Iranian Journal of Child Neurology

Anxiety disorders (ADs) are a group of mental disorders characterized by feelings of tension, fear, and excessive worrying in the face of life experiences. Aberrant signaling of adenosine A2a receptor (ADORA2A) is believed to be involved in the pathogenesis of ADs. Polymorphisms in the ADORA2A gene were shown to be associated with some of the patterns presented by ADs. The results of these studies have been inconsistent, making it hard to draw definitive conclusions. Therefore, this study performed a systematic review to clarify the associations between ADORA2A gene polymorphisms and ADs susceptibility. PubMed/Medline, Web of Science, and Scopus database using appropriate keywords, then screened for separation of suitable studies based on inclusion/exclusion criteria. Collectively, rs5751876 (1976T>C or previously 1083C>T) and rs35060421 (2592C>Tins) polymorphisms of ADORA2A were associated with an increased susceptibility to ADs. Moreover, rs2298383 TT genotype may be the causal regulatory factor, and ADORA2A T/C (rs2298383/rs3761422) haplotypes have significant susceptibility to ADs development. Additional research is needed to further define the role of ADORA2A gene polymorphisms in the pathogenesis of ADs.

Objectives
To evaluate the need for lumbar puncture (LP) in children aged 6 to 60 months experiencing their first febrile seizure, regardless of seizure type, and to determine if LP is particularly beneficial for those under 12 months old.
Materials & Methods
In this retrospective study, data from 253 children who presented with first febrile seizure were analyzed. All patients in this study underwent LP and were divided into two groups based on their cerebrospinal fluid (CSF) results: non-pleocytosis and pleocytosis. Patients were evaluated for age, sex, familial history of seizure, and type and duration of seizures. They were also evaluated based on laboratory results, including blood tests, CSF analysis, and electroencephalography.
Results
Sixty-seven (25.9%) of the 253 patients were under 12 months of age, and only two of the 67 patients (2.8%) had pleocytosis. Patients younger than 12 months did not have a higher rate of complex febrile seizure or pleocytosis than those over 13 months of age. None of the patients had bacterial meningitis. Regarding viral meningitis, seven patients (5.3%; age mean SD, 12.3±1.8 months) were diagnosed with enteroviral meningitis, though only one of them had pleocytosis. When compared to the non-pleocytosis group, the pleocytosis group showed no differences in clinical characteristics (age, sex, familial history of seizure, type, and duration of seizure), laboratory results, or the use of antiepileptic drugs.
Conclusion
The present study suggests that LP should be carefully considered in children with first febrile seizure, including children under 12 months of age

Objectives
Acute Flaccid Paralysis (AFP) in children can stem from a diverse array of potential diagnoses.
Materials & Methods
This retrospective study sought to diagnose children referred to a referral pediatric emergency unit with AFP between 2011 and 2016. The study gathered clinical observations, conducted stool and cerebrospinal fluid analyses, and assessed electrophysiological and imaging data.
Results
The present study enrolled 118 fully immunized children with a mean age of 6.09 ± 3.60 years. The most prevalent diagnoses included Guillain-Barré Syndrome (GBS-80 cases), acute viral myositis (20 cases), Transverse Myelitis Syndrome (TMS) (TMS-6 cases), and Vaccine-Associated Paralytic Poliomyelitis (VAPP) (VAPP-6 cases). All these six patients had primary immunodeficiency. Notably, all patients tested negative for poliovirus in stool analyses. This study encountered a unique case of a 2.5-monthold male patient who presented with acute limb motor weakness, along with fever, irritability, new-onset hypotonia, and generalized decreased deep tendon reflexes. Notably, no signs of upper motor neuron involvement were found. The Cerebrospinal Fluid (CSF) analysis was compatible with the diagnosis of viral meningitis. Moreover, among the 60 brain and spinal imaging series performed, five were indicative of GBS, six cases showed evidence of TMS, and one revealed a spinal mass. Besides, clinical investigations pointed toward acute viral myositis as a secondary etiology of AFP in 20 patients in this study.
Conclusion
In this hospital-based study, the most frequent diagnoses for children arriving at a third-level pediatric Emergency Room (ER) with acute flaccid paralysis AFP were GBS, acute viral myositis, TMS, and VAPP). These findings suggest a distinct pattern of AFP causes compared to those found in community-based epidemiological studies. Additionally, notably, unusual conditions, such as viral meningitis, can rarely present with AFP-like symptoms. Assessment for primary immune deficiency should be considered in cases of VAPP. Lastly, this research has implemented a pediatric AFP Management Protocol: A Local Practical Approach

Objective
Neurological manifestations of Severe Acute Respiratory Syndrome coronavirus-2 have been well documented in adults during and after infection with the virus as well as after vaccination. The incidence of severe neurological symptoms among children is very low. This study aimed to analyze the varied neurological manifestations after COVID-19 infection among children and give a report on a single center experience with these severe neurological symptoms
Materials & Methods
Case records of patients less than 18 years admitted between July 2021 to December 2022 with neurological manifestations and COVID-19 infection or with elevated COVID-19 antibodies after exclusion of other etiological diagnosis were analyzed.
Results
There were 10 cases in the age range of 1-15 years. All the cases had elevated COVID-19 antibodies with history of contact 2-3 weeks prior except one who was positive for COVID-19 infection. Two cases presented with acute ascending paralysis suggestive of Guillain-Barre syndrome. Four cases presented with features of encephalopathy with clinical presentation fulfilling the criteria of Multisystem inflammatory syndrome in children. One case presented with fever and focal seizures with MRI showing sagittal sinus thrombosis, and one presented with fever and altered sensorium with MRI showing leukoencephalopathy. One child had cerebral mucormycosis without any evidence of immunosuppression. There was one child with features of encephalopathy with active COVID-19 infection.
Conclusion
The varied presentation highlights the central and peripheral nervous system involvement by the virus in the pediatric population. It also emphasizes the need to investigate for COVID-19 in children presenting with these complaints during the pandemic.

Objectives
Extra gastrointestinal symptoms in celiac disease (CD), such as neurological manifestations, might be common in pediatrics. The present study aimed to evaluate the frequency of CD in children with idiopathic epilepsy.
Materials & Methods
In a cross-sectional study, signs and symptoms of CD were evaluated in 40 children aged 2-14 years with idiopathic epilepsy who were referred to the Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran. Then, serum levels of tissue transglutaminase antibody (tTG) and total IgA were measured in them. Upper gastrointestinal endoscopy and small intestine biopsy were recommended for patients with abnormal serum IgA Anti-tTG.
Results
Eighteen girls and 22 boys with a mean age of 5.29±2.4 years were evaluated. In this study, only three patients (7.5%) with epilepsy had abnormal serum IgA Anti-tTG and serum Total IgA. Upper gastrointestinal endoscopy and pathological examination of duodenal biopsy of those three children reported total villous atrophy (Marsh type 3). The age of onset of seizures in children with CD was more than three years, while in children without CD, 62.2% of cases were less than three years. These results indicate that CD is associated with the age of onset of seizures in children.
Conclusion
Due to the accompaniment of celiac with neurological manifestations, patients with neurological symptoms and gastrointestinal symptoms should be examined for celiac.

Objectives
Based on case reports, researchers have observed the incidence and clinical manifestations of Guillain-Barré Syndrome (GBS) following COVID-19 infection. Current hypotheses suggest that the risk of GBS may increase with COVID-19, and worsening GBS could elevate the risk of infection and exposure to the virus. This study aimed to assess the cognitive epidemic and mortality of children under 15 years of age with GBS during the COVID-19 pandemic and to compare them to two years earlier without addressing the etiology.
Materials & Methods
This cross-sectional study was conducted on all children admitted to Iranian hospitals with a diagnosis of GBS and whose clinical information was available in the national flaccid paralysis patient information registration system between April 2018 and April 2021.
Results
The total number of registered cases of GBS in the pre-COVID-19 period and during this period was 778 cases and 504 cases, respectively (total N=1282), indicating a decrease in registered GBS during COVID-19. The mean age of the patients in the pre-COVID-19 period was 9.00 ± 2.78 years, and during the COVID-19, it was 8.99 ± 2.03 years (P-value =0.998). No significant difference was found in gender distribution between the two periods (P-value =0.427). The total number of paralysis cases studied after 60 days was 14.3% before the COVID-19 period and 17.3% during the pandemic (P-value =0.216). The mortality rate in patients with GBS was 0.13% in the pre-COVID-19 period and 0.19% in the COVID-19 period (P-value =0.757).
Conclusion
Despite the decline in the frequency of diagnosis and referrals of patients with GBS during the COVID-19 period, no difference was found in the demographic characteristics and clinical outcomes of children with GBS in the pre-COVID-19 period and during this pandemic.

Objectives
Seizures are changes in the electrical activity of the brain. These changes can cause significant or otherwise asymptomatic symptoms. Phenobarbital and phenytoin are known drugs for treating neonatal seizures, but little clinical experience exists using other drugs. The present study aims to evaluate the efficacy of other drugs, such as Levetiracetam and Topiramate, compared to Phenobarbital in treating neonatal seizures.
Materials & Methods
In a double-blind clinical trial, all neonates admitted to a referral hospital for two years (2020-2022) due to seizures were included. All of the neonates were treated with a dosage of 10-40mg/kg/state IV Phenobarbital to control the acute seizure. After that, they were divided into three groups with specific treatment programs. Groups were ordered with oral Phenobarbital 5mg/kg/day maintenance (first group), oral Topiramate 3-8mg/kg/day (second group), and 10-40mg/kg/day Levetiracetam (third group). Seizures and potential side effects were investigated through interviews and medical EEG tests. The data was analyzed using the Chi-square test.
Results
Sixty infants (20 neonates in each group) were studied. Phenobarbital, Italept, and Topiramate did not significantly differ in controlling convulsions and changes related to brain paroxysmal discharges.
Conclusion
Due to the long treatment duration and side effects, it is essential to choose the appropriate drug for treating treatment-resistant seizures of neonates. The present study found that Phenobarbital, Levetiracetam, and Topiramate are equally effective in controlling seizures. These medications can also help eliminate abnormalities in children’s brain paroxysmal

Objectives
This study investigated the effects of transcranial direct current stimulation (tDCS) before and during the mirror visual feedback (MVF) on hand grip strength (HGS) and range of motion of the affected hand in children with spastic hemiplegia cerebral palsy (SHCP).
Materials & Methods
Twelve children with SHCP participated in this randomized, crossover, and double-blind study. They were randomly exposed to one of four intervention conditions, including 1) a-tDCS-offline, 2) s-tDCS-offline, 3) a-tDCS-online, and 4) s-tDCS-online, with a one-week interval. Participants in the online condition received either anodal or sham tDCS during MVF, while those in the offline condition received tDCS before performing MVF. The tDCS was applied over the M1 area of the affected hemisphere for 20 minutes at 1 mA intensity. The HGS and range of motion of the wrist and elbow (ROM-W and ROM-E) of the affected limb were measured before (pre) and immediately after (post) interventions in each session.
Results
The results showed that the HGS was significantly higher under a-tDCS-offline (p=0.001), s-tDCS-offline (p=0.004), and s-tDCS-online (p=0.005) compared to the a-tDCS-online. Moreover, the ROM-W was significantly higher under a-tDCS-offline (p=0.034), s-tDCS-offline (0.011), and s-tDCS-online (p=0.027) compared to the a-tDCS-online. Eventually, the ROM-E was significantly higher under a-tDCS-offline, s-tDCS-offline, and s-tDCS-online compared to the a-tDCS-online (p˂0.001; p˂0.001; p=0.01, respectively).
Conclusion
The results might have practical implications regarding the timing of the application of tDCS in conjunction with MVF in children with SHCP.

Objectives
Acute necrotizing encephalopathy of childhood (ANEC) is a rare, potentially life-threatening condition. This study aimed to identify clinical profiles and outcomes of ANEC while assessing the accuracy of severity scoring in the Iranian population.
Materials & Methods
The present study collected demographic, clinical, laboratory, and radiological data from children diagnosed with ANEC. Severity was measured using the ANE-Severity Score (ANE-SS), while outcomes were assessed with the Glasgow Outcome Score (GOS). This research analyzed the relationship between these scores and various parameters for statistical significance.
Results
Seven patients were included over three years, with an average age of 4.4±2.7 years (5 males). ANE-SS varied from moderate to high, with most patients experiencing moderate to severe disabilities, as indicated by the GOS. Significant correlations were found with initial serum magnesium levels, pupil light reactivity, and initial GCS score (P-value < 0.05).
Conclusion
Controlling initial magnesium levels may improve ANEC outcomes. Additionally, intact pupil light reactivity at admission was associated with a better prognosis.

Absence epilepsy is one of the most common epileptic syndromes in children, and despite its benign nature, a percentage of these children are drug-resistant. This study presents four cases of drug-resistant absence epilepsy in children who were unresponsive to traditional antiepileptic drugs. The study reports the successful use of Lacosamide as an adjunctive therapy to completely control symptoms and electroencephalogram (EEG) abnormalities. The patients, aged four to ten years, had previously failed treatment with Ethosuximide, Sodium Valproate, Levetiracetam, and Topiramate in various combinations. Lacosamide was initiated at a dose of 10 mg/kg per day in combination with Sodium valproate, resulting in rapid and sustained improvement. The patients remained symptom-free and showed no EEG abnormalities for one to two years. These findings suggest that Lacosamide can be considered a safe add-on drug for refractory absence epilepsy. However, it may be contended that additional confirmatory trials are necessary to investigate the effects of Lacosamide in a larger patient population

Ewing sarcoma (ES) is a highly malignant tumor that originates from bones, especially long bones. ESarising from the epidural extramedullary space is highly unlikely, especially the cervical region. There have been only 6 cases of cervical epidural extraskeletal Ewing sarcoma (EEES) in children reported in the literature all of whom were older than 7-years-old. Out of 7 cases, including the one mentioned in this study, 4 were male (57%). Herein, we report a 1.5-year-old girl who presented with quadriparesis without cognitive impairment and had initially undergone metabolic disorder evaluation. The spine MRI revealed a mass in C2-T6 region and she underwent a biopsy of the tumor via laminectomy.

Microscopic examination confirms a diagnosis of ES based on immunohistochemistry. This is the first literature that presents an infant with EEES.