Simple Febrile Seizure: The Role of Serum Sodium Levels in Prediction of Seizure Recurrence during the First 24 Hours

ObjectiveSimple febrile seizures are the most common form of childhood seizures,often recurring within the first twenty-four hours. This study was conducted to determine the probable role of low serum  sodium levels in predicting seizure recurrence in febrile children.Materials & MethodsFor the study, 226 patients with seizures, aged between 6 months to 5 years, were divided into 3 groups of simple febrile seizure, simple febrile seizure with recurrence, and the control group of afebrile patients with seizures. For all groups, serum sodium levels were evaluated.ResultsThe mean age of our cases, predominantly male, was 22 months. No significant difference was observed in the serum sodium levels between the simple febrile seizure and the simple febrile seizure with recurrence groups (P value 0.465); however a significant relative hyponatremia was observed in the simple febrile seizure group as compared to the afebrile seizure control group (P value: 0.016).ConclusionBased on the findings, although serum sodium levels cannot assist in prediction of recurrence of simple febrile seizures in children, relative hyponatremia may predispose the febrile child to occurrence of simple febrile seizure.

TORTICOLLIS CAUSED BY NEUROENTERIC CYST OF UPPER CERVICAL REGION

Objective:Torticollis is a symptom that can be related to different pathological mechanisms ranging from simple to life-threatening conditions. Here we report a child with torticollis caused by a neuroenteric cyst in the upper cervical region; this is a very rare condition in childhood and  in this case, it was successfully resolved by surgery.Clinical presentation:A 2.5 year old boy presented with a 2 month-history of torticollis, he had developed paraparesia 2 weeks before admission. At examination he was found to be quadriparetic. Radiographic study of  the cervical spine revealed widening of the cervical canal. Brain and spinal magnetic resonance imaging revealed a hypointense lesion on the T1 at the craniovertebral junction having a  compressive effect on the anterior aspect of the brain stem and spinal cord.Intervention:The patient underwent surgery. After craniotomy and opening of the dura, a cystic lesion was seen; clear fluid was aspirated and the cyst wall was removed.Conclusion:Considering the quadriparesis and torticollis, the patient improved significantly within the first few days after surgery. No relapse of symptoms occurred during the follow up period. This is the first case report of a child in whom torticollis was due to a neuroenteric cyst of the upper cervical intradural region.Keywords:Torticollis - Neuroenteric cyst - Child - Quadriparesi

Epilepsy Surgery in Children

ObjectiveIn the majority of patients with intractable epilepsy, seizures can be well controlled with appropriate medication. However, current estimates indicate that some of patients with epilepsy are refractory to all forms of medical therapy. The surgical treatment of intractable epilepsy in children has  evolved with advances in technical innovations. These medically intractable patients are candidates for surgical treatment in an attempt to achieve better seizure control. The definitive successful outcome of epilepsy surgery is a seizure-free state without significant neurological impairments.In this article, we will outline the essential elements of presurgical evaluation and describe a variety of therapeutic surgical options, and the related indications, techniques, results and complications of each procedure.

ROSA DAMASCENA OIL: AN ADJUNCTIVE THERAPY FOR PEDIATRIC REFRACTORY SEIZURES

ObjectiveSeveral investigations have demonstrated that Rosa damascena has an inhibitory effect on the hypothalamus and on pituitary system reactivity in the rat; it has also been shown that the essential oil of Rosa damascena has significant antiepileptic effects on pentylentetrazole (PTZ) induced seizures in rats. We aimed at assessing the effects of the essential oil of Rosa damascena when used as an adjunct treatment to treat children with refractory seizuresMaterials and MethodsIn this double-blind clinical trial, conducted as a pilot study between April 2004 and March 2005, we administered essential oil of Rosa damascena to sixteen children with refractory epilepsy as an adjunct therapy, and evaluated its effects.Results16 patients, age range 3-13 years, were enrolled; 56.3% (n=9) girls and 43.8% (n=7) boys. All has been under treatment for 3-6 weeks (baseline phase). They received either the essential oil or placebo for a period of 4 weeks and in between these periods, they took only their pre-existing antiepileptic drugs for two weeks (washout phase).The mean frequency of seizures in those using essential oil, showed significant decrease as compared to the controls using placeboes (p=0.00).ConclusionIt can be concluded that the essential oil of Rosa Damascena has beneficial antiepileptic effect in children with refractory seizures.Keywords:Rosa damascena, refractory epilepsy, children, oil

Unbalanced segregation of a paternal t(9;11)(p24.3;p15.4) translocation causing familial Beckwith-Wiedemann syndrome: a case report.

BACKGROUND: The vast majority of cases with Beckwith-Wiedemann syndrome (BWS) are caused by a molecular defect in the imprinted chromosome region 11p15.5. The underlying mechanisms include epimutations, uniparental disomy, copy number variations, and structural rearrangements. In addition, maternal loss-of-function mutations in CDKN1C are found. Despite growing knowledge on BWS pathogenesis, up to 20% of patients with BWS phenotype remain without molecular diagnosis. CASE PRESENTATION: Herein, we report an Iranian family with two females affected with BWS in different generations. Bisulfite pyrosequencing revealed hypermethylation of the H19/IGF2: intergenic differentially methylated region (IG DMR), also known as imprinting center 1 (IC1) and hypomethylation of the KCNQ1OT1: transcriptional start site (TSS) DMR (IC2). Array CGH demonstrated an 8 Mb duplication on chromosome 11p15.5p15.4 (205,827-8,150,933) and a 1 Mb deletion on chromosome 9p24.3 (209,020-1,288,114). Chromosome painting revealed that this duplication-deficiency in both patients is due to unbalanced segregation of a paternal reciprocal t(9;11)(p24.3;p15.4) translocation. CONCLUSIONS: This is the first report of a paternally inherited unbalanced translocation between the chromosome 9 and 11 short arms underlying familial BWS. Copy number variations involving the 11p15.5 region are detected by the consensus diagnostic algorithm. However, in complex cases which do not only affect the BWS region itself, characterization of submicroscopic chromosome rearrangements can assist to estimate the recurrence risk and possible phenotypic outcomes

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation

Abstract BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential