Migraine and Epilepsy in Children: A Narrative Review of Comorbidity and Similar Treatment Option.

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.

A novel homozygous variant in an Iranian pedigree with cerebellar ataxia, mental retardation, and dysequilibrium syndrome type 4.

BACKGROUND: Cerebellar ataxia, mental retardation, and dysequilibrium (CAMRQ) syndrome is a rare and early-onset neurodevelopmental disorder. Four subtypes of this syndrome have been identified, which are clinically and genetically different. To date, altogether 32 patients have been described with ATP8A2 mutations and phenotypic features assigned to CAMRQ type 4. Herein, three additional patients in an Iranian consanguineous family with non-progressive cerebellar ataxia, severe hypotonia, intellectual disability, dysarthria, and cerebellar atrophy have been identified. METHODS: Following the thorough clinical examination, consecutive detections including chromosome karyotyping, chromosomal microarray analysis, and whole exome sequencing (WES) were performed on the proband. The sequence variants derived from WES interpreted by a standard bioinformatics pipeline. Pathogenicity assessment of candidate variant was done by in silico analysis. The familial cosegregation of the WES finding was carried out by PCR-based Sanger sequencing. RESULTS: A novel homozygous missense variant (c.1339G > A, p.Gly447Arg) in the ATP8A2 gene was identified and completely segregated with the phenotype in the family. In silico analysis and structural modeling revealed that the p.G477R substitution is deleterious and induced undesired effects on the protein stability and residue distribution in the ligand-binding pocket. The novel sequence variant occurred within an extremely conserved subregion of the ATP-binding domain. CONCLUSION: Our findings expand the spectrum of ATP8A2 mutations and confirm the reported genotype-phenotype correlation. These results could improve genetic counseling and prenatal diagnosis in families with clinical presentations related to CAMRQ4 syndrome.

The first report of two homozygous sequence variants in FKRP and SELENON genes associated with syndromic congenital muscular dystrophy in Iran: Further expansion of the clinical phenotypes.

BACKGROUND: Congenital muscular dystrophy (CMD) refers to hypotonia and delayed motor development that is manifested at or near the birth. Additional presentations have been observed in CMD syndromes. METHODS: Thorough clinical examinations were performed on two unrelated Iranian families with typical symptoms of CMD and uncommon features such as intellectual disability and nephrolithiasis. The genomic DNA of probands were subjected to whole exome sequencing. Following the detection of candidate variants with a bioinformatic pipeline, the familial co-segregation analysis was carried out using polymerase chain reaction-based Sanger sequencing. RESULTS: We identified a missense homozygous variant in the fukutin-related protein (FKRP) gene (c.968G>A, p.Arg323His) related to CMD-dystroglycanopathy type B5 (MDDGB5) and a frameshift homozygous variant in the selenoprotein N (SELENON) gene (c.1446delC, p.Asn483Thrfs*11) associated with congenital rigid-spine muscular dystrophy 1 (RSMD1), which were completely segregated with the phenotypes in the families. These variants were not found in either the 1000 Genomes Project or the Exome Aggregation Consortium. The present study provides the first report of these homozygous sequence variants in Iran. Moreover, our study was the first observation of nephrolithiasis in FKRP-related dystroglycanopathy and intellectual disability in SELENON-related myopathies. Based on in silico studies and molecular docking, these variations induced pathogenic effects on the proteins. CONCLUSIONS: Our findings extend the genetic database of Iranian patients with CMD and, in general, the phenotypical spectrum of syndromic CMD. It is recommended to consider these variants for a more accurate clinical interpretation, prenatal diagnosis and genetic counseling in families with a history of CMD, especially in those combined with cognitive impairments or renal dysfunctions.

Eleven-year surveillance of acute flaccid paralysis in southwestern Iran.

Momen AA, Shakurnia A, Momen M. Eleven-year surveillance of acute flaccid paralysis in southwestern Iran. Turk J Pediatr 2019; 61: 544-551. The purpose of the study was to report the results of acute flaccid paralysis (AFP) surveillance in the southwestern Iran in the 11 years' period. This is a retrospective descriptive study based on WHO guidelines. The collected data includes all pediatric AFP cases reported between of January 2006 to December 2016 by all health centers of Khuzestan province in Southwest of Iran. During an eleven-year period, 274 cases of AFP were reported in Khuzestan Province. Among them, 56.9% were younger than five years of age, and 55.9% were male. None of these cases was confirmed as poliomyelitis. The annual incidence of non-polio AFP ranged from 1.46/100,000 to 3.11/100,000 (Mean: 2.04 cases/100,000). The incidence rate of AFP in children under five years of age was significantly higher compared to older children (p=0.001), and the most common cause of paralysis (74.5%) was Guillain-Barre syndrome. All performance indicators met the WHO-specified targets. The follow-up of patients with AFP is essential to the eradication of poliomyelitis.

The Epidemiology of Guillain-Barré Syndrome in Children under 15 Years Old in Southwest Iran.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy, which has become the most common cause of acute flaccid paralysis. An accurate estimation of GBS occurrence would be useful for investigating the potential causal relationships between risk factors and GBS. The aim of the study was to analyze the incidence, annual time trend, and some epidemiological aspects of GBS in children in the Southwest of Iran. METHODS: This was a retrospective study conducted by the Department of Pediatrics of Ahvaz Jundishapur University of Medical Sciences from January 2006 to December 2015. We extracted data from the national database of Acute Flaccid Paralysis Surveillance System. RESULTS: A total of 184 subjects with GBS were assessed. The mean age of subjects was 5.43 ± 4.07 years. The average annual incidence rate of GBS was 1.51 per 100,000 children under 15 years old (95% CI: 1.29-1.73). There was no significant statistical difference in GBS incidence rate between girls and boys (p = 0.376). The highest and lowest proportions of the GBS occurrences were in autumn (32.2%) and summer (14.7%), respectively. CONCLUSIONS: The findings indicated that the annual incidence rate of GBS in this study was similar to those in other studies in this area.

Evaluation of Hospitalized Intractable Epileptic Children with SPECT Scan in Ahvaz, South West of Iran.

INTRODUCTION: Seizures are the most frequent neurologic disorder seen in childhood. Epilepsy is a group of disorders that includes an abnormally increased susceptibility to seizures. AIM: To examine the effectiveness of SPECT (Single Photon Emission Computerized Tomography) in detecting seizure foci in 21 Iranian children who had medically refractory epilepsy. MATERIALS AND METHODS: Children between 2 to 15 years of age with uncontrolled seizures were investigated using SPECT scan as a standardized protocol. RESULTS: In 16 cases (76.2%), likely seizure foci were evident, as were seen in the form of decreased regional blood flow, while in 5 cases (23.8%), SPECT scan results were normal. Left temporal lobe was the most common area which had decreased regional blood flow. CONCLUSION: SPECT scan can potentially be used to investigate children with uncontrolled seizures.

An epidemiological analysis of acute flaccid paralysis in Khuzestan Province, southwest Iran, from 2006 to 2010.

OBJECTIVES: Investigations into the epidemiology of acute flaccid paralysis (AFP) are an essential strategic component of the Global Poliomyelitis Eradication Initiative of the World Health Organization (WHO), and are part of the certification process for polio eradication worldwide. This is an epidemiological report of AFP incidence in children less than 15 years old in southwest Iran. METHODS: This was a retrospective cohort study, carried out based on WHO guidelines, in which we reviewed non-polio AFP cases recorded from January 2006 to December 2010 in different regions of Khuzestan Province, southwest Iran. In this study, the records of all children under 15 years old with AFP were evaluated. RESULTS: During a 5-year period, 137 cases of AFP were reported (incidence rate, 2.21 per 100,000 children <15 years old). More than 50% (73 of 137) of the cases were boys, and 52.6% (72 of 137) were under 5 years of age, with a mean age of 5.39±3.98 years. The incidence of AFP was significantly higher in older children (p=0.001). The most common cause of paralysis was Guillain-Barré syndrome (117 of 137). None of the cases were diagnosed with acute poliomyelitis. CONCLUSIONS: In this study, we found that the incidence rate of AFP in the region was almost in agreement with the expected incidence of AFP in children less than 15 years old; therefore, the AFP surveillance program in Khuzestan Province is satisfactory in terms of reliability and effectiveness. Nevertheless, routine vaccination against polio and ensuring that patients with AFP receive follow-up are essential for eradicating polio.

Double Cortex Syndrome (Subcortical Band Heterotopia): A Case Report.

Objective Approximately 5-10% of preschool age children are considered developmentally disabled. Brain Magnetic Resonance Imaging (MRI) plays a key role in the diagnostic evaluation in these children. Many congenital or acquired brain anomalies are revealed with MRIs. Although the majority of these abnormalities are sporadic but patients with subcortical band heterotopia or double cortex syndrome have sex-linked inheritance. We are going to present the first case in Iran from Ahvaz city, which was presented with status epilepticus associated with developmental delay and finally diagnosed as double cortex syndrome, because band heterotopia cases especially for continuous or generalized form is rare. A 4.5-year-old developmentally delayed girl was admitted for generalized tonic clonic seizure attack of 1 hr, upward gaze, locked mouth, and urinary incontinence (status epilepticus) in the child neurology ward. She had a history of recurrent seizures that started as febrile seizures since she was 12 months of age and had frequent admissions for having recurrent seizure attacks. She was the only child of consanguineous parents with negative family history of any neurologic problems. She was a product of uneventful term pregnancy, vaginal delivery with a low Apgar score at birth who was admitted for six days in the neonatal ward for hypotonia and cyanosis. At 4.5 years of age, she had HC: 45cm (<3%) Length: 102 cm (25-75%), and BW: 18kg (75%). She was able to sit, walk with support, speak a few words, and communicate with others. A physical exam was unremarkable. Lab data including CBC, blood biochemical, and urinalysis results were all within normal limits, but the electroencephalography (EEG) revealed generalized poly spike-wave discharges. A brain MRI showed corpus callosal dysplasia, generalized band heterotopia, and polymicrogyria. She was discharged home with oral valproate and regular outpatient follow-ups. In the diagnostic evaluation of developmentally delayed and epileptic children, a brain MRI is strongly recommended for accurate diagnosis of anomalies such as neuronal migration disorders (band heterotopia) and others, because appropriate therapeutic management, prognosis, prevention, and genetic counseling for prenatal diagnosis are dependent on definite diagnosis of the proband case.

Usability of the head upright tilt test for differentiating between syncopal and seizure-like events in children.

The common diagnosis of loss of consciousness and clonic movements in children is seizure or epilepsy, but in a number of patients these symptoms could also be due to syncope. Over interpreted electroencephalography is misleading in a number of patients; therefore, in addition to a detailed and thorough history, a reliable test is needed to differentiate between these conditions. The aim of the study was to evaluate the utility of the head upright tilt test to differentiate between seizure-like events and syncope in children. A chart review descriptive study was conducted in a tertiary medical center in Ahvaz, Iran. We selected sixteen children (nine boys and seven girls) with convulsions of any type who were first diagnosed as epileptic based on the event description by their parents or caregivers to undergo the head upright tilt test. The main findings were the reproduction of previously presyncopal or syncopal symptoms in the tilted position. Fourteen children showed positive results after conducting the head upright tilt test, and their heart rates were significantly decreased compared to baseline at the onset of the syncopal or presyncopal manifestations. Systolic and diastolic blood pressures were significantly reduced in patients with positive results. In three children who initially had negative head upright tilt tests, intravenous isoproterenol was administered, and all three showed presyncopal and syncopal symptoms. The results indicate that the head upright tilt test could differentiate presyncopal and syncopal events in children who present with seizure-like movements but their history has clues for conclusive syncope.

Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of intramuscular midazolam in controlling convulsive status epilepticus in children, by comparing it with rectal diazepam. METHODS: In this randomized trial, 100 children (50 in each group) with convulsive status epilepticus aged 1 month to 16 years were enrolled and randomly assigned into two groups to receive either 0.3 mg/kg intramuscular midazolam or 0.5 mg/kg rectal diazepam. Main outcome measure was stopping of all motor activity after drug administration. Another measures were times between patient's arrival to emergency department till drug administration, between drug administration to seizure cessation, and between patient's arrival to seizure cessation. RESULTS: Both medication were effective for seizure control and no significant difference was found between successful treatments after administering the medication (P = 0.061). In the midazolam group, in 96% (48/50) of cases treatment was successful and in the diazepam group, in 94% (47/50) of cases treatment was successful. Time from arrival to administering the medication was significantly shorter in midazolam group (P = 0.017). The majority of seizures in midazolam group were stopped in less than 66 s (median) compared to 130 s (median) for diazepam group, (P < 0.001). No serious adverse effects were seen in both groups. CONCLUSION: IM midazolam is not superior but may be at least as effective as rectal diazepam for controlling of status epilepticus in children. Midazolam via IM route could be one of the choices in children with convulsive status seizures who have difficult IV access.

Brain magnetic resonance imaging findings in developmentally delayed children.

Background. Developmental disorders are failure or inability to acquire various age-specific skills at expected maturational age, which affects about 5-10% of preschool children. One of the most important methods for evaluation of developmentally delayed children is neuroimaging, especially, brain magnetic resonance imaging (MRI) that provides useful information regarding brain tissue structures and anomalies. Method and Material. In this study, hospital records of 580 developmentally delayed children (aged 2 months to 15 years) who admitted in pediatric ward of Golestan Hospital from 1997 to 2009 were selected. Information such as age, MRI findings were collected in the questionnaire and statistically analyzed. Results. Total, 580 children including 333 males (57.4%) and 247 females (42.6%) were studied. Abnormal brain MRI was observed in 340 (58.6%) cases (204 Males, 136 females). The finding includes nonspecific in 38 (6.6%), congenital and developmental anomalies of brain in 39 (6.7%), recognizable syndromes in 3 (0.5%), neurovascular diseases or trauma in 218 (37.6%), and metabolic or neurodegenerative diseases in 42 (7.2%) cases. Conclusion. Because 60% of all study groups showed abnormal brain MRI, using this method could be effective in diagnosis, management, and almost prognosis determination processes.