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.

Plasmapheresis in Pediatric Intensive Care Unit.

INTRODUCTION: Plasmapheresis also known as a therapeutic plasma exchange (TPE) is extracorporeal procedure by which individual components of plasma that are harmful or blood cells can be removed from organism by using a blood separation technology. AIM: To present the results of the implementation of plasmapheresis in children in the Department of Pediatric Intensive Care of Pediatric Clinic, Clinical center of Sarajevo University, Bosnia and Herzegovina. PATIENTS AND METHODS: Research (period from December 2011 to June 2016) analyzed 66 plasmapheresis (11 patients-6 plasmapheresis per patient). RESULTS: Out of 11 patients, 7 (63.6%) were girls and 4 (36.4%) were boys. The average age of patients was 11.6 ± 3.9 years (the youngest patient had 4 years and 7 months, while the oldest had 16 years and 10 months). Plasmapheresis were significantly more often done in the winter and summer. Underlying disease was in 54.5% of cases of neurological origin. The treatment was in form of receiving IVIG in 7 patients, or the application of mechanical ventilation in 6 patients. The most common complication was hypotension, which occurred in 45.5% of patients, followed by bleeding in 36.3%, hypercoagulability in 27.2% of patients and hematoma in 27.2% of patients. Lethal outcome occurred in 3 (27.2%) patients. CONCLUSION: Plasmapheresis represents an invasive method due to need for placement of centralized venous catheter that provides adequate blood flow during the procedure. Although complications can be serious, they are rare and are mainly related to the presence of central venous catheter, hemostasis disorders due to use of anticoagulant therapy, and hypotension of the cardiovascular system. It should be noted that for success of plasmapheresis in children multidisciplinary approach is necessary (children's nephrologist, neuropediatrician, intensive care doctor) as well as well-trained team of doctors and nurses with the acquired knowledge and skills.

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.

Usefulness of laboratory data in estimation of Crohn's disease activity.

Crohn's disease (CD) is a chronic inflammatory disease characterized by unpredictable and severe course. Most clinicians use simple laboratory parameters of inflammatory activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the number of leukocytes (Le) and platelet count to assess disease activity. The aim of this paper was to determine the value of various laboratory parameters in the assessment of Crohn's disease activity. The study included 36 patients, 15 men and 21 women, treated for Crohn's disease at the Gastroenterohepatology Clinic, Clinical Centre, University of Sarajevo, in period 2006 and 2007. Assessed patients were divided into three groups, according to the degree of disease activity, which was determined using the Crohn's Disease Activity Index (CDAI). Mild disease (MD) was present in 15, moderately severe disease (MSD) in 14, and severe disease (SD) in 7 patients. Statistical significance of association between values of laboratory parameters with the degree of severity of illness was investigated using the 95% Confidence Interval test. CRP showed a statistical significance for the relationship between MD-MSD (95% CI 6,645-74,333) and the relationship between MD-SD (95% CI 4,114-135,278), while the relationship between MSD-SD was not statistically significant. MPV showed statistical significance only for the relationship between MD-MSD (95% CI 0,060-2,909). Sedimentation rate and the number of red blood cells showed statistical significance for the relationship MD-SD (95% CI 10,638-62,943 and 0,077-1,080). Haemoglobin, hematocrit and platelet count showed statistical significance for the relationship between MD-MSD and MD-SD. Number of leukocytes did not show any statistically significant relationship with clinical activity of disease. The most reliable indicators of activity of Crohn's disease in this study were CRP, MPV, haemoglobin, hematocrit and platelet count, while leukocyte number did not correlate with disease activity. Neither parameter was sensitive enough to distinguish the relationship between moderately severe disease and severe disease. Until finding a "gold standard" for assessment of clinical disease activity, various laboratory and other parameters must be combined and compared with other indicators, such as endoscopic findings and radiological results.

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.

[Infant walkers: the prevalence of use]. / Upotreba hodalica kod dojencadi.

UNLABELLED: Infant walkers are mobile wheeled seats that allow infants to move around with their feet on the floor. They enable precocious locomotion in very young, otherwise prelocomotor infants. Prelocomotor walker experience prevents visual access to the moving limbs. Infant walker use can be associated with delay in achievement of normal locomotor milestones. Besides delayed motor development, contractures of the calf muscles and motor development mimicking spastic diparesis may appear. In the case of infant walker's use for the infants at risk for development of cerebral palsy, multiple side effects can be produced: the persistence of positive support reflex, heel cord contractures, subluxation and dislocation of the hips or pronation contractures of the upper extremities. The use of infant walkers increases the risk of injuries. The study has enrolled 150 children and their mothers, from three big cities in Bosnia and Herzegovina (Sarajevo, Bihac, Zenica). All relevant data have been collected through the questionnaires. 130 children (86.6%) have used infant walkers. The mean age when the use of infant walker has started was 7 months. The mean time of daily use of infant walker was 1 hour 49 minutes. Twenty three children had various motor disturbances, 13 out of them (56.5%) have used infant walker. The mild injuries caused by using the infant walkers have been registered in 17 cases (11.3%). 83 mothers (55.3%) were aware of infant walker's nocuous effects. CONCLUSION: The use of infant walkers has been spread widely under our circumstances. There is significant discrepancy between mothers' knowledge about nocuous effects of infant walkers and their practice. The use of infant walkers for infants with motor disturbances is especially harmful. The main reason for using infant walker, despite of its harmfulness, was mother's preoccupation with everyday household activities. It is necessary to engage health professionals to support antiwalker campaign (warning labels on the infant walkers, public education programs, etc). We recommend safer alternatives for child daycare, like stationary activity centers (so called "fenced play gardens".

[Medical data warehousing as a generator of system component for decision support in health care]. / Skladistenje medicinskih podataka kao generator komponenti sistema za podrsku odlucivanju u zdravstvenoj zatiti.

Growth in role of data warehousing as strategic information for decision makers is significant. Many health institutions have data warehouse implementations in process of development or even in production. This article was made with intention to improve general understanding of data warehousing requirements form the point of view of end-users, and information system as well. For that reason, in this document advantages and arguments for implementation, techniques and methods of data warehousing, data warehouse foundation and exploration of information as final product of data warehousing process have been described.

[The value of hospital data bases in the quality of patient care]. / Vrijednost bolnickih baza podataka u vodenju pacijenta i njihov kvalitet.

Massive gathering of clinical records started quite soon, at the turn of the last century, about 100 years ago. In that period keeping and gathering of medical records gradually evolved from paper medical records to computer-based medical records. Software that we use for this is quite different. We are witnessing tendency that each medical institution is creating software solely for their use, that leads to difference of gathered medical data and their validity for further analysis. In this paper we tested value of gathering and processing medical records through a hospital software, regarding time consumption in everyday work, as well as value of gathered and processed data. Statistically significant difference was found in terms of time needed for complete gathering and processing of medical data of hospitalized patients, as well as most of its segments (administering of admission, forming a medical history, forming a discharge letter). No statistically significant differences were found in terms of value of gathered and processed data in the forms of electronical records, compared to those formed on "traditional" basis. We conclude that the future of gathering, forming and processing of medical documentation of hospitalized patients is solely through interactive computer databases, and that their everyday spreading through all systems and levels of health care is absolutely necessary. Only that way we shall be able to fully use possibilities that such interactive system offers in improving management of patients.

[Ultrasound differentiation between benign enlargement of the subarachnoid space and brain atrophy]. / Ultrazvucna diferencijacija benignog prosirenja subarahnoidalnog prostora i atrofije mozga.

Fluid collections surrounding the brain (pericerebral fluid collections) in infants can be caused by a variety of conditions: benign enlargement of the subarachnoid space, passive dilatation of the subarachnoid space due to brain atrophy, subdural hygroma and subdural effusion as a result of meningitis or subdural haematoma. An enlarged frontal subarachnoid space and normal or minimally enlarged ventricular size, with normal or increase head circumference is relatively common finding in infancy. Without associated brain anomalies, this finding predicts normal development of the child. In our study, we have followed up psychomotor development of 22 children, with increased diameters of subarachnoid spaces, detected by ultrasound examination of the brain, without associated brain anomalies. The inclusion criterion for study was enlarged subarachnoid space, measured at the conventional coronal section at the level of the interventricular foramen. The upper limits of each measurements were: 3 mm for sinocortical width, 4 mm for craniocortical width and 6 mm for the interhespheric width. The patients have been followed up to the age of 24 months. Each of them had normal development. 16 of them had normal head circumference. 6 of them had head circumference above the 97th percentile and their head circumference measurements have been plotted for the next 6 months after the diagnosis, to be certain that growth is paralleling the normal curve. It is important to differ benign enlargement of subarachnoid space from brain atrophy, which is quite "serious" diagnosis, with poor neurodevelopmental prognosis. The brain atrophy has been presented with passive dilatation of subarachnoid space and ventriculomegaly, as well. In the case of benign enlargement of subarachnoid space normal or minimally enlarged ventricular size is present. For proper interpretation of this ultrasound finding, correlation with head circumference is necessary. We recommend the head circumference percentile chart to be enclosed to the each brain sonography finding. The algorithm of the further neurological evaluation differs significantly in the case of benign enlargement of subarachnoid space and brain atrophy. In the case of benign enlargement of subarachnoid space further neuroimaging procedures are not needed (in our study it has been done for 6 patients). If the brain atrophy is suspected, further complete neurological examination is necessary.

[Efficacy and tolerability of carbamazepine as the initial drug used in the treatment of epilepsy]. / Efikasnost i podnosljivost carbamazepina kao primarno uvedenog lijeka u tretmanu epilepsija.

Carbamazepine is the one of the most prescribed antiepileptic drugs in treatment of partial and generalized tonic-clonic seizures. Its efficacy in treatment of seizures was discovered incidentally during the trials of neuroleptic drugs. Generally it is well tolerated with relatively rare serious side effects. Therapy is introduced gradually, with mean dose between 10-20 mg/kg, and given this way it has the least side effects. Aim of the study was to assess interaction between efficacy, tolerability and overall efficacy of the first prescribed drug, in this case carbamazepine, in the group of patients with partial seizures and generalized tonic-clonic seizures. Patients hospitalized at University Pediatric Hospital in Sarajevo with newly diagnosed epilepsy and started therapy with carbamazepine in period from 07.1999 to 07.2002 were investigated. There were 89 patients that fulfilled the criteria. In 29 patients seizures remitted after the introduction of therapy (32.58%). After the subsequent correction of therapy further 8 patients were seizure free. In total, drug was efficient as a monotherapy in 68 patients (76.40%). Other antiepileptic drugs or polytherapy with carbamazepine were tried in the patients that were not seizure free. Adverse effects were reported in 28 patients (31.46%). The most frequent was benign leucopoenia (16 patients, 17.97%) that did not require changes in therapy. Rash was found in 8 patients (8.98%), out of which in 6 therapy had to be stopped. Compliance with therapeutic regime was slightly better with controlled release formulation (89.98%) then with simplex formulation (77.52%), but generally was good. We think that carbamazepine is still the drug of the first choice in treatment of patients with partial epileptic seizures and generalized tonic-clonic seizures. It showed good overall efficacy with relatively rare serious side effects.