Savita Sapra

Pseudoseizures in Children: A Profile of 50 Cases:

In contrast to adulthood hysterical disorders, childhood hysteria has not been accorded due recognition. Pseudoseizures are paroxysmal alterations in behavior that resemble epileptic seizures but are without any underlying organic cause. There is paucity of literature on pseudoseizures in children. In the present descriptive study of 2 years’ duration, a series of consecutively seen 50 children with pseudoseizures is reported. After detailed history from parents, various socio-demographic and clinical variables were noted. Of 110 children seen with conversion disorder, 50 had pseudoseizures (45.5%). The average age was 8.2 years in boys and 9.4 years in girls. There were 28 girls (56.0%) and 22 boys (44.0%), and the majority of patients had the pseudoseizures for 1 to 3 months. When the mode of referral was studied, 52% were referred from pediatric outpatient department and the majority were referred to rule out comorbid psychiatric disorder. The fits mimicking generalized tonic-clonic seizures were most common and the duration of fits ranged from 10 to 35 minutes. The most common frequency of fits was 5 to 6 per week. The average duration of symptoms was 2.6 months in boys and 3.2 months in girls. Only 14 patients (28%) gave the history of having seen the fits in a relative or schoolmate. School phobia and the fear of examinations were the most common precipitating factors. Separation anxiety disorder, school phobia, and mood disorders were common comorbid diagnoses. The patients were put on appropriate drug treatment and/or psychotherapy for 3 months. Of 50 cases, 36 (72.0%) remitted, 10 (20.0%) showed a decrease in frequency of pseudoseizures, and 4 (8.0%) did not improve. With correct diagnosis and treatment, the children with pseudoseizures have a good outcome.

Surgery for Drug-Resistant Epilepsy in Children

BACKGROUND Neurosurgical treatment may improve seizures in children and adolescents with drug‐resistant epilepsy, but additional data are needed from randomized trials. METHODS In this single‐center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug‐resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical‐therapy group, 59 patients). The patients in the medical‐therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet–Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical‐therapy group (P<0.001). Between‐group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet–Kamat intelligence quotient (difference, 2.5; 95% CI, ‐0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS In this single‐center trial, children and adolescents with drug‐resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry–India number, CTRI/2010/091/000525.)

Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients

Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p.Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p.Asn392Glufs*5), c.1238A>G (p.Tyr413Cys) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy.

Follow-up of high risk neonates.

The improvement in perinatal care has led to increase in survival as well as reduction of morbidity in sick newborns. These babies need to be followed up regularly to assess growth and neurodevelopmental outcome and for early stimulation and rehabilitation. We present a protocol describing the various components of a follow up program, and services.

Emotional, behavioral and cognitive profile, and quality of life of Indian children and adolescents with type 1 diabetes.

Background and Aims: The psychological stress associated with type 1 diabetes (T1D) may be higher in children from developing world due to limited health resources. The aims of the study were to assess the quality of life (QoL), emotional well-being, behavioral, and cognitive profile of children/adolescents with T1D diagnosed at least 6 months prior. Materials and Methods: Forty-nine children with T1D, aged 6−18 years were assessed using DAWN Youth QoL questionnaire, WHO-5 Well-Being Index, Child Behavior Checklist (CBCL), and Malins Intelligence Scale for Indian children (MISIC). The association of the scores was studied with age, gender, socioeconomic status (SES), frequency of hypoglycemia, HbA1c, and age of onset and duration of T1D. Results: The mean (standard deviation (SD)) for DAWN QoL, WHO-5, CBCL, and MISIC scores was 24.7 (16.7), 74.6 (19.4), 52.6 (8.8), and 96.0 (11.2), respectively. The significant associations noted were: Elevated HbA1c with poorer emotional well-being; higher negative impact on ‘symptoms of disease’ and ‘future prospects’ sub-areas of QoL; shorter duration of disease with more behavioral issues; lower maternal education with more ‘withdrawn/depressed’ behaviors and ‘worry about future prospects’; and lower SES with lower MISIC scores. Earlier onset (age <5 years) was associated with fewer behavioral problems and less negative impact on QoL. Conclusion: Children with recent diagnosis, older age at onset, lower maternal educational level, elevated HbA1c, or belonging to lower SES were identified to have higher prevalence of various psychological and cognitive problems. In resource-limited settings, these children should be prioritized for behavioral and cognitive evaluation.

Behavioral comorbidity in children and adolescents with epilepsy

This cross sectional study assessed the prevalence of behavioral comorbidity and its association with epilepsy-related factors in children and adolescents with epilepsy. One hundred consecutive patients with active epilepsy, aged 6-16 years, were screened for behavioral comorbidity using the Child Behavior Checklist and those who qualified as having behavioral comorbidity were compared with those who did not have it. Behavioral comorbidity was found in 43 of 100 participants. Being treated with antiepileptic drug polytherapy (odds ratio 6.3, 95% confidence interval 1.4-17.3, p=0.01) independently predicted behavioral comorbidity in the patients studied. The demonstrated high frequency of behavioral comorbidity in children with epilepsy suggests that pediatricians and pediatric neurologists should be sensitive to this fact in order to identify and manage behavioral comorbidity in children with epilepsy.

Novel non-identical MECP2 mutations in Rett syndrome family: a rare presentation.

INTRODUCTION Rett syndrome (RS), an X-linked neurodevelopmental disorder and the common cause of mental retardation in females, is caused by methyl CpG binding protein 2 (MECP2) gene mutations with a frequency of more than 95% in classical Rett patients. Majority of RS cases are sporadic but few familial cases caused by either skewed X-chromosome inactivation in healthy female carriers or mosaicism in male carriers are also reported. Most of the times, the mutation carried in a family is the same as found in affected child. METHODS AND RESULTS Here we report a unique family carrying non-identical MECP2 mutations in exon 2 wherein the proband with classical RS was carrying a de-novo early truncating frameshift mutation while her asymptomatic mother was carrying a missense mutation, both predicted as pathogenic mutations. CONCLUSIONS These findings further validate the importance of MECP2 mutation screening in parents of all mutation positive patients and careful evaluation of the pathogenicity of the mutation found in asymptomatic carriers before providing genetic counseling to the family. The results also propose the role of other factors including other gene mutations, environmental and epigenetics factors in modifying the expression of MECP2 mutations.

A Novel MECP2 Change in an Indian Boy With Variant Rett Phenotype and Congenital Blindness: Implications for Genetic Counseling and Prenatal Diagnosis:

Mutations in MECP2 gene are the primary cause of Rett syndrome, a neurodevelopmental disorder that primarily affects girls, and affect 90% to 95% patients with classical Rett syndrome. MECP2 mutations, once thought to be lethal in males, now present a broad spectrum of clinical manifestations in males. This article reports a family with a 9-year-old boy with Rett-like phenotype and congenital blindness, who inherited a novel MECP2 variant (p.P430S) from his asymptomatic mother. The variant was also identified in the asymptomatic maternal grandfather and maternal aunts of the proband, ruling out the possibility that the p.P430S was involved in the phenotype. Findings of the study suggest that a careful evaluation of the pathogenic nature of MECP2 variants identified in males be conducted before proposing genetic counseling or prenatal diagnosis to the family and that the interference of other factors like modifier genes, environment, epigenetics, and mosaicism be taken into account.

Application of chromosomal microarrays in the evaluation of intellectual disability/global developmental delay patients - A study from a tertiary care genetic centre in India.

Intellectual disability (ID)/Global developmental delay (GDD) is a diverse group of disorders in terms of cognitive and non-cognitive functions and can occur with or without associated co-morbidities. It affects 1-3% of individuals globally and in at least 30-50% of cases the etiology remains unexplained. The widespread use of chromosomal microarray analysis (CMA) in a clinical setting has allowed the identification of submicroscopic copy number variations (CNVs), throughout the genome, associated with neurodevelopmental phenotypes including ID/GDD. In this study we investigated the utility of CMA in the detection of CNVs in 106 patients with unexplained ID/DD, dysmorphism with or without multiple congenital anomalies (MCA). CMA study was carried out using Agilent 8×60K chips and Illumina Human CytoSNP-12 chips. Pathogenic CNVs were found in 15 (14.2%) patients. In these patients, CNVs on single chromosome were detected in 10 patients while 5 patients showed co-occurrence CNVs on two chromosomes. The size of these CNVs ranged between 322kb to 13Mb. The yield of pathogenic CNVs was similar for both mild and severe ID/GDD cases. One patient described in this paper is considered to harbour a likely pathogenic CNV with deletion in 17q22 region. Only few cases have been described in literature for 17q22 deletion and patient reported here was found to have an atypical deletion in 17q22 region (Case 90). This study re-affirms the view point that CMA is a powerful diagnostic tool in the evaluation of idiopathic ID/GDD patients irrespective of the degree of severity. Identifying pathogenic CNVs helps in counseling and prenatal diagnosis if desired.

Neurodevelopmental and epilepsy outcome in children aged one to five years with infantile spasms—A North Indian cohort

PURPOSE The present study was planned as there is paucity of outcome data of children with infantile spasms, from India where profile of patients is different from the western world. Moreover, most previous studies have either not used strict inclusion criteria or standardized psychometric tests for developmental outcome. METHODS Ninety-five children, aged one-to-five years under follow up for more than six months in Pediatric Neurology Clinic of a tertiary care hospital with the diagnosis of infantile spasm were enrolled in this cross-sectional study if they had completed one or more years after the onset of spasms. The study period was January-December 2011. Neurodevelopment of each child was assessed using Development Profile 3 and Gross Motor Function Classification System. History regarding epilepsy frequency and control in the last one year was taken. RESULTS Perinatal asphyxia was the commonest etiology in 43/95 children (45.2%). Favorable neurodevelopmental outcome was observed in 8/95 patients. Favorable epilepsy outcome in 58/95 (61.1%) patients was associated with treatment lag≤3 months between apparent onset of spasms and institution of therapy {OR 2 (1.1-3.8)} and response to first line antiepileptic drug {5 (2.6-10)}. CONCLUSIONS The commonest etiology was potentially preventable perinatal cause. Early appropriate treatment may have a favorable epilepsy outcome.