The Spectrum of Inherited Gray Matter Degenerative Brain Disorders (DBD) in Children: A Single-Center Study.

Objectives: To study the clinical spectrum of inherited gray matter degenerative brain disorders (DBD) in children. Methods: This cross-sectional study evaluated children up to 12 y of age, diagnosed with an inherited gray matter DBD in a tertiary care pediatric hospital between July 2019 and December 2020. Results: A total of 314 children with progressive neuroregression were screened. Of these, 117 children with inherited gray matter DBD were included in the study. The clinic-based prevalence of DBD was 8.2%, and inherited gray matter DBD was 3.1%. The proportion of the inherited gray matter DBD was 37.3% among the overall DBD cases. Children were categorized into three groups based on the age at onset of disease: below 2 years (N = 57, 48.7%), between 2 and 5 years (N = 32, 27.3%), and between 6 and 12 years (N = 28, 23.9%). Based on the predominant cerebral structure involved, gray matter DBD were classified as cerebral gray matter disorders (53%), basal ganglia disorders (34.1%), and cerebellar disorders (12.8%). Overall, the most common disorders were Wilson disease (18%), neuronal ceroid lipofuscinosis (NCL) (17%), and neurodegeneration with brain iron accumulation (NBIA) (16%). The most common gray matter DBD in children <2 years of age were NBIA (n = 11), Rett syndrome (n = 11), and gangliosidoses (n = 10). NCL (n = 14) and ataxia telangiectasia (n = 6) were most common in the age group of 2-5 years. Wilson disease (n = 19) was the most common disorder in the age group of 6-12 years followed by NCL (n = 4) and NBIA (n = 3). Conclusion: Our study highlights the burden and spectrum of gray matter DBD in children. The clinic-based prevalence of DBD was 8.2%, and of inherited gray matter DBD was 3.1%. The proportion of inherited gray matter DBD was 37.3% among the overall DBD cases. Wilson disease, NCL, and NBIA are the most common gray matter DBD in children. Timely diagnosis is important for the prevention of recurrence in subsequent pregnancies.

Growth Reaction of Gold Nanorods in the Presence of Mutated Peptides and Amine-Modified Single-Stranded Nucleic Acids.

Conformation of biomolecules like DNA, peptides and amino acids play vital role during nanoparticle growth. Herein, we have experimentally explored the effect of different noncovalent interaction between a 5'-amine modified DNA sequence (NH2 -C6 H12 -5'-ACATCAGT-3', PMR) and arginine during the seed-mediated growth reaction of gold nanorods (GNRs). Amino acid-mediated growth reaction of GNRs results in a snowflake-like gold nanoarchitecture. However, in case of Arg, prior incubation of GNRs with PMR selectively produces sea urchin-like gold suprastructures, via strong hydrogen bonding and cation-π interaction between PMR and Arg. This distinctive structure formation strategy has been extended to study the structural modulation caused by two structurally close α-helical RRR (Ac-(AAAAR)3 A-NH2 ) peptide and the lysine mutated KKR (Ac-AAAAKAAAAKAAAARA-NH2 ) peptide with partial helix at the amino terminus. Simulation studies confirm that a greater number of hydrogen bonding and cation-π interaction between the Arg residues and PMR resulted in the gold sea urchin structure for RRR peptide against KKR peptide.

Asymmetry in cerebral perfusion from circle of Willis arterial variations in normal population.

BACKGROUND: Angiographic and cadaveric studies have evidenced variations in the circle of Willis (CoW). Age-related changes in cerebral hemodynamics may be attributable to vascular variations. OBJECTIVES: The objective is to assess interdependence of completeness of CoW with age using non-invasive MRA and cerebral perfusion using arterial spin labeling (ASL). METHODS: This single-center, prospective study segregated 189 subjects into three groups: ≤5, 5 to 18, and >18 years. Angiographic (complete CoW and vascular asymmetry index) using TOF and contrast-enhanced- (CE-) MRA, and perfusion (perfusion asymmetry index) data using ASL were obtained. RESULTS: One hundred and six (56.08%) subjects showed complete CoW on TOF and 100 (52.91%) on CE-MRA. Anterior and posterior collateral pathways were more prevalent in the younger population. Completeness of CoW decreased with increasing age, group 1 (54/60, 90% TOF; 51/60, 85% CE), group 2 (39/64, 60% TOF; 37/64, 56.92% CE), and group 3 (13/65, 20.31% TOF; 12/65, 18.75% CE); p-value < .0001. A statistically significant decrease in cerebral and cerebellar perfusion with increasing age was seen. Cerebellar to frontal perfusion change was higher in group 1. Fetal posterior cerebral artery (PCA) led to ipsilateral low and contralateral hyperperfusion flow asymmetries between occipital lobes. CONCLUSIONS: This study shows that a complete CoW is commoner in pediatrics than adults and with increasing age, the completeness of CoW decreases paralleled by decrease in cerebral and cerebellar perfusion. There is age-related shift of perfusion from hindbrain to forebrain and the regression of PCoA occurs with increasing age leading to alterations in cerebral perfusion and hemodynamics.

Transition Services for Children and Young Adults with Movement Disorders: A Survey by the MDS Task Force on Pediatrics.

Background: There is currently very limited data related to transition services for movement disorders. Objectives: Movement Disorders Society (MDS) Task Force on Pediatrics conducted a survey of current provision of transition for young adults with movement disorders. Methods: The survey questionnaire was based on review of available evidence, with questions designed to capture service location, transition clinic structure, and core issues discussed. The questionnaire was digitalized as an online survey and sent to all members of the MDS. Results: Responses were received from a total of 252 MDS members representing 67 countries. Of the responders, 59% confirmed that they provided transition clinics for adolescents with movement disorders. Overall, there was some consensus regarding transition services in terms of patient age at transition, movement disorder etiologies, staffing the service, and medical/social issues discussed. Conclusion: This survey provides first-hand data of existing movement disorder transition services and provides useful insights on transition clinics.

Treatment of children with infantile spasms: A network meta-analysis.

AIM: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms. METHOD: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed. RESULTS: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'. INTERPRETATION: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms. WHAT THIS PAPER ADDS: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.

Deflazacort dose optimization and safety evaluation in Duchenne muscular dystrophy (DOSE): A randomized, double-blind non-inferiority trial.

BACKGROUND: 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. OBJECTIVE: 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. METHOD: 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). RESULT: 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). DISCUSSION: 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. TRIAL REGISTRATION: Clinical Trial Registry-India Identifier: CTRI/2019/02/017388.

Methionine-Controlled Impediment of Secondary Nucleation Leading to Nonclassical Growth within Self-Assembled De Novo Gold Nanoparticles.

The conventional key steps for seed-mediated growth of noble metal nanostructures involve classical and nonclassical nucleation. Furthermore, the surface of the seed catalytically enhances the secondary nucleation involving Au+ to Au0 reduction, thus providing in-plane growth of the seed. In contrast to this well-established growth mechanism, herein, we report the unique case of a methionine (Met)-controlled seed-mediated growth reaction, which rather proceeds via impeding secondary nucleation in the presence of citrate-stabilized gold nanoparticles (AuNPs). The interaction between the freshly generated Au+ and the thioether group of Met in the medium restricts the secondary nucleation process of further seed-catalyzed Au+ reduction to Au0. This incomplete conversion of Au+, as confirmed by X-ray photoelectron spectroscopy, results in a significant enhancement of the zeta (ζ) potential even at low Met concentrations. Nucleation of in situ generated small-sized particles (nAuNPs) takes place on the parent seed surface followed by their segregation from the seed. The self-assembly process of these nAuNPs arises from the aurophilic interaction among the Au+. Furthermore, the time-dependent growth of smaller particles to larger-sized particles through assembly and merging within the same self-assembly validates the nonclassical growth. This strategy has been successfully extended toward the seed-mediated growth reaction of AuNPs in the presence of three bio-inspired decameric peptides having varying numbers of Met residues. The study confirms the nucleation strategy even in the presence of a single Met residue in the peptide and also the self-assembly of nucleated particles with increasing Met residues within the peptide.

PPP2R5D-Related Neurodevelopmental Disorder or Developmental and Epileptic Encephalopathy?: A Novel Phenotypic Description and Review of Published Cases.

BACKGROUND: Protein phosphatase 2 regulatory subunit B' delta (PPP2R5D)-related neurodevelopmental disorder is caused by pathogenic variations in the PPP2R5D gene, product of which is involved in dephosphorylation. This is a rare disorder with description limited to case reports. Its phenotypic spectrum has expanded over the last decade. METHODS: We report a child with a developmental and epileptic encephalopathy phenotype with a pathogenic PPP2R5D variant. This phenotype has not been previously reported. We also reviewed the previously published reports of patients with this disorder. RESULTS: Including the index child, 28 cases (15 girls) were identified from nine relevant research items for analysis. All patients had developmental delay. History of seizures was observed in seven patients while macrocephaly was seen in nearly 80% of patients. Nonneurological manifestations were observed in 13 patients with the most common one being ophthalmological manifestations. The most common genetic variation was c.G592A (p.E198K). The common phenotypic associations of this variation were developmental delay, macrocephaly (11/15), and epilepsy (6/15). CONCLUSION: PPP2R5D gene variations should be suspected in children with developmental delay, autistic features, macrocephaly with or without epilepsy in the absence of any clear etiology. Dysmorphic features might provide a diagnostic clue. DEE phenotype may also be the presenting feature and might be an underreported entity.

Comparison of Five Different Electrophysiological Criteria for Childhood Guillain Barre Syndrome.

BACKGROUND: Internationally approved electrodiagnostic criteria for Guillain Barre syndrome lack in children. We intended to compare the diagnostic accuracy of the currently available five electrophysiological criteria for childhood Guillain Barre Syndrome (GBS) at the time of sentinel assessment. METHODOLOGY: In this single-center study, data of children diagnosed with GBS between January 2013 to December 2017 were retrieved. Patient charts were reviewed for clinical features, electrophysiological recordings. The electrodiagnostic results (4 motor nerves and two sensory nerves in upper limbs and lower limbs) were reanalyzed and were classified based on Dutch group; Ho; Hadden; Hughes and Rajabally criteria for GBS. RESULTS: During this study period, of the 205 children with clinical features of GBS, 15 children had incomplete electrophysiological data, and four children were excluded due to missing data. The mean age of onset of the 186 children enrolled was 77 months; the median duration from symptom onset to electrodiagnostic evaluation was seven days; pure motor and motor-sensory form of GBS was seen in 71 and 115 children. Based on the Hadden criteria, a demyelinating pattern was noted in 57 children; axonal in 37; Inexcitable in 84 and Equivocal in 8 children. The sensitivity of the various criteria ranged from 71% to 100% for demyelination, 97% to 100% for axonal. The degree of agreement using Hadden and Rajabally criteria for Equivocal subtypes was 0.93. CONCLUSIONS: The Rajabally criteria showed the best sensitivity, specificity and diagnostic accuracy for electrodiagnosis of GBS in children when compared against Hadden criteria.

Bone density and bone health alteration in boys with Duchenne Muscular Dystrophy: a prospective observational study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Etiologic Profile of Childhood Stroke from North India: Is It Different from Developed World?

OBJECTIVE: To describe the etiology of childhood arterial-ischemic stroke from a developing country and assess short-term neurologic outcome. METHODS: Prospective observational study. Consecutive children between the age of >28 days to <12 years, admitted with the diagnosis of arterial-ischemic stroke were enrolled during the study period from January 2017 to December 2018. Short-term neurologic outcome was assessed with Pediatric Cerebral Performance Category (PCPC) scale and Pediatric Stroke Outcome Measure (PSOM). RESULTS: We enrolled 76 children with arterial-ischemic stroke, with a median age of 24 months (interquartile range 12-69), and 43 (57%) were boys. The most common risk factor for childhood arterial-ischemic stroke was arteriopathy in 59 (77%), followed by cardiovascular disorder in 12 (16%) children. Among 59 children with arteriopathy, 32 (42%) had infection-associated arteriopathies, 10 (13%) had mineralizing angiopathy, 10 (13%) had moyamoya disease. Pediatric stroke risk factors were classified according to Pediatric Stroke Classification and CASCADE primary classification. Short-term neurologic outcome was assessed at 3 months in 62 (82%) survivors. Among stroke survivors, 33 (61%) had sensory-motor deficits, and 24 (39%) had severe neurologic disability (PCPC ≥ 4). The presence of fever, encephalopathy, low Glasgow coma score at presentation, seizures, and infection-associated arteriopathy predicted severe neurologic disability at follow-up. CONCLUSION: The risk factors for pediatric arterial-ischemic stroke are different from developed countries in our cohort. Infection-associated arteriopathies, mineralizing angiopathy, and moyamoya disease are the most common risk factors in our cohort. Two-thirds of pediatric stroke survivors have neurologic disability at short-term follow-up.

Diagnostic values of 68Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

OBJECTIVES: Opsoclonus myoclonus ataxia (OMA) syndrome, also known as "Kinsbourne syndrome" or "dancing eye syndrome," is a rare, paraneoplastic entity which may be associated with pediatric neuroblastic tumors and carry a grave prognosis. We aimed to evaluate the role of 68Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome. METHODS: We retrospectively evaluated the 68Ga-DOTANOC PET/CT data of pediatric patients presenting with OMA syndrome from March 2012 to November 2018. A somatostatin receptor (SSTR)-expressing lesion with corresponding morphological change on CT image was considered PET-positive, while no abnormal SSTR expression or lesion was noticed in PET-negative patients. Histopathology and/or clinical/imaging follow-up (minimum one year) was considered a reference standard for comparing the PET/CT findings. The results of 68Ga-DOTANOC PET/CT were also compared with 131I MIBG whole-body scintigraphy, which was available in five patients. RESULTS: Of 38 patients (13 males, 25 females, aged 3-96 months), 18 (47.3%) had SSTR-expressing lesions (PET-positive), and histopathology revealed neuroblastic tumors in 17/18 lesions (neuroblastoma 14, ganglioneuroblastoma 2, and ganglioneuroma 1) and reactive hyperplasia in 1/18. The remaining 20/38 (52.6%) patients did not demonstrate SSTR-expressing lesions (PET-negative) and had an uneventful follow-up. The average SUVmax of the PET-positive lesions was 10.3 (range 2.8-34.5). The PET/CT results revealed 17 true-positive, one false-positive, 20 true-negative, and zero false-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 95.2%, 94.4%, 100%, and 97.3% respectively. CONCLUSIONS: 68Ga-DOTANOC PET/CT identified neuroblastic tumors with a high diagnostic accuracy in our cohort compared to histology and follow-up. KEY POINTS: • Opsoclonus myoclonus ataxia (OMA) syndrome or "dancing eye syndrome" is a rare paraneoplastic entity which may be associated with pediatric neuroblastic tumors with a grave prognosis. • 123I/131I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of 68Ga-DOTANOC PET/CT is not yet studied. • 68Ga-labelled DOTANOC PET/CT (SSTR) imaging, in our cohort, was able to positively identify neuroblastic tumors with high diagnostic accuracy when compared with histology.

A prospective cohort study to assess the frequency and risk factors for calcification in single lesion parenchymal neurocysticercosis.

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.

KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases.

OBJECTIVE: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants. METHODS: A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. RESULTS: Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. SIGNIFICANCE: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.

Prevalence of autism spectrum disorder in Indian children: A systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disability and is of public health importance. It affects not only the child and the family. It also has direct and indirect cost implications on the nation that are incurred in providing health care, support for education, and rehabilitative services. There is a lack of evidence-based estimate of the population prevalence of ASD in India. Therefore, this systematic review was aimed at determining the prevalence of ASD in the Indian population. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the published studies evaluating the prevalence of ASD in the community setting. A search within the published literature was conducted from different databases (PubMed, OvidSP, and EMBASE). The analysis of data was done using STATA MP12 (StataCorp, College Station, TX, USA). RESULTS: Four studies were included in this systematic review. Of the four included studies, one had studied both urban and rural populations, and the other three had studied the urban populations only. The study from the rural setting showed a pooled percentage prevalence of 0.11 [95% confidence interval (CI) 0.01-0.20] in children aged 1-18 years; and, four studies conducted in the urban setting showed a pooled percentage prevalence of 0.09 (95% CI 0.02-0.16) in children aged 0-15 years. CONCLUSION: The scarcity of high-quality population-based epidemiological studies on ASD in India highlights an urgent need to study the burden of ASD in India. The proper acquisition of data related to the prevailing burden of ASD in India would lead to a better development of rehabilitative services in our country.

Safety, tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome.

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30-60 IU) or oral zonisamide (4-25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.