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The objective of this study was to look at the clinical outcomes, and to determine the proportion of children with visual recovery after the first demyelinating event of optic neuritis (ON). In this observational study, children with the first clinical event of optic neuritis at an age less than 18 years were evaluated. High-contrast visual acuity, colour vision, Expanded Disability Status Scale (EDSS), Anti-MOG and AQP-4 antibodies were assessed. Of the 55 screened, 45 children (77 eyes), median age-98 months, 30 (67%) bilateral were enrolled. Fifty of 77 eyes (67%) had Snellen visual acuity less than 6/60. Twelve children (27%) were MOG seropositive and 3 had AQP-4 positivity. At median follow up of 35 months, 10 (22%) children had one or more relapses. At follow up, the median (IQR) visual acuity improved from nadir of 2.1 (1–2.7) logMAR to 0 (0–0.18) logMAR and 64/77 eyes (83%) had visual recovery. The diagnosis at last follow up was isolated ON in 39/45 (86.6%), relapsing ON (5, 11%), AQP-4 positive NMOSD (3, 7%), MOG antibody associated demyelination (12, 27%), dual seronegative ON (30,67%) and Multiple sclerosis (1, 2%). Most children with first demyelinating event as ON have a monophasic illness. Despite severe acute-phase visual loss, most eyes with ON will recover good visual functions. The risk of AQP-4 disease and multiple sclerosis is low in this group. • This study observational study looked at visual recovery after optic neuritis in children. • At a median follow up of 35 months, 10 (22%) children had one or more relapses. • Eighty-three percent of affected eyes had visual recovery. • At last follow up, MOG antibody associated demyelination was the cause in 12 (27%). • The risk of AQP-4 disease and multiple sclerosis was less than 10%. [ABSTRACT FROM AUTHOR]

To evaluate the pathogenic variants in GCDH gene and to assess the neurodevelopmental outcomes in children with Glutaric aciduria type 1 (GA-1). Cross-sectional observational study between January 2019 and June 2020 in consecutive North Indian children with a clinical and biochemical suspicion of GA-1. Variants in the coding regions of GCDH gene were identified through Sanger sequencing. Neurodevelopmental and quality of life assessment was done using standardized scales. 24 children with GA-1 were identified. The median age at diagnosis was 12 months and the median delay in diagnosis was 3 months. Genetic analysis was done in 14 cases. It revealed 12 variants (11 missense and one nonsense) from 13 patients. Most of the pathogenic variants were in exon 9 and exon 5. Three novel variants were identified in three patients: two missense variants c.169G > A (p.Glu57Lys), c.1048T > C (p.Cys350Arg) and one nonsense variant c.331C > T (p.Lys111Ter). On neurodevelopmental assessment, majority of children with GA-1 were non ambulatory (62.5%), had limited hand skills (58.3%) and impaired communication (58.3%). Overall, poor global development was noted in 43.7%. A pre-existing developmental delay was significantly associated with impaired communication skills (p = 0.03), and the number of episodes of encephalopathy were significantly associated with impaired gross motor skill (p = 0.02). Presence of encephalopathy was significantly associated with poor performance in social emotional (p = 0.01) and cognitive (p = 0.03) domains of Developmental Profile-III scale and development of severe dystonia (p = 0.01). Our findings highlight the clinical, biochemical, radiological and genetic spectrum of GA-1 in children in North India and report the presence of novel pathogenic variations. • Identification of exon 9 and 5 as hotspots in the GCDH gene in North Indian children. • Identification of three novel pathogenic variations. • Detailed neurodevelopmental and quality of life assessment. • Identification of predictors of poor neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD) and recommended the dosage of 0.9 mg/kg/d for patients aged ≥5years. However, data assessing the minimal efficacious dose and need of dose-titration based on age or disease severity is limited. To determine whether deflazacort 0.45 mg/kg/d (proposed lower dosage) is non-inferior to 0.9 mg/kg/d among newly diagnosed patients with DMD. A double-blinded, non-inferiority, randomized trial, conducted between December 2018 and July 2020. Newly diagnosed patient aged 5–15 years with genetic or muscle biopsy confirmed DMD and baseline 6-min walk distance (6MWD) > 150 m were screened. Patients were randomly assigned (1:1), stratified to prespecified subgroups by age (≤7years and >7years), and baseline 6MWD (≤350 m and >350 m), to receive either 0.45 mg/kg/d or 0.9 mg/kg/d regimens. The primary endpoint was the change in 6MWD, from baseline to week-24 of intervention. The trial was powered with a predefined, non-inferiority margin of 30 m. The analyses were by modified intention-to-treat (mITT). A total of 97 patients were enrolled, 40 receiving 0.45 mg/kg/d and 45 receiving 0.9 mg/kg/d deflazacort comprised of mITT population. For primary endpoint analysis the mean (SD) change in 6MWD from baseline to week-24 was 9.7 m (41.5) in deflazacort 0.45 mg/kg/d, and 34.7 m (43.5) for 0.9 mg/kg/d. The mean difference in change in 6MWD across the group was 24.8 m (95% CI 6.7 to 43, p value 0.008). The mean difference in change in 6MWD in the subgroups of boys ≤7 years of age was 21.8 m (95% CI -0.82, 44.5, p = 0.059), with baseline 6MWD of >350 m was 19.9 m (95% CI -2.4, 42.4; p = 0.08). The incidence of combined moderate to severe treatment-related adverse events was significant in the 0.9 mg/kg/d group by week 24 (odds ratio 0.36 [95% CI, 0.14 to 0.89], p = 0.03). The efficacy of proposed low dose deflazacort in comparison to the standard dose did not meet the prespecified criteria for non-inferiority. The low dose deflazacort was non-inferior in subgroup of patients with age ≤7 years and baseline 6MWD of >350 m. Clinical Trial Registry-India Identifier: CTRI/2019/02/017388. • US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD). • Data assessing dose response and minimal efficacious dose is limited. • Efficacy of low dose deflazacort (0.45 mg/kg/day) is inferior to standard recommended (0.9 mg/kg/day) dose measured by change in 6-min walk distance (6MWD) from baseline to week 24. • The proposed low dose deflazacort was non-inferior to standard dose in a subgroup of boys with age <7 years and baseline 6MWD >350 m. • Combined moderate to severe side-effects were significantly less with low dose deflazacort. [ABSTRACT FROM AUTHOR]

Objective: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome.Methods: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m2/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks.Results: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms.Conclusions: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design. [ABSTRACT FROM AUTHOR]

Boys with Duchenne Muscular Dystrophy (DMD) are at increased risk for compromised bone health, manifesting as low-impact trauma long bone fractures and vertebral compression fractures. In a prospective observational study, we studied bone health parameters in North Indian boys with DMD. We consecutively enrolled ambulatory boys with DMD on glucocorticoid therapy. Bone health was evaluated with X-ray spine, Dual-energy X-ray absorptiometry (DXA), serum calcium, vitamin D3 (25[OH]D), 1,25-dihyroxyvitamin D3 (1,25[OH]2D3), serum osteocalcin, osteopontin, and N terminal telopeptide of type 1 collagen (Ntx) levels. A total of 76 boys with DMD were enrolled. The median age was 8.5 (interquartile range [IQR] 7.04–10.77) years. Among these, seven (9.2%) boys had long bone fractures, and four (5.3%) had vertebral compression fractures. Fifty-four (71%) boys underwent DXA scan, and among these 31 (57%) had low bone mineral density (BMD, ≤−2 z-score) at the lumbar spine. The mean BMD z-score at the lumbar spine was −2.3 (95% confidence interval [CI] = −1.8, −2.8), and at the femoral neck was −2.5 (95% CI = −2, −2.9). 25(OH)D levels were deficient in 68 (89.5%, n=76) boys, and 1,25(OH)2D3 levels were deficient in all. Mean serum osteocalcin levels were 0.68 ± 0.38 ng/mL (n=54), serum osteopontin levels were 8.6 ± 4.6 pg/mL (n=54) and serum Ntx levels were 891 ± 476 nmol/L (n=54). Boys with low BMD received glucocorticoids for longer duration, in comparison to those with normal BMD (median, IQR [16.9 (6–34) months vs. 7.8 (4.8–13.4) months]; p=0.04). Bone health is compromised in North Indian boys with DMD. BMD at the lumbar spine is reduced in more than half of boys with DMD and nearly all had vitamin D deficiency on regular vitamin D supplements. Longer duration of glucocorticoid therapy is a risk factor for low BMD in our cohort. [ABSTRACT FROM AUTHOR]

Background: Calcified neurocysticercosis (NCC) predisposes patients to an enduring state of epilepsy. The predictors for calcification in parenchymal neurocysticercosis are not well defined.Method: In this prospective cohort study, consecutive children with single-lesion parenchymal NCC were enrolled and followed up for one year. All patients were investigated with brain 3 T-MRI and electroimmunotransfer blot (EITB). Clinical follow-ups were performed every 3 months. Radiology was repeated at the 6-month and one-year follow-ups. The proportion of calcified lesions at one year and the predictors of calcification were studied.Result: During the study period from June 2013 to December 2015, 93 children with single lesion parenchymal NCC were enrolled. At presentation, 90 % of the lesions were in the colloidal stage, and 71 % of the lesions had moderate to severe perilesional oedema. All children had 6 months of follow-up, and 86 (92.5 %) had one year of follow-up. Seizure recurrence was present in 13 (14 %) children. Follow-up radiology at one year showed lesion resolution in 51 (59 %) lesions and calcification in 28 (32.5 %) lesions. Children with calcified lesions during follow-up had a higher odds of seizure recurrences {OR, 95 % CI 3.6(2.3-5.6)}. The presence at baseline of diffusion restriction {OR, 95% CI 2.9 (1.01-8.8)}, scolex or wall calcification in the T2 Star weighted angiography MRI images {OR, 95% CI 3.7 (1.7-8.2)} and >10 mm size of the lesion {OR, 95 % CI 2.4 (1.2-5.01)} predicted lesion calcification.Conclusion: Children with calcification of the parenchymal NCC lesions have a higher risk for seizure recurrence during follow-up. The presence of diffusion restriction, calcified nidus in the colloidal nodular stage, and >10 mm size of the lesion at baseline predicted calcification of the lesion during follow-up. [ABSTRACT FROM AUTHOR]

Background Acute transvers myelitis (ATM) is a rare and disabling condition in childhood. There are only few reports of clinical profile, prognosis and predictors of ATM from developing countries. Objective To study the clinical profile of children with ATM and predictors of its outcome. Method Retrospective analysis of children <12 years of age diagnosed with ATM over a period of 6 years from a tertiary care institute. Results Thirty six children (21 boys, median age-7.5 years) were diagnosed with ATM. Weakness was symmetrical at onset in 27 (75%) children with progression over a median of 2 days (IQR 1–5 days). Severe weakness at onset with lower limb power ≤1/5 on MRC scale was present in 27 (75%), a sensory level in 25(69.4%) and bladder dysfunction in 31(86.1%) children. MRI showed longitudinal extensive myelitis (LETM) in 27 (75%) children and the thoracic cord was most commonly affected [18 (50%)]. On a median follow up of 35 months (range IQR 11–57 months); 15 (41.7%) were non ambulatory or required assistance to walk. Severe weakness at onset with power ≤1 on MRC scale, spinal shock, respiratory muscle weakness, mechanical ventilation, greater mean time to diagnosis and treatment was associated with bad outcome. ATM was a monophasic illness in all, except in 3 children; all with neuromyelitis optica spectrum disorder. Progression to multiple sclerosis was not seen in any child in our cohort. Conclusion In this series of childhood ATM from North India, the disease was severe, monophasic and involved long segments (≥3) of cord in majority. Nearly half the children remain dependent on follow up. Delayed diagnosis and delayed initiation of steroid therapy was associated with poor outcome. [ABSTRACT FROM AUTHOR]

Abstract Neurocysticercosis is a common parasitic infection in children in developing countries and neurological symptoms such as seizures are the most common manifestations. However, symptoms of encephalopathy are an unusual presentation in children. A 4-year-old boy presented with recurrent episodes of febrile encephalopathy. His magnetic resonance imaging of the brain was suggestive of milliary neurocysticercosis of various stages. Reports on recurrent encephalopathy following neurocysticercosis are scarce in literature. Hence, we report this case who presented with recurrent episodes of encephalopathy. [ABSTRACT FROM AUTHOR]

We present a 2-month-old male affected by Zellweger syndrome, a rare peroxisomal disorder. The diagnosis was supported by clinical and radiological findings and established by biochemical tests. The characteristic radiological features included anomalous ossification (epiphyseal stippling). We also discuss main differential diagnoses of epiphyseal stippling and a brief literature review. [ABSTRACT FROM AUTHOR]

Background: The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome caused by a defect in cholesterol synthesis. Affected individuals have dysmorphism, short stature, failure to thrive, microcephaly, multiple congenital malformations, and mental retardation. Diagnostic biochemical features include low plasma cholesterol levels and elevated levels of cholesterol precursors, including 7-dehydrocholesterol (7DHC). Aims: The aim of this study is to report a case of SLOS with hypercortisolism and hypothyroidism. Settings and design: This is a case report from the genetic and metabolic unit of a tertiary care teaching hospital in north India. Methods and material: A 5-month-old male child presented with progressively increasing weight since birth. On examination, he had cyanosis, facial dysmorphism, obesity, bilateral cryptorchidism, hypospadias, inverted nipples, and systolic murmur over the left parasternal area. Investigations revealed a decreased serum cholesterol and elevated 7DHC. His serum cortisol and adrenocorticotropic hormone levels were elevated, and there was suppression of cortisol after the high-dose dexamethasone test. Magnetic resonance imaging of the brain and the pituitary region was normal. The thyroid-stimulating hormone was also elevated. Echocardiography revealed a double-outlet right ventricle with ventricular septal defect and pulmonary stenosis. Conclusions: SLOS is an inborn error of cholesterol synthesis associated with failure to thrive and malformations involving almost all the systems of the body. The occurrence of hypercortisolism, hypothyroidism, obesity, and complex cyanotic cardiac lesion in association with SLOS has not been described earlier. [ABSTRACT FROM AUTHOR]

Lissencephaly is a rare brain malformation characterized by a smooth cerebral surface, thickened cortical mantle and microscopic evidence of incomplete neuronal migration. Association of congenital hypothyroidism with lissencephaly is seldom reported. We report a case of lissencephaly with congenital hypothyroidism. [ABSTRACT FROM AUTHOR]