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.

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.

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.

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.

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.

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.

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.

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.

Relationship between functional promoter polymorphism in the XBP1 gene (-116C/G) and atherosclerosis, ischemic stroke and hyperhomocysteinemia.

ER stress is associated with a range of pathological conditions, among which, the ischemia/reperfusion injury is also found. The mechanistic array of links among the ER stress and thrombovascular diseases is poorly understood. The XBP1 gene is a transcription factor which modulates the ER stress response; and the XBP1 (-116 C/G) gene polymorphism causes an impairment of its positive feedback system. In the present study we investigated the prevalence of XBP1 gene (-116 C/G) polymorphism, separately among the patients with atherosclerosis, ischemic stroke and hyperhomocysteinemia. The G allele and the (-116 G/G) genotype of the XBP1 (-116 C/G) gene polymorphism were found to be a significant risk factor for the patients with Ischemic Stroke. Yet, this allele was seemingly less significant in case of patients with atherosclerosis and hyperhomocysteinemia. Hence, the XBP1 (-116 C/G) gene polymorphism and especially its involvement in a homozygous state are suggested to take active role in the ER stress related ischemia/reperfusion injury.

Fetal and neonatal cardiac rhabdomyomas: clinical presentation, outcome and association with tuberous sclerosis complex.

Rhabdomyoma is the most common pediatric heart tumor. Cardiac rhabdomyomas (CRs) have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC). We aimed to evaluate the clinical presentation and outcome of CRs and their association with TSC. Patients with CRs diagnosed in last six years were retrospectively analyzed. A total of 25 tumors were identified in seven patients by echocardiography. Three patients were diagnosed prenatally by fetal echocardiography, three patients in the neonatal period and one patient in early infancy. The median followup period was two years (range: 5 months-6 years). Five patients (71%) had multiple tumors. Three patients had arrhythmias and two patients required surgery. Only 36% (9/25) of the tumors regressed. TSC was diagnosed in four patients during the follow-up. CRs may have different presentations and clinical course. Surgery is only necessary when hemodynamically significant obstruction is present. As CRs are associated with long-term development of TSC and other diagnostic features are not yet typically apparent in the prenatal and neonatal periods, careful evaluation and follow-up are essential to exclude TSC.

Thrombophilic risk factors in epileptic children treated with valproic Acid.

There are few reports on valproic acid related to thrombophilia. Thrombophilic risk factors were investigated in 21 children (age range, 1-13 years) diagnosed with epilepsy and newly treated with valproic acid monotherapy. None of the children had been previously treated with any anticonvulsant agent. Before starting valproic acid therapy, homocysteine, lipoprotein(a), factor VIII, factor IX, protein C, protein S, antithrombin III levels, and activated protein C resistance levels were evaluated in all patients, with repeat evaluation after 9 months or 1 year of the therapy. Thrombosis gene mutations (factor V Leiden and prothrombin G20210A) were also evaluated in all patients before therapy. There was statistically significant elevation in lipoprotein(a) levels and reduction in fibrinogen levels after treatment. Reduction in protein C levels and elevation in homocysteine levels were also observed, but without statistical significance. Before therapy, no thrombotic event had occurred, despite thrombotic risk factors in some patients. Valproic acid can increase lipoprotein(a) and decrease fibrinogen, which may increase the risk of stroke or other thrombotic events. No clinical adverse effects resulted from changes in the levels or activity of thrombophilic factors associated with valproic acid treatment. Thus, routine investigation of factors implicated in thrombosis prior to initiation of valproic acid is not warranted for all patients. Nonetheless, caution is advised when initiating valproic acid treatment in children who have had prior stroke or thrombotic events.

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.

Severe muscle-eye-brain disease is associated with a homozygous mutation in the POMGnT1 gene.

Muscle-eye-brain (MEB) disease is an autosomal recessive disorder characterized by a broad clinical spectrum including congenital muscular dystrophy, ocular abnormalities, and brain malformation (type-II lissencephaly). Herein, we report on two Turkish siblings with a homozygous mutation in the POMGnT1 gene. A 6-year-old sibling has a severe form of MEB disease, which in some aspects is more suitable with the diagnosis of Walker-Warburg syndrome. However, the same mutation resulted in a less severe form of MEB in the older sibling, who is 14 years old. These two cases suggest that POMGnT1 mutations may cause MEB disease with different phenotypes even in the same family.

Tau and S100B proteins as biochemical markers of bilirubin-induced neurotoxicity in term neonates.

We investigated the relationship between total serum bilirubin and serum Tau and S100B protein levels, and predicted a cutoff level of bilirubin-induced neurotoxicity in term newborns. Total serum bilirubin, serum Tau, and S100B levels were measured in 92 jaundiced term newborns. A neurologic examination, electroencephalogram, brainstem auditory-evoked response, and otoacoustic emission were performed in the infants on admission and at age 3 months. Serum Tau (r = 0.921, P < 0.001) and S100B (r = 0.927, P < 0.001) levels were correlated with total serum bilirubin levels in all infants. Serum Tau and S100B protein levels remained at a steady level up to a total serum bilirubin level of 19.1 mg/dL, and then demonstrated a significant increase. Mean total serum bilirubin, serum Tau, and S100B levels of infants who manifested auditory neuropathy, neurologic abnormalities, or electroencephalogram abnormalities were significantly higher than in infants without these abnormalities (P < 0.05). Clinical and laboratory findings of bilirubin-induced neurotoxicity developed after a total serum bilirubin level of 22 mg/dL was reached. Serum levels of Tau and S100B proteins in jaundiced term newborns were strongly correlated with early-phase bilirubin encephalopathy.

Protein Z G79A polymorphism in Turkish pediatriccerebral infarct patients.

Protein Z (PZ) plays an enhancer role in coagulation as an anticoagulant. This is the first study in which G79A polymorphism investigated in Turkish paediatric stroke patients. Ninety-one paediatric stroke patients with cerebral ischemia and 70 control subjects were analyzed for PZ G79A and also FVL, PT mutations. PZ 79 'A' allele in homozygous state was found in five patients (5,5%), while it was found only in one control subject (1,4%) and it was seemed as a risk factor for peadiatric ischemia [OR=3,94 (0,44-35,1)]. When patients and controls who had FVL and PT carriers were excluded, AA genotype carried a risk [OR=3,88 (0,41-36,5)]. Also plasma protein Z levels measured in 21 stroke patients and 52 controls. Plasma protein Z levels were not different between stroke patients (500,95 ngmL-1±158,35) and controls (447,34 ngmL-1±165,97). But the plasma levels of protein Z was decreased in patients with AA genotype. Our data showed that carrying 79 AA genotype could be a genetic risk factor for cerebral infarct in peadiatric patients.

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.

EPCR gene A3 haplotype and elevated soluble endothelial protein C receptor (sEPCR) levels in Turkish pediatric stroke patients.

INTRODUCTION: High plasma levels of sEPCR lead to dysfunction of the EPCR-mediated coagulation. We have evaluated the role of EPCR A3 haplotype with its representative promoter variant 1651 C-G in a total of twenty-seven pediatric stroke patients and fifty-nine healthy subjects. MATERIALS AND METHODS: Genotyping of the A3 haplotype was performed with RFLP analysis. Plasma sEPCR levels were measured with ELISA. The mutant 1651 G allele frequency was observed to be 0.166 in the patient group. Common risk factors such as FV 1691 G-A and PT 20210 G-A mutations were also screened. RESULTS AND CONCLUSIONS: None of the patients with sEPCR levels below 100 ng/ml carried the A3 haplotype, while patients with elevated sEPCR levels carried the A3 haplotype either in a heterozygous or homozygous state. Our study confirms that there is a strong association between A3 haplotype and elevated sEPCR levels. We suggest that elevated sEPCR levels might increase the risk of stroke at pediatric age when compared to controls. Studies with large series of patients are warranted to confirm this hypothesis.

FXIII gene Val34Leu polymorphism in Turkish children with cerebral infarct.

A common polymorphism of the FXIIIA gene, which is characterized by a Val --> Leu exchange at amino acid position 34 (FXIII Val34Leu), was studied in this case-control study. The authors sought to determine whether there was an association between this polymorphism and pediatric stroke. The case-control study included 116 patients with cerebral infarct who were younger than 18 years. All were clinically diagnosed, and the infarction was verified with cranial imaging of the brain. The data revealed that the FXIII gene Val34Leu polymorphism was not associated independently with pediatric stroke in the population and that it does not have any effect in PT 20210A carriers. However, although the difference was not significant, the risk of thrombosis decreased 2-fold to the protective side in patients carrying FV1691A. This may be an important clue and needs further study in FV1691A carriers with and without thrombosis.