy and super-refractory status epilepticus and tailor-made formulations such as cooking oil-based KD in predominantly rice-fed populations. Increasing body of clinical experience, improved nutritional designs and translational research are promoting KD as a major therapeutic modality. Currently, KD forms a core essence in the armamentarium against refractory epilepsy. In this review, we summarize the recent advances and current perspectives in the use of KD in refractory epilepsy.Keywords: Modified Atkins Diet, low glycemic index diet, ketosis, intractable epilepsy, epileptic encephalopathies, ketogenic diet, epilepsy

Hepatitis A is the most prevalent viral hepatitis in India and rarely can lead to life-threatening complications such as acute liver failure (ALF). Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world, and in the setting of acute viral hepatitis, it can cause massive intravascular hemolysis, resulting in acute kidney injury. Here, we report a case of a 12-year-old male child who had hepatitis A-associated ALF, which was complicated by massive hemolysis due to underlying G6PD deficiency, manifesting as acute renal failure requiring renal replacement therapy with other supportive management. He had a prolonged, protracted stormy clinical course, which was further complicated by dialysis disequilibrium syndrome, posterior reversible encephalopathy syndrome, and nosocomial sepsis, which improved over 4 weeks. Our case highlights the importance of having high index of clinical suspicion for G6PD deficiency in a child with acute viral hepatitis with complications., Competing Interests: The authors have none to declare., (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

An infant presented with recurrent episodes of encephalopathy, responding to nonspecific management of sepsis. High index of suspicion helped uncover underlying error of metabolism., Competing Interests: The authors have none to declare., (© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. 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.

Objective: Pediatric dystonic storm is an underrecognized entity. We aimed to evaluate the profiles of children presenting with dystonic storm in a referral hospital. Management schema and treatment responsiveness of this uncommonly reported entity were analyzed., Methods: Retrospective review of all children (up to 18 years) hospitalized with dystonic storm over 39 months in the aforementioned facility., Results: Twenty-three children whose ages ranged from 2 years 2 months to 14 years 4 months years (median: 6 years 11 months) (males: 13, females: 11) presented with dystonic storm. The annual incidence was 0.4 per 1,000 fresh admissions with an event rate of 0.9 per 1,000 for all admissions. All had Dystonia Severity Action Plan grades 4/5 with identifiable trigger in 13 (50%). Underlying dystonic disorder preexisted in 10 (43.4%); 8 of these had cerebral palsy. Polypharmacotherapy with >4 drugs out of trihexyphenidyl, tetrabenazine, clonazepam, gabapentin, levodopa-carbidopa, trichlorophos, and melatonin was needed. Supportive care and adequate sedation helped in symptom control. All children were managed with midazolam infusion over 2-10 days (median: 5 days). Mechanical ventilation was resorted to in 6 children (3-22 days). Vecuronium and propofol were used in 3/23 (13%) and 4/23 (17%) children, respectively. Deep brain stimulation was curative in 1 child. Hospitalization ranged from 5 to 31 (median: 11) days. Although there were no deaths, rhabdomyolysis was noted in 1 child. Postdischarge, 6 (26%) children relapsed., Conclusions: Dystonic storm is a medical emergency mandating aggressive multimodal management. Supportive care, antidystonic drugs, and early elective ventilation alongside adequate sedation with benzodiazepines ameliorate complications. Relapses of dystonic storm are not uncommon., (© 2021 American Academy of Neurology.)

Background: : Institutional physiotherapy as a standard of care for management of cerebral palsy (CP) has certain shortcomings, especially in resource-constrained settings. This is a proof-of-concept trial to evaluate the efficacy of individualized home-centered activity-based therapy in children with spastic diplegic CP., Design: Randomized controlled trial (open-label)., Settings: Tertiary-care hospital with pediatric neurology services (July, 2014 to July, 2016)., Participants: Consecutive sample of 59 children (5-12 y) with spastic diplegic CP (Gross Motor Function Classification System scores II-III) without fixed lower-limb contractures, illnesses impeding physiotherapy or history of recent botulinum toxin injection/surgery were recruited., Procedure: Children were randomized to Intervention or Control arms. Their 6-minute-walk Test (6MWT) scoring and clinical examination were performed at baseline, 3 and 6 months. Children in Intervention arm (n=30) were prescribed parent-supervised home-centered activity-based therapy (walking, standing, squatting, climbing upstairs/downstairs, kicking a ball, dancing, riding a tricycle/bicycle) in addition to their institutional physiotherapy. Children in Control arm (n=29) were prescribed ongoing institutional physiotherapy alone. Logbooks, home videos and telephonic follow-ups were used to ensure compliance., Main Outcome Measures: Comparison of the mean change in 6MWT scores at 6 months (from baseline) between the two groups., Results: Median (IQR) change in 6MWT scores at 6 months (from baseline) in the Intervention and Control arms were 3.5 (-5.3, 9) m and 3 (-7.8, 6.3) m., Conclusions: Adjunct home-centered activity-based therapy was safe and feasible, but did not result in appreciable gains over 6 months.

Competing Interests: Competing interests: None declared.

Justification: West syndrome is one of the commonest causes of epilepsy in infants and young children and is a significant contributor to neurodevelopmental morbidity. Multiple regimens for treatment are in use., Process: An expert group consisting of pediatric neurologists and epileptologists was constituted. Experts were divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed a consensus. The evidence was reviewed, and for areas where the evidence was not certain, the Delphi consensus method was adopted. The final guidelines were circulated to all experts for approval., Recommendations: Diagnosis should be based on clinical recognition (history/home video recordings) of spasms and presence of hypsarrhythmia or its variants on electroencephalography. A magnetic resonance imaging of the brain is the preferred neuroimaging modality. Other investigations such as genetic and metabolic testing should be planned as per clinico-radiological findings. Hormonal therapy (adrenocorticotropic hormone or oral steroids) should be preferred for cases other than tuberous sclerosis complex and vigabatrin should be the first choice for tuberous sclerosis complex. Both ACTH and high dose prednisolone have reasonably similar efficacy and adverse effect profile for West syndrome. The choice depends on the preference of the treating physician and the family, based on factors of cost, availability of infrastructure and personnel for daily intramuscular injections, and monitoring side effects. Second line treatment options include anti-epileptic drugs (vigabatrin, sodium valproate, topiramate, zonisamide, nitrazepam and clobazam), ketogenic diet and epilepsy surgery.

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.

Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Sing Rana K, Goswami JN, Sareen N. Acute ischemic stroke following water immersion seizure: a case report. Turk J Pediatr 2019; 61: 453-455. Water immersion epilepsy or bathing epilepsy is a rare form of reflex epilepsy. We report a 4-year-old child with water immersion epilepsy who manifested with an unusual presentation in the form of acute onset right hemiparesis triggered by sudden splashing of water on his face. The case is an attempt to sensitize clinicians about this entity. It also highlights the role of meticulous history-taking, examination, relevant investigations and management plan in such scenarios.

A 12-y-old boy presented with developmental delay, autism, epilepsy, limb tremors and behavioral problems which posed a diagnostic challenge. Though his clinical profile and electroencephalogram were suggestive of Angelman syndrome, initial genetic tests were unyielding. Exome sequencing revealed a previously unreported mutation of Ubiquitin Protein Ligase E3A (UBE3A) gene, confirming the diagnosis of Angelman syndrome. The case is aimed to sensitize pediatricians about Angelman syndrome and to highlight the role of sequential investigations in establishing the diagnosis.

Competing Interests: There are no conflicts of interest.

Background: Tyrosine Hydroxylase deficiency is a rare neurotransmitter disorder., Case Characteristics: An Indian family with the disorder., Observations: Phenotypic variation, elevated serum prolactin, genetic confirmation, and partial treatment-responsiveness., Message: Tyrosine Hydroxylase deficiency is a treatable inborn error of metabolism and serum prolactin assists in diagnosis.

The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

Goswami JN, Vaidya PC, Saini AG, De D, Radotra BD, Singhi PD. Drug reaction with eosinophilia and systemic symptoms in a child on multiple antiepileptics. Turk J Pediatr 2017; 59: 197-199. Drug reaction with eosinophilia and systemic symptoms (DRESS) is an adverse drug-reaction that may mimic systemic illnesses and have a fulminant presentation. We describe an 8-year-old girl with epilepsy and exposure to multiple anti-epileptics who presented with fever, extensive maculopapular rash, cervical lymphadenopathy, hepatomegaly, progressive anemia and transaminitis. Infections, autoimmune disorders and hematological or reticuloendothelial malignancies were excluded. Based on the proposed diagnostic criteria, a diagnosis of DRESS was concluded. Her skin biopsy showed atypical findings consistent with erythema multiforme. Suspected anti-epileptic drugs were discontinued. She was administered pulse methyl-prednisolone therapy and broad-spectrum antibiotics along with adequate supportive management. Unfortunately, the child succumbed to nosocomial sepsis. Our case highlights the importance of early suspicion for diagnosis of pediatric DRESS, avoidance of polytherapy and institution of early immunomodulation to improve the outcomes in children in this condition.

The search for water on the surface of the anhydrous Moon had remained an unfulfilled quest for 40 years. However, the Moon Mineralogy Mapper (M3) on Chandrayaan-1 has recently detected absorption features near 2.8 to 3.0 micrometers on the surface of the Moon. For silicate bodies, such features are typically attributed to hydroxyl- and/or water-bearing materials. On the Moon, the feature is seen as a widely distributed absorption that appears strongest at cooler high latitudes and at several fresh feldspathic craters. The general lack of correlation of this feature in sunlit M3 data with neutron spectrometer hydrogen abundance data suggests that the formation and retention of hydroxyl and water are ongoing surficial processes. Hydroxyl/water production processes may feed polar cold traps and make the lunar regolith a candidate source of volatiles for human exploration.

Records of now-extinct short-lived nuclides in meteorites provide information about the formation and evolution of the solar system. We have found excess 10B that we attribute to the decay of short-lived 10Be (half-life 1.5 million years) in hibonite grains from the Murchison meteorite. The grains show no evidence of decay of two other short-lived nuclides-26Al (half-life 700,000 years) and 41Ca (half-life 100,000 years)-that may be present in early solar system solids. One plausible source of the observed 10Be is energetic particle irradiation of material in the solar nebula. An effective irradiation dose of approximately 2 x 10(18) protons per square centimeter with a kinetic energy of >/=10 megaelectronvolts per atomic mass unit can explain our measurements. The presence of 10Be, coupled with the absence of 41Ca and 26Al, may rule out energetic particle irradiation as the primary source of 41Ca and 26Al present in some early solar system solids and strengthens the case of a stellar source for 41Ca and 26Al.

Aluminum-magnesium isotopic analysis of plagioclase in the eucrite Piplia Kalan, with 27Al/24Mg ratio between 2000 to 7000, reveals the presence of excess magnesium-26 resulting from in situ decay of the short-lived nuclide aluminum-26. This observation confirms aluminum-26 as a plausible heat source for melting and differentiation of the eucrite parent body in particular and for planetesimals in general. The inferred initial abundance of 26Al/27Al of (7.5 +/- 0.9) x 10(-7) indicates that melting, differentiation, and crust formation in the parent body of Piplia Kalan was complete within 5 million years of the formation of the solar system.