Therapeutic Effects of Adrenocorticotropic Hormone ACTH in Children with Severely Intractable Seizure

How to Cite This Article: Nasiri J, Sarajan A, Salari M, Sedghi M. Therapeutic Effects of Adrenocorticotropic Hormone ACTH in Children withSeverely Intractable Seizure. Iran J Child Neurol. Summer 2017; 11(3):19-26.AbstractObjectiveTreatment of intractable seizures other than spasms is difficult and controversial.There are few studies on efficacy of adrenocorticotropic hormone (ACTH) in treatment of patients with intractable seizure.Materials & MethodsTwenty-five patients with intractable seizure other than spasm including 14 boys and 11 girls with median age of 58 months referred to university clinics of Pediatric Neurology in Isfahan, Iran, during 2014-2015 were prospectively investigated. ACTH was administrated according to our protocol. All cases were followed regularly and assessed for response to treatment and probable side effects, 3 wk after beginning of ACTH therapy and three months after the ACTH therapy. EEG finding were recorded before and three months after the end of ACTH therapy. Statistical analysis using Freidman test and Wilcoxon signed – rank test were performed in order to compare seizure frequency and EEG changes, respectively.ResultsMean A significant reduction (>80%) in seizure frequency in 11 cases (44%) and moderate reduction (50%-80%) in 7 (28%) after 3 wk of ACTH therapy.Despite initial positive response, recurrence of seizure was observed in 7 out of 18 cases with favorable initial response within 3 months after ACTH therapy cessation. The comparison of EEG finding before and 3 months after ACTH therapy using Wilcoxon signed – rank test showed  significant differences.ConclusionACTH therapy may be useful in treatment of children with intractable seizures who are resistant to usual antiepileptic drugs. However further studies should be performed to determine the long-term efficacy of ACTH in treatment of intractable seizure.References1. Dunin-Wąsowicz D, Mazurkiewicz-Bełdzińska M, Steinborn B, Wheless J, Jóźwiak S. Treatment of pediatric epilepsy in Poland. Eur J Paediatr Neurol 2015;19(3):320-6.2. Oka E, Ohtsuka Y, Yoshinaga H, Murakami N, Kobayashi K, Ogino T. Prevalence of Childhood Epilepsy and Distribution of Epileptic Syndromes: A Population-based Survey in Okayama, Japan. Epilepsia 2006;47(3):626-30.3. Beleza P. Refractory epilepsy: a clinically oriented review. Eur Neurol 2009; 62(2):65-71.4. Pentella K, Bachman D, Sandman CA. Trial of an ACTH4-9 Analogue (ORG 2766) in children with intractable seizures. Neuropediatrics 1982;13(2):59-62.5. Snead OC, Benton JW, Myers GJ. ACTH and prednisone in childhood seizure disorders. Neurology 1983;33(8):966-70.6. Okumura A, Tsuji T, Kato T, Natsume J, Negoro T, Watanabe K. ACTH therapy for generalized seizures other than spasms. Seizure 2006;15(7):469-75.7. Verhelst H, Boon P, Buyse G, Ceulemans B, D’Hooghe M, De Meirleir L, et al. Steroids in intractable childhood epilepsy: clinical experience and review of the literature. Seizure 2005;14(6):412-21.8. Oguni H, Funatsuka M, Sasaki K, Nakajima T, Yoshii K, Nishimura T, et al. Effect of ACTH therapy for epileptic spasms without hypsarrhythmia. Epilepsia 2005;46(5):709-15.9. Haberlandt E, Weger C, Sigl SB, Rauchenzauner M, Scholl-Bürgi S, Rostásy K, et al. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr Neurol 2010;42(1):21-7.10. Inutsuka M, Kobayashi K, Oka M, Hattori J, Ohtsuka Y. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain Dev 2006;28(5):281-6.11. Fujii A, Oguni H, Hirano Y, Osawa M. Atypical benign partial epilepsy: recognition can prevent pseudocatastrophe. Pediatr Neurol 2010;43(6):411-9.12. Inui T, Kobayashi T, Kobayashi S, Sato R, Endo W, Kikuchi A, et al. Efficacy of long term weekly ACTH therapy for intractable epilepsy. Brain Dev 2015;37(4):449-54.13. Kalra V, Sharma S, Arya R. ACTH therapy in refractory generalized epilepsy. Indian J Pediatr 2009;76(1):91-3.14. Kurian M, Korff CM. Steroids in pediatric epilepsy: infantile spasms and beyond. Epileptologie 2011; 28(1):15-20.15. Rogawski MA, DS R. Neurosteroids and infantile spasms: The deoxycorticosterone hypothesis. In: JMR PAS, editor. International Review of Neurobiology Volume 49: Academic Press; 2002. p. 199-219.16. Snead OC. How does ACTH work against infantile spasms? Bedside to bench. Ann Neurol 2001;49(3):288-9.17. Jacobson L, Sapolsky R. The Role of the Hippocampus in Feedback Regulation of the Hypothalamic-Pituitary- Adrenocortical Axis. Endocr Rev 1991;12(2):118-34.18. Sinclair DB. Prednisone therapy in pediatric epilepsy. Pediatr Neurol 2003;28(3):194-8

Accessibility and Types of Online Sources Cited in Scholarly Biomedical Journal in Iran

One type of frequently used references in scientific papers is online references. The aim of this study is to study the prevalence, accessibility and types of online sources in biomedical journals in Iran from 2010 to 2012. We analyzed online references cited in 401 articles from 21 scientific journals indexed in PubMed, Web of Science, and Scopus. Findings revealed that only 73 papers (18.2%) had cited online sources in their references. of 186 online citations, 72 (38.7%) citations were accessible, and the URLs to 114 citations did not work (61.3%). The majority of unreachable citations were unstable citations (32.3%). Most online sources (62%) were cited in “Iranian Journal of Public Health”. An increase in the number of online citations was observed over the studied years. The study indicated that the rate of online citations is low in the studied journals, and most online citations were unreachable. The lack of clear guidelines in citing online sources seemed to be a major reason for the inaccessibility of online citations

Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations

  Infantile neuroaxonal dystrophy (INAD) is a rare recessive neurodegenerative disorder manifested by symptoms, including hypotonia, extrapyramidal signs, spastic tetraplegia, vision problems, cerebellar ataxia, cognitive complications, and dementia, before the age of three. Various reports evaluated the relationship with the incidence of INAD and different mutations in the PLA2G6 gene. We describe cases of two children with INAD whose diagnoses were challenging due to misleading findings and had a mutation in the position C.2370 T>G (p. Y790X) in the PLA2G6 gene based on NM_001349864 which has been reported previously

Total graph of a 00-distributive lattice

Let £ be a $0$-distributive lattice with the least element $0$, the greatest element $1$, and ${rm Z}(£)$ its set of zero-divisors. In this paper, we introduce the total graph of £, denoted by ${rm T}(G (£))$. It is the graph with all elements of £ as vertices, and for distinct $x, y in £$, the vertices $x$ and $y$ are adjacent if and only if $x vee y in {rm Z}(£)$. The basic properties of the graph ${rm T}(G (£))$ and its subgraphs are studied. We investigate the properties of the total graph of $0$-distributive lattices as diameter, girth, clique number, radius, and the  independence number

Genetic Analysis of MECP2 Gene in Iranian Patients with Rett Syndrome

AbstractObjectivesRett syndrome is an X linked dominant neurodevelopmental disorder which almost exclusively affects females. The syndrome is usually caused by mutations in MECP2 gene, which is a nuclear protein that selectively binds CpG dinucleotides in the genome.Materials & MethodsTo provide further insights into the distribution of mutations in MECP2 gene, we investigated 24 females with clinical characters of Rett syndrome referred to Alzahra University Hospital in Isfahan, Iran during 2015-2017. We sequenced the entire MECP2 coding region and splice sites for detection of point mutations in this gene. Freely available programs including JALVIEW, SIFT, and PolyPhen were used to find out the damaging effects of unknown mutations.ResultsDirect sequencing revealed MECP2 mutations in 13 of the 24 patients. We identified in 13 patients, 10 different mutations in MECP2 gene. Three of these mutations have not been reported elsewhere and are most likely pathogenic.ConclusionDefects in MECP2 gene play an important role in pathogenesis of Rett syndrome. Mutations in MECP2 gene can be found in the majority of Iranian RTT patients. We failed to identify mutations in MECP2 gene in 46% of our patients. For these patients, further molecular analysis might be necessary

A semiprime filter-based identity- summand graph of a lattice

Let $F$ be a proper filter of a lattice $L$ with the leastelement $0$ and the greatest element $1$. The filter-basedidentity-summand graph of $L$ with respect to $F$, denoted by$\Gamma_{F} (L)$, is the graph with vertices I^*_{F} (L) = \{x\in L \setminus F: x \vee y \in F \, \, \mbox{for some} \, \, y\in L \setminus F \}, and distinct vertices $x$ and $y$ areadjacent if and only if $x \vee y \in F$. We will make anintensive study of the notions of diameter, grith, chromaticnumber, clique number, independence number, domination numberand planar property of this graph. Moreover, Beck$^sconjecture is proved for$\Gamma_{F} (L)$

Identification of Proximal and Distal 22q11.2 Microduplications among Patients with Cleft Lip and/or Palate: A Novel Inherited Atypical 0.6 Mb Duplication

Misalignments of low-copy repeats (LCRs) located in chromosome 22, particularly band 22q11.2, predispose to rearrangements. A variety of phenotypic features are associated with 22q11.2 microduplication syndrome which makes it challenging for the genetic counselors to recommend appropriate genetic assessment and counseling for the patients. In this study, multiplex ligation probe dependent amplification (MLPA) analysis was performed on 378 patients with cleft lip and/or palate to characterize rearrangements in patients suspected of 22q11.2 microduplication and microdeletion syndromes. Of 378 cases, 15 were diagnosed with a microdeletion with various sizes and 3 with duplications. For the first time in this study an atypical 0.6 Mb duplication is reported. Illustration of the phenotypes associated with the microduplications increases the knowledge of phenotypes reported in the literature

Motor neuron diseases caused by a novel VRK1 variant – A genotype/phenotype study

Background: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia- related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly. Results: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsensemediated decay machinery and results in a premature termination codon. Conclusions: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases

Gastrointestinal symptoms of patients with autism spectrum disorder

Background: Concern about possible GI dysfunction in ASD is intensified by high rates of feeding concerns and consequent medical sequelae in ASD. Etiological factors contributing to the pattern and prevalence of atypical intake in ASD remain elusive, but may involve pathophysiological processes in the GI tract. In this study, we evaluated the gastrointestinal symptoms of patients with autism spectrum disorder in Mashhad, Iran.Methods: This is a cross-sectional study performed during September 2015 and April 2018 on patients referred to pediatric gastrointestinal clinics of Ghaem and Noor Hedayat centers by definite diagnosis of autism spectrum disorder (ASD). All subjects were interviewed to answer some questions about the gastrointestinal manifestations like constipation, chronic abdominal pain, diarrhea, recurrent vomiting, gastro-esophageal reflux, nausea, and agitation. For each patient a checklist was completed including demographic, history and physical examination variables.Results: During the period of study, 46 definite ASD patients were enrolled in the study. The mean age of the participants was 7.72± 2.80 years (range: 2-16). Most of the patients were male (37, 80.4%). Diarrhea (occasional or chronic) was seen in six patients (13%) and constipation in 21 patients (45.7%).  There was no significant difference between the gastrointestinal symptoms and gender or age of the patients (P>0.05). An important finding in physical examination was tooth decay, which was found in 21 patients (45.7%).Conclusion: GI symptoms, with the high prevalence in ASD patients, should be considered as major problems; and preventive strategies must be taken for resolving them. Constipation was the most prevalent symptom, which can be related to the nature of the disease or other mechanisms