Search

Background: Negative regulator of reactive oxygen species (NRROS) related microgliopathy, a rare and recently recognized neurodegenerative condition, is caused by pathogenic variants in the NRROS gene, which plays a major role in the regulation of transforming growth factor-beta 1. Methods: We report a child presenting with infantile spasms syndrome (ISS) with subsequent progressive neurodegeneration who was identified to harbour a novel likely pathogenic NRROS variant (c.1359del; p.Ser454Alafs*11). The previously published reports of patients with this disorder were also reviewed systematically.Results: Including our index patient, 11 children (6 girls) were identified in total. Early development was normal in seven of these eleven children. All had a history of drug-resistant epilepsy, with 3 having epileptic spasms. The median age at seizure onset and developmental regression was 12 months, and the median age at death was 36 months. Intracranial calcifications were described in eight of eleven children. Neuroimaging revealed progressive cerebral atrophy and white matter loss in all children. The most common reported genetic variation was c.1981delC; (p.Leu661Serfs*97) observed in two families (likely due to a founder effect). Conclusions: Pathogenic variants in NRROS should be suspected in children with neuro-regression and drug-resistant epilepsy including ISS with onset in the first two years of life. Punctate or serpiginous calcifications at the grey-white matter junction and acquired microcephaly are further clues towards the diagnosis

To assess the short-term and long-term comparative efficacy and safety of ASMs for Lennox-Gastaut syndrome (LGS).Following a systematic literature search, randomized controlled trial (RCT) and open-label extension (OLE) studies on LGS comparing ASMs with placebo or other ASMs were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes. For short-term outcomes, a network meta-analysis (NMA) reporting odds ratio (OR) with 95% confidence intervals (CIs) and hierarchy of competing interventions [surface under the cumulative ranking curve(SUCRA)] was done. Long-term outcomes were reported as proportion with 95% CIs using the random-effects model.Fifteen studies including 1263 participants with LGS (aged 2-54years) receiving any of six ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. High-dose CLB (1.0 mg/kg/day; CLB_H) [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with ≥50% reduction in drop seizure frequency as compared with placebo, and achieved the highest-ranking probability (0.89) based on SUCRA values (although there was an overlap between confidence intervals of effect sizes of CLB, RFM and CBD), while high-dose CBD (20 mg/kg/day; CBD_H) [OR: 3.8; 95% CI:1.6-9.0] had significantly higher odds for occurrence of any TEAEs and had the highest-ranking probability (0.85). Furthermore, the long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs.The study findings suggest that CLB_H, CBD and RFM are the most efficacious and safest in terms of both short and long-term outcomes with CLB_H probably leading the hierarchy. Future head-to-head trials comparing these ASMs are needed.

Objective To explore a set of inflammation associated circulatory miRNAs with potential role in etiopathology of psoriasis as differential disease biomarker/s. Subjects and Methodology: Expression profiling of 15 immunologically relevant miRNA candidates was done on plasma samples from psoriasis vulgaris patients compared to healthy subjects by qRT-PCR. Receiver operating characteristic (ROC) curve was analyzed for significantly altered miRNAs to evaluate their disease diagnostic potential. Correlation analysis among significantly altered miRNAs and their association with disease severity (PASI) was done to validate the candidates as robust disease biomarker/s. Downstream targets and the pathways for each of the significant miRNAs were deciphered using miR target prediction tools and pathway enrichment to elucidate their functional relevance in disease pathogenesis. Results: 5 miRNAs exhibited a significant change in their expression level among the 15 candidates tested viz miR-215, miR-148a, miR-125b, miR-223 and miR-142-3p. ROCs for all the 5 miRNAs individually as well as in combination exhibited a significant disease discriminatory area under the curve, AUC = 0.762 and p< 0.0001 for all the miRNAs taken together. Statistically, all 5 miRNAs in combination depicted a robust model as disease severity correlate compared to individual miRNAs with highest R2 value = 0.94 and least AIC score =131.8. Each of the miRNA also exhibited a significant association with at least one of the other miRNAs in the panel. All the 5 miRNAs exhibited functional role in psoriasis immune-pathogenesis in terms of their downstream targets and signaling pathways. Conclusion: In summary our findings identify a panel of blood-based circulatory miRNAs comprising miR-215, miR-148a, miR-125b-5p, miR-223 and miR-142-3p that can differentiate psoriasis vulgaris patients from healthy individuals. In light of the role of each of these miRNAs in modulating immune-inflammatory pathways, the panel provides a rationalized combination of biomarkers that can be tested further on an expanded cohort of patients for its diagnostic value.

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.

Objective This systematic review and meta-analysis were conducted to study the prevalence and pattern of sleep disturbances in children and adolescents during the COVID-19 pandemic. Methods MEDLINE, EMBASE, and Web of Science were searched for original studies describing sleep abnormalities in children and adolescents with or without pre-existing neurobehavioral disorders during the COVID-19 pandemic. The pooled estimates for various sleep abnormalities were calculated using a random-effect model. Results Of 371 articles screened, 16 studies were included. Among these, five studies were in preschool children, two were in children with pre-existing neurobehavioral disorders and the remaining were in school going children and adolescents. The outcome measures used for sleep were markedly heterogeneous across the studies. The pooled prevalence of any sleep disturbance in children during the pandemic was 54%(95%CI:50–57%). Interestingly, the prevalence in pre-school children was lower than pre-pandemic times (RR = 0.87; 95% CI:0.58–1.30) but this was not statistically significant. The pooled prevalence of children not meeting sleep recommendation was 49% (95%CI: 39–58%). Conclusion The prevalence of sleep problems in children and adolescents during the COVID-19 pandemic is alarming. Pre-school children had a trend towards relatively fewer sleep disturbances due to home confinement measures in comparison with pre-pandemic times. Sleep duration recommendations were not met in nearly half of healthy children. However, these conclusions need to be seen in light of limited literature on the topic, few included studies done in heterogenous populations, and dubious quality of inferences drawn from these studies which were predominantly online surveys. Prospero registration id CRD42020213788.

This study aimed to determine the seropositivity of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-4 antibodies (AQP4-Ab) and outcomes in children with acquired demyelinating syndromes (ADSs). Children (6 months–15 years) with suspected ADS were enrolled and tested for MOG-Ab and AQP4-Ab prospectively over 18 months at a tertiary care hospital in North India. Children with proven nonimmune-mediated neurological disorders were enrolled as controls. Of 79 children with suspected ADS, 66 were enrolled. Among the enrolled children with ADS, acute demyelinating encephalomyelitis (ADEM) (25) was the most common first clinical event followed by optic neuritis (ON) (20) and transverse myelitis (TM) (19; one child had ON and TM simultaneously [neuromyelitis optica spectrum disorders [NMOSDs]]), while two children had clinically isolated syndrome (CIS) apart from ON and TM. Fourteen (21.2%, confidence interval [CI] 11.3–31.1) tested positive for one antibody (12 [18.1%; 95% CI 10.5–25.5%] for MOG-Ab and 2 [3%; 95% CI 0–7.2%] for AQP4-Ab). None of the 62 controls tested positive for any antibody. The final diagnosis in those with the monophasic ADS was ADEM (21), ON (13), TM (16), and other CIS (1) while that in children with recurrent events was multiphasic disseminated encephalomyelitis (MDEM) (2), NMOSD (3), ADEM-ON (4), recurrent ON (4), and MS (2). Among those with the first event, 4/51 (7.8%; 95% CI 0.5–15.2%) were MOG-Ab positive and 2 AQP4-Ab positive, whereas 8/15 (53.3% [95% CI 28.1–78.6%]) with recurrent events (MDEM [2], ADEM-ON [4], recurrent ON [1], and recurrent TM [1]) were MOG-Ab positive. Hence, MOG-Abs are the most common antibodies detected in one in five children with pediatric ADS, especially in relapsing disease. AQP4-Abs are rare in children with ADS.

Click-evoked auditory-brainstem-response (ABR) is widely used for hearing screening in neonates and infants. However, their normative values are based on small studies. This retrospective study was done at a tertiary-care centre where click-ABR based screening is done in all newborns. ABR records (Nihon-Kohden machine, model MEB-9400K) of 420 healthy neonates (preterm 75; full-term 32) and infants (113) done over a period 4 years (2014–2018) were analysed retrospectively. Sick neonates and those with Wave V threshold > 40 dbnHL were excluded. Infants were divided into four groups based on post-conceptual age, Group A (75): 34–36 weeks; Group B (44): 37–40weeks; Group C (188):41 weeks-1 month; and Group D (113): 1–6months. The mean absolute latencies for wave I, wave III, and wave V varied from 1.45–1.56 milliseconds (ms), 4.14–4.37 ms, and 6.36–6.81 ms respectively. Interpeak latencies for I–V and I–III varied from 4.91 ms to 5.22 ms and 2.69 ms to 2.81 ms respectively. Older infants had lower absolute and interpeak latencies. Late preterm babies were not different from term babies suggesting early maturation of brainstem pathways.

ImportanceDespite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.ObjectiveTo evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.Data SourcesSystematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.Study SelectionRandomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.Data Extraction and SynthesisData extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.Main Outcomes and MeasuresShort-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.ResultsOf 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event–related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.Conclusions and RelevanceThis study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

To achieve intensive activity-based and goal-directed rehabilitation for unilateral cerebral palsy (UCP), several static and functional upper limb orthoses have been used but with limited robust evidence-base. The current pilot study evaluated the feasibility and efficacy of a customized 3D-printed orthotic device in children with UCP. The attainment of a prespecified goal and Shriners Hospital Upper Extremity Evaluation (SHUEE) at 3 and 6 mo were the efficacy measures. Of the 14 screened children, 5 (median age: 7.9 y; 3 boys) were included. The 3-mo follow-up could be completed for 3 children while 6-mo follow-up could be completed for 1 child. Rest could not be assessed due to pandemic restrictions. Although none attained set goals till the last follow-up, all 3 children (at 3-mo follow-up) showed improvement in SHUEE scores without any significant safety concerns. Further studies on 3D-printed orthosis in UCP are the need of the hour.

To assess the feasibility, effectiveness, and safety of pulse methylprednisolone in comparison with intramuscular adrenocorticotropic hormone (ACTH) therapy in children with West syndrome (WS). This open-label, pilot study with a parallel-group assignment included 44 recently diagnosed children with WS. Methylprednisolone therapy was given as intravenous infusion at a dose of 30 mg/kg/d for five days followed by oral steroids 1 mg/kg gradually tapered over 5–6 wk. The efficacy outcomes included a cessation of epileptic spasms (as per caregiver reporting) and resolution of hypsarrhythmia on electroencephalogram; safety outcome was the frequency of various adverse effects. By day 14 of therapy, 6/18 (33.3%) children in the methylprednisolone group and 10/26 (38.5%) children in the ACTH group achieved cessation of epileptic spasms [group difference − 5.2%; confidence interval (CI) -30.7 to 22.8; p = 0.73]. However, by six weeks of therapy, 4/18 (22.2%) children in the methylprednisolone group and 11/26 (42.3%) children in the ACTH group had cessation of epileptic spasms (group difference − 20.1%; CI -43.0 to 8.4; p = 0.17). Hypertension was more commonly observed in the ACTH group (10 children) than in the methylprednisolone group (2 children; p = 0.046). Pulse methylprednisolone therapy was relatively safe. The study observed limited effectiveness of both ACTH and pulse methylprednisolone therapy, which may partially be due to preponderance of structural etiology and a long treatment lag. However, pulse methylprednisolone therapy appeared to be safe, tolerable, and feasible for management of WS.

Status dystonicus (SD) is a life-threatening movement disorder associated with significant morbidity and requires immediate and urgent intervention. It usually develops from both primary and secondary dystonias and rarely can be a complication of symptomatic insults such as infections, brain insults, or drugs. Compared to adults, it is seen more commonly in children due to the risk of many trigger factors and vulnerability of the developmental brain. Due to the delay in the identification and prevention of the triggering factors, nowadays most children require intensive care. Here, we report a 1-year-old boy, who was a known case of dyskinetic cerebral palsy, presented with increased twisting movements after an episode of febrile illness. The SD partially resolved after midazolam infusion, however, after treating the triggering factors (constipation and pneumonia), the SD resolved completely.

Neurofibromatosis type 2 (NF2) is a monogenic condition caused by mutations in the NF2 gene. Examination of skin and eyes and parental screening play a key role in the diagnosis of pediatric NF2. We report a four-year-old boy, who presented sub-acutely with unilateral vision loss, ptosis and exotropia with a positive family history of NF2.

Objectives Considering the dearth of literature on West syndrome (WS) from South Asian countries, this study aimed to evaluate the management practices in South Asia by an online survey and meta‐analysis. Methods An online questionnaire was sent to 223 pediatric neurologists/pediatricians in India, Pakistan, Myanmar, Sri Lanka, Bhutan, Nepal, and Bangladesh. Their responses were evaluated and supplemented by a meta‐analysis. Results Of 125 responses received (response rate: 56%), around 60% of responders observed male preponderance and an approximate lead‐time‐to‐treatment (LTTT) of 4‐12 weeks. The commonest etiology observed was a static structural insult (88.6% of responders). Most commonly used first‐line drug (country‐wise) was as follows: India—adrenocorticotropin hormone (ACTH, 50%); Pakistan—oral steroids (45.5%); Myanmar, Sri Lanka, and Nepal—oral steroids (94.4%); Bangladesh—ACTH (2/2); Bhutan—vigabatrin (3/5). ACTH and vigabatrin are not available in Myanmar and Nepal. The most commonly used regime for ACTH was maximal‐dose‐at‐initiation‐regime in India, Sri Lanka, and Bangladesh and gradually escalating‐regime in Pakistan. Maximum dose of prednisolone was variable—most common response from India: 3‐4 mg/kg/d; Pakistan, Bhutan, and Bangladesh: 2 mg/kg/d; Sri Lanka, Nepal, and Myanmar: 5‐8 mg/kg/d or 60 mg/d. The total duration of hormonal therapy (including tapering) ranged from 4 to 12 weeks (67/91). Most responders considered cessation of spasms for four weeks as complete response (54/111) and advised electroencephalography (EEG; 104/123) to check for hypsarrhythmia resolution. Difficult access to pediatric EEG in Bhutan and Nepal is concerning. More than 95% of responders felt a need for more awareness. The meta‐analysis supported the preponderance of male gender (68%; confidence interval [CI]: 64%‐73%), structural etiology(80%; CI 73%‐86%), longer LTTT (2.4 months; CI 2.1‐2.6 months), and low response rate to hormonal therapy(18% and 28% for ACTH and oral steroids respectively) in WS in South Asia. Significance This study highlights the practices and challenges in the management of WS in South Asia. These include a preponderance of male gender and structural etiology, a longer LTTT, difficult access to pediatric EEG, nonavailability of ACTH and vigabatrin in some countries, and low effectiveness of hormonal therapy in this region.

Opsoclonus, an uncommon clinical sign, and is often described in the context of opsoclonus myoclonus ataxia syndrome (OMAS). OMAS may be paraneoplastic or postinfectious. However, opsoclonus with or without OMAS may occur in association with a wide gamut of infections. Infection-associated opsoclonus/OMAS (IAO) needs recognition as a separate entity, since it demands relatively brief immunosuppression, symptomatic treatment, and has a better outcome. Case records of children, who presented with opsoclonus to a tertiary-care teaching hospital of North India over a period of 1 year (2017-2018), were reviewed. Those with opsoclonus in the setting of an acute infection/febrile illness (symptomatic opsoclonus; IAO) were included. Of 15 children with opsoclonus, 6 children [median age: 42 months (range: 8 months to 7 years); 2 boys] had opsoclonus associated with an infective or febrile illness. Additional clinical findings in these children included myoclonus (n = 2), ataxia (n = 4) and behavioral abnormalities (n = 4). All these patients had an associated neurologic or nonneurologic illness- scrub typhus (n = 1), tuberculous meningitis (n = 1), mumps encephalitis (n = 1), brainstem encephalitis (n = 1), acute cerebellitis (n = 1), and subacute sclerosing panencephalitis (SSPE, n = 1). Children with acute cerebellitis, brainstem encephalitis, and mumps encephalitis were treated with steroids while those with scrub typhus, tuberculosis, and SSPE were treated with antibiotics, antitubercular therapy, and Isoprinosine, respectively. None of them needed long-term maintenance immunotherapy. The evaluation for tumor was negative in all. Three of the 6 children are functionally normal at the last follow-up. Acute neuro infections may trigger opsoclonus. A careful analysis of clinical data and suitable investigations can help differentiate these children from those with OMAS. This distinction may avoid unwarranted long-term immunosuppression.

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.

Autistic epileptiform regression is an uncommon but extensively described malady in children. The clinico-etiological spectrum of this entity ranges from electrical status epilepticus in sleep to various neurogenetic and neurodegenerative disorders. Identification of these disorders is crucial considering their therapeutic and prognostic implications. Simple investigations such as neuroimaging and electroencephalography with activation procedures can provide valuable diagnostic clues in resource-limited settings; facilitating targeted genetic/metabolic testing. Here we report a 3.5-year-old girl with autistic regression and epilepsy. Neuronal ceroid lipofuscinosis was suspected as her electroencephalogram showed photoparoxysmal response on low-frequency (1-3 Hz) intermittent photic stimulation. A deficient leukocyte tripeptidyl peptidase 1 enzyme confirmed the diagnosis of late infantile neuronal ceroid lipofuscinosis.

To study the course of West syndrome (WS) and coronavirus disease-19 (COVID-19) in children with WS who contracted SARS-CoV-2 infection.This ambispective study was conducted at a tertiary-care center in North India between December 2020 and August 2021 after approval from the Institute Ethics Committee. Five children with WS, positive for COVID-19 based on RT-PCR, fulfilled the inclusion criteria.One child with COVID-19 during the first wave was retrospectively included while four children (of the 70 children screened) were prospectively enrolled. The median age at onset of epileptic spasms was 7 mo (2 boys), and that at presentation with COVID-19 was 18.5 mo. Three had underlying acquired structural etiology. Three were in remission following standard therapy, while two had ongoing spasms at the time of COVID-19 illness. During the illness, two of those in remission continued to be in remission while one child had a relapse. The children with ongoing epileptic spasms had variable course [one had persistent spasms and other had transient cessation lasting 3 wk from day 2 of COVID-19 illness, but electroencephalography (on day 8 of COVID-19 illness) continued to show hypsarrhythmia]. Fever was the most typical symptom (and sometimes the only symptom) of COVID-19, with a duration ranging from 1-8 d. Two children had moderate COVID-19 illness requiring hospitalization, while the rest had a mild illness. All the affected children had complete recovery from COVID-19.The severity of COVID-19 illness in children with WS is often mild, while the subsequent course of WS is variable.

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.

To translate Quality of Life of the Infant (QUALIN), cross-culturally adapt the Hindi version of QUALIN (Hi-QUALIN), and evaluate its psychometric properties in children.This cross-sectional study was performed at the tertiary-care center in North India over 21 mo (April 2019 to January 2021). Healthy children (aged 3 to 36 mo) visiting the hospital for vaccination, minor ailments, routine health checkup, and accompanying an ill sibling were included. Children with infantile spasms in same age group were also included. Hindi translations were carried out by bilingual translators who could fluently communicate and write in Hindi and English. Standard Hindi was used to avoid the misinterpretation or misunderstanding. Discriminant and Construct validity was determined utilizing the known-groups method and factor analysis. Reliability was analysed as internal consistency and test-retest reliability.Four hundred and sixty-four children were recruited through opportunity sample selection method with statistically significant difference between healthy and unhealthy children in total score of Hi-QUALIN (3-12 mo) and (13-36 mo). Finally, Hi-QUALIN (3-12 mo and 13-36 mo) consisted of 29 and 30 items constituting the five extracted factors respectively. Overall internal consistency was excellent (α = 0.92 and 0.88, respectively). Intra-class correlation coefficients (ICC) were 0.84 (95% CI: 0.78-0.89; p 0.0001) and 0.94 (95% CI: 0.93-0.96; p 0.0001) indicating excellent test-retest reliability.Hi-QUALIN has good psychometric properties and can be used for health-related quality of life (HRQoL) measurement in young children.

Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions.

Retrospective case record analysis of children with Neurobehavioral Deterioration associated with Sleep-augmented Epileptiform abnormalities (NDSE).Hospital records of children with NDSE (July, 2015 through December, 2016) were analyzed. Children were categorized as: Encephalopathy with electrical status epilepticus in sleep (ESES) if sleep EEG Spike-wave-Index (SWI) was ≥50% and sleep-induced epileptiform activity (SIEA)-related cognitive dysfunction if SWI ≥25% but50%. Demography, neurobehavior profile (IQ/SQ and behavior using validated psychometric tools), etiology, investigations and treatment details were documented. Outcome assessment was based on three-month follow-up records.Eighteen children with NDSE {12 boys; median age at diagnosis: 7.5 years (IQR: 6-10 years); SIEA (7); ESES (11)} were included. Etiology was structural (23%) and presumed genetic (77%). All children received intravenous-methylprednisolone pulse followed by oral steroids for eight weeks. Electroencephalography of children with SIEA was partly organized with median SWI of 40% (IQR 35, 42), with anterior-predominant epileptiform abnormalities and less apparent secondary synchronization. Children with ESES had a disorganized EEG background with median SWI of 80% (IQR 66, 95). Both SIEA and ESES groups had a similar neurobehavior profile. Behavior scores improved in 6/8 children with ESES and 5/7 in SIEA post steroids. In both the groups, median SWI improved (to5% in SIEA, 45% in ESES). Mild improvement in IQ/SQ was also noted {SIEA [Median (IQR): 3 (1.6, 4.3)]; ESES [Median (IQR): 3.8 (2.8, 7)]}.The study supports the fact that SWI50% in the nap EEG is not mandatory for the diagnosis of ESES, thus it should not be a constraint for steroid treatment.

This study evaluated 32 children (mean age: 8.5 y) with autism spectrum disorder (ASD) and 23 healthy controls (similar age, sex, and Tanner stage) for hyperandrogenism. These children underwent sexual maturity rating (Tanner staging), ASD severity assessment (Childhood Autism Rating Scale), and quantitative estimation for plasma testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione. There was no significant difference in androgen levels in the two groups. Elevated ( 95 centiles) testosterone, DHEAS, and androstenedione levels were seen in 12.3%, 6.2%, and 9% children with ASD, and 7/9 of these children (78%) with hyperandrogenism had severe ASD. However, there was no significant correlation between ASD severity and androgen levels.

Neurofibromatoses are inherited tumour-suppressive disorders that are characterised by multiple neoplastic and non-neoplastic tumours. Neurofibromatosis type 1 is a common disorder with multiple neurofibromas with widespread complications. We here report a seven-year old boy presenting with first episode of seizure and multiple café-au-lait macules but neuroimaging revealed corpus callosal changes without any focal areas of signal intensities.

To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS). This cross-sectional study was initiated after approval from Institutional Ethics Committee. A follow-up cohort of 114 children (aged ≥ 2 y) diagnosed and treated for WS at the authors' center were assessed in-person for epilepsy and neurodevelopmental outcomes using Vineland Social Maturity Scale - Malin’s adaptation for Indian children. Subsequently, age at onset, lead-time-to-treatment, etiology, and response to any of the standard therapies were analyzed as possible predictors of these outcomes. Of 114 children (mean age: 55 ± 32 mo, 91 boys), structural etiology was the predominant underlying etiology (79.8%) for WS. At 2 y of age, 64% had ongoing seizures. At the last follow-up, 76% had social quotient