Prevalence, nature, and severity of the psychiatric comorbidities and their impact on quality of life in adolescents with Juvenile myoclonic epilepsy.

INTRODUCTION: Adults with Juvenile myoclonic epilepsy (JME) are at increased risk for psychiatric comorbidities, personality traits, and abnormality in executive function. But studies on adolescents and their impact on quality of life are scarce in the literature. MATERIALS AND METHODS: This cross-sectional study was performed between August 2019 and October 2022 to compare the prevalence of psychiatric comorbidities in adolescents with JME and age and gender-matched healthy controls. After completing DSM-5 Structured Clinical Interview (SCID-5) initially in all patients, we measured the severity of individual psychiatric problems like anxiety, depression, and somatic symptoms by using an appropriate psychometric scale. We also measured both groups' intelligence quotient (IQ), executive function, and quality of life. RESULTS: One hundred patients with JME (14.3 ± 2.5 years, 48 boys) and 100 controls were enrolled. Psychiatric disorders were observed in 46% of JME and 6% of controls (p < 0.01). Psychiatric comorbidities noted in the patients with JME were: somatic symptom and related disorders(n = 14), anxiety (n = 13), adjustment disorders (n = 12), depression (n = 11), oppositional defiant disorder (n = 6), conduct disorder (n = 5), anorexia nervosa (n = 3), narcissistic (n = 3), histrionic (n = 1), substance-related disorder (n = 1), borderline (n = 2) and antisocial personality disorder (n = 2). The prevalence of depressive disorders, anxiety disorders, adjustment disorders, somatic symptoms, related disorders, and any personality disorder was significantly more in the JME group (p < 0.01 for all). Female gender, higher Epilepsy Stigma Scale score, and lower Epilepsy Outcome Expectancy Scale were significantly associated with depressive disorders (p = 0.04, 0.03, 0.03 respectively). Similarly, for anxiety, only female gender and lower Epilepsy Outcome Expectancy Scale were significant associated factors (p = 0.03, 0.02 respectively). CONCLUSIONS: Psychiatric disorders like anxiety, depression, and personality disorders are more frequent in adolescents with JME than in controls.

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial.

BACKGROUND: Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. METHODS: This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. RESULTS: Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (-4.5 ± 2.9 vs -3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. CONCLUSION: A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.

Efficacy and safety of phenytoin and levetiracetam for acute symptomatic seizures in children with acute encephalitis syndrome: an open label, randomised controlled trial.

INTRODUCTION: Seizures represent a significant comorbidity in children with acute encephalitis syndrome (AES). Despite this, there is a notable absence of randomized controlled trials (RCTs) directly comparing antiseizure medications (ASMs) in children with AES. MATERIALS AND METHODS: This RCT aimed to assess the efficacy and safety of phenytoin and levetiracetam in controlling seizures among children with AES. Both ASMs were administered with a loading followed by maintenance dose. After a 12-week period, children exhibiting a normal electroencephalogram and no seizure recurrence underwent tapering and discontinuation of ASM. Clinical follow-up occurred daily for the first week, and subsequently at 4, 12, and 24 weeks, evaluating seizure recurrence, incidence of status epilepticus, cognition, behavior, functional status, ASM acquisition cost, and adverse effects. RESULTS: A total of 100 children (50 in each group) were enrolled. Within the first week, 5 and 3 children in the phenytoin and levetiracetam groups expired. Up to 1 week or death (whichever occurred earliest), 46 (92 %) and 44 (88 %) children remained seizure-free. Intention-to-treat analysis for both best and worst-case scenarios showed insignificant differences (p=0.52 and 1.0). No children experienced seizure recurrence after 1 week in either group. The number of patients with breakthrough status epilepticus, need for mechanical ventilation, duration of hospital stay, presence of epileptiform abnormalities in repeat electroencephalogram at 12 weeks, functional outcomes at 1, 12, and 24 weeks, as well as cognition and behavioral profiles at 24 weeks, were comparable in both groups (p>0.05 for all). However, the incidence of treatment-emergent adverse events (TEAEs) causally related to study medications was significantly higher in the phenytoin group (p=0.04). CONCLUSION: Levetiracetam and phenytoin are comparable in efficacy in terms of achieving clinical seizure control in children with acute encephalitis syndrome, although levetiracetam group demonstrated fewer adverse effects.

Effectiveness of IMPUTE ADT-1 mobile application in children with autism spectrum disorder: An interim analysis of an ongoing randomized controlled trial.

Objectives: IMPUTE Inc., a software firm dedicated to healthcare technology, has developed a mobile medical application known as IMPUTE ADT-1 for children with autism spectrum disorder (ASD) based on the principle of applied behavior analysis. Materials and Methods: The primary objective of this trial was to compare the efficacy of add-on treatment with IMPUTE ADT-1 in children with ASD aged two to six years as compared to standard care alone for 12 weeks (in terms of change in Autism Diagnostic Observation Schedule [ADOS-2] scores). The secondary objective of the study was to assess the compliance with IMPUTE ADT-1 among participants and also to evaluate the feedback of parents regarding IMPUTE ADT-1 at the end of 12 weeks. The application provides personalized programs tailored to each user's needs, and the program evolves based on the user's progress. It also utilizes face tracking, eye tracking, and body tracking to gather behavior-related information for each child and apply it in reinforcement learning employing artificial intelligence-based algorithms. Results: Till the time of interim analysis, 37 and 33 children had completed 12-week follow-up in IMPUTE ADT-1 and control arm. At 12 weeks, as compared to baseline, change in social affect domain, repetitive ritualistic behavior domain, total ADOS-2 score, and ADOS-2 comparison score was better in the intervention group as compared to the control group (P < 0.001 for all). A total of 30 (81%), 28 (75%), and 29 (78%) caregivers in the IMPUTE ADT-1 group believed that the ADT-1 app improved their child's verbal skills, social skills, and reduced repetitive behavior, respectively. Conclusion: IMPUTE ADT-1 mobile application has the efficacy to improve the severity of autism symptoms in children. Parents of these children also feel that the application is beneficial for improving the socialization and verbal communication of their children.

Nutritional vitamin B12 deficiency-associated Infantile epileptic spasms syndrome: Clinico-neurophysiological presentation, response to treatment, and neurodevelopmental outcome.

INTRODUCTION: Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. METHODS: In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables. RESULTS: Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p<0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p<0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p<0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p<0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml). CONCLUSIONS: Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology.

Development and Validation of an Outpatient Clinical Predictive Score for the Diagnosis of Duchenne Muscular Dystrophy/Becker Muscular Dystrophy in Children Aged 2-18 Years.

Introduction: There is no bedside clinical examination-based prediction score for Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in children with neuromuscular diseases (NMDs) presenting with proximal limb-girdle weakness. Methods: We compared the details of 200 cases of lower motor neuron type of weakness and had some proximal limb-girdle muscle weakness and divided them into 2 groups: with/without a confirmed diagnosis of DMD/BMD. We determined the predictive factors associated with a diagnosis of DMD/BMD using multivariate binary logistic regression. We assessed our proposed prognostic model using both discrimination and calibration and subsequently used the bootstrap method to successfully validate the model internally. Results: A total of 121 patients had DMD/BMD and the rest of the patients had other diagnoses. Male gender, presence of Gower's sign, valley sign, toe walking, calf pseudohypertrophy, and tongue hypertrophy were independent predictors for a confirmed diagnosis of DMD/BMD and included in the final CVT2MG score (Calf pseudohypertrophy, Valley sign, Toe walking, Tongue hypertrophy, Male gender, and Gower's sign). The final model showed good discrimination (AUC = 87.4% [95% CI: 80.5-92.3%, P < 0.001]) and calibration (P = 0.57). A score of 6 or above appeared to be the best cutoff for discriminating between the DMD/BMD group and the rest of the group with both sensitivity and specificity of 98%. The interrater reliability was almost perfect between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.91 and 0.87). Conclusion: The CVT2MG score has good sensitivity and specificity in predicting a confirmed diagnosis of DMD/BMD in subsequent tests.

Efficacy of a pre-specified timeline-based treatment protocol in children with acute repetitive seizures or seizure clusters.

Objectives: Acute repetitive seizures (ARSs) are one of the few commonly encountered neurological emergencies in children. There is a need for an appropriate timeline-based treatment protocol, which will be shown to be safe and efficacious in a clinical study. Materials and Methods: This was a retrospective chart review to determine the efficacy of a pre-specified treatment protocol for the management of ARSs in children aged 1-18 years. The treatment protocol was specifically applied in children with a diagnosis of epilepsy and not critically ill, who met the criteria for ARSs, with the exemption of new onset of ARSs. The first tier of treatment protocol focused on intravenous lorazepam, optimization of dose of existing anti-seizure medications (ASMs), and control of triggers like acute febrile illness, while second-tier focused on adding one or two additional ASMs, commonly used in cases with seizure clusters or status epilepticus. Results: We included the first 100 consecutive patients (7.6 ± 3.2 years, 63% boys). Our treatment protocol was successful in 89 patients (58 and 31 required first-tier and second-tier treatment). The absence of pre-existing drug-resistant epilepsy and the presence of acute febrile illness as a triggering factor (P = 0.02 and 0.03) were associated with the success of the first tier of the treatment protocol. Excessive sedation (n = 29), incoordination (n = 14), transient gait instability (n = 11), and excessive irritability (n = 5) were the most common adverse effects observed during the initial 1 week. Conclusion: This pre-specified treatment protocol is safe and efficacious in controlling ARSs in cases with established epilepsy who are not critically sick. External validation from other parts of the world/centers and a more diverse epilepsy population are required before generalizing the protocol into clinical practice.

Development and validation of a predictive model assessing the risk of seizure recurrence in children with neurocysticercosis.

INTRODUCTION: Neurocysticercosis (NCC) is a significant factor contributing to the incidence of seizures in developing countries. While numerous studies have investigated the recurrence of seizures in NCC, their reliability is often limited. METHODS: We assessed the socio-demographic, clinical, and neuroimaging details of 161 children with seizures caused by NCC. We monitored them for seizure recurrence over a 6-month follow-up period. We divided the children into two groups: those with seizure recurrence and those without. Subsequently, we identified predictive factors associated with seizure recurrence through univariate analysis, followed by multivariate binary logistic regression. We evaluated the prognostic model for discrimination and calibration and then internally validated it using the bootstrap method. RESULTS: A total of 23 children experienced breakthrough seizures. In multivariate analysis, the presence of epileptiform abnormalities in electroencephalogram (EEG), more than 5 NCC lesions, the presence of perilesional edema greater than 2 cm in maximum dimension, and a cluster of seizures before presentation were significantly associated with seizure recurrence (p < 0.05). These factors were included in the final NEPC (Number of NCC lesions, Epileptiform EEG abnormality, Perilesional edema, and Cluster of seizures) score. The final model exhibited good discrimination (AUC = 89.1 %; 95 % CI=80.5-95.3 %, p < 0.001) and calibration (p = 0.54). A score of 4 appeared to be the optimal threshold for discriminating between individuals with and without seizure recurrence, with sensitivity and specificity values of 85 % and 87 %, respectively. Interrater reliability was very strong between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.92 and 0.86, respectively). CONCLUSION: The NEPC score demonstrates good sensitivity and specificity in predicting seizure recurrence in pediatric children with NCC.

Validity and prognostic utility of clinical assessment scale for autoimmune encephalitis (CASE) score in children with autoimmune encephalitis.

INTRODUCTION: The clinical assessment scale for autoimmune encephalitis (CASE) is a recently developed and validated scale to rate the severity of autoimmune encephalitis (AE) in adults. But it is yet to be validated in pediatric AE cases. METHODS: In a prospective observational study, we determined the validity and prognostic utility of CASE in the pediatric population with a diagnosis of probable or definite AE. We also determined clinical, neuroimaging, or laboratory-based prognostic factors for favorable clinical outcomes at 3 months after presentation. We used weighted kappa statistics and the intra-class correlation coefficient of individual item scores and total scores for determining inter-observer and intra-observer reliability respectively. RESULTS: We enrolled a total of 54 patients (28 girls, probable [45%] or definite [55%] AE). Functional status score (FSS), CASE score, and other scores showed significant improvement at the time of discharge and 3-months, as compared to baseline (p < 0.0001). The intra-observer and interobserver reliability of the total scores was excellent (k = 0.94 and 0.95 respectively). CASE was also found to have good internal consistency (Cronbach-α = 0.83). The corrected item-total correlations of all items were >0.40. The correlation between the total CASE score and FSS score at admission, at discharge, and at 3 months was strong (r = 0.90, 0.92, and 0.94, p < 0.001). In multivariate analysis, only seropositivity or definite AE and CASE score at baseline was found to be significant predictive factors for functional status at 3 months (p = 0.03, 0.01). CONCLUSION: CASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up.

Performance of a pediatric adaptation of the RITE2 and APE2 scores in children with autoimmune epilepsy: P-RITE2 and P-APE2 scores.

INTRODUCTION: In adult patients with epilepsy, predictive models have been developed and validated for anticipating a favorable response to immunotherapy. However, no such model has been evaluated in children. METHODS: This retrospective cohort study intended to assess the performance of a pediatric adaptation of the Response to Immunotherapy in Epilepsy (RITE2) score: P-RITE2 score and Antibody Prevalence in Epilepsy (APE2) score: P-APE2 score in patients aged 1-18 years. We included data of those patients who had epilepsy duration of not more than 12 months, no other known etiology (e.g., genetic, metabolic, neoplastic, or structural causes), and tested for neural-specific antibody in cerebrospinal fluid or serum for P-APE2 score and only those who received immunotherapy for P-RITE2 score. We added cognitive dysfunction, speech dysfunction, sleep disturbance, and movement disorder to the original scores to increase specificity for pediatric autoimmune epilepsy. We assumed at least a 50% reduction in seizure frequency at 6 months as a favorable response to immunotherapy. Cut-offs were chosen for both scores to maximize true positives and minimize false negatives using ROC curves. RESULTS: We included data from a total of 237 patients with epilepsy (10.4 ± 2.5 years, 129 boys, 54%), out of which, 25 (10.5%, 13 girls, 52%) tested positive for autoantibodies. The median P-APE2 score in the subgroup with and without antibody positivity were 7 (IQR: 5-11) and 2 (IQR: 1-5), respectively (p<0.0001). ROC analysis of the P-APE2 score determined an AUC of 0.96. The sensitivity and specificity values of the P-APE2 score ≥6 were 94% and 92%, respectively. A total of 162 patients (10.3 ± 2.5 years, 88 boys, 54%) received immunotherapy, out of which, 101 had a favorable response at 6 months. The median P-RITE2 score in the subgroup with and without favorable response following a trial of immunotherapy were 10 (IQR: 6-17) and 3 (IQR: 1-6), respectively (p<0.0001). ROC analysis of the P-RITE2 score determined an AUC of 0.96. The sensitivity and specificity values of P-RITE2 score ≥8 were 95% and 93%, respectively. The AUC of both these ROCs was significantly higher than the AUC of ROCs for original scores in our cohort. CONCLUSION: The P-RITE2 and P-APE2 scores can be used to predict the response to immunotherapy and predict autoantibody positivity in children with epilepsy with/without encephalopathy or cognitive dysfunction.

Peritoneal dialysis in children with sepsis-associated AKI (SA-AKI): an experience in a low- to middle-income country.

Background: In critically ill children, sepsis-associated acute kidney injury (SA-AKI) has significant morbidity and mortality.Aim: To estimate whether early initiation of peritoneal dialysis (PD) has a better short-term outcome than standard PD.Methods: Early PD (n = 25) was defined as a need for PD in Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 AKI, while those fulfilling the criteria for stage 3 KDIGO were categorised as a standard PD group (n = 25). The primary outcome measure was the estimated glomerular filtration rate (eGFR) at discharge or at 4 weeks after initiation of PD, whichever occurred earlier.Results: A prospective cohort of 50 children (32 boys) aged 2 months to 16 years with SA-AKI who underwent PD were recruited. The most frequent indication for PD was fluid overload (40%), followed by persistent metabolic acidosis (36%). Children in the early PD group had lower creatinine and higher eGFR at discharge/4-week follow-up (p < 0.001). The duration of PD was less if it was commenced early (p < 0.04); 24 of 25 (96%) children in the early PD group were off PD within 6 days of initiation compared with 13 of 25 (52%) in the standard PD group (p < 0.001).Conclusions: Compared with standard PD, early PD in SA-AKI resulted in a favourable renal outcome, decreased duration of PD and early discontinuation of dialysis.Abbreviations : AKI: acute kidney injury; CRRT: continuous renal replacement therapy; CS-AKI: cardiac surgery-associated acute kidney injury; eGFR: estimated glomerular filtration rate; ELAIN: early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury; ESCAPE: effect of strict blood pressure control and ACE inhibition on the progression of chronic kidney disease in paediatric patients; HIC: high-income countries; ISN: international society of nephrology; KDIGO: Kidney Disease: Improving Global Outcomes; LMIC: low- to middle-income countries; PD: peritoneal dialysis; PICU: paediatric intensive care unit; RRT: renal replacement therapy; SA-AKI: sepsis-associated acute kidney injury; SYL: Saving Young Lives; SOFA: sequential (sepsis-related) organ failure assessment score; STARRT-AKI: standard versus accelerated initiation of renal replacement therapy in acute kidney injury.

Infantile tremor syndrome and laryngomalacia: A novel association?

BACKGROUND: Infantile tremor syndrome (ITS) is a rare clinical entity, predominantly characterized by coarse tremors, regression of motor and/or cognitive, and language milestones. Although the exact pathogenesis yet remains to be unknown, various micronutrient deficiencies like vitamin B12, zinc, magnesium, and vitamin C have been shown to be associated with ITS. Vitamin B12 deficiency is the most accepted etiology of this entity. Here we are describing a seemingly novel association of laryngomalacia with infantile tremor syndrome. METHODS: Clinical details, laboratory investigations, demographic and socioeconomic parameters of all children<2 years of age, diagnosed with ITS between August 2019 and November 2020 was obtained by a retrospective chart review. The study population was divided into two subgroups based on the presence/absence of laryngomalacia and different variables were compared between the two subgroups. RESULTS: During the study period, 22 ITS and 13 pre-ITS cases were identified, out of which 5 ITS cases had laryngomalacia, the prevalence is higher as compared to estimated prevalence in reported literature (p < 0.0001). All these 5 cases had associated gastro-esophageal reflux and swallowing dysfunction and all of them were managed conservatively, apart from standard care treatment for ITS. On follow-up, all 5 of them showed improvement in symptoms of laryngomalacia, apart from clinical and hematological improvement. Differences between various clinical and biochemical parameters in the subgroup with and without laryngomalacia were not significantly different. Seventeen out of twenty-two children with ITS and 10/13 children with pre-ITS had macrocytic anemia and the rest had dimorphic anemia on peripheral smear. There was moderate vitamin B12 deficiency in 13/22 and 8/13 children with ITS and pre-ITS respectively, and the rest had a severe vitamin B12 deficiency. CONCLUSION: Clinicians need to screen cases with ITS for probable symptoms of laryngomalacia and accordingly advise management measures. Although our study showed a seemingly apparent association between ITS and laryngomalacia, large prospective controlled studies with long-term follow-up are necessary to prove this association.