Efficacy and Safety of Levetiracetam for Childhood Epilepsies.

Background: Levetiracetam (LEV) is a broad spectrum second-generation antiepileptic drug (AED). Objective: The objective of the study was to investigate the efficacy and safety of levetiracetam for childhood epilepsies. Methods: This is single, tertiary centre observational, prospective study, that included paediatric patients who were treated with levetiracetam at Paediatric hospital University Clinical Centre Sarajevo, during the period of 15 years (2008-2022). Inclusion criteria were: paediatric patients age > 1 month, diagnosed with epilepsy according to International League Against Epilepsy. After the introduction of levetiracetam, each patient has been followed up at least 12 months. According to the outcome the patients were divided into 5 groups: seizure reduction >50%, seizure reduction <50%, complete seizure freedom, the same number of seizures and increased number of seizures. From these groups two intergroups have been formed: responders (seizure reduction >50% and complete seizure freedom) and non-responders (seizure reduction <50%, the same number of seizures and increased number of seizures). Results: The study enrolled 259 patients (141 female and 118 male), with mean age 7 years (3,0-12.0). Comorbidities were present at 129/259 (49.8%) patients. After 12 months of treatment, 25/259 (9.7%) patients had seizure reduction >50%, 30/259 (11.6%) patients had seizure reduction <50%, 154/259 (56.5%) patients had achieved seizure freedom, 31/259 (12%) patients had same number of seizures, while 19/259 (7.3%) patients had increased number of seizures. Seizure frequency between responders and non-responders, before treatment and after 12 months of treatment was statistically significant (p<0.001). Discussion: Non responders had the best outcome with ditherapy (30/79; 38%), while responders had the best outcome with monotherapy (161/180;89.4%). Conclusion: Levetiracetam is efficient antiepileptic drug for different types of epilepsies in childhood, used as mono, di or polytherapy.

The Causes of Acute Kidney Injury in Critically Ill Children Who Needs Renal Replacement Therapy.

Background: Acute kidney injury (AKI) is the result of various causes and is associated with significant morbidity and mortality as well as long-term renal sequelae in pediatric patients. Objectives: The aim of the study is to determine the causes of AKI in pediatric patients who needed renal replacement therapy (RRT) and were admitted to the Pediatric and Neonatal Intensive Care Unit (PICU and NICU) at the Pediatric Clinic, University Clinical Center Sarajevo (UCCS). Methods: Our research included 81 children with AKI who needed RRT. We used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI. Severe acute kidney injury was defined as stage 2 or 3 of AKI when plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours. Other laboratory findings and imaging tests were made depending on their primary disease that led to the AKI and its complications. Results: Our research analyzed 81 children with AKI who needed RRT 38 girls and 43 boys ages from birth to 18 years. Mean age of presentation was 6.28 years. Male female ratio in this study was 1.1:1. Non-olyguric AKI was diagnosed in 12 (14.8%) of children with AKI, while the rest 69 (85.2%) had the olyguric type. Patients with AKI were analyzed after a rough division on prerenal in 57 (70.4%) children, intrarenal in 23 (28.4%) and post-renal in 1 (1.2%) patient. Conclusion: As the AKI plays a key role in the mortality and morbidity in pediatric patients, especially in infants, it is important to recognise and treatment on time different etiologies of this serious condition. Some causes of AKI in our country can be prevented by better organization of primary and secondary health care, which would also reduce mortality and morbidity from AKI.

Hand function in children with unilateral spastic cerebral palsy.

Aim To assess hand function and explore the relationship between hand function and neuroimaging findings in children with unilateral spastic cerebral palsy (US CP). Methods Hand function was assessed using Manual Ability Classification System (MACS, I-V). Brain lesions were divided into five groups: brain maldevelopment (MAL), periventricular white matter lesions (PV WM), cortical/subcortical gray matter lesions (C/SC GM), nonspecific and normal findings. Results Of 114 children with US CP (77 boys and 37 girls), 56 were with right-sided and 58 with left-sided involvement. MACS I was found in 49 (42.9%), MACS II in 19 (16.7%), MACS III in 19 (16.7 %), MACS IV in 9 (7.9%) and MACS V in 18 (15.8%) children (p=0.002). Computed tomography (CT) as the only neuroimaging has been done in 18 (15.8%), magnetic resonance imaging (MRI) at 94 (82.5%) children, whereas 2 (1.7%) children had neither CT nor MRI. The CT showed PV WM in eight (44.4%), C/SC GM lesions in 6 (33.3%), and normal findings in 4 (22.2%) children (p=0.709). The MRI showed MAL in 8 ( 8.5%), PV WM in 46 (48.9%), C/SC GM in 28 (29.8%), miscellaneous in 2 (2.1%), and normal finding in 10 (10.7%) children (p=0.0001). Mild hand dysfunction (MACS I and II) was assessed in 68 (59.7%) children, of which 33 had PV WM lesions (p=0.001). Conclusion Mild hand dysfunction in children with US CP has been significantly associated with PV WM lesions. The type of brain lesion may help to identify its timing and predict the level of hand dysfunction.

Effects of Carbamazepine and Valproate on Serum Aspartate Aminotransferase, Alanine Aminotransferase and Gamma - Glutamyltransferase in Children.

INTRODUCTION: Epilepsy is one of the most common neurological diseases in childhood and adolescence. Carbamazepine (CBZ) and valproate (VPA) have been widely used as the first generation of antiepileptic drugs (AED). AIM: The aim of the study has been to evaluate and compare the effect of CBZ and VPA monotherapy on aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) serum levels in children. MATERIAL AND METHODS: The study has included 100 patients (boys 57/girls 43, age range 1 to 18 years), who have been treated with CBZ or VPA, as initial monotherapy, for at least 12 months. Patients with liver lesions or patients who have been treated with other drugs have been excluded from the study. The initial serum enzyme levels (AST, ALT and GGT) and after 12 months of treatment have been compared. RESULTS: 53/100 (53%) patients have been treated with CBZ and 47/100 (47%) patients have been treated with VPA.The initial level of enzymes were within the referece range. After one year-long treatment AST was elevated at 4/53 (7.5%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =3.965, p<0.05). ALT was elevated at 5/53 (9.4%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =6.953, p<0.05). GGT was elevated at 18/53 (34%) CBZ patients and 7/47 (14.9%) VPA patients (x2 test =4.831, p<0.05). CONCLUSION: The levels of enzymes AST and ALT have been elevated statistically significant in VPA group and GGT in CBZ group.

Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.

INTRODUCTION: Unilateral spastic cerebral palsy (US CP) is the second most common subtype of cerebral palsy. AIM: The aim of the study was to analyze neuroimaging findings in children with unilateral spastic cerebral palsy. MATERIAL AND METHODS: The study was hospital based, which has included 106 patients with US CP (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified into 5 groups: Brain maldevelopment, predominant white matter injury, predominant gray matter injury, non specific findings and normal neuroimaging findings. RESULTS: Predominant white matter lesions where the most frequent (48/106,45.28%; term 35/preterm 13), without statistically significant difference between term and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically significant difference between term and preterm born children (x2=0.902; p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were term born. Other finding had 2/106 children, 1.89%, both of them were term born. Normal neuroimaging findings were present in14/106 patients (13.21%). CONCLUSION: Neuroimaging may help to understand morphological background of motor impairment in children with US CP. Periventricular white matter lesions were the most frequent, then gray matter lesions.

Predictors of Mortality in Neonates with Seizures; a Prospective Cohort Study.

OBJECTIVE: The aim of this study was to analyze prognostic indicators for mortality in neonates with seizures in a level III Neonatal Intensive Care Unit (NICU). PATIENTS AND METHODS: A cohort of 100 neonates with clinically manifested seizures hospitalized in the NICU during 4 years period was prospectively monitored for the first year of life. The cohort consisted of 33 preterm and 67 full-term babies with 60 male and 40 female infants. RESULTS: The mortality rate in the first year of life of infants with seizures in the neonatal period was 23%. The most common cause of seizures was birth asphyxia for full-term infants and intra-periventricular hemorrhage for preterm infants. Death was more common in pre-term than term infants (p <0,005). Simple regression demonstrated statistically significant associations between death in the first year of life and a cluster of highly associated variables: resuscitation (p<0, 01), mechanical ventilation (p<0,01) and asphyxia (p<0,05). This cluster of variables significantly correlates with: gestational age (p<0, 05), birth weight (p<0, 05) and intracranial hemorrhage (p<0, 05). CONCLUSION: In this cohort of neonates with seizures asphyxia requiring neonatal resuscitation was the primary risk factor for death.

Neurodevelopmental Follow Up After Therapeutic Hypothermia for Perinatal Asphyxia.

INTRODUCTION: Neuroprotective benefit of therapeutic hypothermia in term newborns with hypoxic-ischemic encephalopathy (HIE) was assessed by analyzing survival and neurodevelopmental outcome of neonates subjected to this procedure. MATERIAL AND METHODS: Newborns with gestational age > 36 weeks and < 6 hours of age with moderate to severe asphyxial encephalopathy underwent cooling protocol at a temperature of 33.5 °C for 72 hours and rewarming period of 6 hours. Outcome measures assessed were death and neurodevelopmental characteristics, which were compared at the different age using ASQ-3. Twenty-five children were assessed at age 3-6, 12-18 and 24-36 months. Median gestational age was 40 weeks, birth weight 3470 g, Apgar score 2/4 and pH on admission to the hospital 7.02. Four (16%) children died. RESULTS: At the first assessment developmental categories of communication were normal in 78.9%, problem solving in 63.2%, personal-social in 68.4%, gross motor in 68.4%, and fine motor in 42.1% with a high need of retesting in this area. Second assessment was done in 17 patients: developmental categories of communication normal in 58.8%, problem solving in 70.6%, personal-social in 64.7%, gross motor in 64.7%, and fine motor in 35.3%. Third evaluation was done in 14 patients: developmental categories of communication were normal in 64.3%, problem solving in 71.4%, personal-social in 57.1%, gross motor in 64.3%, and fine motor in 42.9%. CONCLUSION: There was no correlation between baseline parameters and outcome. Results of the study are showing that therapeutic hypothermia in term newborns can provide better survival and less neurologic sequels in HIE patients.

Interictal Electroencephalography (EEG) Findings in Children with Epilepsy and Bilateral Brain Lesions on Magnetic Resonance Imaging (MRI).

INTRODUCTION: Neuroimaging procedures and electroencephalography (EEG) are basic parts of investigation of patients with epilepsies. AIM: The aim is to try to assess relationship between bilaterally localized brain lesions found in routine management of children with newly diagnosed epilepsy and their interictal EEG findings. PATIENTS AND METHODS: Total amount of 68 patients filled criteria for inclusion in the study that was performed at Neuropediatrics Department, Pediatric Hospital, University Clinical Center Sarajevo, or its outpatient clinic. There were 33 girls (48,5%) and 35 boys (51,5%). Average age at diagnosis of epilepsy was 3,5 years. RESULTS: Both neurological and neuropsychological examination in the moment of making diagnosis of epilepsy was normal in 27 (39,7%) patients, and showed some kind of delay or other neurological finding in 41 (60,3%). Brain MRI showed lesions that can be related to antenatal or perinatal events in most of the patients (ventricular dilation in 30,9%, delayed myelination and post-hypoxic changes in 27,9%). More than half of patients (55,9%) showed bilateral interictal epileptiform discharges on their EEGs, and further 14,7% had other kinds of bilateral abnormalities. Frequency of bilateral epileptic discharges showed statistically significant predominance on level of p<0,05. Cross tabulation between specific types of bilateral brain MRI lesions and EEG finding did not reveal significant type of EEG for assessed brain lesions. CONCLUSION: We conclude that there exists relationship between bilaterally localized brain MRI lesions and interictal bilateral epileptiform or nonspecific EEG findings in children with newly diagnosed epilepsies. These data are suggesting that in cases when they do not correlate there is a need for further investigation of seizure etiology.

Outcome of patients with infantile spasms.

PURPOSE: To assess outcome of children diagnosed with infantile spasms (IS) during the six-year-period (2002-20006), at the Pediatric Clinic of Clinical Center of University of Sarajevo, as well as to present other important clinical characteristics in this group of patients. METHODS: All patients had medical histories with detailed description orvideo recordings of their seizures, as well as profound neurological exam, series of video-EEG registrations, neuroimaging studies and laboratory studies that were possible to perform. RESULTS: Total of 19 patients with IS were treated (14 male, 5 female). Etiologically symptomatic IS were present in 78.9% of cases, cryptogenic in 21.1%. Flexor and mixed spasms were the most common (47.4% and 31.6% respectively). Therapeutic response was satisfactory: 42.1% of patients were seizure-free, 47.4% had partial response with more than 50% decrease of seizures, 10.5% had poor therapeutic response. Most of the patients were treated with polytherapy. The follow-up period was 15-70 months (mean 42.5 months). At last check-up four patients had normal development and were without seizures, two were lost to follow-up, two patients have died (21.4%, 10.5% and 10.5% respectively). Out of remaining patients seven (36.8% of total) had a severe psychomotor retardation with spastic tetraparesis, while the rest had hemiparesis and developmental difficulties. DISCUSSION: Treatment of infantile spasms presents a great challenge, especially in the developing countries like Bosnia and Herzegovina in which the treatment modalities are limited. Our results indicate that despite the lack of the proper treatment options, outcome of the patients regarding control of seizures and latter psychomotor development did not differ significantly from the reports from the other countries. CONCLUSION: Although prognosis for most patients with infantile spasms remains poor, further studies identifying predictors of favorable prognosis and recent advances in understanding the pathophysiology of infantile spasms offer hope of safer and more-effective therapies that improve long-term outcome.

Use of lamotrigine in medically intractable epilepsies in children.

Medically intractable epilepsies are defined as seizures that are not controlled after an adequate trial with 2 first-line antiepileptic drugs (AED). Evidence in the literature show that these patients have many dysfunctions in their lifes. Lamotrigine is part of group of "newer antiepileptic drugs". Goal of this paper was to show what benefit is expected with introduction of add-on therapy with lamotrigine in patients with medically intractable epilepsies. Study was done in period 2002-2007 at Paediatric Hospital in Sarajevo. Inclusion criteria were: established diagnose of epilepsy, medical intractability defined as seizures not controlled after an adequate trial with 2 first-line antiepileptic drugs, age of more than 2 years and less than 18 years. Total of 61 children were assessed, 35 male and 26 female. Average age was 61.3 months at diagnosis of epilepsy. Add-on therapy with lamotrigine started in average about sixteen months after the diagnosis, with average age at starting the therapy of 77.4 months. Predominant type of seizures were partial seizures (with or without secondary generalization) in 67.20% cases, primarily generalized tonic clonic seizures in 13.11% cases, typical and atypical absences in 11.48% cases and myoclonic seizures in 8.20% cases. Reduction in seizure frequency was very good (76-100% reduction) in 37.70% of patients, good (51-75%) in 21.31%, fair (26-50%) in 9.84 and poor (less than 25%) in 31.14%. Chances of poor outcome were greater in patients with partial seizures. Side effects were noticed in 8.2% patients (6,56% with skin rash). Lamotrigine has showed good efficacy and safety profile. It is providing new efficient and well tolerated options for treatment for medically intractable epilepsies.

Congenital malformations of the central nervous system: clinical approach.

Central nervous system (CNS) malformations represent important factor of morbidity and mortality in children. The aim of the study was to determine the incidence, type and clinical features of CNS malformations in children who were admitted at the Neonatal and Child Neurology Department, Neonatal Intensive Care Unit and Paediatric Intensive Care Unit of Paediatric Clinic, University of Sarajevo Clinics Centre, from January 1st, 2002 to December 31st, 2006. There were total of 16520 admissions at the Paediatric Clinic over the studied period. CNS malformations, solitary or multiple, have been diagnosed in 100 patients (0,61%). The total number of various CNS malformations was 127. Lethal outcome was established in 9/100 cases (9%). The most frequent CNS malformations were neural tube defects 49/127 (38,6%). Hydrocephalus was seen in 34/127 (26,8%), microcephaly in 24/127 (18,9%), agenesis of corpus callosum in 10/127 (7,9%), Dandy Walker malformation in 6/127 (4,7%) and other CNS malformations in 4/127 (3,1%). In 20/100 of patients neural tube defect was associated with hydrocephalus (20%). CNS malformations were prenatally diagnosed in 13/100 of patients (13%). Primary prevention of CNS malformations can be improved in our country by better implementation of preconceptional folic acid therapy for all women of childbearing age. Secondary prevention by prenatal diagnosis requires advanced technical equipment and adequate education of physicians in the field of foetal ultrasonography. In our circumstances, prenatal diagnostics of CNS malformations is still not developed enough.

Familiar spastic paraplegia presenting in a boy with Klinefelter syndrome--case report.

In this case report, the boy with familiar spastic paraplegia, the relatively rare genetic disorder and Klinefelter syndrome that was found during investigation, has been presented. The diagnosis of the disease has been established by anamnesis, clinical features and relevant diagnostic procedures, so the criteria for autosomal dominant type of the familiar spastic paraplegia have been fulfilled. The therapeutic possibilities are limited to the physical therapy and orthopedic treatment of feet deformities.

Posttraumatic seizures - prevention or not.

Early posttraumatic epilepsies (EPTE) are epileptic attacks that appear in first seven days after brain injury, with incidence of 3-5%. Predictors for development of EPTE are: impressive skull fracture with rupture of dura, intracranial haemorrhage, neurogical deficit (brain contusion), and posttraumatic amnesia longer than 24 hours. It is more common in children than in adolescents and adults. It carries four times increased risk for development of late posttraumatic epilepsy. Aspects of pharmacological prophylaxis was often considered, but scientifically neglected, without clear standings regarding controversial data in literature. Patients with severe head injury, hospitalised at Neurosurgical Hospital and Pediatric Hospital, Clinical Centre University of Sarajevo, in period from 6th of April 1992 till 1st of July 1994, were included in study. Prophylaxis of EPTE was carried out with phenobarbital (2-3 mg/kg) or phenytoin (3 mg/kg) parenterally. Decision was made upon clinical findings. CT scan was done in 13.5% patients, and in 31.9% patients serum concentrations of antiepileptic drugs were monitored. 310 patients aged 0-18 years (105 patients 0-10 years, and 205 patients 11-18 years) were investigated. Predictors of EPTE presented were posttraumatic amnesia longer than 24 hours in 90.6%, neurogical deficit in 86.45%, impressive skull fracture with rupture of dura in 81.3% and intracranial haemorrhage in 40.6%. Only two boys developed EPTE in first 24 hours after injury. This study has showed that use of antiepileptic drugs can decrease incidence of EPTE. However, problem remains, management of injured patients is still highly individualised, based on different experiences of doctors that treat patient, and without clear guidelines.

[Detection and treatment of intracranial hemorrhage at the intensive care unit of the Pediatric Clinic in Sarajevo]. / Otkrivanje i lijecenje intrakranijalne hemoragije na odjelu intenzivne njege djecje klinike u Sarajevu.

Intracranial haemorrhage (ICH) is the common name for periventricular and intraventricular haemorrhage. We analyzed patients diagnosed as ICH in period January 2001 till May 2002. In 29/323 (8.9%) pts was verified ICH, 16/29 (55.1%) were male sex. Birth weight under 1000 grams had 6/29 (20.6%), birth weight 1000-1499 grams was 10/29 (34.4%), than 1500 to 2499 grams 8/29 (27.5%) and over 2500 grams 5/29 (17.2%). APGAR score were under 7 in 20/29 (68.9%), and four of tham 4/20 (20%) had severe and 16/20 (80%) pts had modest and mild forms of perinatal asphyxia. According to Papile classification of ICH, we found: I degree ICH had 12.29 (41.3%) pts, II degree 8/29 (27.5%) pts, while severe forms III and IV degree of of ICH had 9/29 (31.2%) pts. In 3/29 (10.4%) pts, posthemoragic hydrocephalus were registrated. Risk-factors for development of ICH were low birth weight, small gestational age and perinatal asphyxia.

[The Patau syndrome]. / Patau sindrom.

Known as D trisomy, Patau syndrome is the third chromosomopathy according to frequency. One of the 5000 newborn carries the trisomy 13. In over 80% cases there is fresh mutation with non separation in myeosis of older mother. The mosaic or translocation forms are not rare. The mail newborn with Patau syndrome is shown in this article. We notice: microcephalia, dolihocephalia, microphthalmia, cheilognatopalatoshisis, polydactilia, and found ultrasound changes at the brain, hearth and genitourinary system. Cytogenetic finding show: mail cariotype with aberrations 47, XY + 13, Sy Patau.