ABSTRACT
BACKGROUND: Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. METHODS: We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. CONCLUSION: In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.
Subject(s)
Data Analysis , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , High-Throughput Nucleotide Sequencing/methods , Nervous System Diseases/genetics , Child , Child, Preschool , Cohort Studies , Female , Genetic Predisposition to Disease/epidemiology , Humans , India/epidemiology , Male , Multifactorial Inheritance/genetics , Mutation/genetics , Nervous System Diseases/diagnosis , Nervous System Diseases/epidemiologyABSTRACT
INTRODUCTION: Childhood epilepsy is a generalized epilepsy syndrome with a favorable response to antiepileptic drugs; however, a small percentage of typical absence seizures remain refractory to drugs. We studied the safety and efficacy of amantadine in children with refractory absence seizures. MATERIALS AND METHODS: Of 48 children with typical absence seizures attending the outpatient department of a tertiary care neurological center over a period of 3 years from July 2013 to June 2016, 4 children who were refractory to standard treatment for at least 1 year were selected and were started on amantadine 4-6 mg/kg/day, after obtaining informed consent. OBSERVATIONS: The children, aged between 7 and 14 years, had more than 10 episodes of seizures per day in spite of polytherapy with valproate, lamotrigine, clonazepam, levetiracetam, and topiramate in various combinations. Electrographically, all showed the typical generalized 3 Hz spike wave discharges activated by hyperventilation. All the children became seizure free within 1 week after starting amantadine, and there was improvement in their school performance. The children continue to remain seizure free for 6-30 months now. No significant adverse effects were observed on addition of amantadine. DISCUSSION: Amantadine can be tried as a safe add-on drug for children with absence epilepsy refractory to multiple drugs. Further multicenter trials may be needed to prove its effectiveness, as the numbers are small.
ABSTRACT
OBJECTIVE: To assess the effect of monotherapy with Carbamazepine (CBZ) and Sodium valproate (VPA) on serum 25-OH Vitamin D levels in children with epilepsy compared to controls. DESIGN: Cross-sectional study. SETTING: Outpatient department of a tertiary-care Pediatric Neurology centre, and a nearby day-care centre and school. STUDY PERIOD: June 2012 to May 2013. PARTICIPANTS: Children with epilepsy aged 2 to 13 years on monotherapy with CBZ (n=28) or VPA (n=28) for at least 6 months; 109 age-matched controls from a nearby day-care centre and school. RESULTS: The median (IQR) values of 25 (OH) vitamin D was 18.0 ng/mL (13.7-27.3), 21.35 ng/mL (16.4 -25.2) and 30.5 ng/mL (19.1-43.7) in CBZ, VPA and control group, respectively (P= 0.008). 60.7% of patients in CBZ group and 35.7 % in VPA group had low 25 (OH) D levels (%20 ng/mL) compared to 27.8% in controls (P=0.001).The serum alkaline phosphatase level was higher in children on carbamazepine therapy (P=0.001) than controls. CONCLUSION: This study identifies significant risk of vitamin D deficiency in ambulant children with epilepsy on monotherapy with CBZ or VPA.
