Khalid Ibrahim

Nebulized 5% or 3% Hypertonic or 0.9% Saline for Treating Acute Bronchiolitis in Infants

OBJECTIVE To compare the efficacy and safety of 5%, 3%, and 0.9% saline solution for treating acute bronchiolitis in the prehospital setting. STUDY DESIGN This was a double-blind trial including consecutive infants aged <18 months treated in an urban urgent care setting. A total of 165 patients were randomized to receive nebulized 5%, 3%, or 0.9% (normal) saline with epinephrine every 4 hours. The primary efficacy outcome was bronchiolitis severity score improvement at 48 hours (chi2 analysis). Scores and oxygen saturation immediately before and after each treatment were recorded to assess safety. RESULTS A total of 187 previously healthy infants (median age, 3.1 months) diagnosed with bronchiolitis were enrolled. Positivity for respiratory syncytial virus was similar in the 3 treatment groups (mean, 56%). At 48 hours, the mean severity score for the 5% saline group was 3.69+/-1.09, and that for the 0.9% saline group was 4.12+/-1.11 (P=.04; difference, 0.43, 95% confidence interval for the difference, 0.02-0.88). The mean severity score for the 3% saline group was intermediate at 4.00+/-1.22. Revisit rates after discharge were similar in the 3 treatment groups. No adverse reactions or other safety concerns were identified. CONCLUSIONS Nebulization with 5% hypertonic saline is safe, can be widely generalizable, and may be superior to current treatment for early outpatient treatment of bronchiolitis.

Natural course of glutamine synthetase deficiency in a 3 year old patient

Glutamine deficiency with hyperammonemia due to an inherited defect of glutamine synthetase (GS) was found in a 2 year old patient. He presented neonatal seizures and developed chronic encephalopathy. Thus, GS deficiency leads to severe neurological disease but is not always early lethal.

Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance

Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.

Oral Dexamethasone for Bronchiolitis: A Randomized Trial

OBJECTIVE: Determine whether dexamethasone treatment added to salbutamol reduces time to readiness for discharge in patients with bronchiolitis and possible asthma. METHODS: We compared efficacy and safety of dexamethasone, 1 mg/kg, then 0.6 mg/kg for 4 more days, with placebo for acute bronchiolitis in patients with asthma risk, as determined by eczema or a family history of asthma in a first-degree relative. All patients received inhaled salbutamol. Time to readiness for discharge was the primary efficacy outcome. RESULTS: Two hundred previously healthy infants diagnosed with bronchiolitis, median age 3.5 months, were enrolled. Five placebo recipients needed admission to intensive care unit during infirmary treatment (P = .02). Among 100 dexamethasone recipients, geometric mean time to readiness for discharge was 18.6 hours (95% confidence interval [CI], 14.9 to 23.1 hours); among 90 control patients, 27.1 hours (95% CI, 21.8 to 33.8 hours). The ratio, 0.69 (95% CI, 0.51 to 0.93), revealed a mean 31% shortening of duration to readiness for discharge favoring dexamethasone (P = .015). Twenty-two dexamethasone and 19 control patients were readmitted to the short stay infirmary in the week after discharge (P = .9). No hospitalizations or side effects were reported during 7 days of surveillance. CONCLUSIONS: Dexamethasone with salbutamol shortened time to readiness for infirmary discharge during bronchiolitis episodes in patients with eczema or a family history of asthma in a first-degree relative. Infirmary and clinic visits in the subsequent week occurred similarly for the 2 groups.

Mutation in non-coding RNA, RNU12 causes early-onset cerebellar ataxia.

Exome sequences account for only 2% of the genome and may overlook mutations causing disease. To obtain a more complete view, whole genome sequencing (WGS) was analyzed in a large consanguineous family in which members displayed autosomal recessively inherited cerebellar ataxia manifesting before 2 years of age.

Secondary NAD+ deficiency in the inherited defect of glutamine synthetase.

Glutamine synthetase (GS) deficiency is an ultra-rare inborn error of amino acid metabolism that has been described in only three patients so far. The disease is characterized by neonatal onset of severe encephalopathy, low levels of glutamine in blood and cerebrospinal fluid, chronic moderate hyperammonemia, and an overall poor prognosis in the absence of an effective treatment. Recently, enteral glutamine supplementation was shown to be a safe and effective therapy for this disease but there are no data available on the long-term effects of this intervention. The amino acid glutamine, severely lacking in this disorder, is central to many metabolic pathways in the human organism and is involved in the synthesis of nicotinamide adenine dinucleotide (NAD+) starting from tryptophan or niacin as nicotinate, but not nicotinamide. Using fibroblasts, leukocytes, and immortalized peripheral blood stem cells (PBSC) from a patient carrying a GLUL gene point mutation associated with impaired GS activity, we tested whether glutamine deficiency in this patient results in NAD+ depletion and whether it can be rescued by supplementation with glutamine, nicotinamide or nicotinate. The present study shows that congenital GS deficiency is associated with NAD+ depletion in fibroblasts, leukocytes and PBSC, which may contribute to the severe clinical phenotype of the disease. Furthermore, it shows that NAD+ depletion can be rescued by nicotinamide supplementation in fibroblasts and leukocytes, which may open up potential therapeutic options for the treatment of this disorder.

Flavored Intravenous Ondansetron Administered Orally for the Treatment of Persistent Vomiting in Children.

OBJECTIVE To study the serum level of ondansetron after oral administration of intravenous ondansetron, and test the palatability of the drug after being flavored. METHOD This is a single-center prospective study enrolling children aged 3-8 years with gastroenteritis treated for persistent vomiting; patients received single dose of flavored intravenous ondansetron orally. The primary outcome was ondansetron serum level at 4 hours. Secondary outcome was palatability of the drug. RESULTS Forty previously healthy patients presenting with acute gastroenteritis were enrolled. The mean age was 4.86±1.37 years. Serum level at 4 h had a median of 26.23 ng/ml, range (8.3-52 ng/ml). Palatability of the drug had a mean of 3.23 (of 5) ± 0.80, based on score from visual analog scale. CONCLUSIONS Flavored intravenous ondansetron administered orally is a safe and an effective option and can be considered in the absence of the oral forms of the drug.

Cerebellar Stroke in Children, a case report from Qatar & Brief Literature Review

Introduction: Cerebro-vascular accidents do happen for both adults & children. Pediatric data in contrary to adult data are clearly deficient & lacking behind. Childhood cerebellar strokes are much more rare & difficult to pick up. Case Report: We are reporting a toddler girl, who happened to be an ex premature & part of quadruplet. She presented with severe headache & head tilting in the absence of other focalizing CNS symptoms. Her brain MRI showed changes suggestive of cerebellar stroke. The Patient has improved clinically & radiologically after proper therapy. Discussion: Cerebellar infarctions are likely to be arterial occlusion as a result of vertebral artery dissection, mainly with PICA involvement. An association with some biomarkers & antibodies like anti-2GPI which has been suggested. Trauma, drugs & CNS infection have all been explored as risk factors for childhood cerebellar strokes. Long term outcomes remain poorly studied. Conclusion: High index of suspicion is required to diagnose cerebellar strokes in children. Clinical presentation is often non specific. Our case report represents a successful story of diagnosis, treatment and improvement. However, our understanding of underlying pathological processes, risk factors, management guidelines & future outcome is very limited. Further large scale studies are apparently needed.

Idiopathic Non-traumatic Facial Nerve Palsy (Bell’s Palsy) in Neonates; An Atypical Age and Management Dilemma

Idiopathic (Bells) palsy is the commonest cause of unilateral facial paralysis in children. Although being idiopathic by definition, possible infectious, inflammatory, and ischemic triggers have been suggested. Bells palsy is thought to be responsible for up to three-fourths of cases of acute unilateral facial paralysis worldwide. The diagnosis has to be reached after other causes of acute peripheral palsy have been excluded. However, it is rarely described in neonates and young infants. Steroids may have some role in treatment, but antiviral therapies have doubtful evidence of benefit. Prognosis is good, though residual dysfunction is occasionally encountered. We report the case of a two-week-old neonate with no prior illnesses who presented with acute left facial palsy. Clinical findings and normal brain imaging were consistent with the diagnosis of Bells palsy. The patient had a good response to oral steroids.

Homozygous Nonsense Mutation in SCHIP1/IQCJ-SCHIP1 Causes a Neurodevelopmental Brain Malformation Syndrome

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria‐cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C‐terminal region shared by the Schwanomin‐Interacting Protein1 (SCHIP1) isoforms including the IQCJ‐SCHIP1. The in vitro expression of SCHIP1 and IQCJ‐SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full‐length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ‐SCHIP1 point mutation in humans associated with a neurological‐developmental phenotype.