Renal manifestations in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neurocutaneous syndrome affecting various parts of the body, including the renovascular and urinary systems. We evaluated the renovascular, urinary, glomerular, and tubular functions of children with NF1. We compared blood pressures, urinary findings, and renal glomerular and tubular functions in children with NF1 with those of a healthy age- and gender-matched control group. We evaluated 46 NF1 patients and 33 healthy controls. The mean ages of the NF1 group (female/male: 20/26) and the control group (female/male: 15/18) were 10.1 ± 4.6 and 10.6 ± 4.3 years respectively. Six NF1 patients were hypertensive. The mean blood pressures of the NF1 group were significantly higher than those of the control group. Renal artery stenosis was detected in one NF1 patient. Urinary tract anomalies were evident in 21.7% of NF1 but only 9% of control subjects. The mean estimated glomerular filtration rate (eGFR) of the NF1 group was significantly lower than that of the control group. Six NF1 patients evidenced eGFRs < 90 mL/min. In the NF1 group, tubular phosphorus reabsorption was significantly lower and uric acid excretion significantly higher than in the control group.Conclusion: Hypertension, urinary tract anomalies, and impaired renal function were more common in NF1 patients than healthy controls. Regular blood pressure measurements and evaluation of urinary tract and kidney function are essential for NF1 patients. What is Known: • NF1 is most commonly associated with systemic hypertension due to renal artery vasculopathy and the development of a pheochromocytoma. • Hydronephrosis and bladder involvement have been documented in NF1. What is New: • Renal glomerular and tubular functions may be affected in NF1.

Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey.

Background Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), tremor in 2 patients (9.1%), and multiple sclerosis in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF.

Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis.

Migraine is a commonly seen neurovascular disorder during childhood. Inflammation induced by the activation of cytokines and neuropeptides is implied in its pathophysiology. There is an association between inflammation and atherosclerosis in patients with migraine. In addition, there is a strong correlation between early atherosclerotic wall lesions and carotid intima-media thickness (CIMT). The study population consisted of 57 migraine patients aged 5-17 years, as well as 47 healthy children who served as the control group. Those migraine patients who were not receiving any medications at the interictal period were compared to healthy controls in terms of their measured lipid levels, thyroid function, vitamin B12 levels, serum iron levels, iron binding capacity, complete blood count, C-reactive protein (CRP) levels, and carotid intima-media thickness (CIMT) scores, which may comprise risk factors for atherosclerosis. When children in the migraine and control groups were compared in terms of those risk factors that are known to be related to vascular changes, no significant differences were found. However, a significant difference was detected in CIMT values (P < 0.05). Atherosclerosis commences in childhood, and there is a long period of time before the onset of ischemic symptoms occurs. In children with migraine, an evaluation of CIMT can be used as a non-invasive imaging modality to detect atherosclerosis, which develops in the context of chronic inflammation. In this way, measures to reduce morbidity and mortality, which may result from cardiovascular diseases, can be implemented.

Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation.

Tyrosinemia type II is a rare autosomal recessive disorder caused by deficiency of tyrosine aminotransferase (TAT). It may occur with ocular and cutaneous symptoms with or without mental retardation, but epileptic seizure is a rare presentation of this disease. Herein we report the clinical, biochemical and genetic features of a 4-year-old boy who presented with afebrile seizure and photophobia. Genomic DNA was obtained from peripheral blood leukocytes from the whole family. Sequencing analysis was performed using the MiSeq next-generation sequencing platform. Sequencing of TAT indicated two new homozygous mutations p.L312P (c.935T>C) and p.T408M (c.1223C>T) for the proband and his asymptomatic sister. During a 2 year follow-up period, the patient had overall poor compliance with protein-restricted diet, but his asymptomatic sister had good compliance with the diet. Cognitive function of the patient worsened steadily, but his asymptomatic sister maintained normal mental status. Tyrosinemia type II should be considered in the differential diagnosis of children presenting with epileptic seizure and photophobia; furthermore, early diagnosis and protein-restricted regimen are important to reduce the risk of long-term complications of tyrosinemia type II such as mental disability.

Combination of two different homozygote mutations in Pompe disease.

Pompe disease (OMIM no 232300) is an autosomal recessive inherited metabolic disorder, caused by glycogen accumulation in the lysosome due to deficiency of the lysosomal acid 03B1-glucosidase enzyme. Here we report the case of an 8-month-old girl of consanguineous Turkish parents, who was diagnosed with the infantile form of Pompe disease. Two different uncommon homozygote mutations (c.32-13 T > G homozygote and c.1856G > A homozygote) were detected. The patient had a more progressive clinical course than expected. We emphasize the rare combination of genetic mutations in this Turkish family with Pompe disease.

Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

Different etiologies of acquired torticollis in childhood.

INTRODUCTION: Torticollis can be congenital or may be acquired in childhood. Acquired torticollis occurs because of another problem and usually presents in previously normal children. The causes of acquired torticollis include ligamentous, muscular, osseous, ocular, psychiatric, and neurologic disorders. OBJECTIVE: We performed this study to evaluate the underlying causes of torticollis in childhood. MATERIAL AND METHODS: Ten children presented with complaints of torticollis between April 2007 and April 2012 were enrolled in this study. The additional findings of physical examination included neck pain, twisted neck, walking disorder, imbalance, and vomiting The identified etiologies of the enrolled children was acute disseminated encephalomyelitis in a 2.5-year-old boy, posterior fossa tumor in a 10-month-old boy, spontaneous spinal epidural hematoma in a 5-year-old hemophiliac boy, cervical osteoblastoma in a 3-year-old boy, arachnoid cyst located at posterior fossa in a 16-month-old boy, aneurysm of the anterior communicating artery in a 6-year-old girl, pontine glioma in a 10-year-old girl, and a psychogenic torticollis in a 7-year-old boy were presented. CONCLUSION: There is a wide differential diagnosis for a patient with torticollis, not just neurological in etiology which should be considered in any patient with acquired torticollis. Moreover, early diagnosis of etiological disease will reduce mortality and morbidity. Therefore, clinicians managing children with torticollis must be vigilant about underlying neurological complications.

Postnatal outcome of isolated, nonprogressive, mild borderline fetal ventriculomegaly.

BACKGROUND: This study aimed to evaluate postnatal outcome of fetuses affected by nonprogressive, isolated, mild (≥10 and ≤12 mm) borderline ventriculomegaly (BVM). METHODS: We studied 25 consecutive fetuses with BMV and evaluated patients' characteristic, ultrasonographic findings, and the neurodevelopmental outcome at age ≥24 months. RESULTS: The mean gestational age at diagnosis was 23.84 ± 5.02 weeks (min-max; 17-34 weeks). In 16 cases, BVM was bilateral (16/25, 64 %), 4 left sided (4/25, 16 %), and 5 right sided (5/25, 20 %). Fourteen cases were males (14/25, 56 %), and 11 cases were females (11/25, 44 %). In two cases, ventriculomegaly was regressed 4 weeks after the initial diagnosis (2/25, 8 %), and in the remaining cases, ventriculomegaly persisted between initial measurement and 12 mm. The mean age of the infant at the time of the neurodevelopmental evaluation was 45.9 months (24-77 months). The neurodevelopmental outcome at the mean age of 45.9 months was completely normal in 16 infants (16/25, 64 %). The remaining nine infants (9/25, 36 %) had mild degree of neuromotor developmental delay. CONCLUSION: Prenatal counseling for isolated, nonprogressive, mild BVM should be mainly reassurance since it is not associated with severe neurodevelopmental delay. However, parents should be educated about the developmental milestone of children to observe and detect mild neurodevelopmental delay which can be associated with mild BVM.

Transverse myelitis and acute motor sensory axonal neuropathy due to Legionella pneumophila: a case report.

Guillain-Barré syndrome is a rapidly progressive symmetrical muscle weakness associated with acute inflammatory disease. Transverse myelitis (TM) is the inflammation of the spinal cord characterized by rapidly evolving muscle weakness in the lower extremities, defects in sensory level and sphincter dysfunction. Guillain-Barré syndrome, and TM association occurs very rarely in childhood. A 7-year-old girl presented with complaints of neck pain, spout-style vomiting, cough, shortness of breath, and acute paraparesis with sensory and sphincter disturbance. The patient was intubated because of increased respiratory distress. A positive direct fluorescein antigen test in bronchoalveolar lavage confirmed Legionella pneumophila infection. Imaging and neurophysiologic studies were diagnostic for TM with acute motor and sensory axonal neuropathy. She was treated with a combination of high-dose methylprednisolone and intravenous immunoglobulins, and we observed incomplete recovery. The presented case is the first child with concomitant TM and acute motor and sensory axonal neuropathy related to L. pneumophila infection.

Prenatal diagnosis of split cord malformation by ultrasound and fetal magnetic resonance imaging: case report and review of the literature.

INTRODUCTION: Split cord malformation (SCM) is rare congenital disorder of spine in which bony, fibrous, or cartilaginous septum subdivides partially or completely the vertebral canal. SCM can be associated with other spinal abnormalities such as spina bifida, Arnold-Chiari malformation, hemivertebra, butterfly vertebra, or kyphoscoliosis and also can be seen as part of Jarcho-Levin syndrome. Prenatal diagnosis of SCM is possible by ultrasonography (US). Fetal magnetic resonance imaging (MRI) and amniotic fluid acetylcholine esterase (AF-AChE) levels can be helpful to rule out additional anomalies. We present a case of fetal SCM diagnosed by US and fetal MRI. CASE: An 18-year-old woman with no obstetrics risk factor was referred for routine US screening. At sagittal section, fetal spine was seen to be disordered. A coronal view of the spinal canal showed evidence of widening at the lower thoracic and lumbar level. An echogenic mass was identified within the enlarged spinal canal at level of T6-L5. Fetal MRI and AF-AChE analysis confirmed diagnosis and ruled out other anomalies and spina bifida. Neurological examination of the baby at 16 months of age was normal.

Acute demyelinating encephalomyelitis and transverse myelitis in a child with COVID-19.

BACKGROUND: Corona virus disease 2019 (COVID-19) includes a wide range of diseases with varying pathophysiology in children and adults. Although the disease mainly affects the respiratory tract, neurological involvement is also reported in the literature. The most common neurological complaints due to COVID-19 are headache, dizziness and anosmia. Acute necrotizing myelitis, acute demyelinating encephalomyelitis (ADEM), acute axonal neuropathy, acute transverse myelitis, and Guillian-Barre syndrome have been reported as neurological dysfunctions associated with COVID-19. CASE: A ten-year-old male patient presented with complaints of fever, headache and generalized muscle pain. The patient developed inability to walk and significant muscle weakness during the disease course, and he was diagnosed with ADEM and transverse myelitis on magnetic resonance imaging (MRI). As the etiological agent, COVID-19 was detected in both the respiratory panel sample and the cerebrospinal fluid (CSF) sample by the polymerase chain reaction (PCR) technique. Pulse steroid, IVIG, and plasmapheresis treatment were administered. He started to stand with support during follow-up. CONCLUSION: We presented a case of COVID-19 related ADEM and transverse myelitis who responded to pulse steroid, IVIG, and plasmapheresis.

Predictive value of laboratory parameters in childhood migraine.

Migraine is a neurovascular disease characterized by inflammation of the cerebral and extra cerebral vessels and appears in the form of attacks. Although the pathophysiology of migraine is not fully known, the data obtained because of long-term studies reliably support the presence of a potential relationship between migraine pathogenesis and platelet biology. The aim of this study was to investigate the effect of migraine on MPV and other blood parameters as well as the relationship between the hematologic parameters and characteristics of the headache and whether they possess diagnostic value as inflammation and platelet biology play a fundamental role in the disorder. The study group consisted of 56 patients who were followed up and treated with a diagnosis of migraine and 45 healthy patients. The median creatinine, CRP and TSH values of the children in the migraine group were found to be statistically significantly higher than the healthy control group. Serum iron levels of the migraine group were found to be statistically significantly lower than the control group. No statistically significant difference was found between the two groups in terms of MPV. However, when we examined only the patient group, we found MPV to be statistically significantly higher in girls. Increased MPV and decreased serum iron levels may be related to migraine. More comprehensive studies including a larger population are required to evaluate the specific parameters that may guide the follow-up and treatment of the disorder with simple tests to be used in routine practice and to elucidate the underlying pathophysiology.

Effects of L-thyroxine treatment on heart functions in infants with congenital hypothyroidism.

BACKGROUND: Impaired heart functions in newborns with hypothyroidism should be reversed by levothyroxine substitution therapy. The aim of the study was to investigate heart functions with congenital hypothroidism (CH) in newborns and changes after levothyroxine substitution therapy, measured with tissue Doppler echocardiography and conventional echocardiography. METHODS: The study included 30 neonates with CH and 34 healthy controls. Echocardiography were performed at baseline, 2nd week and 6th month of therapy. RESULTS: Heart systolic function was normal. Mitral E velocities and mitral E/A ratios were significantly lower in patients at baseline. Tei indices were significantly higher in patients and a significant negative correlation was detected between free thyroxine levels and Tei indices.When early and late post-treatment echocardiography findings are compared, a non-significant difference was detected. CONCLUSIONS: Neonates with CH may exhibit systolic and diastolic heart dysfunction, which can be reversed by early L-T4 substitution treatment. The Tei index index should be measured in addition to conventional echocardiography.

Bone mineral density and bone metabolic markers' status in children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder characterized by progressive manifestations, which is inherited in an autosomal dominant manner. The majority of patients with NF1 experience a diffuse, significant reduction in bone mass over time, with osteoporosis, osteopenia in the absence of severe scoliosis, or gross bone deformities. This study aimed to determine the bone mineral density (BMD) status, evaluate bone metabolism, and to determine the relevant factors in children with NF1. METHODS: The study population included 33 pediatric NF1 patients (20 males and 13 females). Bone metabolic markers, such as total calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin D, the urinary calcium/creatine ratio were measured. In addition, BMD was measured at both the lumbar spine (LS) and the femoral neck in all the patients. RESULTS: All the patients had a low 25-OH vitamin D level, but it was significantly lower in the females than in the males (p<0.009). Overall, 18.2% of the patients had skeletal abnormalities. The lumbar Z-score was ≤2 in 21.2% of the patients, whereas the femoral neck Z-score was ≤2 in 9.1%. The urinary calcium/creatine ratio was significantly higher in the female than in the male patients (p<0.027). In all, six patients had skeletal abnormalities. CONCLUSIONS: It is widely known that bone mineral metabolism markers and BMD are significantly affected in NF1 patients; however, the present study did not identify any effective parameters that could be used to predict skeletal abnormalities, or diagnose early osteoporosis and osteopenia in pediatric NF1 patients.

Assessment of Psychopathology and Quality of Life in Children and Adolescents With Migraine.

AIM: The aims of this study were to investigate comorbid psychiatric disorders and to identify anxiety and depression levels and quality of life in children and adolescents with migraine; and to assess their relationship with migraine. METHOD: 35 patients aged 9-16 years were followed in our neurology clinic and their parents were included into the study. 35 age- and sex-matched patients were employed as the control group. In the subjects included, psychiatric disorders were assessed by using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version. All children and adolescents were assessed by using the Children's Depression Inventory, the State-Trait Anxiety Inventory and the Pediatric Quality of Life Inventory. In addition, the Pediatric Migraine Disability Assessment Tool and visual analog scale were used to identify the degree of disability and pain severity in patients with migraine. FINDINGS: In the psychiatric assessment of children and adolescents with migraine, it was found that a psychiatric diagnosis was made in 40% of patients; and depression scale scores were significantly higher than those of controls. Quality of life was found to be poorer in patients with migraine compared to controls. It was found that quality of life was negatively correlated with pain severity and degree of disability; while it was positively correlated with depression scores. DISCUSSION: In children and adolescents with migraine, treatment of psychiatric disorders in addition to migraine therapy can facilitate migraine management and may decrease the need for prophylactic therapy.

The prevalence of migraine and tension-type headache among schoolchildren in Kayseri, Turkey: an evaluation of sensitivity and specificity using multivariate analysis.

This study aimed to determine the prevalence as well as psychosocial and demographic features of migraine and tension-type headache among school children between the ages of 7 and 17, and using the International Classification of Headache Disorders II. The study was conducted during the questionnaire phase and the interview phase. The prevalence of recurrent headache was 47.5%, whereas that of primary recurrent headache was 21%. The estimated prevalence rates of migraine and tension-type headache were 7.2% and 7.8%, respectively. Unilateral headache, throbbing-type headache, severe headache, and the severity of the headache with physical activity were specific for migraine. Headache was significantly higher in first-degree relatives of the children with migraine compared to the children with tension-type headache (P < .0001). We determined the prevalence rates of migraine and tension-type headache and revealed the characteristics as well as the psychosocial and demographic features of migraine and tension-type headache. Sensitivity, specificity, and multivariate analysis were also evaluated.

Comparison of Effects of Different Dexmedetomidine and Chloral Hydrate Doses Used in Sedation on Electroencephalography in Pediatric Patients.

The aim of this study was to compare the efficacy and safety of different oral chloral hydrate and dexmedetomidine doses used for sedation during electroencephalography (EEG) in children. One hundred sixty children aged 1 to 9 years with American Society of Anesthesiologists physical status I-II who were uncooperative during EEG recording or who were referred to our electrodiagnostic unit for sleep EEG were included to the study. The patients were randomly assigned into 4 groups. In groups D1 and D2, patients received oral dexmedetomidine doses of 2 and 3 µg/kg, respectively. In group C1 and C2, patients received oral chloral hydrate doses of 50 and 100 mg/kg, respectively. The induction time was significantly shorter in group C2 compared with other groups (P = .000). The rate of adverse effects was significantly higher in group C2 compared with the dexmedetomidine groups (D1 and D2; P = .004). In conclusion, dexmedetomidine can be used safely for sedation during EEG in children.

Three patients with lafora disease: different clinical presentations and a novel mutation.

Lafora disease is a rare, fatal, autosomal recessive hereditary disease characterized by epilepsy, myoclonus and progressive neurological deterioration. Diagnosis is made by polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy. Responsible mutations of Lafora disease involves either the EPM2A or NHLRC1 (EPM2B) gene. Mutations in the NHLRC1 gene are described as having a more benign clinical course and a later age of death compared with EPM2A mutations. We report 2 genetic mutations and clinical courses of Lafora disease in 3 adolescents with homozygote NHLRC1 mutation and novel homozygous EPM2A mutation.

Prevalence and risk factors of epilepsy among school children in Kayseri City Center, an urban area in Central Anatolia, Turkey.

PURPOSE: To investigate the prevalence of epilepsy in schoolchildren aged 7-17 in the province of Kayseri together with the accompanying risk factors. METHODS: Ten thousand individuals selected using the "stratified cluster sampling method" from a total population of 259,428 students within the borders of Kayseri city center constituted the study sample. A questionnaire was prepared in line with the epidemiological studies protocol recommended by the International Epilepsy Union Epidemiology and Prognosis Committee in 1993. Data were analyzed on IBM SPSS Statistics 20. Significance was set at p<0.05. RESULTS: Of the 15,000 questionnaires distributed, 72% (n=10,742) were returned fully completed. Eighty-three students had been or were still being monitored with a diagnosis of epilepsy. The raw prevalence of epilepsy was 6/1000 in females, 9/1000 in males and 8/1000 in both groups together. Prevalence of active epilepsy was 4/1000 in females, 7/1000 in males and 6/1000 in both groups together. Premature birth increased the risk of epilepsy 2.6 times, and average and poor family income levels increased the risk of epilepsy 3.3 and 1.6 times, respectively. A history of febrile convulsion increased the risk of epilepsy 15.1 times. CONCLUSION: The prevalence of epilepsy in the 7-17 age group in Kayseri is closer to that in developed rather than developing countries. We conclude that the risk factors for epilepsy, and particularly febrile convulsion, and the true prevalence rates need to be determined through studies involving wide socioeconomic strata.