Hemi-ESES associated with agenesis of the corpus callosum and normal cognition.

Corpus callosum plays the important role in bilateral synchronous expression of focal discharges of ESES. Sparing dominant hemisphere form continuous spike and slow waves during sleep accounts for normal cognitive scores. Early detection and treatment of ESES have a great impact on cognitive and language scores and final prognosis

Prognosis of Epilepsies and Epileptic Syndromes in Children: A Narrative Review

Epilepsies and epileptic syndromes are among the most common chronic neurological disorders in neonates, infants, and children. Remission occurs in 70% of epileptic children, while other cases experience frequent seizures and become refractory to various treatment modalities. Refractory seizures have a significant adverse impact on the quality of life of epileptic children and their families. Prognosis of epilepsies is determined based on the risk of seizure or convulsion recurrence. Some of the most important risk factors for recurrence are the age at seizure presentation, neurodevelopment of the child, etiology of seizures, seizure frequency before anticonvulsant withdrawal, response to antiepileptic medications, type of epileptic syndromes, and electroencephalography of the patient. Recognition of the risk factors for seizure recurrence results in the optimal management of the treatment protocols, thereby reducing the adverse effects of epileptic seizures on patients and their families. The present study aimed to provide a narrative review of the most important risk factors for the recurrence of epilepsies in children by two child neurologists

Sleep Inducing for EEG Recording in Children: A Comparison between Oral Midazolam and Chloral Hydrate

How to Cite This Article: AshrafiMR, Azizi Malamiri R, Zamani GR, Mohammadi M, Hosseini F. Sleep Inducing for EEG Recording in Children: A Comparison between Oral Midazolam and Chloral Hydrate. Iran J Child Neurol. 2013 Winter;7(1):15-19.ObjectiveElectroencephalography (EEG) recording is a long duration procedure that needs patient’s cooperation for device setup and performing the procedure. Many children lose their cooperation during this procedure. Therefore, sedation and sleep are frequently induced using a few agents as pre procedure medication in children before EEG recording. We aimed to compare the sedative effects of oral midazolam versus chloral hydrate before the procedure along with their impacts on EEG recording in children.Materials & MethodsA randomized trial was carried out to compare the sedative effects of oral midazolam versus chloral hydrate and their impacts on EEG recording in children. A total of 198 children (100 in the midazolam group and 98 in the chloral hydrate group) were enrolled in the study and randomly allocated to receive either oral moidazolam or chloral hydrate.ResultsOral midazolam had superiority neither in sleep onset latency nor in sleep duration when compared to chloral hydrate. Moreover, the yield of epileptiform discharges in the chloral hydrate group was more than the midazolam group.ConclusionThe results of this study showed that both chloral hydrate 5% (one ml/kg) and oral midazolam (0.5 mg/kg) could be administered as a pre medication agent for EEG recording in children. However, oral midazolam at this dose had no advantage compared with chloral hydrate.ReferencesAshrafi MR, Mohammadi M, Tafarroji J, Shabanian R, Salamati P, Zamani GR. Melatonin versus chloral hydrate for recording sleep EEG. Eur J Paediatr Neurol 2010;14(3):235-8.Slifer KJ, Avis KT, Frutchey RA. Behavioral intervention to increase compliance with electroencephalographic procedures in children with developmental disabilities. Epilepsy Behav 2008;13 (1):189-95.Gauillard J, Cheref S, Vacherontrystram MN, Martin JC. [Chloral hydrate: a hypnotic best forgotten?]. Encephale 2002;28(3 Pt 1):200-4.Cote CJ, Karl HW, Notterman DA, Weinberg JA, McCloskey C. Adverse sedation events in pediatrics: analysis of medications used for sedation. Pediatrics 2000;106(4):633-44.Greenblatt DJ, Ehrenberg BL, Culm KE, Scavone JM, Corbett KE, Friedman HL, et al. Kinetics and EEG effects of midazolam during and after 1-minute, 1-hour, and 3-hour intravenous infusions. J Clin Pharmacol 2004;44(6):605-11.Gurakan F, Yuce A, Ozen H, Saltic IN. Midazolam and pethidine for the sedation of children undergoing gastrointestinal endoscopy. Crit care med 2000;28(6):2176-7.Karl HW, Cote CJ, McCubbin MM, Kelley M, Liebelt E, Kaufman S, et al. Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors. Pediatr Emerg Care 1999;15(3):167-72.Lightdale JR, Mitchell PD, Fredette ME, Mahoney LB, Zgleszewski SE, Scharff L, et al. A Pilot Study of Ketamine versus Midazolam/Fentanyl Sedation in Children Undergoing GI Endoscopy. Int J Pediatr 2011; 2011:623710.Massanari M, Novitsky J, Reinstein LJ. Paradoxical reactions in children associated with midazolam use during endoscopy. 1997;36(12):681-4.Scott RC, Besag FM, Boyd SG, Berry D, Neville BG. Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics. Epilepsia 1998;39(3):290-4.Loewy J, Hallan C, Friedman E, Martinez C. Sleep/sedation in children undergoing EEG testing: a comparison of chloral hydrate and music therapy. Am J electroneurodiagnostic technol 2006;46(4):343-55.Rodriguez E, Jordan R. Contemporary trends in pediatric sedation and analgesia. Emerg Med Clin North Am 2002;20(1):199-222.Sisson DF, Siegel J. Chloral hydrate anesthesia: EEG power spectrum analysis and effects on VEPs in the rat. Neurotoxicol Teratol 1989;11(1):51-6.Thoresen M, Henriksen O, Wannag E, Laegreid L. Does a sedative dose of chloral hydrate modify the EEG of children with epilepsy? Electroencephalogr Clin Neurophysiol 1997;102(2):152-7

Thalassemia major may decrease the frequency of febrile convulsions in children

AbstractAim: We aimed to determine the relative frequency of febrile convulsion in children with major thalassemia to theorize that higher serum iron levels could reduce the incidence of febrile convulsion. Background: Febrile convulsion is the most common type of seizure in childhood that its causes are not fully understood. However, some risk factors have been cited such as the serum iron level. Materials and methods: Three hundred and fifty-nine children aged more than 5 years with major thalassemia who were receiving blood were enrolled as the case group. The control group consisted of 357 children without thalassemia aged 4–7 years (151 boys, 206 girls) who were referred to healthcare centers for routine health monitoring. Included data were the history of febrile convulsion, age of onset and type and the frequency of convulsions. Results: Children in control group significantly experienced more febrile convulsions than thalassemic children [4/359 (1.1%) in the thalassemic children and 14/357 (3.9%) in the control group had experienced febrile convulsions (P=0.017)]. Conclusion: The frequency of febrile convulsion in children with major thalassemia is less than that of normal children. Children with thalassemia major may have higher serum levels of iron and such high serum iron levels might have a protective role in the children who have a vulnerability for febrile convulsions

The impact of N-myc amplification on median survival in children with neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression

Serum Total Antioxidant Capacity of Epileptic Children before and after Monotherapy with Sodium Valproate, Carbamazepine,

Background: Brain is highly vulnerable to free radical damage due to a large quantity of mitochondria, a considerable amount of oxidizable polyunsaturated fatty acids, a ratio of high oxygen consumption, and less antioxidant capacity. The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of seizures and epileptic syndromes.Objectives: A case-control study was carried out to compare serum total antioxidant capacity in the newly diagnosed children with epilepsy and that of a control group of healthy children at the same age.Patients and Methods: A total of 130 participants (65 in each group) aged between 1 and 17 years participated in this study. Serum total antioxidant capacity was compared between two groups before drug administration. The effect of antiepileptic therapy on the serum total antioxidant capacity also was studied in children with epilepsy before and 3 months after antiepileptic drug administration. Serum total antioxidant capacity values were measured based on Erel's method using an automated commercial kit. This method is based on the bleaching of the characteristic color of a more stable 2,2’‑azinobis‑(3‑ethylbenzothiazoline‑6‑sulfonic acid) radical cation by antioxidants. The results were expressed in mmol Trolox equivalent/lResults: Serum total antioxidant capacity values was significantly lower in the patients group before drug administration [mean (SD): 1.31 (0.19) mmol/L] than that of the control group [mean (SD): 1.46 (0.21) mmol/L] (P < 0.001). In the patients group, no differences were found in the serum total antioxidant capacity before and 3 months after anticonvulsant monotherapy.Conclusion: Reduced serum total antioxidant capacity, and an increased vulnerability to oxidative stress should be considered in the children with epilepsy

Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking

Charcot-Marie-Tooth type 4 (CMT4) is an autosomal recessive severe form of neuropathy with genetic heterogeneity. CMT4B1 is caused by mutations in the myotubularin-related 2 (MTMR2) gene and as a member of the myotubularin family, the MTMR2 protein is crucial for the modulation of membrane trafficking. To enable future clinical trials, we performed a detailed review of the published cases with MTMR2 mutations and describe four novel cases identified through whole-exome sequencing (WES). The four unrelated families harbor novel homozygous mutations in MTMR2 (NM_016156, Family 1: c.1490dupC; p.Phe498IlefsTer2; Family 2: c.1479+1G>A; Family 3: c.1090C>T; p.Arg364Ter; Family 4: c.883C>T; p.Arg295Ter) and present with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity. The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. Whereas the few reported missense mutations and also those truncating mutations occurring at the C-terminus after the phosphatase domain cause a rather mild phenotype and patients were still ambulatory above the age 30 years. Charcot-Marie-Tooth neuropathy and Centronuclear Myopathy causing mutations have been shown to occur in proteins involved in membrane remodeling and trafficking pathway mediated by phosphoinositides. Earlier studies have showing the rescue of MTM1 myopathy by MTMR2 overexpression, emphasize the importance of maintaining the phosphoinositides equilibrium and highlight a potential compensatory mechanism amongst members of this pathway. This proved that the regulation of expression of these proteins involved in the membrane remodeling pathway may compensate each other's loss- or gain-of-function mutations by restoring the phosphoinositides equilibrium. This provides a potential therapeutic strategy for neuromuscular diseases resulting from mutations in the membrane remodeling pathway

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2-48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course

Efficacy of combined virtual reality with constraint-induced movement therapy on upper limb function of children with hemiparetic cerebral palsy

Introduction: Hemiparetic cerebral palsy refers to an impairment caused by non-progressive damages to premature brain which is more sever in one side of the body than the other side. The aim of the present study was to determine the effects of combining constraint-induced movement therapy (CIMT) with virtual reality (VR) on upper limb functioning of children with hemiparetic cerebral palsy. Materials and Methods: In a single blind randomized, controlled trial, 16 children with hemiparetic cerebral palsy, who were selected through a simple random sampling method in Ahvaz city, were divided into 4 groups of CIMT, VR, CIMT+VR, and controls. Subjects in experimental groups participated in one-and-half-hour therapeutic sessions which were held every other day during a four-week period. Measures were conducted pre, post and 3-month after the treatment period using Pediatrics Motor Activity Log and Bruininks-Oseretsky Test of Motor proficiency (BOTMP). Sample randomization and statistical analysis of data through analysis of variance with repeated measures were conducted via SPSS-16 software in which alpha level was set at 0.05. Results: Data analysis for measurement tools was indicative of significant difference of combined group compared to VR, CIMT, and control groups (P < 0.01) (mean amounts of BOTMP, speed and dexterity changed from 0.15 ± 0.08 to 1.89 ± 0.33 in post-test). Data analysis for follow-up session revealed the retention of results for 4 groups (P = 0.32). Conclusion: Incorporating VR and CIMT may improve upper limb functioning of children with hemiparetic cerebral palsy through combining the advantages of both protocols and implementing them in an integrated program. Keywords: Constraint-induced movement therapy, Virtual reality, Upper limb function, Hemiparetic cerebral pals