Iranian Journal of Child Neurology

Migraine and epilepsy belong to the category of chronic paroxysmal neurological disorders and share numerous clinical features, as well as potential treatment options. This narrative review emphasizes the similarities between pediatric migraine and epilepsy, exploring epidemiology, pathophysiology, genetics, clinical presentation, and pharmacology. Although various syndromes exhibit symptoms common to both conditions, further research is needed to clarify the underlying pathophysiological and genetic connections contributing to their coexistence. Prophylactic medications used in the management of both migraines and epilepsy exhibit similar pharmacological characteristics. The review assesses treatment strategies for epilepsy and migraines, emphasizing antiseizure medications alongside nonpharmacological interventions like ketogenic diet, supplements, and vagal nerve stimulation. It aims to highlight how these interventions, originally targeted for epilepsy, may also show promise in preventing migraines. The urgent need for further randomized, controlled clinical trials investigating both pharmacological and nonpharmacological interventions for treating both disorders is emphasized, aiming to pave the way for innovative therapeutic strategies.

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG.

Objectives
Premature infants (born before 37 weeks of gestational age) frequently experience feeding difficulties due to underdeveloped oral motor skills and poor chewing, swallowing, and breathing coordination. In order to improve oral feeding efficiency in these infants, Oral-Motor Stimulation (OMS) has been used in various studies. This systematic review study will aim to assess the effectiveness of OMS for oral feeding in preterm infants.
Materials & Methods
The authors will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. They will conduct a search in electronic databases, including PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL), Medline via PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for nursing and related healthcare texts without language restrictions from the first month of 1991 to the fifth month of 2024 to achieve the study objectives. All Randomized Controlled Clinical Trials (RCT) examining the effect of OMS on oral feeding in preterm infants will be included in this study.
Results
The primary outcome of this systematic review will be oral feeding, and the secondary outcomes will include duration of hospitalization, weight gain, and feeding efficiency. Two independent reviewers will select and extract data for the study. The Cochrane Risk of Bias Tool (RoB2) will be used to evaluate potential biases in the study. Publication bias will be evaluated using funnel plots, Begg’s, and Egger’s tests. The degree of heterogeneity among the studies will be assessed using the I2 statistic and the χ2 test. Analyses of subgroups will also be carried out. All meta-analyses will be conducted using Stata V.14.
Conclusion
This systematic review protocol for preterm infants will aim to promote evidence-based decision-making and support the development of clinical practice guidelines in preterm feeding.

Objectives
Migraine is one of the common diseases of children, which can disrupt their quality of life. Some studies have shown the effect of melatonin in reducing migraine headaches. This study aims to investigate the effect of melatonin administration in reducing headaches in children with migraine without sleep disorders.
Materials & Methods
In this clinical trial study, fifty-five children aged five to 15 years with migraines who had no sleep disorder were enrolled. The control group (twenty-seven patients) was treated with propranolol tablets, and the intervention group (thirty patients) was treated with propranolol tablets plus melatonin tablets for three months. Patients were visited before, one month, and three months after the start of treatment, and their data was collected and recorded.
Results
The number of headache attacks decreased significantly in the intervention group compared to the control group three months after the treatment (P=0.006). The number of patients with a good response to treatment in the intervention group was significantly more than the control group (p=0.023). Parents’ satisfaction with the treatment in the intervention group was significantly higher than the control group (P=0.026). There was no significant difference in the intensity of disability caused by headaches after treatment in the two groups. No significant drug side effects were seen in any of the two groups.
Conclusion
Adding melatonin to the treatment of children with migraine without sleep disorders significantly reduces the frequency of headache attacks and increases satisfaction with the treatmen

Objectives
Migraine is one of the common diseases of children, which can disrupt their quality of life. Some studies have shown the effect of melatonin in reducing migraine headaches. This study aims to investigate the effect of melatonin administration in reducing headaches in children with migraine without sleep disorders.
Materials & Methods
In this clinical trial study, fifty-five children aged five to 15 years with migraines who had no sleep disorder were enrolled. The control group (twenty-seven patients) was treated with propranolol tablets, and the intervention group (thirty patients) was treated with propranolol tablets plus melatonin tablets for three months. Patients were visited before, one month, and three months after the start of treatment, and their data was collected and recorded.
Results
The number of headache attacks decreased significantly in the intervention group compared to the control group three months after the treatment (P=0.006). The number of patients with a good response to treatment in the intervention group was significantly more than the control group (p=0.023). Parents’ satisfaction with the treatment in the intervention group was significantly higher than the control group (P=0.026). There was no significant difference in the intensity of disability caused by headaches after treatment in the two groups. No significant drug side effects were seen in any of the two groups.
Conclusion
Adding melatonin to the treatment of children with migraine without sleep disorders significantly reduces the frequency of headache attacks and increases satisfaction with the treatment

Objectives
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is prevalent worldwide. The incidence of autism has increased worldwide. However, there is a dearth of data in sub-Saharan Africa. The study is aimed at determining the clinical and socio-developmental profile of children with ASD in a tertiary hospital in Nigeria.
Materials & Methods
This study is a six-year retrospective review of the medical records of children who presented with clinical autism diagnoses at the Department of Pediatrics, University of Calabar Teaching Hospital. Relevant data were extracted from the medical records of those who met the diagnostic criteria. Descriptive statistics were presented in proportions, percentages, and tables.
Results
Of the 1806 children with neurological disorders seen in the clinic within the study period, twenty-eight were found to have symptoms of autism based on the American Psychiatric Association›s Diagnostic and Statistical Manual V (DSM -5) criteria, giving a prevalence of 1.6%. The mean age at diagnosis was 3.8 ±1.4 (range 2 to 10) years, with a male-to-female ratio of 3:1. About two-thirds of the children diagnosed were older than three years. Seven percent of the children had siblings with autism, 53.5% of children with autism in the study had hyperactivity as comorbidity, while seizures were found in 7% of cases.
Conclusion
The prevalence of ASD among children seen in Calabar is 1.6%. Hyperactivity, mental retardation, and seizure disorders are associated comorbidities in the study. Late presentation is a common feature in this facility. Thus, increasing awareness is essential to enhance early recognition, timely diagnosis, and appropriate intervention

Objectives
Viruses are the most common infectious causes of aseptic meningitis (AM). After the COVID-19 pandemic, AM following the COVID-19 disease and its different vaccines were reported. This study compares some characteristics of patients with AM before and after the COVID-19 pandemic.
Materials & Methods
This retrospective cross-sectional study analyzed patients’ demographic and laboratory data (one month to 14 years old) with AM from March 2018 to March 2022. The first period involves two years before the COVID-19 outbreak (March 2018 to March 2020). The second period starts with the COVID-19 pandemic (from March 2020 until March 2022).
Results
A significant decrease was observed in the frequency of patients admitted with AM after the COVID-19 pandemic in the referral children’s hospital in Qazvin. The incidence of AM in children older than five decreased significantly, and as a result, the average age of patients with this diagnosis decreased, too. A meaningful decline in the prevalence of AM in the summer and fall seasons has been observed.
Conclusion
After the COVID-19 outbreak, the incidence of AM in children significantly decreased. Implementing the hygienic recommendations for inhibiting COVID-19 virus transmission also protected children from the spread of other viruses.

Objectives
Increasing evidence demonstrated that there are altered levels of both pro-and anti-inflammatory cytokines in autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study aimed to investigate the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD.
Materials & Methods
Forty boys with ASD (mean age: 10.90; age range: 6–14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/week. This study evaluated the serum levels of IL-6 and IL-10, as well as the participants’ social interaction at baseline and post-intervention.
Results
Compared to the control group, all three interventions improved social skills scores (p< 0.001). Surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD.
Conclusion
Aqua-based exercise programs combined with vitamin D supplementation are recommended to benefit children with ASD and improve social and communication dysfunction

Objectives
Maternal smoking is a potent teratogen among congenital malformations, however its role in the development of Neural Tube Defects (NTDs) is still unclear. In this systematic review, we intend to further investigate the interaction of smoking during pregnancy and the incidence of NTDs.
Materials & Methods
This article was written according to PRISMA criteria from February 2015 and August 2022. After examining the four stages of PRISMA criteria, we selected clinical articles. These articles were selected from PubMed, Scopus and Google scholar (for results follow-up) databases. We gathered NTDs effect and types, smoking type and habit of parents, from neonates.
Results
Eventually, 8 articles were included by two separated authors, Smoking was associated with an increase NTDs in the population of pregnant mothers and also among children whose fathers smoked. The main side effects that were considered to be the cause of NTDs besides smoking were alcohol and BMI (18.5-24.9). Smoking also affects the level of folic acid as a substance with an essential role that affects the closure of the neural tube. folic acid available to infants changing along with the level of other blood elements such as zinc, that necessary prevent for NTDs condition.
Conclusion
Parental smoking can be considered as one of the strong teratogens in the occurrence of NTDs. Smoking, whether active or passive by the mother, or by the father, is associated with the occurrence of NTDs, In order to reduce the prevalence this disorder, we advise pregnant mothers and neonate’s fathers to quit smoking.

Objectives
Mutations in the TREX1 gene cause Aicardi-Goutières syndrome (AGS) 1, associated with a spectrum of autoimmune and neurodegenerative manifestations. AGS 1, the most severe neonatal type of AGS, is characterized by abnormal neurologic findings, visual inattention, hepatosplenomegaly, thrombocytopenia, skin rash, restlessness, and fever.
Materials & Methods
The present study described two affected siblings from an Iranian family whose phenotypes overlap with intrauterine infections. They had almost similar presentations, including developmental delay, microcephaly, no fix and follow epileptic seizures and the same pattern of brain CT scan involvements. Following clinical and paraclinical assessments, whole-exome sequencing was employed to determine the disease-causing variant, and subsequently, PCR-Sanger sequencing was performed to indicate the segregation pattern of the candidate variant in family members.
Results
Genetic analysis revealed a novel homozygous missense variant (c.461A>C; p.D154A) in the TREX1 gene in affected family members. Sanger sequencing of other family members showed the expected zygosities.
Conclusion
This study identifies a novel mutation in the TREX1 gene in this family and highlights the efficiency of next-generation sequencing-based techniques for obtaining a definite diagnosis in patients with early-onset encephalopathy

Spinal muscular atrophy (SMA) with progressive myoclonic epilepsy (PME) affects the nervous system. Symptoms appear in early childhood and include muscle weakness, difficulty walking, seizures, and cognitive decline. Despite introducing various therapies to restore acid ceramidase function or reduce ceramide accumulation and gene therapy to correct genetic mutations, there are still unknown underlying molecular mechanisms related to this disorder. This article reports a novel variant c.118G>C in the ASAH1 gene. The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epileptic discharge. A significant temporal interval was observed between the initial diagnosis of SMA and the subsequent manifestation of myoclonic seizures. The proband was genetically assessed through whole exome sequencing (WES) followed by variant confirmation and bioinformatics analysis. According to this article’s findings and previous research, further diagnostic testing and management are needed to determine the severity and progression of the patient’s condition

COVID-19 can cause a wide range of ocular manifestations. The most common ocular manifestation is conjunctivitis. Neuro-ophthalmic presentations of COVID-19 are rare. Case reports suggest that COVID-19 infection can cause cranial nerve palsy, including nerves that regulate ocular movements. The present studypresented a case of fourth nerve palsy in a healthy and asymptomatic COVID-19-infected child. A healthy 10-year-old boy was referred to our eye clinic with a complaint of recent abnormal head posture and squint. His past medical history was unremarkable, and he had not received any medication or vaccinations within the last few weeks. No history of ocular or head trauma was observed. The patient was afebrile and had no respiratory symptoms. A comprehensive ocular examination was performed. All examinations, including slit-lamp, pupils, eyelids, and optic nerve heads, were normal. In ocular motor evaluations, left eye hyperdeviation was observed. Because of the history of COVID-19 in the mother of the child, he was referred to an infectious disease specialist and was tested for SARS-COV-2 with a nasopharyngeal swab specimen. The test was positive and SARS-COV-2 was detected. In addition, the patient was referred to a pediatric neurology department. Brain and orbital MRI was performed, and it was unremarkable. The post-viral fourth nerve palsy is uncommon, and post-COVID-19 has not been reported before. Clinicians should consider this infection in any recent strabismus in pediatrics. The children rarely complain of diplopia, and a recent abnormal head posture may be a sign of acquired strabismus.

Kleefstra Syndrome is a rare genetic neurodevelopmental disorder caused by a microdeletion in chromosomal region 9q34.3 or a mutation in the EHTM1 gene. Patients with KS show a range of clinical symptoms, including delay in motor and speech development, intellectual disability, autistic-like features, childhood hypotonia, and distinctive facial dysmorphic features. The patient is a 4-year-old girl who was initially diagnosed with developmental motor delay by a pediatric neurologist and referred to an occupational therapy clinic at 6 months of age. The initial assessment showed hypotonia and difficulties with rolling. Occupational therapy intervention was based on principles of neurodevelopmental treatment and sensory integration with cognitive integration and activities of daily living training. With continuous occupational therapy services over more than 3 years, she overcame many disabilities and improved in occupational performance skills such as gross and fine motor skills as well as cognitive abilities, although her verbal communication skill is not effective. The patient's progress was as follows: she began rolling over at 7 months, achieved independent sitting at 10 months, crawled at 18 months, stood with support at 20 months, and took her first steps at 26 months. The predominant problem was speech delay which was noticeable in this syndrome. When a patient is being referred because of Kleefstra syndrome, occupational therapy, and speech therapy assessments should be accurately implemented.

Extrapyramidal symptoms (EPS) that include akathisia, dystonia, pseudoparkinsonism, and dyskinesia are abnormal movements commonly induced by antipsychotic medications. These symptoms are also associated with specific non-antipsychotic agents. This case report describes a case of a 9-year-old boy on antibiotics treatment that developed EPS.
A 9-year-old boy presented to the emergency department of Imam Hossein Children›s Hospital with chief complaints of trismus, difficulty speaking, and tongue protrusion. One week before these presentations, he had been prescribed Tavanex® (levofloxacin) and clindamycin. His symptoms improved after the withdrawal of antibiotics and administering Biperiden, and he was discharged in good condition. On a follow-up visit one week after discharge, no remaining symptoms were present, and he was in good condition.
Based on the questions in the Naranjo criteria, levofloxacin receives a score of 7 and is a probable cause of adverse drug reaction (ADR). Clindamycin, with a score of 6, is also a probable cause for this adverse drug reaction, but clinical judgment was in favor of levofloxacin as the culprit.
Clinicians should be aware of the potential EPS of levofloxacin at standard doses. Effective management of adverse events is necessary to ensure patient safety and optimal outcomes