Ünsal Yılmaz

The effect of antiepileptic drugs on thyroid function in children

BACKGROUND Limited and conflicting data exist for the influence of antiepileptic drugs on thyroid function in children. OBJECTIVE The aim of this study was to investigate the effects of phenobarbital, valproate, carbamazepine, oxcarbazepine, and levetiracetam monotherapy on thyroid function in daily clinical practice during a 12-month treatment period. METHOD A total of 223 children (103 females and 120 males) with new onset and controlled epilepsy treated with valproate (n=129), phenobarbital (n=33), carbamazepine (n=36), oxcarbazepine (n=14), levetiracetam (n=11) were enrolled in the study. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels were measured before and at first, sixth and twelfth months of therapy. RESULTS At baseline, average fT4 and TSH concentrations were not different between the drug groups. Valproate-treated patients had decreased fT4 and increased TSH levels at months 1, 6, and 12. Carbamazepine-treated patients had decreased fT4 levels at months 1, 6, and 12 and increased TSH levels at months 1, and 6. Phenobarbital-treated patients had decreased fT4 levels at months 1, and 6, and increased TSH levels at months 6 and 12. Oxcarbazepine-treated patients had decreased fT4 levels at month 1. Levetiracetam-treated patients showed no significant change of fT4 and TSH at any times. The frequency of subclinical hypothyroidism at month 12 was 28% in valproate, 21.4% in oxcarbazepine, 18.2% in phenobarbital, 13.9% in carbamazepine, and 0% in levetiracetam groups. CONCLUSION Our data suggest that all antiepileptic drugs studied except levetiracetam had varying degrees of deleterious effects on thyroid function.

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.

The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children

The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta.

Peripheral Facial Palsy in Children

The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential.

Efficacy and tolerability of the first antiepileptic drug in children with newly diagnosed idiopathic epilepsy

PURPOSE Limited data are available for the effectiveness of the antiepileptic drugs in children in daily clinical practice. The aim of this study was to investigate the efficacy and tolerability of the first prescribed old and new antiepileptic drugs in children with newly diagnosed idiopathic epilepsy during a 12-month period. METHOD A total of 289 children (141 females and 148 males) who received phenobarbital (n=33), valproate (n=142), carbamazepine (n=42), oxcarbazepine (n=38), or levetiracetam (n=34) as the first-line treatment, were enrolled in the study. Seizure control and the occurrence of adverse events were assessed during a treatment period of 12 months. RESULTS Overall, 245 (84.8%) patients remained seizure-free during the study period. The rate of seizure control did not differ significantly between the drug groups (p=0.099). Forty-four (15.2%) patients including 1 (3.0%) treated with phenobarbital, 22 (15.5%) with valproate, 7 (16.7%) with carbamazepine, 10 (26.3%) with oxcarbazepine, and 4 (11.8%) with levetiracetam had treatment failure. There was no significant difference between seizure-free and failure groups in terms of age, gender, seizure type, and drugs used. Overall, 80 (27.7%) patients had adverse events, of those the most common ones were behavioral problems, nausea and/or vomiting, weight gain, and learning difficulties. The reasons for treatment failures were lack of seizure control in 29 (10.0%) patients and intolerable adverse events in 15 (5.2%) patients. CONCLUSION It appears that old (phenobarbital, valproate and carbamazepine) and new antiepileptic drugs (oxcarbazepine and levetiracetam) have similar efficacy and tolerability profiles. Institutional ethic number is 28.3.2013/14.

Efficacy and Safety of IV Levetiracetam in Children With Acute Repetitive Seizures

BACKGROUND Levetiracetam has been proven to be effective in both partial and generalized seizures in children. However, few studies have reported its efficacy in the treatment of acute repetitive seizures. We aimed to investigate the efficacy and safety of levetiracetam in children with acute repetitive seizures. METHODS The medical records of children from the age of 1 month-18 years who received levetiracetam because of acute repetitive seizures in the pediatric intensive care unit between 2010 and 2013 were reviewed retrospectively. RESULTS Of the 133 patients, levetiracetam terminated seizures in 104 (78.2%). Side effects such as agitation and aggression were observed in three patients (2.2%). The likelihood of treatment failure was increased by four times by younger age at seizure onset; by six times in the individuals with neurological abnormalities; and by 22 times in the patients with West syndrome. The patients who used levetiracetam as the first treatment option for acute repetitive seizures had a longer duration of epilepsy, a higher rate of neurological abnormality, and a higher proportion of medically resistant epilepsy compared with the individuals who used levetiracetam as an add-on treatment to the other intravenous antiepileptic drugs. However, no differences were detected between these two groups in terms of treatment response. CONCLUSIONS Intravenous levetiracetam appears to be effective and safe in the treatment of acute repetitive seizures. Randomized clinical trials are needed to determine whether intravenous levetiracetam may replace other antiepileptic drugs as the first-line therapy in the management of acute repetitive seizures.

Recurrent peripheral facial palsy in a child with familial Mediterranean fever.

BACKGROUND Recurrent peripheral facial palsy is uncommon in children. It mostly occurs as an idiopathic disorder and to a lesser extent in the setting of some infectious, genetic, or systemic disorders. However, its association with familial Mediterranean fever has not been reported before. PATIENT We present a 14-year-old girl who experienced three episodes of right-sided peripheral facial palsy during a 9-month interval. She had a diagnosis of familial Mediterranean fever (homozygous with M694V mutation) and she had been receiving colchicine for 8 years. Recurrent peripheral facial palsy could be a neurological manifestation of vasculitis in familial Mediterranean fever. CONCLUSION Recurrent peripheral facial palsy may be a manifestation of familial Mediterranean fever in children.

Childhood paroxysmal nonepileptic events.

We aimed to determine the types and clinical characteristics of paroxysmal nonepileptic events (PNEs) in children. During a 13-year period, 765 patients underwent long-term video-EEG monitoring, and 95 (12.4%) of them were identified to have PNEs. The most common diagnoses were conversion disorder, parasomnias, staring spells, movement disorders, and hypnic jerks. Paroxysmal nonepileptic events originated from physiologic or organic (43.2%) and psychogenic (56.8%) causes. Mean delay in diagnosis was 3.1 years. Mean ages at diagnosis were 8.8 and 13.8 years in physiologic or organic and psychogenic groups, respectively. A marked female predominance was seen in the psychogenic group, whereas males slightly predominated in the physiologic or organic group. In the physiologic or organic group, events were less frequent, longer in duration, and commonly manifested as subtle motor activity, whereas subtle and prominent motor activities were encountered equally in both groups. Concomitant epilepsy was present in 10.5% of the patients. Differences in clinical characteristics may be helpful in differentiating physiologic or organic PNEs in children from psychogenic PNEs.

Atypical phenotypes of DYT1 dystonia in three children.

UNLABELLED DYT-1 dystonia is the most common primary dystonia seen in childhood. It is an autosomal dominantly inherited disorder caused by deletion of a GAG triplet in exon 5 of the DYT1 gene. It characteristically starts in a distal limb during late childhood, subsequently spreads to involve other body regions sparing oromandibular muscles. However, clinical presentation can vary remarkably with respect to age, site of onset and progression. In this study we present three early-onset DYT-1 dystonia patients who are atypical according to age of onset and localization. Dystonia has started at 2, 3 and 7years of age and generalized to involve other limbs in all patients and also oromandibular muscles in one patient. None of them have benefited from medical treatments including L-dopa. All had normal brain MRI scan, a history of normal birth without significant perinatal asphyxia, infection or trauma and all are neurodevelopmentally otherwise normal. CONCLUSION In children with dystonia; if brain imaging is unremarkable and when there is no history of CNS disorders such as perinatal asphyxia, infections, drug exposure or trauma; genetic analysis for GAG deletion of DYT-1 gene may be performed even if dystonia starts at a very young age or it spreads to involve oromandibular muscles.

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-β-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-β-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-β-d-glucosaminidase/creatinine levels. Our data suggest that valproate has adverse effects on renal tubular functions.