Comparison between Phenobarbitone and Levetiracetam as the initial anticonvulsant in preterm neonatal seizures - a pilot randomized control trial in developing country setup.

This study aimed to compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of seizures in preterm neonates. It was an open-labeled, parallel randomized controlled trial conducted in a tertiary Neonatal Intensive Care Unit, India. Total 48 preterm neonates (28-36+6 weeks) with clinical seizures were randomized to receive either Levetiracetam (LEV; 40 mg/kg, then 20 mg/kg) or Phenobarbitone (PB; 15 mg/kg, then 10 mg/kg) intravenously as first loading dose in ratio 1:1; second loading was given for persistent seizure. Efficacy was denoted by cessation of clinical seizures with first or second doses of the allotted antiepileptic, and remaining seizure-free for the next 24 h. The demographic characteristics of preterm neonates and seizure types were comparable between both groups. Clinical seizure was controlled in 19 (79%) neonates in LEV group and 17 (70%) neonates in PB group, RR 1.12 (95% CI: 0.80 to 1.55), p = 0.504. There was increased respiratory support in PB group 9 (38%) vs. 3 (13%) in LEV group, RR 3.0 (95% CI: 0.92 to 9.74), p = 0.06.  Conclusion: Levetiracetam and Phenobarbitone were equally efficacious for clinical neonatal seizure control, but increased respiratory support was found with Phenobarbitone use. What is Known: • Preterm neonates are at higher risk of neonatal seizure and Phenobarbitone is commonly used as the first line antiepileptic drugs in treating them. What is New: • Levetiracetam found equally efficacious as Phenobarbitone for cessation of clinical seizures in preterm neonates, with less adverse effect.

Genetic analysis of a Fanconi anemia case revealed the presence of FANCF mutation (exon 1;469>C-T) with implications to develop acute myeloid leukemia.

BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder and one of the most common inherited forms of aplastic anemia. FA is an autosomal recessive or X-linked genetic disorder that is characterized by typical physical malformations and haematopoietic anomalies. In most cases of FA, patients harbor homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~ 10%), FANCD2 (3-6%) or FANCF (2%) genes in different ethnic populations, which leads to inherited bone marrow failure (IBMF). Hence, it is important to screen such mutations in correlation with clinical manifestations of FA in various ethnic populations. APPROACH: An 11 year old female pediatric patient of an East India family was presented with febrile illness, having thrombocytopenia with positive dengue IgM (Immunoglobulin M) and treated as a case of dengue hemorrhagic fever at the initial stage of diagnosis. Chromosomal breakage study was performed based on the abnormal physical examination, which showed 100% breaks, triradials, and quadrilaterals in mitomycin (MMC)-induced peripheral blood lymphocyte culture. Importantly, conventional cytogenetic assay in most of the bone marrow cells revealed an additional gain in chromosome 3q+ [46,XX,add(3)(q25)] and terminal loss in chr8p- [46,XX,del(8)(p23)], which might have a prognostic relevance in the outcomes of the FA patient. The bone marrow aspiration and biopsy were repeated and the results showed acute leukemia with 39% blast cells. Whole-genome sequencing analysis of the patient confirmed the presence of (exon 1; 496 > C-T) non-sense mutation leading to a truncated FANCF protein attributed to a stop codon at the amino acid position 166. CONCLUSION: The study reported the presence of a homozygous C-T exon 1 mutation in FANCF gene in the female pediatric patient from Odisha, India associated with FA. Furthermore, both parents were found to be carriers of FANCF gene mutation, as this allele was found to be in heterozygous state upon genome sequencing. The pathogenicity of the agent was robustly supported by the clinical phenotype and biochemical observations, wherein the patient eventually developed acute myeloid leukemia. The findings of the study infer the importance of early detection of FA and the associated mutations, which might lead to the development of acute myeloid leukemia.

Antiphospholipid Antibody Syndrome in Childhood Systemic Lupus Erythematous With a Unique Presentation: A Case Report.

Initial presentation of childhood systemic lupus erythematosus (SLE) as antiphospholipid syndrome (APS) is uncommon; moreover, APS presenting with both hemorrhage and thrombosis is very rare. We report a case of a previously healthy eight-year-old boy, without any significant past or family history, who presented with ecchymotic patches, epistaxis, and right-side hemiparesis. Investigation showed severe thrombocytopenia and isolated high activated partial thromboplastin time (aPTT) not corrected by mixing study. During his hospital stay, the child developed left-sided focal seizure and digital gangrene as thrombotic events. Neuroimaging revealed initially hemorrhagic stroke and subsequently bilateral infarct of middle cerebral artery (MCA) territory. The child was diagnosed as a case of SLE with APS based on Systemic Lupus International Collaboration Clinics (SLICC) criteria, revised APS classification, clinicoimmunological profile and neuroimaging. As the child was progressing towards catastrophic APS, he was treated aggressively with intravenous pulse methylprednisolone, intravenous cyclophosphamide and plasmapheresis with successful recovery. A simple bleeding manifestation may mask a serious disorder. A simple test like mixing study is helpful in diagnosis and in avoiding unnecessary investigations. A combination of both hemorrhage and thrombosis is an unusual presentation of APS and should always be suspected in case of autoimmune disorder, especially in SLE.