Özlem Hergüner

Asymptomatic hyperammonemia in children treated with valproic acid.

It was also reported that therapy with valproic acid led to the decreased plasma free carnitine concentration associated with hyperammonemia .6,1 Ohtani et all reported that there was a negative correlation between plasma ammonia and carnitine levels in patients taking valproic acid, and after giving L-carnitine (50 mg/kg/day) for 4 weeks, both hyperammonemia and carnitine deficiency were improved. We planned this study in patients without hepatic dysfunction and taking valproic acid to evaluate: (1) whether or not hyperammonemia rises; (2) if it is symptomatic; (3) if it rises, to what extent; (4) which variables affect it; and (5) if it is responsive to oral L-carrdtine, and if so, how long carnitine therapy should be given to these patients.

Serum and hair zinc levels in epileptic children taking valproic acid.

This study was performed to investigate the serum and hair zinc levels in patients having epilepsy diagnoses who were intended to be put on valproic acid (VA) monotherapy and had never ingested antiepileptics before. A total of 16 patients having normal growth, development, and nutrition was selected as Group 1, and Group 2 was made up of 10 patients who had received VA monotherapy for 2 yrs or more and had normal growth, development, and nutrition characteristics. A control group (Group 3) was formed of 15 subjects who applied to the hospital for upper respiratory tract disorders.Serum and hair samples were taken for zinc assays from the Group 1 patients on the d 0, 15, 30, 45, 60, 75, and 180. Groups 2 and 3 were sampled only once, and zinc levels were determined.We found that both serum and hair zinc levels in Group 1 were higher than those of Group 2 and control group before the beginning of VA therapy, but they returned to normal during VA treatment. There was no zinc deficiency, and zinc replacement treatment may therefore be considered as unnecessary.

Risk Factors Predicting Refractoriness in Epileptic Children with Partial Seizures

The aim of this retrospective study was to determine the risk factors associated with intractability to therapy in childhood epilepsy. Fifty children with intractable epilepsy as evidenced by at least 1 epileptic fit per month were included in the study group, whereas the control group consisted of children who did not experience any recurrent seizure for at least 1 year at the time of the study. A χ 2 test was used to evaluate the relationship between the test variables for the 2 groups, and the estimated relative risk (odds ratio) for each variable was calculated. The risk factors were subsequently determined by logistic multiple regression analysis. Univariate analysis showed that mental retardation, neurological abnormality, neuroradiological abnormality, perinatal anoxia, neonatal convulsion, presence of status epilepticus, and symptomatic etiology were significant risk factors for the development of refractory epilepsy (P < .05). For multivariate logistic regression analysis, age at seizure onset, status epilepticus, mixed type of seizures, and history of frequent seizures (more than once a month) were all found to be significant and independent risk factors for refractory epilepsy, and the number of drugs used in the study group was significantly higher than that in the control group (P < .05). In line with these findings, it was concluded that children who present with epilepsy and have these risk factors should be referred to a center where epileptic surgery is carried out without delay.

Prognosis of Patients With Seizures Occurring in the First 2 Years

The aim of this study is to determine the prognosis of patients with seizure onset from 1 to 24 months of age in respect to epilepsy, developmental outcome, and neurological status. It also aims to determine predictive factors regarding an unfavorable prognosis. Seventy-five patients were retrospectively analyzed. Univariate analysis revealed the following findings: (1) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on electroencephalography (EEG) of neonatal seizure, and perinatal anoxia were significant risk factors with regard to developmental outcome; (2) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, symptomatic etiology, history of neonatal seizure, and perinatal anoxia were significant risk factors regarding neurological status; and (3) mental retardation at initial admission, neurological abnormality, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, status epilepticus, symptomatic etiology, seizure frequency of more than once per week, history of perinatal anoxia, and neonatal seizure were significant risk factors regarding epilepsy prognosis. In addition, multivariate analysis revealed that neurological abnormality and use of more than 1 antiepileptic drug were significant for developmental outcome, that epileptic activity on EEG and use of more than 1 antiepileptic drug were significant for neurological status, and that perinatal anoxia, infantile spasm, and status epilepticus were significant for epilepsy prognosis. These findings suggest that neurological abnormality, use of more than 1 antiepileptic drug, infantile spasm, status epilepticus, and perinatal anoxia are unfavorable predictive risk factors regarding the prognosis of patients with seizures that have an onset from 1 to 24 months of age.

Electroconvulsive therapy for refractory status epilepticus in a child: A case report.

1. McGrath A, Reid N, Boore J. Occupational stress in nursing. Int J Nurs Stud 2003;40:555-65. 2. Hughes RG, Rogers AE. Are you tired? Am J Nurs 2004;104:36-8. 3. Johnson CJ, Croghan E, Crawford J. The problem and management of sickness absence in the NHS: Considerations for nurse managers. J Nurs Manag 2003;11:336-42. 4. McVicar A. Workplace stress in nursing: A literature review. J Adv Nurs 2003;44:633-42. 5. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 1989;28: 193-213. 6. Johns MW. A new method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 1991;14:540-5. 7. Short MA, Gradisar M, Lack LC, Wright HR. The impact of sleep on adolescent depressed mood, alertness and academic performance. J Adolesc 2013;36:1025-33. 8. Vanderlind WM, Beevers CG, Sherman SM, Trujillo LT, McGeary JE, Matthews MD, et al. Sleep and sadness: Exploring the relation among sleep, cognitive control, and depressive symptoms in young adults. Sleep Med 2014;15:144-9. 9. Sivertsen B, Lallukka T, Salo P, Pallesen S, Hysing M, Krokstad S, et al. Insomnia as a risk factor for ill health: Results from the large population-based prospective HUNT Study in Norway. J Sleep Res 2014;23:124-32. 10. Baldwin DC Jr, Daugherty SR. Sleep deprivation and fatigue in residency training: Results of a national survey of firstand second-year residents. Sleep 2004;27:217-23. 11. Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E, Katz JT, et al. Effect of reducing interns’ work hours on serious medical errors in intensive care units. N Engl J Med 2004;351:1838-48.

Multiple sulfatase deficiency: A case series of four children

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.

Factors Affecting Epilepsy Development and Epilepsy Prognosis in Cerebral Palsy

A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy.

A Turkish family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the aldehyde dehydrogenase family 3 member A2 (ALDH3A2) gene that encodes fatty aldehyde dehydrogenase. Affected patients display ichthyosis, mental retardation, and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients. We diagnosed two brothers age of 12 and 20 years with characteristic features of this rare syndrome. Magnetic resonance imaging showed demyelinating disease in both of them. We described a novel homozygous, c. 835 T > A (p.Y279N) mutation in exon 6 in two patients.

Acute rhabdomyolysis associated with levetiracetam therapy in a child

Levetiracetam (LEV) is a new antiepileptic drug (AED) that is effective in adults and children with partial-onset seizures or idiopathic or symptomatic generalized seizures. LEV does not bind to plasma proteins, and is eliminated by the kidneys. It has been argued that LEV can act on the N-type Ca channel and can reverse the gammaaminobutyric acid (GABA) and glycine-gated currents [1]. Side effects include fatigue, somnolence, infection, headache, behavioral changes and skin rashes [2]. Herein, we present the first case of rhabdomyolysis in a child treated with LEV. A 13-year-old girl presented with a history of myalgia (mainly in her lower extremities) since last 2–3 days to our hospital. She was born of an uneventful full-term pregnancy. Developmental milestones were normal. On medical history, she had partial onset of secondarily generalized seizures during sleep since 2 months. The seizure activity consisted of twitching of the right face, tonic deviation of the mouth involving the lips, tongue, and pharyngeal and laryngeal muscles, resulting in speech arrest and drooling and progressing into bilateral tonic stiffening of the arms and legs. The EEG revealed left centrotemporal spikes and was subsequently diagnosed with benign epilepsy with centrotemporal spikes. The patient was administered LEV monotherapy. LEV had started 10 mg/kg/day, but her brief partial seizures continued. The dose was increased to 20 mg/kg/day (500 mg/day), and her seizures were ceased. One week after starting LEV therapy, she experienced mild myalgia. On her examination, the vital signs, including the blood pressure were normal. Her height and weight were in normal limit for her age. The physical and neurological examinations were normal. There was no evidence of trauma, exercise or infection. On laboratory examination, blood urea was 29 mg/dL (normal range 17–43), creatinine 1.0 mg/dL (normal range 0.6–1.2), myoglobin 78 ng/mL (normal range 14.3–65.8), and creatinine phospho kinase (CPK) was 986 U/L (normal range 27–168). Plasma carnitine (42 lmol/L; reference range 19–59 lmol/L) and free carnitine levels (35 lmol/L; reference range 12–46 lmol/L) were normal as acylcarnitine profile. Brain MRI showed no abnormal findings. Rhabdomyolysis was diagnosed with clinical and biochemical findings. We thought LEV may be the cause of her complaints and ceased LEV therapy. Hydration therapy were started to avoid potential complications. After stopping LEV, serum CPK and myoglobin levels gradually decreased and returned into normal values. Muscle biopsy was not performed. Several studies have reported that various AEDs may induce rhabdomyolysis [2, 3]. In the literature, few adult patients have been reported, but there have been no reports in children [4, 5]. Akiyama et al. [4] reported a 29-year-old woman with epilepsy in whom rhabdomyolysis was induced by LEV. The other case, a 19-year-old man, was described by Isaacson et al. [5]. Rhabdomyolysis is the destruction of skeletal muscle and release into the bloodstream of various cellular components, including CPK and myoglobin. The main causes of rhabdomyolysis may be direct muscle damage, intense physical exercise, certain drugs (some of them commonly used, such as statins), toxins, infections, and genetic & Faruk Incecik fincecik@cu.edu.tr

Prognostic significance of failure of the initial antiepileptic drug in children with benign childhood epilepsy with centrotemporal spikes.

BACKGROUND Benign epilepsy with centrotemporal spikes is the most common partial epilepsy syndrome in children. The long-term prognosis for children with BECTS is believed to be generally excellent with seizures usually responding well to AEDs. The goal of the present study was to determine the risk factors associated with a poor prognosis. METHODS Eighty-four children with BECTS were retrospectively analyzed. Fifty-four (64.3%) were boys and 30 (35.7%) were girls with the mean age at seizure onset 7.1 ± 2.01 years (range: 3-12 years). RESULTS Of the 84 patients, 72 (85.7%) were treated successfully with the first AED (Group A), and 12 (14.3%) failed to responded to the initial AED treatment (Group B [poor prognosis]). Univariate analyses suggested that younger age of seizure onset, presence of generalized seizures, and frequent seizures (>3 prior to the initial treatment) were associated with failure to control seizures with the initial AED. Multivariate analysis suggested that younger age of seizure onset was the independent risk factor predicting a poor response to initial AED treatment. CONCLUSION About 14% of our cohort of children with BECTS continued to have seizures following the initial AED treatment. Further prospective studies are warranted to determine how well prognosis can be predicted by age of seizure onset, type of seizures, and frequency of pre-existing seizures in children with BECTS.