Landscape of genetic infantile epileptic spasms syndrome-A multicenter cohort of 124 children from India.

OBJECTIVE: Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce in developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children. METHODS: Between January 2021 and June 2022, this cross-sectional study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural-genetic and structural-metabolic etiology, were recruited and underwent detailed in-person assessment for phenotypic characterization. The multicentric data on the genotypic and phenotypic characteristics of genetic IESS were collated and analyzed. RESULTS: Of 124 probands (60% boys, history of consanguinity in 15%) with genetic IESS, 105 had single gene disorders (104 nuclear and one mitochondrial), including one with concurrent triple repeat disorder (fragile X syndrome), and 19 had chromosomal disorders. Of 105 single gene disorders, 51 individual genes (92 variants including 25 novel) were identified. Nearly 85% of children with monogenic nuclear disorders had autosomal inheritance (dominant-55.2%, recessive-14.2%), while the rest had X-linked inheritance. Underlying chromosomal disorders included trisomy 21 (n = 14), Xq28 duplication (n = 2), and others (n = 3). Trisomy 21 (n = 14), ALDH7A1 (n = 10), SCN2A (n = 7), CDKL5 (n = 6), ALG13 (n = 5), KCNQ2 (n = 4), STXBP1 (n = 4), SCN1A (n = 4), NTRK2 (n = 4), and WWOX (n = 4) were the dominant single gene causes of genetic IESS. The median age at the onset of epileptic spasms (ES) and establishment of genetic diagnosis was 5 and 12 months, respectively. Pre-existing developmental delay (94.3%), early age at onset of ES (<6 months; 86.2%), central hypotonia (81.4%), facial dysmorphism (70.1%), microcephaly (77.4%), movement disorders (45.9%) and autistic features (42.7%) were remarkable clinical findings. Seizures other than epileptic spasms were observed in 83 children (66.9%). Pre-existing epilepsy syndrome was identified in 21 (16.9%). Nearly 60% had an initial response to hormonal therapy. SIGNIFICANCE: Our study highlights a heterogenous genetic landscape and phenotypic pleiotropy in children with genetic IESS.

Clinical and Electrophysiological Factors Predicting Prolonged Recovery in Children with Guillain-Barré Syndrome.

OBJECTIVE: To compare clinical and nerve conduction studies (NCS) parameters predictive of outcome in children with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). METHODS: In this prospective observational study, NCS was done on all children at admission and repeated before discharge. Functional status of patients was graded as per Hughes Disability score. These children were followed up till they achieved independent walking. Clinical and NCS criteria were compared between (a) AMAN and AIDP and (b) two subgroups of children with AMAN-those who achieved early (within 60 d) versus delayed (i.e., after 60 d) walking. RESULTS: Fifty-seven children were initially enrolled, first NCS showed inexcitable nerves in 10, AMAN in 29, acute motor-sensory axonal neuropathy (AMSAN) in 3, AIDP in 13, and 2 were normal. Subsequent NCS showed AMAN in 37, AIDP in 15, AMSAN in 3 patients. There were no deaths, 16 required ventilation. Follow-up till independent walking, was available for 40 patients. AMAN was associated with faster progression, greater peak disability, prolonged hospital stay, and delayed walking (p < 0.05). Asymmetrical nerve involvement predicted prolonged hospital stay as well as delayed walking. In the AMAN group, prolonged ulnar F-wave latencies were significantly associated with delayed walking (p = 0.02). CONCLUSION: Long term prognosis of pediatric GBS is generally satisfactory. AMAN, asymmetric involvement and prolonged ulnar F-wave latencies in children with AMAN were associated with delayed walking.

Significant treatment gap and co-morbidities identified in an epidemiological survey of pediatric epilepsy in rural suburbs of India.

PURPOSE: A cross-sectional epidemiological survey of children was conducted in two rural clusters to estimate the point prevalence and study various aspects of childhood epilepsy. MATERIAL AND METHODS: In the first stage, a house-to-house survey was conducted by health workers using a screening questionnaire, which was pre-validated in a pilot study. All screen positive houses were visited by pediatric neurologist for detailed evaluation. Children with a clinical diagnosis of epilepsy underwent EEG and were evaluated for type of seizure, epilepsy syndrome, etiology, co-morbidities and treatment gap. Knowledge, attitude and practice regarding epilepsy was assessed amongst caregivers of the affected children. RESULTS: A total population of 75,455 population was screened, 19,181 children aged 2 months to 18 years were identified. Out of 355 screen positive children, 66 were diagnosed with epilepsy. The point prevalence of pediatric epilepsy was 3.44 per 1000 children. 53% had focal epilepsy, 31.8% had an identifiable epilepsy syndrome, 44% had at least one comorbidity. The etiology was identified in 68%, the commonest being perinatal brain insult. The magnitude of treatment gap was 45.45%, with significant deficits in knowledge. CONCLUSION: There are significant deficits in diagnosis and treatment of pediatric epilepsy among the rural population of India. The existing rural health care facilities need to be augmented to facilitate the timely diagnosis and optimum care of these children, including care of associated co-morbidities.

Efficacy and tolerability of Melatonin vs Triclofos to achieve sleep for pediatric electroencephalography: A single blinded randomized controlled trial.

PURPOSE: To compare Melatonin with Triclofos for efficacy (proportion of successful EEG, need of augmentation, sleep onset latency (SOL), yield of discharges, duration of sleep, presence and grade of artifacts) and tolerability (adverse effect profile). METHODS: A randomized trial was performed (block randomization). All children were advised regarding sleep deprivation, EEG technician administered the drug. EEG was labelled successful if at least 30 min of record could be obtained (sleep with or without awake state). Pediatric neurologist reported the EEG findings-sleep onset latency, epileptiform abnormalities and graded the artifacts (excess beta activity and movement artifacts if present). The parents were interviewed telephonically next day by a pediatric resident for any adverse effects. The parents, pediatric neurologist and pediatric resident were blinded for the drug given. RESULTS: 228 children were randomized (114 each received Melatonin and Triclofos). Both the groups were comparable at baseline for age group and demographic data. The proportion of successful EEG was 89.4% in Melatonin and 91.2% in Triclofos. First dose was effective in 64% in Melatonin and 63.15% in Triclofos group. Augmentation dose was needed in 25.4% in Melatonin and 28% in Triclofos group. Mean total sleep duration was 80 min after Melatonin and 82.39 after Triclofos administration. Adverse effects were observed in 6.14% of Melatonin and 8.65% of Triclofos group. None of the results were statistically significant. CONCLUSION: There was no significant difference between efficacy and tolerability of Melatonin and Triclofos. Melatonin can be safely used to achieve sleep for EEG in children.

Efficacy, Tolerability and Serum Phenytoin Levels after Intravenous Fosphenytoin Loading Dose in Children with Status Epilepticus.

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous fosphenytoin in children with status epilepticus, and resulting serum total phenytoin levels. METHODS: In this prospective study, 51 children aged less than 18 years received intravenous loading dose of fosphenytoin (18-20 mg/kg). Serum total phenytoin levels were estimated at 90 -100 minutes. Outcomes studied were (i) seizure control and local and/or systemic adverse effects in next 24 hours and (ii) phenytoin levels and its correlation with dose received, seizure control and adverse effects. RESULTS: The actual dose of fosphenytoin received varied from 15.1 to 25 mg/kg. Seizures were controlled in 45 (88%) children and, two required additional dose of 10 mg/kg. None of the children showed any local or systemic adverse effects. Serum total phenytoin levels were in the therapeutic range (10-20 µg/mL) in 12 (23.5%), sub-therapeutic in 16 (31.3%) and supra-therapeutic in 25 (49%) children. There was weak correlation of the phenytoin levels with dose of fosphenytoin received, seizure control, or adverse effects. CONCLUSIONS: Intravenous fosphenytoin loading dose of 20 mg/kg is effective in controlling seizures in 88% of children with status epilepticus, with a good safety profile. Seizure control and adverse effects appear to be independent of serum total phenytoin levels achieved.

Spectrum of congenital CNS malformations in pediatric epilepsy.

This study was conducted in a tertiary pediatric epilepsy clinic to ascertain the spectrum of development malformations in children, with seizures. Seventy Six Children (0-12 yr) with seizures and CNS malformations based on neuroimaging were included. Observed anomalies included dysgenetic corpus callosum (DCC), lissencephaly, focal cortical dysplasia (FCD), pachygyria, polymicrogyria, heterotopia, schizencephaly, holoprosencephaly, hemimegalencephaly, and phakomatoses like tuberous sclerosis, Sturge Weber syndrome and linear cutaneous nevus syndrome. Seizure semiology varied in all categories. Microcephaly, developmental delay and tone abnormalities were common clinical findings. 60.5 percent cases presented in infancy. The characteristic EEG features provided a clue to the diagnosis of anomalies like lissencephaly, agenesis of corpus callosum and alobar holoprosencephaly.