Refugee and asylum-seeker children and health problems in the city of Duzce, Türkiye.

INTRODUCTION: This study examines the health problems and healthcare needs of refugee and asylum-seeker children and aims to develop strategies for improvement. METHODS: Based on quantitative data from 448 refugee and asylum-seeker children and 222 non-refugee local children, this study was conducted at Düzce University, Department of Paediatrics, between 2010 and 2021. The refugee children originated from three countries: Iraq (n = 304), Syria (n = 101) and Afghanistan (n = 43). The data were analysed using the SPSS data analysis program. Ethical clearance was obtained from the Ethics Committee of Düzce Üniversity. RESULTS: The results suggest that refugee and asylum-seeker children have significantly higher rates of acute illness or infection, malnutrition (p < 0.001) and anaemia (p < 0.001) than local children as a result of living in overcrowded families (p = 0.017) and unhealthy conditions. Adolescent pregnancy (p = 0.049) emerges as an important social problem as a result of child marriage among refugee children, mostly in the form of consanguineous marriages (p < 0.001). The rate of having at least two adolescent pregnancies (under 18) was highest among Syrian refugee girls (p = 0.01). Although refugee and asylum-seeker children have higher rates of health insurance (between 74% and 95%), they have lower rates of insurance compared to local children. This research also compares the data from three nationalities, including Syria, Afghanistan and Iraq children; Iraqi and Afghan children under the international protection (IP) system with limited social support and rights had worse health conditions compared to other groups. Although Iraqi children had the highest rates of health insurance on admission (p < 0.001), they also had higher rates of chronic diseases (p = 0.001), infections (p = 0.004), allergic rhinitis (p = 0.001) and malnutrition (p < 0.001). The youngest age of admission (p = 0.006) and the shortest length of stay (p = 0.004) were for Afghan children who also had higher rates of upper respiratory infections (p = 0.021). CONCLUSIONS: This study highlights the urgent need for improved screening programmes and the importance of collaborative efforts to address the specific health needs of these populations. Addressing the health status of child refugees is a complex and multifaceted task that requires the active participation of healthcare professionals, policymakers and researchers, each of whom has a crucial role to play.

Mitochondrial metabolism related markers GDF-15, FGF-21, and HIF-1α are elevated in pediatric migraine attacks.

OBJECTIVE: The purpose of this study was to investigate the serum levels of mitochondrial metabolism/reactive oxygen species (ROS)-related peptides (hypoxia inducible factor-1α [HIF-1α], fibroblast growth factor-21 [FGF-21], growth differentiation factor-15 [GDF-15]) and key migraine-related neuropeptides (calcitonin gene-related peptide [CGRP], pituitary adenylate cyclase-activating peptide-38 [PACAP-38], substance P [SP], and vasoactive intestinal peptide [VIP]) during migraine attacks and to evaluate their diagnostic value in pediatric migraine. BACKGROUND: There is increasing evidence for the important role of impairment in oxidative mitochondrial metabolism in the pathophysiology of migraine. Potential biomarkers that may reflect the relationship between migraine and mitochondrial dysfunction are unclear. METHODS: A total of 68 female pediatric migraine patients without aura and 20 female healthy controls aged 8-18 years, admitted to the hospital, were enrolled in this cross-sectional study. Serum concentrations of these molecules were determined by enzyme-linked immunosorbent assays, and clinical features and their possible diagnostic value were analyzed. RESULTS: Serum levels of HIF-1α (252.4 ± 51.9 [mean ± standard deviation]) pg/mL), GDF-15 (233.7 ± 24.7 pg/mL), FGF-21 (96.1 ± 13.1 pg/mL), CGRP (44.5 ± 11.3), and PACAP-38 (504.7 ± 128.9) were significantly higher in migraine patients compared to healthy controls (199.8 ± 26.8, 192.8 ± 20.7, 79.3 ± 4.1, 34.1 ± 3.5 and 361.2 ± 86.3 pg/mL, respectively). The serum levels of these peptides were also higher in patients with chronic migraine than in patients with episodic migraine, and higher in the ictal period than in the interictal period. A positive correlation was found between attack frequency and both HIF-1α and FGF-21 levels in migraine patients. Serum levels of VIP and SP were not different between the migraine patients and healthy controls. CONCLUSION: Migraine attacks are accompanied by elevated HIF-1α, FGF-21, GDF-15, CGRP, and PACAP-38 in medication-naive pediatric patients with migraine. Elevated circulating mitochondrial metabolism/ROS-related peptides suggest a mitochondrial stress in pediatric migraine attacks and may have potential diagnostic value in monitoring disease progression and treatment response in children. Novel approaches intervening with mitochondrial metabolism need to be investigated.

Can the Gut Microbiota Serve as a Guide to the Diagnosis and Treatment of Childhood Epilepsy?

BACKGROUND: To investigate the activity of the gut-brain axis in the pathogenesis of childhood epilepsy and to define biomarkers capable of assisting with determining new strategies in that context. METHODS: Twenty children with epilepsy of "unknown etiology" and seven healthy controls in the same age group were included in the study. The groups were compared using a questionnaire. Stool samples were stored in tubes containing DNA/RNA Shield (Zymo Research) with a sterile swab. Sequencing was carried out using the MiSeq System (Illumina). The 16S rRNA sequencing of samples using next-generation sequencing involved V4 variable region polymerase chain reaction amplification concluded by 2 × 250-bp paired-end sequencing of amplicons and at least 50,000 reads (>Q30) per sample. DNA sequences were classified at the genus level using the Kraken program. Bioinformatics and statistical analysis were then performed. RESULTS: Individuals' gut microbiota relative abundance values differed between the groups at the genus, order, class, family, and phylum levels. Flavihumibacter, Niabella, Anoxybacillus, Brevundimonas, Devosia, and Delftia were seen only in the control group, whereas Megamonas and Coriobacterium were observed only in the epilepsy group. The linear discriminant analysis effect size method identified 33 taxa as important in differentiating the groups. CONCLUSIONS: We think that bacterial varieties (such as Megamonas and Coriobacterium) that differ between the two groups can be employed as useful biomarkers in the diagnosis and follow-up of epileptic patients. We also predict that, in addition to epilepsy treatment protocols, the restoration of eubiotic microbiota may increase the success of treatment.

Myoclonic Astatic Resistant Epilepsy and Disproportionate Overgrowth Carrying a Duplication in 2q13 and Deletion in the 6p21.32 Chromosomal Regions.

Copy number variants have been increasing due to a rise in the availability of array comparative genomic hybridisation, which occupies an important place in diagnosis, especially in patients with epilepsy, dysmorphic findings, and intellectual disability. We detected 2q13 chromosomal duplication and 6p21.32 chromosomal deletion in a patient under follow-up due to epilepsy, developmental retardation, dysmorphic findings, and asymmetric overgrowth in our clinic since the age of six months. The parents had only 2q13 mutations. Copy number variation in 2q13 is associated with dysmorphic findings, psychiatric disorders, and developmental delays. However, the exact pathogenicity is not yet known. We think that 6p21.32 chromosomal deletion caused resistant epilepsy and lipodystrophy in this patient. We anticipate that this case will contribute to the literature by linking disorders caused by the current chromosomal abnormality to clinical findings. Key Words: Myoclonic astatic seizure, Resistant epilepsy, Dermal atrophy, Chromosomal microarray analysis.

Evaluation of sleep habits, sleep chronotype, and quality of life in children with drug-resistant epilepsy in Turkey.

BACKGROUND/AIM: Drug-resistant epilepsy (DRE) is a condition that affects sleep habits and the quality of life of children unfavorably. The aim of our study was to evaluate the relationship of sleep habits and sleep chronotype with the quality of life and behavioral problems in children with DRE. MATERIALS AND METHODS: In our study, 2-11-year-old children, who were either healthy or diagnosed with DRE, were evaluated. A sociodemographic data form was filled out to evaluate the general characteristics of children. The Children's Sleep Habits Questionnaire (CSHQ) and the Children's Chronotype Questionnaire (CCTQ) for sleep habits, the Pediatric Quality of Life Inventory (PedsQL) for the quality of life, and the Aberrant Behavior Checklist (ABC) for behavioral problems were filled out through face-to-face interviews with parents. RESULTS: Thirty children with DRE and 31 healthy children were included in our study. Statistically significant differences were found in children with DRE compared to the control group in terms of the total and the subscale scores of CSHQ, including sleep onset delay, sleep duration, sleep anxiety, parasomnias, and sleep-disordered breathing (p < 0.001). There were no significant differences between the groups in terms of CCTQ total scores and sleep patterns (p > 0.05). Significant differences were found in PedsQL total and subscale scores, and ABC scores in children with DRE compared to the control group (p < 0.001). Children's Sleep Habits Questionnaire, PedsQL, and ABC scores were significantly correlated with each other in children with DRE. CONCLUSIONS: Our results have shown that sleep habits and the quality of life are poor in children with DRE. Our study has shown that sleep disturbances, quality of life, and behavioral problems are strongly associated with each other in DRE. The recognition and appropriate treatment of sleep disturbances are important for improving the quality of life in children with DRE.

White-Sutton syndrome with hot water epilepsy and coexistence of SHOX gene variations.

The purpose of this study is to reveal the effect on the clinical phenotype of variants detected at family examination of a case of combined pogo transposable element derived with zinc finger domain (POGZ) gene, tubulin folding cofactor E (TBCE) gene, and short stature homeobox (SHOX) gene variation. A Turkish non-consanguineous family consisting of five members was investigated. Whole exome sequence analysis and chromosomal microarray analysis (CMA) were performed for a 2-year-old male patient (the proband) with global developmental delay, hypotonia, dysmorphia, and hot water epilepsy. Targeted sequence and chromosomal microarray analyses were performed for each family member. A heterozygous c.3908_3911delTCTG/p.V1303fs*6 variant was detected in the POGZ gene and a heterozygous c.626 T > G(p.L209X) variant in the TBCE gene in the proband. In addition, a gain of 0.1 MB was detected in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region at CMA. The SHOX (312865) gene defined in Online Mendelian Inheritance in Man is located in this region. While the proband's father and brother had heterozygous variations only in the TBCE gene, neither TBCE nor POGZ mutations were detected in the mother or sister. A gain in Xp22.33(419224-883640) × 3 was detected in the mother at CMA. Except for short stature and Madelung deformity, no phenotypical findings were detected in the mother. Other family members were also phenotypically normal. The family screening confirmed that dysmorphic findings and global developmental delay in the proband resulted from the variation in the POGZ gene, while short stature was caused by the gain in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region. In addition, the pathogenic POGZ gene variation in our patient may be a possible cause of hot water epilepsy. Heterozygous variation in the TBCE gene was clinically insignificant. Hot water epilepsy has not previously been reported in the rare patients with POGZ gene mutation. Additionally, in contrast to the previous literature, the proband exhibited no features of autism. It should also be remembered that posterior fossa abnormalities are frequently seen in these patients. We think that this case and family review involving POGZ and SHOX gene mutations will make a useful contribution to the existing literature.

A novel pathogenic variant in the 3' end of the AGTPBP1 gene gives rise to neurodegeneration without cerebellar atrophy: an expansion of the disease phenotype?

Childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) is a recently described form of the large group of infantile hereditary lower motor neuron diseases (Teoh et al. 2017), resulting from biallelic damaging variants in the AGTPBP1 gene, first described by Shashi et al. in EMBO J 37(23):e100540, 2018. AGTPBP-related neurodegeneration is a severe neurodevelopmental disorder that progresses with global developmental delay and intellectual disability, often accompanied with peripheral nerve damage and lower motor degeneration and a fatal course in the early years of life. The encoded protein is ATP/GTP-Binding Protein1, also known as cytosolic carboxypeptidase 1 (CCP1) or nervous system nuclear protein induced by axotomy (NNA1). Here we report a consanguineous family with four offspring, two of whom are affected. The index patient is a 21-month-old male with global developmental delay and hypotonia. The proband's 17-year-old sister, diagnosed with cerebral palsy, had severe hypotonia accompanied by motor and cognitive retardation. WES analysis revealed a novel homozygous c.3293G > A variant in the AGTPBP1 gene with high pathogenicity scores. Targeted Sanger sequencing confirmed the variant in both affected children and in heterozygous form in the parents. The affected siblings present with hypotonia and motor and cognitive retardation, in line with the studies previously reported. However, in our patients, no signs of cerebellar atrophy in cranial MRI were present, so the acronym CONDCA is not applicable; lower motor neuron findings were also absent. The matching and distinguishing aspects of our patients will add to the present literature and expand our understanding of this rare genetic neurodegenerative disease of early childhood.

Plasma levels of vasoactive neuropeptides in pediatric patients with migraine during attack and attack-free periods.

BACKGROUND: Increasing evidence suggests that vasoactive neuropeptides such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide are involved in the pathophysiology of migraine in adults, but their role in pediatric migraineurs remains unclear. We prospectively investigated plasma levels of these vasoactive neuropeptides in pediatric migraine patients without aura and compared the results with those of age-matched healthy controls. METHODS: Thirty-eight children aged 6-18 years with migraine without aura and 20 age-matched control subjects were included in the study. Neuropeptides in plasma samples from the controls, and in either the ictal or interictal periods in pediatric migraine without aura, were measured using ELISA. RESULTS: PACAP-38 and vasoactive intestinal peptide levels in both ictal and interictal plasma were higher in the patients with pediatric migraine without aura than in the controls (p < 0.001), although calcitonin gene-related peptide and substance P levels remained unchanged. Otherwise, no significant difference was determined between ictal and interictal periods in terms of all neuropeptide levels. CONCLUSIONS: This study demonstrates increased plasma PACAP-38 and vasoactive intestinal peptide levels, but not calcitonin gene-related peptide and substance P levels, in pediatric patients with migraine during both attack and attack-free periods. The study findings suggest that PACAP-38 and vasoactive intestinal peptide may be implicated in the pathophysiology of migraine, particularly in pediatric migraineurs.

The role of clinical signs in the diagnosis of papilledema: development of an algorithm.

PURPOSE: The aim of this study was not only to emphasize the role of clinical signs as well as ophthalmologic evaluation for accurate and differential diagnosis of papilledema (PE), but also to present an instructive algorithm that would help to eliminate unnecessary examinations and treatments. METHOD: The files of 43 patients (ages 0-18) diagnosed with PE were retrospectively reviewed. The study included 25 patients from our pediatric neurology outpatient clinic, who were thought to have PE, and 18 patients, who were referred from the external centers to our hospital with a pre-diagnosis of PE. RESULTS: Of the 43 patients, 28 had PE, 8 had pseudopapilledema (PPE), and 7 had optic nerve pathologies (ONP). For patients who applied directly to our pediatric neurology unit, a margin of error of 8% was detected based on only a simple ophthalmologic examination and an evaluation of clinical findings. For the patients who were forwarded to our pediatric neurology unit from the external centers without examining any clinical findings and with no details, the margin of error was 72%. CONCLUSION: For patients with suspected PE, advanced ophthalmologic opinion is a necessary requirement before invasive radiological examinations are used. When the ophthalmologic evaluation is properly elaborated, the distinction can be made more clearly by using noninvasive methods. In order to determine the gold standard in terms of the methods used in the evaluation of patients who are not clinically diagnosed, new prospective studies with more patients should be planned.

Epilepsy and drug-resistant epilepsy in children with cerebral palsy: A retrospective observational study.

PURPOSE: The objective of this study was to determine risk factors for epilepsy and drug-resistant epilepsy (DRE) development in children with cerebral palsy. METHOD: Two hundred twenty-nine patients presenting to the pediatric neurology clinic and diagnosed as having cerebral palsy between November 2016 and November 2019 were included in the study. Medical histories and clinical, laboratory, and radiological findings were examined retrospectively from patient records in the hospital data system. RESULTS: Girls represented 103 patients (45%) and boys 126 (55%). The patients' mean age was 8.39 ±â€¯4.54 years. Epileptic seizures were present in 120 (52.4%) patients and drug-resistant seizures in 64 (27.9%). The risk of epilepsy was significantly higher in patients with motor or speech impairment, with hearing impairment, or undergoing first seizure in the neonatal period. We also observed a higher risk of epilepsy in patients with psychiatric comorbidity, particularly autism spectrum disorder. The risk of epilepsy was also higher in patients with microcephaly or quadriplegic cerebral palsy and in patients with focal and generalized epileptiform abnormality on electroencephalograms (EEGs). However, no significant difference was identified when all these factors were evaluated in terms of the risk of developing DRE. CONCLUSION: Patients with cerebral palsy have high comorbid epilepsy rates. We think that the risk of epilepsy may be higher in patients undergoing first seizure in the neonatal period, with microcephaly, with quadriplegic type cerebral palsy, and with additional psychiatric comorbidity. The rate of DRE development was very low in patients with normal EEG findings or with only background rhythm abnormalities on first EEGs during neonatal seizures. This may be regarded as a good prognostic factor for nondevelopment of DRE.

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood.

Hot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

The role of obesity and vitamin D deficiency in primary headaches in childhood.

This study evaluates the role of obesity, overweight and vitamin D deficiency in primary headaches in childhood. This retrospective observational study included pediatric patients aged 5-17 years admitted to the pediatric neurology clinic with headaches between January 2015 and August 2018 and diagnosed with primary headache based on ICHD III-beta criteria. The control group consisted of healthy children without headache admitted to the pediatric outpatient clinic for check-ups before engaging in athletic or school activities. The control and patient groups were at the same risk of low 25(OH)D3 levels. The study population was divided into three groups-patients with migraine (group A), patients with tension-type headache (TTH) (group B) and the control group (group C). Participants' demographic data, medical histories, physical examination findings and laboratory results were retrieved retrospectively from the patient charts. BMI was significantly higher in patients with primary headache, the risk of primary headache increasing in patients with a BMI in excess of 25. Comparison of the patients with primary headache and the control group revealed lower 25(OH)D levels in the primary headache group, although the difference was not statistically significant. Girls with primary headache had significantly lower 25(OH)D levels than boys. A relationship may be present between overweight, obesity and primary headache, while female gender may be suggested as a negative factor for primary headache. Patients should be advised to lose weight if BMI indicates overweight or obesity.

Cause or Consequence: The Relationship Between Cerebral Venous Thrombosis and Idiopathic Intracranial Hypertension.

AIM: The aims of our study were to refer to the complex relationship between idiopathic intracranial hypertension (IIHT) and cerebral sinovenous thrombosis (CSVT), and to determine the differences and commonalities between the patients with and without CSVT in their etiology, along with documenting the uncertainties in concluding on the diagnosis and treatment of these patients. MATERIAL AND METHODS: IIHT was diagnosed according to Dandy criteria, while CSVT was screened for by way of a cranial magnetic resonance imaging for all patients and cranial magnetic resonance venography only if the magnetic resonance imaging was nebulous or there was a family history. RESULTS: We retrospectively evaluated a total of 26 patients (9 of whom had CSVT) diagnosed with IIHT between 2014 and 2018. A total of 9 patients with concurrent CSVT were described as suffering from vascular IIHT, while the remaining 17 were described as suffering from other IIHT. Demographic characteristics were similar in both groups (mean age: 12 vs. 11; male/female ratio: 2/7 vs. 5/12 in vascular IIHT and other IIHT, respectively). Clinical findings, cerebrospinal fluid-opening pressure values, and pathologies of etiology were also similar (vitamin D deficiency: 66% vs. 52%; vitamin B12 deficiency: 11% vs. none; iron deficiency: 22% vs. 11%; obesity: 22% vs. 23%). A mixture of acetazolamide, topiramate, anticoagulant therapy, and acetylsalicylic acid were given according to the diagnoses. CONCLUSION: CSVT is a common clinical entity among the causes of IIHT, and it should be taken into consideration in this patient group. However, there is a need for a common guideline for laboratory and imaging methods to understand the etiopathogenesis of childhood IIHT and determine the patients at risk.

Childhood Facial Palsy: Etiologic Factors and Clinical Findings, an Observational Retrospective Study.

The purpose of this study was to determine the etiologic factors, clinical characteristics, seasonal distributions, family history, response to corticosteroid therapy, recurrence and residual paralysis rates, and factors affecting these in pediatric facial palsy. Patients aged <18 years diagnosed with acute peripheral facial palsy were included in the study. Demographic data and clinical findings were retrieved from patients' records. The study was completed with 113 patients. Causes were idiopathic in 74 (65.4%) cases. Complete healing was not achieved in 6 (5.3%) patients, and recurrence was observed in 11 (9.7%). None of the patients with residual paralysis used corticosteroid, but all the patients with recurrence had employed them. We determined that young age may have an adverse impact on complication development and that corticosteroid therapy may be useful in the healing process in idiopathic facial nerve palsy. In conclusion, age may have an adverse impact in idiopathic facial nerve palsy, whereas corticosteroid therapy has a positive effect.