Transplant-Associated Thrombotic Microangiopathy (TA-TMA) in Childhood - A literature review

Transplant-associated thrombotic microangiopathy (TA-TMA) is considered one of the most severe complications after hematopoietic stem cell transplantation (HSCT). Transplant-associated thrombotic microangiopathy (TA-TMA) constitutes a form of microangiopathic haemolytic anemia and thrombocytopenia derived from a generalized endothelial dysfunction with intravascular platelet activation and formation of platelet-rich thrombi within the microcirculation. Since clinical features are common in several post hematopoietic stem cell transplantation (HSCT) complications such as capillary leak syndrome, engraftment syndrome, graft versus host disease (GVHD), diffuse alveolar hemorrhage and veno occlusive disease (VOD), an initial diagnosis of TA-TMA is not always certain, which is a principal reason for the failure of proposed treatments.Keywords: Thrombotic Microangiopathies; Hematopoietic Stem Cell Transplantation; Child; Hemolytic-Uremic Syndrome; Eculizumab

Posterior Reversible Encephalopathy Syndrome in Pediatric Hematologic- Oncologic Disease: Literature Review and Case Presentation

How to Cite This Article: Arzanian MT, Shamsian BSh, Karimzadeh P, Kajiyazdi M, Malek F, Hammoud M. Posterior Reversible Encephalopathy Syndrome in Pediatric Hematologic-Oncologic Disease: Literature Review and Case Presentation. Iran J Child Neurol. 2014 Spring 8(2):1-10.ObjectivePosterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological disease entity, which is represented by characteristic magnetic resonance imaging (MRI) findings of subcortical/cortical hyperintensity in T2-weighted sequences. It is more often seen in parietaloccipital lobes, and is accompanied by clinical neurological changes. PRES is a rare central nervous system (CNS) complication in patients with childhood hematologic-oncologic disese and shows very different neurological symptoms between patients, ranging from numbness of extremities to generalized seizure.In this article, we will review PRES presentation in hematologic-oncologic patients. Then, we will present our patient, a 7-year-old boy with Evans syndrome on treatment with cyclosporine, mycophenolate mofetil (MMF) and prednisone, with seizure episodes and MRI finding in favour of PRES. References1. De Laat P, Te Winkel ML, Devos AS, Catsman-Berrevoets CE, Pieters R, van den Heuvel-Eibrink MM. Posterior reversible encephalopathy syndrome in childhood cancer. Ann Oncol 2011;22(2):472-8.2. Siebert E, Spors B, Bohner G, Endres M, LimanTG. Posterior reversible encephalopathy syndrome in children: radiological and clinical findings - a retrospective analysis of a German tertiary care center. Eur J Paediatr Neurol 2013;17(2):169-75.3. Lucchini G, Grioni D, Colombini A, Contri M, De Grandi C, Rovelli A, et al. Encephalopathy Syndrome in Children With Hemato-Oncological Disorders Is Not Always Posterior and Reversible. Pediatr Blood Cancer 2008;51:629–33.4. Kim SJ, Im SA, Lee JW, Chung NG, Cho B, Kim HK. Predisposing Factors of Posterior Reversible Encephalopathy Syndrome in Acute Childhood Leukemia. Pediatr Neurol 2012;47(6):436-42.5. Endo A, Fuchigami T, Hasegawa M, Hashimoto K, Fujita Y, Inamo Y , et al. Posteriorreversible encephalopathy syndrome in childhood: report of four cases and review of the literature. Pediatr Emerg Care 2012;28(2):153-7.6. Won SC, Kwon SY, Han JW, Choi SY, Lyu CJ. Posterior Reversible Encephalopathy Syndrome in Childhood with Hematologic/Oncologic Diseases. J Pediatr Hematol Oncol 2009;31(7):505-8.7. Legriel S, Pico F, Azoulay E. Understanding Posterior Reversible Encephalopathy Syndrome. Annual update in intensive care and emergency medicine. Springer; 2011.P.631-653.8. Malbora B, Avcı Z, Donmez F, Alioğlu B, Alehan F, Alehan F, et al. Posterior reversible leukoencephalopathy syndrome in children with hematologic disorders. Turk J Hematol 2010;27(3):168-76.9. Komur M, Delibas A, Arslankoylu AE, Okuyaz C, Kara E.. Recurrent and atypical posterior reversible encephalopathy syndrome in a child with hypertension. Ann Indian Acad Neurol 2012;15(3):208-10.10. Dzudie A, Boissonnat P, Roussoulieres A, Cakmak, Mosbah K, Bejui FT, et al. Cyclosporine-Related Posterior Reversible Encephalopathy Syndrome After Heart Transplantation: Should We Withdraw or Reduce Cyclosporine?: Case Reports. Transplant Proc 2009;41(2):716-20.11. Fuchigami T, Inamo Y, Hashimoto K, Yoshino Y, Abe O, Ishikawa T, et al. Henoch-schönlein purpura complicated by reversible posterior leukoencephalopathy syndrome. Pediatr Emerg Care 2010;26(8):583-5.12. Incecik F, Hergüner MO, Altunbasak S, Erbey F, Leblebisatan G. Evaluation of nine children with reversible posterior encephalopathy syndrome. Neurol India 2009;57(4):475-8.13. Chandramohan V, Nagarajan VP, Sathyamoorthi MS, Kumar S, Shanmugasundaram C, Periakaruppan G, et al. Posterior reversible encephalopathy syndrome in a child with autoimmune lymphoproliferative syndrome: Case report and review of literature. J Pediatr Neurosci 2012;7(3):221-4.14. Wright KL, Polito MH, French AE. Posterior Reversible Encephalopathy Syndrome: A Case Study. Am J Nurs 2012;112(5):36-40.15. Pedraza R, Marik PE, Varon J. Posterior Reversible Encephalopathy Syndrome: A Review.Crit Care & Shock 2009;12:135-43.16. Morris EB, Laningham FH, Sandlund JT, Khan RB. Posterior reversible encephalopathy syndrome in children with cancer. Pediatr Blood Cancer 2007;48(2):152-9.

Effect of Cognitive Rehabilitation on Executive Functions in Adolescent Survivors of Leukemia: A Randomized and Controlled Clinical Trial

Objective One of the phenomena that have been observed among survivors of childhood cancers like leukemia is the late side effects of the applied treatments, such as chemotherapy, on executive cognitive functions. These problems lead to various complaints such as experiencing dullness while performing activities, encountering difficulties in conducting various tasks simultaneously, and having no interest in laying out plans. These issues will endanger and negate the advantage of any increase in survival rate. Therefore, the aim of this clinical trial is to evaluate the efficiency of using a series of cognitive rehabilitation exercises in improving executive functions on the level of hope in adolescents who survived leukemia.&nbsp; Methods & Materials This research is a quasi-experimental study with pretest, posttest, and follow-up stages. The study population consisted of all the adolescents between the ages of 12 to 18 years, who survived leukemia, in Tehran city. Purposive sampling method was used. Based on the medical records and inclusion and exclusion criteria, 30 patients, who had been referred to the section of blood diseases at the Mofid hospital in the year 2013, were selected and accidentally classified into intervention (15) and wait list (15) groups. The participants of the intervention group received treatment offered as part of the cognitive rehabilitation program over a period of 12 sessions. The research data was collected using the Wechsler Intelligence Scale, Achenbach Behavior Scale, and the Miller Hope Test. These data were analyzed with the help of descriptive statistics (mean and standard deviation) and inferential statistics (multivariate analysis of covariance). Results The mean treatment duration was found to be 23.27 months in the intervention group and 27.00 months in the waiting list group. The mean treatment completion time of the intervention group is obtained as 25.60, and in the waiting list group as 30.67. The findings of the Miller hope questionnaire revealed that executive functions witnessed a significant positive effect due to cognitive rehabilitation, in adolescents who survived leukemia (P<0.05). This effect remained stable, as shown in a follow-up of one month after the intervention (P<0.05).&nbsp; Conclusion The results of this study have shown that the effect of cognitive rehabilitation on executive functions reaps significant dividends with regard to the promotion of hope in adolescents who survived leukemia and have been under the chemotherapy. The promotion of hope in participants belonging to the intervention group was more than in the participants of the wait list group. Given the fact that, today, one of the main goals of treatment of chronic diseases such as cancer is to enhance the quality of mental health of the surviving patients, the use of inexpensive and accessible programs like cognitive rehabilitation would be very effective. Consequently, healthcare professionals could attempt to reduce the side effects caused by chemotherapy and radiation, in addition to improving the cognitive issues of affected individuals, by placing emphasis on hope among the concerned patients. Therefore, it is recommended to conduct further research by considering the results of this work in order to develop effective cognitive rehabilitation interventions, thereby, enhancing the coping strategies, quality of life, and mental health of patients who are afflicted with cancer and those who survived cancer. Cognitive rehabilitation services should also be considered for post-treatment follow-up projects.&nbsp

Inflammatory myofibroblastic tumor of the pericardium in an 11‐month‐old infant: A case report

Abstract Primary cardiac tumors are very rare in infants. Here we present an 11‐month‐old infant with a pericardial inflammatory myofibroblastic tumor who presented with symptoms of respiratory distress and cardiac tamponade. The tumor was surgically removed, and the patient received medical treatment; the patient had no problem with follow‐up

Congenital Pleomorphic Adenoma in a Submandibular Gland of a Newborn- A Case Report

Introduction: Pleomorphic adenoma is a rare benign salivary gland neoplasm in children, which can be treated by simple excision. This tumor is rarely included in the differential diagnosis of solid submandibular masses in children. In the neonates, congenital pleomorphic adenoma usually presents in the nasopharynx. Surgical excision is the treatment of choice and recurrence is not expected. We report what appears to be the first case of congenital pleomorphic adenoma in the submandibular region in a one-day-old newborn.   Case Report: The case of a one-day-old term baby is presented with a 5x2 cm left submandibualr mass with extension to the oral cavity. The mass was hard and non-mobile. During Ultrasonography and Contrast-enhanced Computed Tomography (CT) scan, the mass was solid with a heterogeneous internal structure. The tumor was completely excised and proved to be a pleomorphic adenoma during histopathological examination.   Conclusion:  Congenital pleomorphic adenoma rarely occurs in the nasopharynx and is treated by surgical excision. Our case is unique because the congenital pleomorphic adenoma is located in the submandibular gland of a newborn

Serum Folate Levels in Major Beta Thalassemia Patients

Objective: Beta major thalassemia is a variant of beta thalassemia syndrome which could be treated with bone marrow transplantation or if not available, regular blood transfusion. In the latter case, supportive therapy is the mainstay of treatment because of low folate intake or absorption. But the main cause of insufficient supportive therapy is the increasing need of bone marrow for ineffective erythropoiesis in the absence of regular blood transfusion. The purpose of regular blood transfusion in β major thalassemia patients is to maintain the range of hemoglobin level between 9 and 11 gr/dl to stop insufficient erythropoiesis completely. Therefore, by regular blood transfusion, supportive therapy with folic acid would not be needed. The aim of this study is to determine serum folate level in regular transfused β major thalassemia patients in Mofid Children's Hospital during 2006. Methods: This is a cross sectional descriptive–analytic study performed on 100 β major thalassemia patients receiving regular blood transfusion and desferal. Post-storage leukodepleted blood is used for transfusion. Patients’ data is achieved from information data sheets. Serum folate level is determined with Electrochemiluminescence method in one of the most reliable laboratory centers. Normal serum folate level was 3-17.5 ng/ml in this laboratory with the sensitivity of 0.6 ng. Data analysis is performed with SPSS analysis software, and with chi squared, T-test and Spearman test. Findings: 56 (56%) girls and 44 (44%) boys entered this study with a median age of 156 (± 71.2) months and an age range of 14-288 months. Patients’ median hemoglobin level was 9.5 (±0.87) g/dl, with minimum of 7.5 and maximum of 11.9 g/dl. Mean MCV was 84.2 (±4.20) fl, with the range of 73.4 -95.3 fl. Serum folate level was in the range of 1-19 ng/ml and median of 9 (± 4.9) ng/ml. Serum folate was less than 3 ng/ml in 3% of evaluated patients. Hemoglobin level was equal or more than 9 g/dl in 73% of patients. Conclusion: It seems that if major β thalassemia patients receive regular blood transfusion, their serum folate level would be in normal range and supplementation therapy with folate will not be necessary

Frequency of Red Cell Alloimmunization in Patients with β-Major Thalassemia in an Iranian Referral Hospital

Objective: Frequency of red cell alloimmunization in patients with β-major-thalassemia in Mofid children's hospital. Tehran. Iran Material & Methods: This is a cross-sectional descriptive study conducted in Mofid children's hospital, March 2007. A total of 121 major thalassemia patients on regular blood transfusion were included in this study. Clinical and laboratory data were collected and analyzed to find out the frequency, pattern and factors influencing red cell immunization secondary to multiple blood transfusions in these patients. Findings: Mean age of patients was 13 (6.19) from 2-26 years.They had received regular blood transfusions during periods ranging from 1 to 25.5 years. Red cell alloimmunization was found in 9 patients (7.4%). In female group, 5 out of 66 (7.6%) patients and in male group 4 out of 55 (7.3%) patients had evidence of alloimmunization.The mean age of patients with alloimmunization was 9.6 (6.5) years (range 3.7-20). Four patients (44.4%) with alloimmunization were more than 3 years old at the time of first blood transfusion. The mean age at first blood transfusion in patients with alloimmunization and without alloimmunization was 2.8 (2.4) and 1.7 (2.0) years (P=0.1). The differential rate of splenectomy as a risk factor between patients with and without alloimmunization (11.1% and8% respectively) was not statistically significant (P=0.5). Direct or indirect antiglobulin tests were positive in 5 (62.5%) patients. The blood alloantibodies by a panel of antibodies using standardized blood bank methods were detected in 4 patients, which were of anti-K and anti-D types. Conclusion: The rate of red blood cell alloimmunization is relatively low in our patients. The age at first blood transfusion and splenectomy were not statistically significant as risk factors for alloimmunization in this study

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene

Abstract Background Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3–4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Case presentation Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from “Lurs” ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. Conclusions Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients

Endogenous Bacteremia Caused by Intestinal Colonization of Carbapenem-Resistant <i>Enterobacteriaceae</i> (CR<i>E</i>) in Immunocompromised Children

Objective: Carbapenem-resistant Enterobacteriaceae (CRE) infection is life-threatening, especially for immunocompromised children. The source tracking of CRE could prevent bacteremia during hospitalization. In this study, the intestinal colonization of CRE and their translocation to blood were investigated. Methods: Stool samples from immunocompromised pediatric patients were collected after admission, and secondary stool and blood samples were collected in case of fever. After CRE phonotypic detection, the OXA-48, NDM-1, VIM, IMP, and KPC genes were detected by PCR. Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) was used to determine the phylogenic relatedness of the blood and fecal isolates. Results: Bacteremia was recorded in 71.4% of the patients. Enterobacteriaceae spp. were recorded in 100% of the stool samples and 31% of the blood samples. The correlation between the length of stay (LOS), days of fever, chemotherapy regimens, and death rate was significant (p-value ≤ 0.05). OXA-48 was present in all CRE isolates in both the primary and the secondary stool samples and the blood samples. According to the phylogenetic data, 58.33% of the patients with bacteremia had identical blood and stool isolates. The death rate was 24.4% in children with CRE bacteremia. Conclusions: The primary intestinal colonization with CRE in immunocompromised pediatrics and their translocation to blood was established in this study. The implementation of infection control programs and the application of infection prevention strategies for immunocompromised children is necessary