An examination of the mutual effects of valproic acid, carbamazepine, and phenobarbital on 25-hydroxyvitamin D levels and thyroid function tests.

BACKGROUND: The effects of antiepileptic drugs (AEDs) on bone metabolism and the endocrine system are not fully known, and publications on the subject are inconsistent. OBJECTIVE: The study aimed to examine the mutual effects of valproic acid (VPA), carbamazepine (CBZ), and phenobarbital (PB)-AEDs frequently used in childhood-on bone mineral metabolism and thyroid function tests. PATIENTS AND METHODS: Children monitored with a diagnosis of idiopathic epilepsy by the pediatric neurology clinic, using AEDs for at least 6 months and with episodes under control, were included in the study. Patients were divided into groups on the basis of the drugs used. Thyroid function tests and 25-hydroxyvitamin D or 25(OH)D levels were measured from blood specimens. The data obtained were then compared with those of the control group. RESULTS: A significantly high level of subclinical hypothyroidism was seen in patients using VPA (p < 0.001). There was no significant difference between any of the three study groups and the control group in terms of 25(OH)D (p > 0.05). CONCLUSIONS: Pediatric patients using AEDs, particularly VPA, should be monitored for subclinical hypothyroidism. VPA, CBZ, and PB have no effect on vitamin D levels.

Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayis University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Oral health status in epileptic children.

BACKGROUND: The aim of the present study was to evaluate the oral hygiene status and dental treatment requirements in children with epilepsy. METHODS: The treatment group consisted of 211 children with epilepsy (120 boys and 91 girls, 4-15 years old, mean age 7.85 + or - 2.98 years). The control group consisted of healthy children, matched by age and gender. Clinical features of the patients were obtained from hospital records. Clinical examinations were conducted, under standard light, using a plane buccal mirror, a dental probe and air drying to evaluate caries experience and to record the periodontal health of each child. Statistical analysis was performed using chi(2) test, Fisher exact test and anova. RESULTS: The number of decayed and missing teeth, the degree of abrasion and periodontal indexes were significantly worse in patients with epilepsy, compared to the control group (P < 0.001). Gingival enlargement was documented in 42% of patients on valproate monotherapy compared to only in 16% of patients on phenobarbital. Dental caries and halitosis were the most common oral disorders. Generalized tonic-clonic seizures often cause minor oral injuries and traumatized anterior teeth. CONCLUSIONS: Epileptic children are at an increased risk of developing caries and gingivitis compared with healthy subjects.

Hartnup disease masked by kwashiorkor.

This report describes an 11-month old girl with Hartnup disease presenting with kwashiorkor and acrodermatitis enteropathica-like skin lesions but free of other clinical findings. This case with kwashiorkor had acrodermatitis enteropathica-like desquamative skin eruption. Since zinc level was in the normal range, investigation for a metabolic disorder was considered, and Hartnup disease was diagnosed.

Bell's palsy as a possible complication of hepatitis B vaccination in a child.

Bell's Palsy is the sudden onset of unilateral temporary paralysis of facial muscles resulting from seventh cranial nerve dysfunction. Presented here is a two-year old female patient with right peripheral facial palsy following hepatitis B vaccination. Readers' attention is drawn to an uncommon cause of Bell's Palsy, as a rare complication of hepatitis B vaccination.

Becker's myotonia: novel mutations and clinical variability in patients born to consanguineous parents.

Myotonia congenita is an inherited muscle disease present from childhood that is characterized by impaired muscle relaxation after contraction resulting in muscle stiffness; moreover, skeletal striated muscle groups may be involved. Myotonia congenita occurs due to chloride (Cl) channel mutations that reduce the stabilizing Cl conductance, and it is caused by mutations in the CLCN1 gene. This paper describes four patients from two different healthy consanguineous Turkish families with muscle stiffness and easy fatigability. A genetic investigation was performed. Mutation analyses showed a homozygous p.Tyr150* (c.450C > A) mutation in patients 1, 2 and 3 and a homozygous p.Leu159Cysfs*11 (c.475delC) mutation in patient 4 in the CLCN1 gene. These mutations have never been reported before and in silico analyses showed that the mutations were disease causing. They may be predicted to cause nonsense-mediated mRNA decay. Our data expand the spectrum of CLCN1 mutations and provide insights for genotype-phenotype correlations of myotonia congenita.

Clinical presentation of anti-N-methyl-d-aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: A series of 24 cases.

OBJECTIVE: The symptomatology and paraclinical findings of antibody-mediated encephalitis, a relatively novel disorder, are still being characterized in adults and children. A high index of suspicion is needed in order to identify these cases among children presenting with various neurological symptoms. The aim of this study is to examine the clinical, demographic and laboratory findings and outcome of children with anti-NMDAR and anti-VGKC encephalitis for any typical or distinctive features. METHODS: Cases diagnosed with anti-N-Methyl d-aspartate receptor (NMDAR) and anti-voltage gated potassium channel (VGKC) antibody-mediated encephalopathy in four major child neurology centers are described. RESULTS: In four years, 16 children with NMDAR and 8 children with VGKC antibody-associated disease were identified in the participating centers. The most frequent initial manifestation consisted of generalized seizures and cognitive symptoms in both groups. Movement abnormalities were frequent in anti-NMDAR patients and autonomic symptoms, in anti-VGKC patients. Cerebrospinal fluid (CSF) protein, cell count and IgG index were normal in 9/15 anti-NMDAR and 5/8 anti-VGKC patients tested. EEG and MRI findings were usually nonspecific and non-contributory. The rate and time of recovery was not related to age, sex, acute or subacute onset, antibody type, MRI, EEG or CSF results. Treatment within 3 months of onset was associated with normal neurological outcome. CONCLUSIONS: Our results suggest anti-NMDAR and VGKC encephalopathies mostly present with non-focal neurological symptoms longer than 3 weeks. In contrast with adult cases, routine CSF testing, MRI and EEG did not contribute to the diagnosis in this series.

Late vitamin K deficiency bleeding: 16 cases reviewed.

In this study, clinical and demographic features of 16 cases with late vitamin K deficiency bleeding are presented. Ages of infants were between 30 and 130 days. Their delivery histories were uneventful, and family histories for bleeding disorders were negative. All parents except one were unaware of whether their children received vitamin K at birth or not. All cases did not have any underlying illness to explain the abnormal coagulation profile. The common presenting finding was pallor (62.5%). Intracranial haemorrhage was the most common bleeding site (37.5%), and two patients (12.5%) died because of it. Late vitamin K deficiency bleeding is still an important handicap in infants. Parents and healthcare providers should be informed about the importance of vitamin K prophylaxis to prevent vitamin K deficiency in infants.

Cerebrospinal fluid pressures in subacute sclerosing panencephalitis.

Increased intracranial pressure can rarely be the initial symptom in subacute sclerosing panencephalitis (SSPE). We examined cerebrospinal fluid (CSF) pressures and their correlation with clinical features in 58 patients with SSPE. CSF pressure varied between 50 and 500 mmH2O, mean 210.9+/-103.7 mmH2O. Twenty-five (42%) patients had pressures above 200 mmH2O and 15/58 (25%), above 250 mmH2O. There was no correlation between CSF pressure and neurological disability, spasticity, or clinical stage. Frequent myoclonia and shorter interval between measles and onset of SSPE were associated with CSF pressure >200 mmH2O (p=0.035). The causes of high pressure in certain SSPE patients is unknown but may include the effect of myoclonic jerks or inflammatory reaction. Because these patients may be unable to express symptoms, increased intracranial pressure should be considered in the presence of irritability or frequent myoclonia.

Acute hydrocephalus caused by mumps meningoencephalitis.

Hydrocephalus is a rare complication of mumps. We report an 8.5-year-old boy with acute hydrocephalus associated with mumps meningoencephalitis.

Morphological alterations produced by zinc deficiency in rat sciatic nerve: a histological, electron microscopic, and stereological study.

Zinc (Zn) is an essential trace element for humans and animals. It is required for normal growth, gene expression, wound healing, protein metabolism, immune function, and membrane integrity. In this study, unbiased stereological methods have been used to quantify the effects of Zn deficiency on the sectioned surface area and the number of myelinated axons in the sciatic nerve of rats. Animals were fed a Zn-deficient or Zn-sufficient diet for a period of 4 weeks. At the end of this time, the samples of sciatic nerves were removed from the animals, processed for electron microscopy and embedded in resin. The Zn-deficient group of rats was found to have a lower body weight compared to rats in the control group (P < 0.05). The sectioned surface area of nerve cross-section and myelinated axon number in Zn-deficient rats decreased by 20% and 29%, respectively, compared to the control group. A significant correlation between sectioned surface area and myelinated axon number was also determined. Morphological findings were as follows: on light microscopy, it was determined that certain abnormalities occur specifically in the experimental group, such as collapsed nerve fascicles, irregular profiles of and degeneration in myelin sheaths, and on electron microscopy, extensive myelin damage was seen in Zn-deficient groups compared with control groups. This study suggests that peripheral nerves require Zn for development and preservation of their structure.

Idiopathic unilateral paralysis of the palate in childhood.

Idiopathic soft palate paralysis is an isolated clinical entity of unknown cause. Typical clinical features are sudden onset, rhinolalia, and nasal escape of fluids from the ipsilateral nostril. The disorder affects mainly male children at the ages of 2 to 3 years and resolves spontaneously. This report presents a 5-year-old female with the rare disorder and discusses its probable physiopathologic mechanisms.

Valproate-induced insulin resistance in prepubertal girls with epilepsy.

Valproate is commonly used for treatment of a variety of seizure types in both children and adults. However, if the medication is started before the age of 20 years, it may affect reproductive endocrine functions. In order to investigate the possible role of valproate treatment in the development of obesity, hyper-insulinism and polycystic ovaries, we studied metabolic parameters and ovarian morphology/size in prepubertal girls with epilepsy. Our study included 14 girls with epilepsy and 15 healthy age-matched controls. The age of the patients ranged from 7 years to 13 years. Mean body weight, fasting serum insulin and glucose levels and HOMA index of girls in the study group were significantly greater than those of the control girls (p < 0.05). Serum androstenedione, prolactin and free testosterone were significantly lower in the VPA-treated girls than in the controls, whereas SHBG level was higher (p < 0.05). There was no difference between the groups for ovarian morphology. In conclusion, our findings showed that valproate treatment may lead to hyperinsulinemia and hypoandrogenism during the prepubertal period. This emphasizes that a mature adult endocrine system may not be necessary for the development of VPA-related hyperinsulinemia.

Pancytopenia due to linezolid treatment.

Antibiotic-resistant infections constitute a significant portion of severe childhood infections. A gradually increasing resistance and treatment difficulty are observed in infections caused by enterococci, staphylococci and pneumococci. Linezolid is one of the new antibiotics which has recently been introduced for clinical use with gram positive efficiency. In this article, a pediatric patient with vancomycin-resistant enterococcus infection who developed reversible bone marrow supression related with use of linesolid was presented. A shunt was inserted in a ten-month old female patient who had been operated at the age of one month because of meningomyelocele and who had developed hydrocephalus. Linezolid and meropenem treatment was started when vancomycin-resistant Enterococcus faecium and extended-spectrum beta-lactamase positive Escherichia coli grew in cerebrospinal fluid culture. In the second week of treatment, cerebrospinal fluid findings improved. However, bone marrow supression was observed. Linezolid treatment was discontinued. In the follow-up, the blood cell counts returned to normal levels.

Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy.

Childhood-onset neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescent material in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular genetic background of the disorder, at least seven different forms are thought to exist. Northern epilepsy is a novel form of NCL so far described only in Finland, where all patients are homozygous for a missense mutation in the CLN8 gene. A variant form of late infantile NCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity among the NCL, the underlying gene (CLN7) being unknown. Recently, we reported homozygosity over the Northern epilepsy CLN8 gene region on 8p23 in four out of five Turkish vLINCL families studied. However, no common mutation in CLN8 was found in these families. We have now extended the Turkish vLINCL family panel to 18 families, of which only one is nonconsanguineous. Nine families were excluded from CLN8 by lack of homozygosity. In the remaining families, four CLN8 gene mutations were identified indicating that in a subset of patients with Turkish vLINCL, the disorder is allelic to Northern epilepsy. There is no apparent genotype-phenotype correlation among the Turkish patients with CLN8 mutations, although their phenotype is distinct from that of Finnish Northern epilepsy patients. The molecular genetic background of the Turkish vLINCL families not linked to CLN8 remains to be clarified.

Pseudotumor cerebri secondary to subacute sclerosing panencephalitis.

Pseudotumor cerebri is characterized by signs of raised intracranial pressure occurring in the absence of obvious brain pathology. We present an 8-year-old boy with pseudotumor cerebri secondary to subacute sclerosing panencephalitis. The reported patient suggests a possible association between subacute sclerosing panencephalitis and pseudotumor cerebri and that subacute sclerosing panencephalitis should be added to the list of disorders known to be associated with pseudotumor cerebri. Patients with subacute sclerosing panencephalitis might benefit from treatment aimed at increased intracranial pressure.

Gingival enlargement in children treated with antiepileptics.

This study was conducted to determine the occurrence, severity, and risk factors of gingival enlargement in children treated with valproate and other nonvalproate antiepileptic drugs. A cross-sectional study was carried out in which data obtained from 68 epileptic children under treatment were compared with those from 50 controls. A structured questionnaire was used to collect data on patients' demographics, dental and oral hygiene practices, and medication history. Gingival enlargement, gingival index, plaque index, and probing depth were measured to assess periodontal health. The chi-square and Fisher exact tests were used in statistical analysis. In case of significance, a detailed chi-square analysis was carried out to determine the origin of the difference. Patients in both the valproate and nonvalproate groups showed significantly higher gingival enlargement, gingival index, plaque scores, and pocketing (P < .001 and P < .01, respectively) than the control group. In the valproate group, the duration of the treatment had a significant effect on gingival enlargement (P < .001) but not on gingival index, plaque index, and probing depth values (P > .05). Toothbrushing was most frequent in the control group (P = .000) and more frequent in the valproate group than the nonvalproate group (P = .024). Our study showed significant differences regarding gingival enlargement in children treated with valproate. These findings illustrate that epileptic children on valproate are at risk of periodontal problems.

Central pontine myelinolysis central pontine myelinolysis manifesting with massive myoclonus.

Central pontine myelinolysis is a rare neurologic disorder defined by symmetric demyelination in the central base of the pons. It usually manifests with neurologic signs such as impaired consciousness, ataxia, spastic quadriparesis, pseudobulbar signs, and the locked-in syndrome which is related to a disconnection syndrome at the pontine level. We report a 17-month-old patient with kwashiorkor and hyponatremia who developed acute massive myoclonus. Magnetic resonance imaging revealed a central pontine lesion. Central pontine myelinolysis is rare in infants, with only a few cases reported in the literature so far. This report presents the first infantile case of central pontine myelinolysis manifesting with massive myoclonus.