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.

Early versus late switch over of antiseizure medications from intravenous to the oral route in children with seizures: Single-blinded, randomized controlled trial (ELAIO trial).

INTRODUCTION: Early switch-over of anti-seizure medications (ASMs) from intravenous to oral route may reduce the duration of hospitalization, drug acquisition costs, and behavioral upset in hospitalized children with seizures. OBJECTIVE: The primary objective was to compare short-term seizure recurrence within 1 week in hospitalized children aged 1 month to 18 years with new-onset/breakthrough seizures after an early versus late switch-over from intravenous to the oral route of ASMs. Secondary objectives were to compare the incidence of status epilepticus, duration of hospital stay, drug acquisition costs, and caregiver-reported satisfaction scores in both groups. METHODS: In this single-blind randomized controlled trial, patients with seizures were categorized based on the number of ASMs required and the history of status epilepticus. Patients in each category were randomized in a 1:1 ratio into either early or late switch-over (ES or LS) groups. In the ES groups, ASMs were tapered one-by-one between 0 and 24 hours of seizure freedom, while in the LS groups, they were tapered one-by-one between 24 and 48 hours of seizure freedom. RESULTS: A total of 112 children were enrolled in the study, with 56 in each arm. Seizure recurrence at 1 week and 12 weeks was comparable in ES and LS groups (3/55 vs. 1/54 at 1 week, p=0.61; 7/49 vs. 6/49 at 12 weeks, p=0.98). Drug acquisition costs were significantly lower in the ES group (393±274 vs. 658±568 INR, p=0.002). Thrombophlebitis and dysphoria were significantly more common in the LS group (p=0.008 and 0.03, respectively). CONCLUSION: The early switch-over of ASMs from intravenous to oral route is safe without any significant increased risk of short-term seizure recurrence and also associated with a reduction in the incidence of thrombophlebitis and ASM acquisition costs. TRIAL REGISTRATION NO: CTRI/2021/03/032145.

Association Between Clinical Severity, Neuroimaging, and Electroencephalographic Findings in Children with Subacute Sclerosing Panencephalitis.

BACKGROUND: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear. METHODS: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers. RESULTS: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P < .05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P < .0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P > .05). CONCLUSION: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour's clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features.

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.

Suspect the Unexpected: A Rare Association of Autoimmune Hemolytic Anemia and Hemophagocytic Lymphohistiocytosis with Visceral Leishmaniasis: A Case Report and Review of Literature.

Visceral leishmaniasis is a common tropical infection presenting with a myriad of hematological abnormalities. We report an unusual case of an 11-year-old girl suffering from a febrile illness with hepatosplenomegaly and anemia. Laboratory findings included pancytopenia and hyperbilirubinemia. The leishmania antigen rK39 was positive and bone marrow examination revealed hemophagocytosis and amastigote forms of Leishmania donovani. Direct Coombs' test was positive (warm type, IgG) and LDH was elevated. Tests for other infections were negative. A diagnosis of visceral leishmaniasis with autoimmune hemolytic anemia (warm antibody type, IgG) with hemophagocytic lymphohistiocytosis was made. Patient showed response with anti-leishmanial treatment with improvement in clinical condition.

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.

A Case of Fibrinous Pericardial Effusion: Masquerading Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with varied presentations varying from nonspecific features like fever, malaise, and arthralgia to serious manifestations like serositis (pleural, pericardial effusions), neurological manifestations, and renal involvement (lupus nephritis). SLE is a great mimicker, especially for infections like tuberculosis (TB) which is rampant in low- and middle-income countries (LMIC). We report a case of massive pericardial effusion, which was initially diagnosed as TB on clinico-radiological basis, but the diagnosis was later revised owing to new findings.

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.

Neurological Deterioration in Three Siblings: Exploring the Spectrum of Argininemia.

Argininemia or hyperargininemia is a urea cycle disorder caused by deficiency of the enzyme arginase 1. It is inherited in an autosomal recessive fashion. It commonly leads to spastic diplegia in childhood, but other important features include cognitive deterioration and epilepsy. Unlike other disorders of the urea cycle, hyperammonemia is not prominent. The authors report three siblings with genetically proven argininemia who presented with diverse phenotypes but with spasticity being a common feature. Sibling 1 developed motor regression in early childhood, sibling 2 developed delayed motor milestones from early infancy, whereas sibling 3 had global developmental delay in late infancy after a period of normal development. All siblings had mild hyperammonemia only. Early recognition is imperative, not only to initiate ammonia scavenging therapy which may lead to definite clinical improvement, but also to provide genetic counselling.

Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial.

OBJECTIVES: We aimed to evaluate the efficacy of the modified Atkins diet in children with epileptic spasms who had failed hormonal therapy. METHODS: Children aged 9 months to 3 years having daily epileptic spasms despite a trial of ACTH or oral prednisolone and 1 additional anticonvulsant medication were enrolled. Children were randomly assigned to receive the modified Atkins diet either immediately or after a delay of 4 weeks. The ongoing anticonvulsant medications were continued unchanged. The primary outcome variable was the proportion of children who achieved spasm freedom as per parental reports at 4 weeks. Secondary outcomes included time to spasm cessation, proportion of children with electroclinical remission, the proportion of children with >50% reduction of spasms at 4 weeks, and adverse effects of the diet. (ClinicalTrials.gov Identifier: NCT03807141). RESULTS: A total of 91 children were enrolled in the study; 46 in the diet group and 45 in the control group. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤ .001). The median time to achieve spasm cessation was 10 days (interquartile range 9-20). Nine of these had resolution of hypsarrhythmia on electroencephalography (EEG). Thirty (65.2%) in the diet group had >50% reduction in spasms, compared with none in the control group (P < .001). The most common side effect was constipation, noted in 34.8% of the children. CONCLUSIONS: The modified Atkins diet was found to be effective and well tolerated in children with epileptic spasms refractory to hormonal therapy.

An Unusual Presentation of Menkes Disease Masquerading as a Leukodystrophy with Macrocephaly.

BACKGROUND: Menkes disease is an X-linked neurodegenerative disease caused by mutation in ATP7A gene, which codes for copper-transporting ATPase. It usually presents in early infancy with neuro-regression, hypotonia, seizures, and kinky hair. Magnetic resonance imaging (MRI) of the brain shows cerebral atrophy, subdural effusions, and tortuous cerebral blood vessels. CASE CHARACTERISTICS: We report the case of a 7-month-old boy who presented with global developmental delay, seizures, and increasing head size since 2 months of age and history of sibling death. He had macrocephaly, sparse, hypopigmented hair, seborrheic dermatitis of scalp, hypotonia, and brisk reflexes. Brain MRI was suggestive of megalencephalic leukodystrophy. Careful reexamination of films revealed tortuous blood vessels. Serum copper and ceruloplasmin levels were significantly reduced, leading to diagnosis of Menkes disease. CONCLUSION: This case exemplifies a rare presentation of Menkes disease, simulating a leukodystrophy with macrocephaly. Tortuosity of cerebral blood vessels is an important finding, which can help in differentiating Menkes disease from white matter disorders.