Visual Perception in Children with a History of Hypoglycemia due to Hyperinsulinism.

Objectives: Hyperinsulinism refers to improper insulin secretion in the presence of low plasma glucose, causing severe and persistent hypoglycemia in infants and children. The brain's occipital lobe, which includes the visual and plays an essential role in visual perception is specifically sensitive to hypoglycemia-induced damage. The present study aims to investigate the visual perception in children suffering from hyperinsulinism and to compare it with the control group. Materials & Methods: This cross-sectional control study, conducted in 2020 in Isfahan, Iran, involved 20 children aged 4-13 years with hyperinsulinism and 20 healthy children of the same age and gender for comparison. In both groups, the measuring instrument was the Test of Visual Perceptual Skills (non-motor) Third Edition. Results: The mean visual perceptual quotient in the case and control groups was 80.50±26.74 and 116.50±7.56 (p-value<0.001), respectively. The results overall indicated that children suffering from hyperinsulinism were weaker than healthy children in all areas of visual perception. Conclusion: Based on the obtained results, it is recommended that children suffering from hyperinsulinism be screened regarding visual perceptual disorders since this screening may be helpful in initiating different rehabilitation programs among these patients.

Whole exome sequencing revealed variants in four genes underlying X-linked intellectual disability in four Iranian families: novel deleterious variants and clinical features with the review of literature.

AIM AND OBJECTIVE: Intellectual disability (ID) is a heterogeneous condition affecting brain development, function, and/or structure. The X-linked mode of inheritance of ID (X-linked intellectual disability; XLID) has a prevalence of 1 out of 600 to 1000 males. In the last decades, exome sequencing technology has revolutionized the process of disease-causing gene discovery in XLIDs. Nevertheless, so many of them still remain with unknown etiology. This study investigated four families with severe XLID to identify deleterious variants for possible diagnostics and prevention aims. METHODS: Nine male patients belonging to four pedigrees were included in this study. The patients were studied genetically for Fragile X syndrome, followed by whole exome sequencing and analysis of intellectual disability-related genes variants. Sanger sequencing, co-segregation analysis, structural modeling, and in silico analysis were done to verify the causative variants. In addition, we collected data from previous studies to compare and situate our work with existing knowledge. RESULTS: In three of four families, novel deleterious variants have been identified in three different genes, including ZDHHC9 (p. Leu189Pro), ATP2B3 (p. Asp847Glu), and GLRA2 (p. Arg350Cys) and also with new clinical features and in another one family, a reported pathogenic variant in the L1CAM (p. Glu309Lys) gene has been identified related to new clinical findings. CONCLUSION: The current study's findings expand the existing knowledge of variants of the genes implicated in XLID and broaden the spectrum of phenotypes associated with the related conditions. The data have implications for genetic diagnosis and counseling.

Causes and Risk Factors of Drug-Resistant Epilepsy in Children.

Objectives: Epilepsy, the tendency to have recurrent unprovoked seizures, is the most common chronic neurological disorder worldwide. About 20% to 40% of children with epilepsy suffer from refractory seizures, causing neurological, cognitive, and psychosocial impairments. Identifying the factors contributing to pediatric refractory seizures can help neurologists effectively prevent, diagnose, and treat their patients. Materials & Methods: In this cross-sectional study, 2 to 16 years old children with refractory seizures (drug-resistant epilepsy) were assessed regarding their demographic and seizure-associated characteristics. Results: Children with refractory seizures had a significantly higher rate of neonatal asphyxia, hospitalization after birth, neonatal seizures, and seizure in the first year of life, history of infantile spasm, and symptomatic epilepsy. Furthermore, polymorphic seizures and brain MRI abnormalities were significantly more frequent among them. Several different mechanisms have been suggested for explaining intractability in epileptic patients. None of the mechanisms can explain all patients. The most common underlying etiologies for seizures in the intractable group were hypoxic-ischemic damage, cerebral dysgenesis, and genetic disorders. Conclusion: Seizure intractability results from a tremendous deleterious change in the brain's structure. Early identification of the risk factors and prediction of patients likely to have pharmaco-resistant epilepsy will allow more aggressive treatment and earlier specialized intervention.

The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy.

BACKGROUND: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. OBJECTIVE: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). METHODS: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. RESULTS: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. CONCLUSIONS: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Inborn Errors of Metabolism Associated With Autism Among Children: A Multicenter Study from Iran.

OBJECTIVE: This study aimed to find the common inborn errors of metabolism in Iranian patients with autism spectrum disorder. METHODS: In this cross-sectional multicenter study, 105 children and adolescents with autism spectrum disorder from six centers in different cities of Iran were enrolled between August, 2019 and October, 2020. Metabolic screening, including measuring plasma levels of amino acids, acylcarnitines, creatine, and guani-dinoacetate, and urinary levels of organic acids, purines, and pyrimidines was performed. Other data, including age, parental consanguinity, history of seizure, developmental mile-stones, and physical examination, were also recorded. RESULTS: An inborn error of metabolism was found in 13 (12.4%) patients. Five patients (4.8%) had cerebral creatine deficiency syndrome, 4 (3.8%) had arginine succinate aciduria, 2- methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria. There was a strong association between positive meta-bolic evaluation and parental consanguinity, history of seizures, microcephaly, and delayed development. CONCLUSIONS: Our results suggest that metabolic screening should be performed in the cases of autism associated with parental consanguinity, developmental delay, and a history of seizures. The assays to be considered as a screening panel include plasma or blood amino acids, acylcarnitines, creatine and guanidinoacetate, and urinary levels of organic acids.

Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations.

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

A Comparative Study on the Efficacy of Coenzyme Q10 and Amitriptyline in the Prophylactic Treatment of Migraine Headaches in Children: A Randomized Controlled Trial.

Background: Migraine, one of the most common headaches in children, has a significant impact on children and their family's quality of life (QoL). There are two approaches for controlling migraine headaches preventative and controlling acute attacks. Several drugs have been used for this purpose, and tricyclic antidepressants were at the top. Amitriptyline has shown not only a desirable effect on controlling the headaches but also some adverse side effects. Recently, finding effective drugs with fewer side effects, become more critical. Among them, nutraceuticals were one of the promising ones. Materials and Methods: In this randomized clinical trial on 72 patients aged 5-15 years old with diagnosis of migraine based on the International Headache Society criteria, we compare the effectiveness of coenzyme Qten on frequency, duration, and severity of childhood migraine. For comparing the QoL, we used the International PedMIDAS questionnaire. Results: Coenzyme Qten showed good therapeutic effects in children, especially in long-term use; however, amitriptyline showed more rapid response. After 3 months of treatment, clinical outcomes in the two groups did not significantly differ from each other. Similarly, Children's QoL increased in the same way. There are more reported side effects in children using amitriptyline compared to coenzyme Qten. Conclusions: According to results, Co-enzyme Q10, with fewer side effects and comparable therapeutic effects, especially in the long term, could be a good drug for prophylactic treatment of migraine headaches.

Efficacy of Lacosamide Add-on Therapy on Refractory Focal Epilepsies in Children and Adolescents: An Open-Label Clinical Trial.

Objective: Epilepsy is a chronic neurological disorder that affects 0.5%-1% of children. 30%-40% of patients are resistant to current anti-epileptic drugs. Lacosamide (LCM) appeared to be effective, safe, and well tolerated in children and adolescents. This study was aimed to evaluate whether LCM could be an effective add-on therapy in children with refractory focal epilepsies. Methods: This study was conducted from April 2020 to April 2021 in Imam Hossein Children Hospital, Isfahan, Iran. We included 44 children aged 6 months to 16 years with refractory focal epilepsy (based on International League Against Epilepsy criteria). LCM was given in divided doses of 2 mg/kg/day, increasing by 2 mg/kg every week. The first follow-up visit was 6 weeks later, when all patients had reached the therapeutic dose. Findings: The average age of the patients was 89.9 months. 72.5% of children had focal motor seizures. Evaluation of percent change in seizure frequency and duration before and after treatment showed a 53.22% reduction in seizure frequency and 43.72% reduction in seizure duration after treatment. Our study group tolerated LCM well, with few side effects. Headache, dizziness, and nausea were common side effects. In line with other studies, none of the suspected risk factors could predict response to LCM treatment. Conclusion: LCM appears to be an effective, safe, and well-tolerated medication in children with uncontrolled drug-resistant focal epilepsy.

Clinical and genetic profile of children with unexplained intellectual disability/developmental delay and epilepsy.

OBJECTIVE: This study was conducted to evaluate the validity of performing whole exome sequencing in children with unexplained intellectual disability (ID), developmental delay (DD), and epilepsy. METHODS: We enrolled 61 Iranian children with unexplained DD/ID, and epilepsy with no etiologic diagnosis. 64 % of cases were male and 36 % were female, with a mean age of 6.2 years (range, 38 days to 15 years). Approximately 79 % of patients were born to consanguineous parents or had non-related parents from a highly inbred local region. Whole-exome sequencing analysis followed by Sanger sequencing was performed in all patients. RESULTS: Pathogenic/likely pathogenic variants were identified in 59% (36/61) of patients, consisting of 26 novel and 14 known alterations. Variants of unknown significance were observed in 6.5 % (4/61) of patients. Variants in 28 genes have not been previously reported in Iranian patients with ID. Several additional phenotypes, mostly microcephaly, were common in 57.4 % of cases. Additionally, epilepsy was refractory in 40 % of patients. Three groups of brain anomalies consisting of brain dysgenesis, brain atrophy, and leukodystrophy were identified in our cohort. Mutations in genes implicated in cellular metabolic pathways were the most common, followed by ion channel/ion transporter and transcription pathways. DISCUSSION: High-throughput DNA sequencing of the Iranian population with a high rate of parental consanguinity is a valuable strategy for identifying genetic etiology in children with unexplained ID/DD and epilepsy. Determining the genetic basis and most commonly involved pathways may help to identify novel genes and targeted antiepileptic treatments.

Neurodevelopmental Outcomes of Infants with Benign Enlargement of the Subarachnoid Space.

Objective: Benign enlargement of the subarachnoid space (BESS) is the most common cause of macrocephaly in infants. This study aimed to evaluate the neurodevelopmental outcomes in infants with BESS. Materials & Methods: In this follow-up study, all records of infants diagnosed with BESS in 2012-2016 were assessed. A clinical follow-up examination was carried out at 6, 12, 18, and 24 months of age to assess the macrocephaly outcomes. Denver Developmental Screening Test-II (DDST-II) was used for evaluating the psychomotor development of infants at 24 months of age. All data were entered in SPSS Version 13, and descriptive statistics were measured. Results: Out of 32 infants included in this study, 28 (87.5%) were boys. Five cases of prematurity history (15.6%), and 23 cases of macrocephaly in the family (71.9%) were recorded. The mean age of BESS diagnosis was 6.8 months (SD=3.2). subdural hematoma was reported in one infant (3.1%). Also, 28 infants showed macrocephaly at 18 months of age (83.3%). Seven patients had developmental delay, according to DDST-II (22%). The mean head circumference at birth and six months of age was significantly greater in infants with developmental delay compared to those with normal development. There was a significant difference between the mean head circumference at birth (P=0.05) and the mean head circumference at six months of age (P=0.02). Conclusion: Developmental delay is frequent in BESS infants, especially those with macrocephaly at birth and six months of age, and requires medical attention.

The Comparison of Levetiracetam and Piracetam Effectiveness on Breath-Holding Spells in Children: A Randomized Controlled Clinical Trial.

BACKGROUND: We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood. MATERIALS AND METHODS: This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up. RESULTS: There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS. CONCLUSIONS: Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS.

The identification of two pathogenic variants in a family with mild and severe forms of developmental delay.

Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.

A Comparative Study on the Efficacy of Levetiracetam and Carbamazepine in the Treatment of Rolandic Seizures in Children: An Open-Label Randomized Controlled Trial.

OBJECTIVE: This study was performed to investigate whether levetiracetam should be preferred to carbamazepine as a treatment choice for benign childhood epilepsy with centro Temporal spikes (BCECTS), the most common partial epilepsy of childhood. METHODS: This randomized clinical trial study included 92 children with rolandic epilepsy aged 4-12 years referred to the Pediatric Neurology Clinic at Imam Hossein Hospital, Isfahan, Iran, from April 2019 to January 2020. Patients were selected consecutively and randomly assigned to two study groups (levetiracetam and carbamazepine groups). Patients were followed and revisited every 2 months for 6 months after starting the medication. The frequency and duration of seizure attacks and drug side effects were recorded before treatment and in bi-monthly visits. Data were analyzed by SPSS software Version 24 using Mann-Whitney U- test and Friedman test. FINDINGS: In our study, the seizure frequency decrease was not significantly different between the two groups; however, patients in both groups showed significantly lower seizure frequency in 2, 4, and 6 months of follow-up compared to starting time. After a follow-up for 6 months, one out of 47 (2.1%) patients using levetiracetam showed intolerance, resulting in changing the medication. In addition, two out of 48 (4.1%) patients in the carbamazepine group had skin rashes. No significant changes had been reported regarding the duration of seizure attacks in both groups after treatment. CONCLUSION: This study showed encouraging results for using levetiracetam, with acceptable results and fewer side effects for the treatment of children with BCECTS in Iran.

Efficacy of Levetiracetam in Treatment of Childhood Stuttering.

BACKGROUND: Stuttering is a kind of speech disorder that affects about 1% of total population. As the origin of this disorder is not obviously diagnosed yet, various remedies have been practiced and among them different medicines have been studied, but unfortunately no significant effective drugs have been recognized yet. As stuttering imposes a great social and mental costs to the patients and their families, finding an effective medicine will help significantly. In this study we have focused on the effects of levetiracetam (LEV) treatment on children suffering from stuttering. METHODS: In this clinical trial study, 30 children aged > 3 years (median 3.8 years) with stuttering and abnormal sleep electroencephalogram (EEG) were treated by LEV and followed-up for a minimum period of 6 weeks. The starting dose of 20 mg/kg/day was increased at an interval of 1 week by 20 mg/kg/day, if necessary, up to maximum dose of 60 mg/kg/day. RESULTS: Overall LEV was effective in 70% of patients, decreasing stuttering to at least 50%. Three children (10%) became stuttering-free and only in one (3.3%) child an increase in stuttering was observed. There were statistically significant differences for efficacy in the presence of variables such as age groups, seizure, stuttering family history, and EEG data. CONCLUSIONS: LEV is an effective drug for treatment of childhood stuttering in those that have abnormal sleep EEG.

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 nonsense-mediated 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.

Genetic Analysis of MECP2 Gene in Iranian Patients with Rett Syndrome.

OBJECTIVES: Rett 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 & METHODS: To 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. RESULTS: Direct 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. CONCLUSION: Defects 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.

Oral Diazepam in Febrile Seizures Following Acellular Pertussis Vaccination.

BACKGROUND: Febrile seizure is the most common type of seizures among children, which is a terrible and frightening experience for parents who are concerned about its recurrence. The aim of this study was to evaluate the effect of diazepam on preventing the recurrence of febrile seizure following acellular pertussis vaccination. MATERIALS AND METHODS: In this clinical trial, 121 children with a history of febrile seizure that required the pertussis vaccination were enrolled and divided into two groups; the first group was treated with oral diazepam for 48 h after vaccine injection and the control group received antipyretics only if fever occurred after the vaccination and used rectal diazepam for controlling seizure if a seizure occurred. The incidence of fever and seizure after the injection of the vaccine and incidence of febrile seizure were compared. RESULTS: Nearly, 85.7% in the oral diazepam group and 87.9% in the rectal diazepam group had fever after receiving the pertussis vaccine, but the incidence of fever was not significantly different between the groups. Seven children (12.06%) in the rectal diazepam group had a seizure after pertussis vaccination, and none of the children in the oral diazepam group had a seizure after receiving the vaccine at 18 months of age. This difference was significant. CONCLUSION: Prophylaxis with diazepam administration in children with a history of febrile seizure can prevent recurrence of febrile seizure after pertussis vaccination.

Short-Term Side Effects of Low Dose Valproate Monotherapy in Epileptic Children: A Prospective Study.

OBJECTIVES: Considering the common use of valproate among children, we investigated the short-term side-effects of low dose valproate monotherapy in epileptic children. MATERIALS & METHODS: In this prospective study, 209 epileptic children (48.3% male, mean age: 7.02 ± 3.13 yr) on low therapeutic dose of valproate monotherapy (20-30 mg/kg/d) were enrolled during 2014-2015 in Isfahan Pediatric Neurology Clinic, Isfahan University of Medical Sciences, Isfahan, Iran and side-effects were evaluated through frequent clinical visits and laboratory tests during 6 months of valproate therapy. RESULTS: Weight gain was reported in 53.1% of patients. Decreased appetite was seen in 11% of patients, more frequent in younger cases (P=0.006). Abdominal pain, nausea/vomiting, diarrhea, and constipation were reported in 16.3%, 2.4%, 1.4%, and 1% of patients, respectively. Headache, tremor, dizziness, abnormal color vision, myoclonus, and bruxism were seen in 5.7%, 1.4%, 1%, 1%, 1%, and 0.5% of patients, respectively. Enuresis, hair loss, and skin rash were reported in 8.1%, 6.7%, and 0.5% of patients, respectively. Thrombocytopenia, impaired liver function tests, and leukopenia occurred in 1%, 1%, and 0.5% of patients, respectively. CONCLUSION: Low dose valproate monotherapy may cause numerous side-effects, mostly not life-threatening and requiring no action. Besides more reported complications, we observed decreased appetite (among younger patients), enuresis, and abnormal color vision which are onlybriefly discussed in the literature and need to be addressed more.

Neurodevelopmental outcomes of the West syndrome in pediatric patients: The first report from the Middle-East.

BACKGROUND: This study aimed to investigate the clinical characteristics and neurodevelopmental outcomes of children with West syndrome (WS) by using the Bayley-III scale of infant development, as the first report from the Middle-East. METHODS: Between January 2013 and February 2016, we prospectively enrolled 67 consecutive patients with a confirmed diagnosis of WS from Isfahan, Iran. Cognition, language and motor outcomes of the studied subjects were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). RESULTS: Overall, 67 cases, including 34 (50.7%) boys and 33 (49.3%) girls (a male/female ratio of 1.03), were enrolled for the study. The mean age was 26.7 ± 12.9 months. Among the subjects, 50 (74.6%) patients had symptomatic WS, and 17 (25.4%) patients had cryptogenic WS. "Severe delay" was found in 76.9% of the patients regarding cognitive evaluation, 67.7% for language and communication abilities, and, 81.5% for motor function. The patients with cryptogenic WS were significantly more likely to have more favorable outcomes in motor (p = 0.035), cognitive (p = 0.035) and receptive language (p = 0.043) in comparison to those who had symptomatic WS. The patients with controlled seizures were significantly more likely to have more favorable outcomes in motor (p = 0.027) and cognition (p = 0.011) as compared to those with uncontrolled seizures. CONCLUSION: WS was associated with poor neurodevelopmental outcome in our study. Severe developmental delay was associated with two major factors: (i) presence of a specific underlying abnormality (symptomatic WS) and(ii) persistent seizures as a result of the former.

Risk Factors of Pediatric Arterial Ischemic Stroke; A Regional Survey.

BACKGROUND: Considering that better understanding of the underlying mechanisms and risk factors of arterial ischemic stroke (AIS) would be helpful for better management of stroke and its outcome in children as well as preventing or reducing the occurrence of its related potential disabilities, the aim of this study was to investigate the most common risk factors and causes of AIS in patients referred to the referral hospitals in Tehran and Isfahan cities of Iran. METHODS: In this study, medical files of all pediatric patients admitted to the Mofid and Imam Hossein children's hospitals with the diagnosis of AIS from 2001 to 2011 and 2011 to 2016, respectively, were evaluated. Identified risk factors of AIS were categorized as arteriopathies, cardiac disorders (CDs), infection, acute head-and-neck disorders, acute systemic conditions, chronic systemic conditions, prothrombotic states, chronic head-and-neck disorders, atherosclerosis-related RFs, and others. RESULTS: In this study, 61 patients were evaluated. Mean (standard deviation) age of the patients was 5.1 (3.9) years. About 62.3% of the patients were boys while 37.7% were girls (P < 0.01). A total of 36 patients (59%) had at least one risk factor for AIS. About 40.9% of patients had undetermined risk factors. CDs (21.31%) and vascular disease (21.31%) were the most common risk factors of AIS in the studied children. Nearly 11.5% of the patients had moyamoya vascular disease (MMD). CONCLUSION: The findings of our study indicated that the most common risk factors for AIS in the two studied regions are congenital heart and vascular diseases. The results of the current study could be used for planning more preventive strategies in patients suffering from the mentioned diseases. In addition, the obtained data could be used for conducting targeted education and management of high-risk patients.