Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies.

BACKGROUND AND AIMS: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam. METHOD: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. RESULTS: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group. CONCLUSION: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Hashimoto's encephalopathy presenting as pseudobulbar palsy.

INTRODUCTION: Hashimoto's encephalopathy (HE) is an autoimmune condition with varied neurological and psychiatric features. HE is very unusual as a cause of pseudobulbar palsy (PSP). CASE PRESENTATION: A 14-year-old male was admitted with right-sided weakness, dysphagia, speech disorder, and aggressiveness. Brain magnetic resonance imaging showed increased intensity in bilateral temporal, insular cortex, amygdala, and parahippocampal area on T2-weighted and fluid-attenuated inversion recovery images. Autoimmune encephalitis was considered as the patient had subacute onset of psychiatric and motor disturbances with normal findings for cerebrospinal fluid. N-methyl-D-aspartate receptor, anti-glutamate-type α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2, anti-contactin-associated protein-like 2, anti-gamma-aminobutyric acid receptor, anti-Leucine-rich, and glioma-inactivated 1 antibodies were negative but the anti-thyroperoxidase (antiTPO) level was greater than 998 IU/ML (n:0-9). Steroid therapy was initiated as pulse therapy and maintained with 2-mg/kg/day dose with the diagnosis of HE. He was symptom free for 6 months. In the follow-up period, he had two recurrences which responded to steroid therapy. CONCLUSION: The common causes of PSP are demyelinating, vascular, and motor neuron diseases and congenital malformations of the opercular or insular cortex. However, there are no cases of PSP developing after any autoimmune encephalitis. This case highlights the importance of early detection of antiTPO antibodies with the findings of PSP due to autoimmune encephalitis.

A case of Dravet Syndrome with a newly defined mutation in the SCN1A gene.

Dravet syndrome is a catastrophic progressive epileptic syndrome. De novo loss of function mutations on the SCN1A gene coding voltage-gated sodium channels are responsible. Disruption of the triggering of hippocampal GABAergic interneurons is assumed as the cause of fall in the seizure threshold. A ten-year-old boy first presented at age 10 months with febrile-clonic seizures, which began when he was aged 8 months. Electroencephalography was found as normal. Phenobarbital was initiated because of long-lasting seizures. However, his seizures continued and the therapy was replaced with valproic acid. On follow-up, different antiepileptics were used, which were stopped due to inefficiency or adverse effects. SCN1A gene analysis was performed and a heterozygous c.4018delC mutation was identified. This new frame-shift mutation resulting from an early stop-codon is thought to be the cause of the disease. Finally, he was prescribed valproic acid and stiripentol. For patients with fever-triggered, treatment-resistant seizures, and delayed psychomotor development, Dravet syndrome should be considered. Genetic diagnosis is important for treatment and follow-up.

The effects of risk factors on EEG and seizure in children with ADHD.

Attention-deficit hyperactivity disorder (ADHD) is one of the most commonly seen developmental disorders in childhood. Its etiology, however, is not well known even though bio-psycho-social reasons have been thought to play a big role. The aims of this retrospective study are to identify the risk factors of ADHD in patients diagnosed with ADHD in childhood, analyze the relationship between clinical symptoms and risk factors to which they were exposed and determine their effects on prospective electrophysiological findings. Longitudinal cohort study of all children with ADHD treated at Ankara University Medical University during 2007-2012, with follow-up to ascertain risk factors and seizure and EEG abnormalities outcome. Multinominal univariate logistic regression analysis was used to calculate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for associations. Epileptiform discharges were found in 32 (22.9%) of the 140 ADHD patients. Of these, 71.9% had focal epileptiform discharges and 28.1% had generalized epileptiform discharges. The focal epileptiform discharges were most prevalent from the rolandic area. Among the 140 patients, 20 (14.3%) had a previous history of seizure, and all twenty had epileptiform discharges on EEG whereas none of the patients who had normal EEG had a seizure history. The rates of epileptiform discharges were significantly related to gestational age and asphyxia (RR: 1.8, 95% CI 0.3, 9.3; RR: 9.6, 95% CI 2.3, 40, respectively), whereas the rates of epilepsy were related to asphyxia but not gestational age. History of asphyxia and prematurity do seem to increase the risk of EEG abnormality in patients with ADHD. Modification of these environmental risk factors by evidence-based prevention programs may help to decrease the burden of ADHD.

Complete paralytic botulism mimicking a deep coma in a child.

Botulism is a rare cause of neuroparalysis. Delay in diagnosis and treatment exerts adverse impact on mortality and morbidity. We report a child with complete flaccid paralysis followed by progression to coma-like consciousness. The patient required mechanical ventilation. As serological tests could not be performed, detailed history and physical examinations led to the suspicion of botulism, and repetitive nerve stimulation tests supported the diagnosis. Botulinum antitoxin was administered. The patient`s neuromuscular function improved rapidly.

Novel plasminogen gene mutations in Turkish patients with type I plasminogen deficiency.

The plasminogen (Plg) protein is the inactive proenzyme form of plasmin that dissolves fibrin thrombi by a process called fibrinolysis. It has been shown that homozygous or compound-heterozygous deficiency of this protein is a major cause of a rare inflammatory disease affecting mainly mucous membranes found in different body sites. In this study, five individual Turkish patients and nine Turkish families with type 1 Plg deficiency were investigated for PLG gene mutations. All of the coding regions of the PLG gene mutations were screened for mutations using denaturing high-pressure liquid chromatography (DHPLC). Samples showing a different DHPLC profile were subjected to DNA sequencing analysis. Here, we described five novel mutations namely, Cys49Ter, +1 IVS6 G>A, Gly218Val, Tyr283Cys, and Gly703Asp. Previously identified five nonsynonymous (Lys38Glu, Glu180Lys, Gly420Asp, Asp453Asn, Pro763Ser), five synonymous (330 C>T, 582 C>T, 771 T>C, 1083 A>G, 2286 T>G), and a 3' untranslated region (3' UTR) mutation (c.*45 A>G) were also reported in this present study. In this study, we have identified a total of eight mutations, five of which are novel. The mutations/polymorphisms identified in eight of the patients do not explain the disease phenotype. These cases probably carry other pathological mutations (homozygous or compound heterozygous) that cannot be detected by DHPLC.

A celiac case mimicking mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Celiac disease (CD) is a chronic disease involving a number of systems in addition to gastrointestinal tract. Although not clear, it has been supposed that the neurological symptoms of CD develop due to immune-mediated mechanisms. In this paper, we present a rare case diagnosed with CD at 12 years of age, and presented with a clinical picture resembling mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). She had onset of her neurological symptoms at the age of 6 years, they progressed despite various therapies, and she became wheelchair-bound.

Neurological findings spectrum in Celiac disease.

We aimed to provide early diagnosis by determining possible Celiac disease related subclinical or symptomatic neurological abnormalities in children in order to decrease risk of mortality and morbidity. Children with Celiac disease were assessed with neurological examination, neurophysiological tests and neuroimaging. A total of 65 patients were included in the study. The neurological examination was abnormal in 4 patients. There were EEG abnormalities in 5 patients, VEP was abnormal in 7 patients, BAER was abnormal in 1 patient, ENMG was abnormal in 8 patients, and there were abnormal findings on neuroimaging in 2 patients. The Celiac disease related neurological complications that manifest in adulthood usually lay their foundations in childhood. Therefore, it must be kept in mind that subclinical neurological abnormalities may be related to Celiac disease, and Celiac disease may be the underlying cause in the patients with overt neurological abnormalities in childhood.

A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation.

Niemann-Pick disease type C (NPC) is a fatal autosomal recessive lipid storage disease associated with impaired trafficking of unesterified cholesterol and glycolipids in lysosomes and late endosomes. This disease is commonly characterized by hepatosplenomegaly and severe progressive neurological dysfunction. There are two defective genes that cause this illness. One of these genes is NPC1 gene which is the cause of illness in 95% of the patients. The other gene is the rare type NPC2 which is the cause of illness in 5% of the patients. Patients with NPC2 usually present with respiratory distress in early infancy, which is rather unusual with NPC1. This article discusses about a patient who died at an early age from pulmonary involvement and who subsequently was found to have a novel homozygous mutation of NPC2 gene.

Epilepsy and autoimmunity in pediatric patients.

Our aim was to determine the presence and possible role of autoantibodies in epileptic patients with an undetermined etiology. Eighty epilepsy patients, who were referred to the Pediatric Neurology Department at Ankara University between November 2011 and April 2012, were enrolled in the study. Antinuclear antibodies (ANA), anticardiolipin IgG, antiphospholipid, antithyroid peroxidase, paraneoplastic, glutamic acid decarboxylase (GAD), and N-methyl-d-aspartate (NMDA) receptor antibodies were studied in our university laboratory. In addition, NMDA receptor (NMDAR), voltage-gated potassium channel (VGKC)-complex, leucine-rich, glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2) antibodies were studied at the Oxford University Immunology Laboratory. The study included 35 girls (44%) and 45 boys (56%) with a mean symptom age of 8.6 ± 4.53 years. ANA was detected in 15 (18.8%), antiphospholipid Ab in 3 (3.75%), anticardiolipin Ab in 1 (1.25%), and antithyroid peroxidase in 3 (3.75%) epileptic patients. In addition, anti-GAD Ab was detected in 7 (8.75%), anti-Yo Ab in 3 (3.75%), and anti-Ma2 in 3 (3.75%) epileptic patients. Anti-VGKC was positive in 13 (16.25%) epileptic patients. We performed a pioneer study to investigate the association between autoimmunity and pediatric epilepsy and we conclude that autoimmunity should be considered in epileptic patients with an undetermined etiology.

Relationship of childhood headaches with preferences in leisure time activities, depression, anxiety and eating habits: A population-based, cross-sectional study.

OBJECTIVES: The objective of this article is to determine the relationship between headache frequency and socio-demographic data, personal characteristics, habits, daily activities, daily loss of ability, depression and anxiety in the headache subtypes in the pediatric population. PATIENTS AND METHODS: Our sample group was composed of approximately 5355 children aged between 9 and 18 years. An eight-stage questionnaire was administered to the children. In the second stage of the study, headache subtypes were created according to the ICHD-II criteria. The resulting data were compared according to the results of the headache subtypes. RESULTS: In school-age children, the prevalence of recurrent headaches was 39.4%, and the prevalence of migraine was 10.3%. The subjects with migraine mostly preferred sedentary activities in their leisure time, and preferred less exercise than the subjects with the other headache types. The PedMIDAS score of the children who preferred to play sports was significantly lower than those who did not prefer to play sports. In the group that preferred reading books, an opposite relationship was found. In overweight and obese migraine sufferers, other types of headache were found to be significantly higher. CONCLUSIONS: In the management of treating childhood headaches, the association of psychiatric comorbidities should be considered. To minimize disability, children should be directed to more useful physical activities.

Cerebral sinovenous thrombosis in children and neonates: clinical experience, laboratory, treatment, and outcome.

Our aim is to present the etiology and risk factors for cerebral sinovenous thrombosis (CSVT) and the radiological findings, anticoagulant therapy used, and treatment outcome of patients with CSVT. This study included 12 patients who were treated for CSVT at the Ankara University, School of Medicine, Department of Pediatric Neurology. This study included 5 girls (41.7%) and 7 boys (58.3%) with a mean age of symptom onset of 5.2 ± 6.29 years (range: 0-18 years), who were followed at our institution for a mean of 1.8 ± 1.73 years (range: 0-6.5 years). Among the patients, 3 had no risk factors, 2 had 1 risk factor, and 7 had multiple risk factors. Anticoagulant therapy was administered to 4 patients, of which 1 had neurological sequelae; neurological sequelae or exitus occurred in 4 of the 8 patients who did not receive anticoagulant therapy. The present findings showed that appropriate prophylaxis in appropriately selected patients reduced the rate of recurrence of CSVT.

Anti-N-methyl-D-aspartate receptor encephalitis that developed after herpes encephalitis: a case report and literature review.

Herpes encephalitis (HE) is among the most common forms of viral encephalitis. Earlier publications indicate the development of acyclovir-refractory choreoathetosis in patients with HE. These reports suggest the development of secondary autoimmunity in the pathogenesis of HE. Combined methylprednisolone and acyclovir treatment reduced the appearance of brain abnormalities relative to treatment with acyclovir alone in a mouse model of encephalitis. We describe a case of a 19-month-old previously healthy girl presenting with sudden onset seizures and loss of consciousness. Initial polymerase chain reaction (PCR) tests for the presence of herpes simplex virus (HSV) were negative as were the tests for the limbic encephalitis antibodies. Steroids were administered with acyclovir to treat suspected autoimmune encephalitis as a result of the patient history of varicella vaccination. HSV PCR testing was positive on the 5th day; however, steroid treatment was continued due to the positive response seen in the patient. Steroid therapy was reduced on the 25th day of treatment due to the development of upper respiratory tract infection and the patient developed orofacial dyskinesia and choreoathetoid movements on the 28th day. Antibodies against N-methyl-d-aspartate receptor were detected in the in the serum and cerebrospinal fluid (CSF) on the 28th day. This case is an example of the emergence of autoimmune symptoms in the pathogenesis of HE.

Chloral hydrate and/or hydroxyzine for sedation in pediatric EEG recording.

PURPOSE: To evaluate and compare the success of chloral hydrate (CH) and hydroxyzine on sedation and assess the changes of these drugs on sleep EEG recordings. METHOD: Three hundred and forty-one patients (mean age: 60.92±53.81months) that were uncooperative with the EEG setup or referred for sleep EEG were enrolled in the study. Patients, partially sleep-deprived the night before, were firstly tried to fall on sleep without any medication, the patients who could not sleep spontaneously were randomly divided in two groups of hydroxyzine and chloral hydrate. RESULTS: In 147 (43%) of cases, CH was given for sedation. In 112 (32%) hydroxyzine and in 8% of cases CH and hydroxyzine were given. 17% of children had spontaneous sleep. The doses of drugs prescribed were as follows: hydroxyzine 1.43±0.74mg/kg CH 38±14.73mg/kg. The time to go on a sleep was 34.68±30.75min in hydroxyzine and 32.34±26.83min in CH group (p>0.05). Eighty-nine percent of cases who were sedated with CH and 89.6% of cases who sedated with hydroxyzine were able to sleep (p>0.05). The background rhythm was faster with CH compared to hydroxyzine (p<0.05). There were no association between the occurrence of fast background rhythm and the doses of CH. CONCLUSION: The study described the clinical practice of sedation with CH and hydroxyzine on EEG recording. Data suggest that CH with low doses and hydroxyzine is equally effective for sleep induction, but the side effects of CH on the sleep EEG is much more prominent.

An unusual case of neurobrucellosis presenting as demyelination disorder.

Brucellosis is a public health problem in most countries in the Mediterranean. Involvement of the central nervous system is seen in 4-13% of patients with brucellosis. A 13-year-old girl was admitted because of gait disturbance, diplopia, and dizziness. Her complaints began about 1.5 years ago. The second symptomatic episode repeated about three months ago and the third two months ago. In total, attacks repeated 3 times over 1.5 years. The magnetic resonance imaging (MRI) and the clinical features mimicked multiple sclerosis. The patient was given pulse steroid treatments. After steroid treatment, her gait disturbance and diplopia improved over the short term. Following positive developments, her symptoms recurred. The tests were repeated; the MRI showed increasingly high signal abnormalities, and Brucella melitensis was grown in cerebrospinal fluid. The patient was started on an oral combination of rifampin, doxycycline, and ciprofloxacin. MRI findings improved markedly after nine months of treatment. Although neurobrucellosis is associated rarely with demyelination in adults, this finding has not been reported previously in children or adolescents. Additionally, this case is the first in terms of involvement of the corpus callosum in neurobrucellosis. In this article, we present an unusual case of neurobrucellosis.

Valproic acid-induced acute pancreatitis and multiorgan failure in a child.

Valproic acid (VPA) is still an important antiepileptic drug, with the broadest spectrum used in all types of seizures and syndromes. It has serious adverse effects such as hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. The incidence of VPA-associated pancreatitis has been estimated to be 1:40,000. We present a 6-year-old boy who developed acute pancreatitis (AP) and multiple-organ failure after 3 months of VPA therapy. The patient's laboratory values showed that his kidney and hepatic function had impaired and thrombocytopenia, and coagulopathy had developed. The patient's abdominal tomography showed a suspected appearance, which was consistent with pancreatitis. Because amylase and lipase levels were found to be high, AP was considered. The patient improved after cessation of VPA treatment. Ten days later, the patient recovered both clinically and laboratorial. Consequently, the patient was discharged with cure. In conclusion, AP is a rare, severe adverse reaction to VPA treatment. If a child, who is receiving VPA, develops abdominal pain and vomits, VPA-associated pancreatitis must be considered.

A novel protein C inhibitor gene mutation in pediatric stroke patients after bone marrow transplantation.

Protein C inhibitor is a heparin dependent serine protease inhibitor found in human plasma, urine and other body fluids. It was originally identified as an inhibitor of activated protein C. Stroke is an important cause of morbidity and mortality in the pediatric age group. In this study we analyzed the protein C inhibitor gene mutations in Turkish pediatric stroke patients. We found a missense mutation of G to A at nucleotide 6760 in exon 2, resulting in a transition serine to asparagine (p.Ser188Asp) and in a child and his father and also we found same alteration in exon 2 in an another pediatric stroke case following bone marrow transplantation.

Endothelial protein C receptor and pediatric arterial stroke.

OBJECTIVE: The aim of this study was to investigate the endothelial protein C receptor (EPCR) gene A3 haplotype and plasma soluble EPCR (sEPCR) levels in Turkish pediatric arterial stroke patients. MATERIALS AND METHODS: We analyzed 44 pediatric arterial stroke patients and 75 healthy controls. Following DNA isolation, genotyping of the A3 haplotype was determined via PCR and RFLP. Additionally, fasting sEPCR levels were determined via ELISA. RESULTS: There wasn't a significant difference in the sEPCR level between the control and patient groups, although the sEPCR level was higher in the patient group. We didn't observe a difference in the distribution of the CC and CG/GG genotypes between the control and patient groups. CONCLUSION: Further study on sEPCR levels at the onset of pediatric stroke is needed in order to reach a more definitive conclusion. CONFLICT OF INTEREST: None declared.