Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

Hypophosphatasia: is it an underdiagnosed disease even by expert physicians?

INTRODUCTION: Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all. MATERIALS AND METHODS: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once. Then, patients were evaluated for the symptoms and signs of HPP with further biochemical and genetic analyses. RESULTS: Thirty-seven patients who had severe musculoskeletal pain, recurrent fractures, and tooth anomalies were then screened with substrate and DNA sequencing analyses for HPP. It was determined that eight patients had variants in the ALPL gene. A total of eight different ALPL variants were identified in eight patients. The variants, namely c.244G > C (p.Gly82Arg), c.1444C > T (p.His482Tyr), c.1487A > G (p.Asn493Ser), and c.675_676insCA (p.Met226GlnfsTer52), had not been previously reported. DISCUSSION: Considering the wide spectrum of clinical signs and symptoms, HPP should be among the differential lists of bone, muscle, and tooth abnormalities at any age.

Evaluation of state and trait anxiety levels of parents and children before electroencephalography procedures: A prospective study from a tertiary epilepsy center.

BACKGROUND: Inadequate or misinformation about electroencephalography (EEG) and epilepsy may lead to anxiety in children and their parents. The purpose of this study was to make a simultaneous evaluation of the anxiety levels of children and parents before EEG procedures and to make a brief assessment of their knowledge about EEG. METHODS AND MATERIALS: Children aged between 8 and 18 years who were referred for EEG tests at Department of Pediatric Neurology, Gazi University Faculty of Medicine, Ankara, Turkey and their parents were included in the study, prospectively. Data were collected through Personal Information Forms; an EEG questionnaire form, which questioned the knowledge of the participants about EEG; the Spielberger's State-Trait Anxiety Inventory (STAI) to determine anxiety levels of the parents; and the State-Trait Anxiety Inventory for Children-State form (STAIC) to determine the anxiety levels of the children. The following parameters were collected in a database: demographic data about children and parents (sex, age), indication of suspected diagnosis on EEG request (i.e., the referral diagnosis), history of epilepsy, number of EEG recordings, and results of previous EEG recordings. The state and trait anxiety test results of the children were compared between the girls and boys, between age groups, and their parents' results in terms of both trait and state anxiety in terms of EEG, sex, ages, educational levels, and working. RESULTS: Eighty-five children (mean age: 13.25 ±â€¯3.02 years) and 85 parents (mean age: 41.16 ±â€¯7.65 years) were included in the study. The children's mean trait anxiety score was 32.51 ±â€¯8.09, and the mean state anxiety score was 34.97 ±â€¯7.62. Half of the children who had a trait anxiety score of ≤30 points had increased state anxiety levels because they received more than 30 points in the state anxiety evaluation score. No significant differences were found between the boys and girls in terms of the state and trait anxiety scores (p > 0.05). The parents' mean trait anxiety score was 39.16 ±â€¯7.74, and the mean state anxiety score was 42.74 ±â€¯6.22. Forty (47%) parents were found to have trait anxiety, and 52 (61.2%) parents had state anxiety before the EEG. The trait anxiety score of the mothers was statistically significantly higher than that of the fathers (p < 0.01). The investigation of the knowledge level of both parents and children about EEG demonstrated some misunderstandings or points of insufficiency. CONCLUSION: The present study revealed that both parents and children had insufficient knowledge about EEG, and the procedure caused anxiety for both the parents and children. When EEG procedures are requested, parents and children should be given brief information about EEG and epilepsy. We think that in this way, the knowledge of both parents and children about this issue may be increased and their anxiety may be decreased.

Temporary Seizure in an Infant Who Had Been Exposed to G-Amino Butyric Acid Receptor Antagonist Thiocolchicoside.

Seizure is the most common presentation of neurological disorder in the pediatric emergency care setting. In evaluating the child after a first seizure, the first consideration should be determining if the seizure was provoked or unprovoked. Investigation listing the causes of the first seizure is considerably long, and adverse drug reactions must be in mind. Epileptic seizures after using thiocolchicoside (TCC) have been reported in several adult patients with epilepsy and acute brain injury. We present a previously healthy 3-month-old female infant who was admitted to the emergency department with a generalized seizure after exposure to TCC. To the best of our knowledge, this is the first case of a child who had an epileptic seizure after TCC intake via breastfeeding in the literature.

Internal carotid artery dissection without intracranial infarct following a minor shoulder trauma: The second pediatric case and review of the literature.

INTRODUCTION: Carotid artery dissections may occur in severe trauma such as motor vehicle accidents or may also develop due to minor trauma. We aimed to present a case with internal carotid artery dissection that referred to the pediatric neurology department due to speech impairment after minor shoulder trauma. CASE: A previously healthy 10-year-old male patient was admitted to the pediatric emergency clinic due to headache, vomiting and speech impairment. In his story, we learned that he had bumped shoulder to shoulder with his friend about 6 h ago. He did not fall or hit his head. On his admission he could not speak and had right central facial paralysis. There was no infarct or diffusion limitation in MRI but MR angiography showed thinning in left internal carotid artery calibration. Fat-suppressed, non-contrast T1-weighted MRI showed that the left carotid artery had ring-shaped pathological signal changes. Low-molecular-weight heparin therapy was initiated with the diagnosis of carotid artery dissection (CAD). No hemiparesis or hemiplejia occurred in the follow-up of the patient. Within a few days, his speech improved. At the end of the first month, facial paralysis completely recovered. CONCLUSION: In carotid artery dissections, prodromal symptoms such as transient ischemic attack, like in our patient, are rarely present in children. For good long term outcomes, it is very important to suspect, diagnose and initiate appropriate treatment in a rapid manner in carotid artery dissection before severe neurological findings such as acute ischemic stroke develops.

A child with atypically subtle clinical presentation of acute arterial ischaemic stroke in the middle cerebral artery.

Arterial ischaemic stroke in the paediatric population is considered a rare disease, and its diagnosis is often delayed due to the subtlety and variability of clinical symptoms, especially in younger patients. The clinical presentation and imaging features of ischaemic stroke in the paediatric population are variable depending on the underlying cause, affected artery and patient's age. Literally, acute occlusion of the middle cerebral artery shows significant clinical signs and symptoms, and riotous imaging findings due to the size of the territory. Here, we present a case of a 15-year-old boy who unusually had subtle and intermittent clinical symptoms in spite of a complete acute occlusion in his right middle cerebral artery.

Multiple Sclerosis with Onset Younger Than 10 Years in Turkey.

OBJECTIVE: To identify the demographics, clinical characteristics, disease course, treatment patterns, and disability levels of multiple sclerosis (MS) patients with onset under the age of 10 years (early onset multiple sclerosis, EOMS). METHODS: EOMS patients were reviewed retrospectively in detailed records from 27 child neurology centers. Patients with preschool (≤7 years) and school age (>7 years) onset were compared. RESULTS: There were 30 children (16 girls, 14 boys) who have disease onset between 4 and 10 (mean8.1 ± 1.8) years. MS was relapsing-remitting in 29 (96.7%) and primary progressive in one (3.3%) of the patients. In patients with onset ≤7 years, motor symptoms (54.5%) and encephalopathy (45.5%) predominated, while in those with onset >7 years brainstem (42.1%), sensory (26.3%), and optic nerve (26.3%) involvement were the most frequent presentations. CONCLUSIONS: MS starting ≤7 years differs from the 7-10-year-old group by the higher rate of motor symptoms and more attacks in the first year: the latter suggests a more inflammatory character for EOMS.

Homozygous Mutations in TBC1D23 Lead to a Non-degenerative Form of Pontocerebellar Hypoplasia.

Pontocerebellar hypoplasia (PCH) represents a group of recessive developmental disorders characterized by impaired growth of the pons and cerebellum, which frequently follows a degenerative course. Currently, there are 10 partially overlapping clinical subtypes and 13 genes known mutated in PCH. Here, we report biallelic TBC1D23 mutations in six individuals from four unrelated families manifesting a non-degenerative form of PCH. In addition to reduced volume of pons and cerebellum, affected individuals had microcephaly, psychomotor delay, and ataxia. In zebrafish, tbc1d23 morphants replicated the human phenotype showing hindbrain volume loss. TBC1D23 localized at the trans-Golgi and was regulated by the small GTPases Arl1 and Arl8, suggesting a role in trans-Golgi membrane trafficking. Altogether, this study provides a causative link between TBC1D23 mutations and PCH and suggests a less severe clinical course than other PCH subtypes.

Regional brain volume reduction and cognitive outcomes in preterm children at low risk at 9 years of age.

OBJECTIVE: More information is needed on "low-risk" preterm infants' neurological outcome so that they can be included in follow-up programs. A prospective study was performed to examine the regional brain volume changes compared to term children and to assess the relationship between the regional brain volumes to cognitive outcome of the low-risk preterm children at 9 years of age. PATIENTS: Subjects comprised 22 preterm children who were determined to be at low risk for neurodevelopmental deficits with a gestational age between 28 and 33 weeks without a major neonatal morbidity in the neonatal period and 24 age-matched term control children term and matched for age, sex, and parental educational and occupational status. METHODS: Regional volumetric analysis was performed for cerebellum, hippocampus, and corpus callosum area. Cognitive outcomes of both preterm and control subjects were assessed by Weschler Intelligence Scale for Children Revised (Turkish version), and attention and executive functions were assessed by Wisconsin Card Sorting Test and Stroop Test TBAG version. RESULTS: Low-risk preterm children showed regional brain volume reduction in cerebellum, hippocampus, and corpus callosum area and achieved statistical significance when compared with term control. When the groups were compared for all WISC-R subscale scores, preterm children at low risk had significantly lower scores on information, vocabulary, similarities, arithmetics, picture completion, block design, object assembly, and coding compared to children born at term. Preterm and term groups were compared on the Stroop Test for mistakes and corrections made on each card, the time spent for completing each card, and total mistakes and corrections. In the preterm group, we found a positive correlation between regional volumes with IQ, attention, and executive function scores. Additionally, a significant correlation was found between cerebellar volume and attention and executive function scores in the preterm group. CONCLUSION: Low-risk preterm children achieve lower scores in neurophysiological tests than children born at term. Preterm birth itself has a significant impact on regional brain volumes and cognitive outcome of children at 9 years of age. It is a risk factor for regional brain volume reductions in preterm children with low risk for neurodevelopmental deficits. The significant interaction between cerebellar volume reduction and executive function and attention may suggest that even in preterm children at low risk can have different trajectories in the growth and development of overall brain structure.

Does nephrotoxicity exist in pediatric epileptic patients on valproate or carbamazepine therapy?

The aim of this study was to investigate the effects of valproate and carbamazepine, on renal glomerular and tubular functions. The patient group comprised 54 children with new-onset epilepsy treated with valproate (n = 30) and carbamazepine (n = 24). Twenty-six healthy children were in the control group. The serum creatinine and cystatin C levels and urinary excretion of N-acetyl-ß-d-glucosaminidase (NAG) levels were measured and the glomerular filtration rate (GFR) was estimated. Serum creatinine and cystatin C concentrations were not different between patients and controls. The glomerular filtration rate of the patient groups were higher than those of the control group. Thus, both drugs probably lead to glomerular hyperfiltration and toxicity for glomerular functions. However, urinary N-acetyl-ß-d-glucosaminidase/creatinine levels were significantly higher in patients receiving only valproate (6.1 ± 5). The difference between carbamazepine and control groups was not significant for urinary N-acetyl-ß-d-glucosaminidase/creatinine levels. Our data suggest that valproate has adverse effects on renal tubular functions.

Opsoclonus-myoclonus syndrome following rotavirus gastroenteritis.

Opsoclonus-myoclonus syndrome (OMS) is a rare neurologic disorder characterized by opsoclonus, myoclonus, ataxia and behavioral disturbance. In the pathogenesis, an autoimmune process with infectious or paraneoplastic trigger has been suggested. We describe the case of a 22-month-old girl with OMS following rotavirus gastroenteritis. Rotavirus should be considered in the differential diagnosis of OMS in children.

The effect of topiramate on body weight and ghrelin, leptin, and neuropeptide-Y levels of prepubertal children with epilepsy.

BACKGROUND: Weight loss is one of the most frequent side effects of topiramate treatment. The aim of our study was to investigate the effect of topiramate on body mass index, serum glucose, insulin, cortisol, leptin, and neuropeptide-Y levels and the role of these variables on the pathogenesis of weight loss in prepubertal children with epilepsy. METHODS: Twenty prepubertal children with epilepsy who were treated with topiramate were enrolled in the study. Topiramate was used at a daily dose of 5 mg/kg. Body mass index and fasting insulin-to-glucose ratio were calculated. Serum glucose, insulin, leptin, neuropeptide-Y, ghrelin, and cortisol levels were measured for all patients before the treatment and at the third and sixth months of the treatment. RESULTS: There were significant decreases in mean body mass index, fasting insulin-to-glucose ratio, and serum cortisol and leptin levels at the third and sixth months of the treatment compared with pretreatment levels. No significant changes were observed in serum glucose, ghrelin, neuropeptide-Y, or insulin levels. CONCLUSIONS: The exact mechanism of topiramate on energy balance regulation is not clearly understood. Topiramate affects body mass index, fasting insulin-to-glucose ratio, and serum leptin and cortisol levels in prepubertal children. These changes may be key factors in weight loss due to topiramate.

Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis.

Matrix metalloproteinases and their tissue inhibitors play a key role in the pathogenesis of adult-onset multiple sclerosis, and were suggested as biomarkers of response to interferon-ß, an established treatment in multiple sclerosis. However, data regarding pediatric population are scarce. We determined serum levels of matrix metalloproteinase-7, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in children, and evaluated effects of interferon-ß therapy on these measures. Serum samples from 14 children with relapsing, remitting multiple sclerosis at baseline and at month 12, and from 15 controls, were collected. Interferon-ß treatment was initiated in eight patients. Mean serum matrix metalloproteinase-9 levels and matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio were higher in patients compared with controls, and were reduced significantly in treated patients at month 12, but did not change in untreated patients. Mean matrix metalloproteinase-7 levels were lower in patients compared with controls, and increased significantly in the treated group, but did not change significantly in the untreated group. In pediatric multiple sclerosis, a shift in matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 balance toward proteolytic activity is evident, and interferon-ß therapy demonstrates a beneficial effect on this disturbed balance.

Reduced retinal nerve fiber layer thickness and macular volume in pediatric multiple sclerosis.

Retinal atrophy is well known in adult-onset multiple sclerosis but remains unexplored in children. We aimed to determine retinal nerve fiber layer thickness and macular volume in pediatric patients, with and without optic neuritis and their relations with visual evoked potentials. We also examined macular volume changes at month 12. Retinal nerve fiber layer thickness of all quadrants and macular volume were measured in 28 relapsing remitting multiple sclerosis eyes and 30 control eyes using optical coherence tomography and were found reduced in patients compared with controls. This reduction was more prominent in eyes with longer time interval from optic neuritis. Retinal nerve fiber thickness was lower in eyes with delayed visual evoked potentials. Visual evoked potential amplitudes were reduced in affected eyes compared to patients without optic neuritis. Macular volume reduced nonsignificantly in patients at month 12. Retinal atrophy occurs in pediatric multiple sclerosis, and previous optic neuritis accelerates this atrophy.

Molecular genetic analysis of the PLP1 gene in 38 families with PLP1-related disorders: identification and functional characterization of 11 novel PLP1 mutations.

BACKGROUND: The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP). PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20% of patients. METHODS: Forty-eight male patients from 38 unrelated families with a PLP1-related disorder were studied. All DNA samples were screened for PLP1 gene duplications using real-time PCR. PLP1 gene sequencing analysis was performed on patients negative for the duplication. The mutational status of all 14 potential carrier mothers of the familial PLP1 gene mutation was determined as well as 15/24 potential carrier mothers of the PLP1 duplication. RESULTS AND CONCLUSIONS: PLP1 gene duplications were identified in 24 of the unrelated patients whereas a variety of intragenic PLP1 mutations were found in the remaining 14 patients. Of the 14 different intragenic lesions, 11 were novel; these included one nonsense and 7 missense mutations, a 657-bp deletion, a microdeletion and a microduplication. The functional significance of the novel PLP1 missense mutations, all occurring at evolutionarily conserved residues, was analysed by the MutPred tool whereas their potential effect on splicing was ascertained using the Skippy algorithm and a neural network. Although MutPred predicted that all 7 novel missense mutations would be likely to be deleterious, in silico analysis indicated that four of them (p.Leu146Val, p.Leu159Pro, p.Thr230Ile, p.Ala247Asp) might cause exon skipping by altering exonic splicing elements. These predictions were then investigated in vitro for both p.Leu146Val and p.Thr230Ile by means of RNA or minigene studies and were subsequently confirmed in the case of p.Leu146Val. Peripheral neuropathy was noted in four patients harbouring intragenic mutations that altered RNA processing, but was absent from all PLP1-duplication patients. Unprecedentedly, family studies revealed the de novo occurrence of the PLP1 duplication at a frequency of 20%.

An unusual presentation of muscle-eye-brain disease: severe eye abnormalities with mild muscle and brain involvement.

Muscle-eye-brain disease (MEB) is characterised by congenital muscular dystrophy, structural brain malformations and eye abnormalities. We report a MEB case whose presenting sign was congenital blindness. She was investigated primarily for eye abnormalities at onset. She had bilateral retinal detachment and microphthalmia. Mild axial hypotonia and motor retardation were attributed to cerebral disorder in another center. Muscle biopsy showed mild myopathic changes and significant alpha-dystroglycan deficiency. Analysis of the POMGnT1 showed a novel homozygous mutation 1814G>C, causing p.Arg605Pro change. This case expands the clinical spectrum of MEB with unusually severe eye abnormalities compared to mild skeletal muscle and brain involvement.

Assessment of mothers' knowledge and perceptions of electroencephalography and determination of the short-term effect of an informational leaflet.

OBJECTIVE: The goal of the study described here was to determine mothers' knowledge and perceptions of electroencephalogram (EEG), to assess mothers' understanding of the main aspects of electroencephalography (EEG), and to determine the effect of an informational leaflet on increasing knowledge and perception. METHODS: A 20-item questionnaire was developed to assess mothers' knowledge and perceptions of EEG. The questionnaire comprised 20 simple statements on aspects of the procedure, to which the mothers answered "yes" or "no." Mothers were interviewed in person by an EEG technician at the beginning of the study. On completion of the questionnaire, the same technician provided the mothers with an informational leaflet. One month later, the mothers were telephoned and administered the same questionnaire over the phone. RESULTS: The response rate was 86%. Before reading the informational leaflet, 89.5% of the mothers stated that they knew why their child was undergoing electroencephalography, and 67.6% knew what electroencephalography was. Furthermore, 78.1% of them believed that their child's brain was mapped by electroencephalography. In addition, nearly 1 in 10 believed that EEG is a hazardous procedure and 6% believed it was addictive. Knowledge and perceptions changed after distribution of the informational leaflet. Comparison of mothers with different income levels, educational status, and numbers of electroencephalograms their child underwent revealed statistically significant differences with respect to knowledge and perceptions of electroencephalography. CONCLUSION: Written information is a simple, inexpensive, easy-to-implement, yet effective method of improving parental understanding of EEG. The present study has significant implications for informing individuals regarding medical procedures.