Clinical Characteristics of Patients with Acute Ischemic Stroke Previously Vaccinated Against COVID-19.

OBJECTIVES: The aim of this study was to examine the clinical characteristics of patients with acute ischemic stroke which were previously vaccinated against Coronavirus Disease 2019 (COVID-19) and determine whether the vaccine had impact on outcome. MATERIALS AND METHODS: In this observational cohort study we analyzed the clinical characteristics of 58 patients with ischemic stroke, previously vaccinated against COVID-19. We analyzed demographic characteristics, risk factors, type of stroke and outcome. We also compared outcome of those patients with outcome in stroke patients hospitalized in the same period but not vaccinated, patients hospitalized during the pandemic, before vaccination began, and stroke patients hospitalized before the pandemic. Further, we compared mortality rate with mortality rate in patients who had acute ischemic stroke and COVID-19 simultaneously. RESULTS: The mean age of the patients was 71.0 years, most were male (58.6%), mostly with risk factors for stroke. In the largest number of patients, 17 (29.3%), the etiopathogenetic mechanism of stroke was atherosclerosis of the large arteries. Mortality in vaccinated patients was identical to mortality in stroke patients before pandemic, without significant difference from mortality in unvaccinated patients (13.8% versus 8.6%; p= 0.23). The mean NIHSS and mRS score at discharge for all examined groups were without significant difference. A significant difference in mortality was found between COVID-19 positive and COVID-19 negative stroke patients (37.8% versus 18.1%; p=0.001). CONCLUSIONS: There are no significant differences in clinical characteristics of stroke in vaccinated compared to unvaccinated patients. We did not find a connection between vaccination and stroke.

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

RATIONALE: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. AIMS: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. METHODS AND DESIGN: This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. SUMMARY: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.

Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis.

INTRODUCTION: Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. MATERIALS AND METHODS: In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. RESULTS: Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P = .002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P = .01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P = .002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. CONCLUSION: Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.

Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene.

BACKGROUND/AIM: Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha motor neurons in the spinal cord and the medulla oblongata, causing progressive muscle weakness and atrophy. The aim of this study was to determine association between the SMN2 gene copy number and disease phenotype in Serbian patients with SMA with homozygous deletion of exon 7 of the SMN1 gene. METHODS: The patients were identified using regional Serbian hospital databases. Investigated clinical characteristics of the disease were: patients' gender, age at disease onset, achieved and current developmental milestones, disease duration, current age, and the presence of the spinal deformities and joint contractures. The number of SMN1 and SMN2 gene copies was determined using real-time polymerase chain reaction (PCR). RESULTS. Among 43 identified patients, 37 (86.0%) showed homozygous deletion of SMN1 exon 7. One (2.7%) of 37 patients had SMA type I with 3 SMN2 'copies, 11 (29.7%) patients had SMA type II with 3.1 +/- 0.7 copies, 17 (45.9%) patients had SMA type III with 3.7 +/- 0.9 copies, while 8 (21.6%) patients had SMA type IV with 4.2 +/- 0.9 copies. There was a progressive increase in the SMN2 gene copy number from type II towards type IV (p < 0.05). A higher SMN2 gene copy number was associated with better current motor performance (p < 0.05). CONCLUSION: In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected.

A CASE OF PROBABLE NEUROSARCOIDOSIS PRESENTING AS UNILATERAL OPHTHALMOPLEGIA.

Sarcoidosis is a multisystem disease of unknown etiology, characterized by the presence of noncaseating epithelioid granulomas and accumulation of T lymphocytes and mononuclear phagocytes, which damages the normal structure of tissues. Isolated form of neurosarcoidosis is very rare and difficult to diagnose and requires histologic confirmation of noncaseating granulomas in the nervous tissue. We report a case of a 55-year-old female who had probable isolated neurosarcoidosis based on magnetic resonance imaging findings of relapsing pachymeningitis with an inflammatory process in the apex of the right orbit and pseudotumor inflammation of the superior and lateral recti of the right eye. Diagnosis was further verified by positive response to dual corticosteroid and immunosuppressive therapy. Our case demonstrates the importance of considering isolated neurosarcoidosis as a potential underlying etiology of painful ophthalmoplegia, even without systemic manifestation of the disease.

Reticulated platelets and antiplatelet therapy response in diabetic patients.

Increased platelet turnover and high level of reticulated platelets are associated with low response to antiplatelet therapy in diabetes mellitus type 2. This study evaluated association between percentage of reticulated platelets (%RP) and the response to antiplatelet therapy in patients with type 2 diabetes mellitus (T2DM). This prospective, pilot, case-control, clinical trial included 79 subjects stratified in three groups: group I included 30 patients with T2DM, group II included 34 non-diabetic patients and 15 healthy age and sex matched healthy volunteers were enrolled in control group. Platelet response to clopidogrel and aspirin was assessed by Multiplate(®) aggregometry analyzer. Individual response to dual antiplatelet therapy was estimated by the percentage of decrease in overall platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated by presented formulas: %DPAadp = 100 × (1 - ADP/TRAP) and %DPAaspi = 100 × (1 - ASPI/TRAP). %RP was significantly higher in diabetics, than in non-diabetics, (3.17 ± 1.26 vs. 2.39 ± 1.56; p < 0.05). Significantly lower response to clopidogrel (31.55 ± 13.02 vs. 50.24 ± 11.38; p < 0.001) and aspirin (52.33 ± 22.67 vs. 64.31 ± 16.47; p < 0.05) therapy was observed in diabetics. %RP negatively correlated with response to clopidogrel therapy, but positively with metabolic profile indicators in diabetics (p < 0.05, all). Correlation of %RP with metabolic profile indicators and poor response to antiplatelet therapy suggest that altered metabolic profile can affect platelet turnover in T2DM leading to low responsiveness to antiplatelet therapy in these patients.

The effect of post stroke depression on functional outcome and quality of life.

In spite of being a common and important complication of stroke, post stroke depression is often overlooked, so its impact on stroke outcome remains under recognized. The aim of the study was to determine the effect of depression on functional outcome and quality of life in stroke patients. The study included 60 patients treated for their first clinical stroke, 30 of them diagnosed with depression and 30 patients without depression. Testing was done in all patients two and six weeks after stroke. Depression was diagnosed according to the Mini International Neuropsychiatry Interview, DSM-IV diagnostic criteria, and depression severity was quantified by the Hamilton Depression Rating Scale; functional impairment was determined by the Barthel Index; and post stroke quality of life was assessed by the Short Form 36 (SF-36) questionnaires. The patients with depression had significantly more severe functional disability both at baseline and after rehabilitation treatment, although the potential for functional recovery in depressed patients was less than in non-depressed ones. The quality of life in patients with post stroke depression was impaired more severely in all SF-36 domains compared with non-depressed stroke patients, with the domains of the role of emotional functioning and social relations being most severely affected.

Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal carotid artery - a Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS).

OBJECTIVE: The benefit of intravenous thrombolysis in patients with internal carotid artery (ICA) occlusion is still unclear. The aim of this study was to assess the influence on outcome of intravenous thrombolysis in patients with ICA occlusion comparing to those without it. METHODS: Data were from the national register of all acute ischemic stroke patients treated with intravenous thrombolysis in Serbia. Patients with nonlacunar anterior circulation infarction were included and were divided into two groups, those with and those without ICA occlusion. We compared the differences in demographic characteristics, risk factors, baseline NIHSS score, early neurological improvement, 3-month functional outcome, complications and death between these two groups. RESULTS: Among 521 included patients there were 13.4% with ICA occlusion. Group with ICA occlusion had more males (82.9% vs. 60.5%; p=0.0008), and more severe stroke (baseline NIHSS score 15.3 vs. 13.6; p=0.004). Excellent functional outcome (mRS 0-1) at 3 months was recorded in 32.9% patients with ICA occlusion and in 50.6% patients without (p=0.009), while favorable functional outcome (mRS 0-2) was recorded in 50.0% of patients with ICA occlusion vs. 60.1% without (p=0.14). Death occurred in 12.9% patients with ICA occlusion and in 17.3% patients without it (p=0.40). There was no significant difference in rate of symptomatic ICH between the two groups (1.4% vs. 4.2%; p=0.5). Multivariate logistic regression analysis showed that ICA occlusion was associated with the absence of early neurological improvement (p=0.03; OR 1.78, 95% CI 1.05-3.04). However, the presence of ICA occlusion was not significantly associated with an unfavorable outcome at 3-month (p=0.44; OR 1.24, 95% CI 0.72-2.16) or with death (p=0.18; OR 0.57, 95% CI 0.25-1.29). CONCLUSION: The patients with ICA occlusion treated with intravenous thrombolysis have a worse outcome than patients without it.

New therapeutic potentials of milk thistle (Silybum marianum).

Silymarin is a bioflavonoid complex extract derived from dry seeds of Milk thistle [(Silybum marianum(L.) Gaemrnt. (Fam. Asteraceae/Compositaceae)] whose hepatoprotective effect has clinically been proved. Low toxicity, favorable pharmacokinetics, powerful antioxidant, detoxifying, preventive, protective and regenerative effects and side effects similar to placebo make silymarin extremely attractive and safe for therapeutic use. The medicinal properties of silymarin and its main component silibinin have been studied in the treatment of Alzheimer's disease, Parkinson's disease, sepsis, burns, osteoporosis, diabetes, cholestasis and hypercholesterolemia. Owing to its apoptotic effect, without cytotoxic effects, silymarin possesses potential applications in the treatment of various cancers. Silymarin is being examined as a neuro-, nephro- and cardio-protective in the damage of different etiologies due to its strong antioxidant potentials. Furthermore, it has fetoprotective (against the influence of alcohol) and prolactin effects and is safe to be used during pregnancy and lactation. Finally, the cosmetics industry is examining the antioxidant and UV-protective effects of silymarin. Further clinical studies and scientific evidence that silymarin and silibinin are effective in the therapy of various pathologies are indispensable in order to confirm their different flavonolignan pharmacological effects.

Significance of adequate postural control in the appearance of habitual upright bipedal locomotion.

Analysis of qualitative indicators of stability of the body during different types of locomotion in primates suggests that bipedal locomotion is not variation of some other type of locomotion. Transition from quadrupedal to bipedal locomotion is accompanied by a qualitative difference in body stability. Because of assuming an upright bipedal posture, the center of mass is lifted, the surface of the base of support is reduced, and the body structure does not provide passive stability in relation to inertial moments of the body around Y-axis. Additional head movements, trunk rotations, forelimb manipulations with objects and surveying the surroundings are necessary for survival, but they increase the degree of freedom of movement and further complicate the task of maintaining balance in the case of a postural change from erect quadrupedal to erect bipedal. This article presents a hypothesis that the transition from quadrupedal to habitual upright bipedal locomotion was caused by qualitative changes in the nervous system that allowed controlling the more demanding type of locomotion. The ability to control a more demanding posture increases possibilities of interactions between the organism and the complex environment and consequently increases the survival rate, breeding possibilities, and chances for occupying a new environmental niche. Existing data show that ability to execute the more demanding type of locomotion was made possible because of changes in the frontal lobe and pyramidal system. Only after the more demanding posture was enabled by changes in the nervous system, could advantages of bipedal over quadrupedal locomotion be utilized, including better scanning of the environment, carrying food and infants, simultaneous upper extremity movements and observation of the environment, limitless manipulation of objects with upper extremities above the individual, and less space for rotating around the Z-axis. The aforementioned advantages of habitual bipedal over quadrupedal locomotion are present in physically complex environments, such as the forest, which is associated with the appearance of habitual bipedal locomotion.

[Ischaemic stroke in children: diagnostic and therapeutic specificity].

INTRODUCTION: Although more common in older adults, stroke occurs in neonates, infants and children as well, resulting in significant morbidity and mortality. EPIDEMIOLOGY: The incidence of childhood ischemic stroke exceeds 3.3 in 100,000 children per year. Stroke is one of the top ten causes of death in children. RISK FACTORS: Children's strokes are often caused by birth defects, injections (e.g. meningitis, encephalitis), trauma, and blood disorders. Risk factors for stroke are recognized in more than 75% of children. The most common cause of stroke in children is probably congenital or acquired heart disease. CLINICAL PRESENTATION: Children often experience different symptoms of stroke to adults. These can include seizures, headache and fever. However, many of" the symptoms of stroke in children are similar to those experienced by adults (paralysis, speech and visual impairment). DIAGNOSTIC EVALUATIONS: Urgent neuroimaging is important for confirming the diagnosis of stroke. It is necessary for clinicians to conduct a thorough investigation for possible cardiac, vascular, and hematologic risk factors in all patients. THERAPY: The appropriate choices for in-hospital acute treatment and secondary preventative strategies, including aspirin and anticoagulants, are controversial. The recommendations for children are based mainly upon extrapolation from studies involving adults, and the clinical experience of experts, as reflected in consensus guidelines. CONCLUSION: Advanced forms of thrombolytic and neuroprotective agents may become more readily available to paediatric stroke patients when both the general public and medical staff become more aware of this disorder.

Fibrinolytic parameters, lipid status and lipoprotein(a) in ischemic stroke patients.

INTRODUCTION: Ischemic stroke is the third leading cause of mortality and morbidity in most countries in the world. Impaired fibrinolysis, as well as disordered lipid metabolism have been recognized as risk factors for this disease. OBJECTIVE: To study some of fibrinolytic parameters, lipid status and lipoprotein(a) - Lp(a) in ischemic stroke patients in Serbia and to examine associations between Lp(a) and fibrinolytic parameters. METHODS: Sixty ischemic stroke patients (case group, mean age 63.48 +/- 9.62 years) and 30 age and sex matched healthy controls (control group, mean age 60.2 +/- 7.96 years) were studied. RESULTS: A significantly longer euglobulin clot lysis time (219.7 +/- 78,8 min. vs 183.5 +/- 58,22 min; p = 0.005) and higher levels of plasminogen activator inhibitor-1 (PAI-1) (48.5 +/- 17.1 ng/ml vs 27.1 +/- 10.1 ng/ml; p = 6.2 x 10(-11)), tissue-type plasminogen activator antigen (t-PA) (11.1 +/- 7.14 ng/ml vs 6.0 +/- 3.66 ng/ml; p = 5.2 x 10(-5)) and D-dimer (382.27 +/- 504.22 ng/ml vs 116.12 +/- 88.81 ng/ml; p = 0.0002) were found in cases compared to controls. There were no significant differences in fibrinogen levels (4.30 +/- 0.84 g/l vs 4.09 +/- 0.64 g/l; p = 0.23) or plasminogen activity (92.67 +/- 11.37% vs 96.87 +/- 9.48%; p = 0.085). There was no significant difference in Lp(a) concentration between cases and controls (0.15 +/- 0.11 g/l vs 0.12 +/- 0.11 g/l; p = 0.261). However, in the cases, but not in the controls, multivariate analysis of associations between fibrinolytic parameters and Lp(a) showed the highest correlation between t-PA and PAI-1, and the latent effect of Lp(a) on t-PA and PAI-1. CONCLUSIONS: Our results show that there are important differences in the characteristics of the fibrinolytic mechanism in ischemic stroke patients compared to healthy population. The major differences are prolonged euglobulin clot lysis time and elevated PAI-1 and t-PA antigen in ischemic stroke patients. In addition, Lp(a) appears to be involved in the inhibition offibrinolysis in ischemic disease through a mechanism unrelated to its serum concentrations.

[Poststroke depression: diagnosis of depression, phenomenology and specificity of depressive symptoms].

THE DIAGNOSIS OF DEPRESSION: Depressive disorder is nowadays diagnosed by the two widely used diagnostic systems--International Classification of Diseases of the World Health Organisation, 10th revision and the Diagnostic and Statistical Manual Criteria of the American Psychiatric Organisation, 4th edition. The criteria for depressive disorder used in these two systems are almost identical. POSTSTROKE DEPRESSION: The dignosis of depression may be difficult to establish in stroke patients, especially in patients with aphasia/dysphasia, anosognosia and other cognitive dysfunction. Major vs. minor poststroke depression, specificity and sensitivity of depressive symptoms: The phenomenology of major poststroke depression has been found to be similar to that of primary depression, and it appears that minor and major are not stages of the same continuum, but rather separate entities. Contrary to common opinion, non specific somatic symptoms do not hinder the diagnosis of poststroke depression and can be highly discriminative and crucial in the evaluation of poststroke depression. VALIDITY OF THE POSTSTROKE DEPRESSION DIAGNOSIS: Studies have shown that a valid diagnosis of poststroke depression may be established successfully using structured or semistructured neuropsychiatric interviews, according to the current Diagnostic and Statistical Manual Criteria. CONCLUSION: It appears that no new diagnostic tools specific for major depression in stroke patients are necessary. The existing diagnostic procedures will fail to diagnose or misdiagnose depression only in few stroke patients.

Decreased expression of the righting reflex and locomotor movements in breech-presenting newborns in the first days of life.

AIM: To investigate differences between the infants born in occipital and breech presentation relative to the passive and active motility. METHOD: A prospective study was conducted in the period from 2006 to 2007 at the Department of Obstetrics and Gynecology in Novi Sad. Subjects were 50 breech-presenting and 87 occipital-presenting term newborns delivered by elective cesarean section following a regular course of pregnancy, without fetal, newborn, and the pregnant female disease. Outcome measures were popliteal angle; extension of the hip-joint; ventral flexion and dorsal extension in the axis; spontaneous displacement; crawling reflex; righting reaction in vertical and sitting positions; righting reaction in horizontal suspension, the automatic walking investigated on the second and fourth day of life. RESULTS: Except for righting reaction in horizontal suspension, the newborns from breech presentation had a significantly lower score for all investigated parameters of active movements at the first and second examination. There was no difference between occipital and breech-group relative to the ventral flexion and dorsal extension in the axis. The popliteal angle was significantly increased, whereas the extension in the hip joint was significantly decreased in the breech group. CONCLUSIONS: Investigations showed a significantly decreased expression of active movements in the breech group, which cannot be explained only by postural deformities.

[Influence of fibrinolitic potential reduction in ischemic brain disease development].

INTRODUCTION: Vascular brain disease are the third leading cause of morbidity and mortality today. Among them ischemic brain disease caused mostly by cerebral atherosclerosis makes almost 80%. The main risk factors for this disease are arterial hypertension, dislipoproteinemia and diabetes but, recently hemostatic system disorders have also been underlined, especially fibrinolytic disorders. PHYSIOLOGY OFFIBRINOLYSIS: The primary role of fibrinolytic system is to make blood vessels passable by prevention of thromb forming or by removing the existing ones. This role is enabled by constant dynamic balance between activators and inhibitors of fibrinolysis. The leading activators are tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) and the most important inhibitors are 2-antiplasmin, plasminogen activator inhibitor 1 (PAI-1) and thrombin activated fibrinolytic inhibitor (TAFI). FIBRINOLYSIS AND THROMBOSIS: In patients with atherosclerosis there is clear insufficiency of fibrinolysis caused mainly by the increased activity of fibrinolytic inhibitors. There is evidence that the level of PAI-1 connected to fibrin directly affects thromb resistance to fibrinolysis and that velocity of thromb lysis in vitro predominantly depends on TAFI concentration. Factor XIII also has influence on thromb structure and stability and Lp(a) lipoprotein is one more factor that is responsible for resistence of thromb to fibrinolysis. FIBRINOLYSIS IN ISCHEMIC BRAIN DISEASE: Reduced fibrinolytic capacity is noticed in patients with ischemic brain disease resulting from the increased PAI-1 activity. Higher risk for ischemic brain disease is veryfied among people with 4G/4G PAI-1 genotype. Raised level of t-PA anti-gene can also induce reduction of endogenous fibrinolysis. CONCLUSION: In conclusion we want to underline that a possible pathophysiological significance of fibrinolytic system is assumed in a high percentage of patients with ischemic brain disease. Because of that we need further investigations to establish precise role of fibrinolytic mechanisms in genesis of this disease.

[Depression as the cause and consequence of cerebrovascular diseases].

INTRODUCTION: Recent epidemiological, clinical, neuroimaging and neuropathological studies have reported substantial evidence on the complex interactive relationships between depression and cerebrovascular diseases, especially in older populations, and plausible explanations of the etiopathogenetic mechanisms in both directions have been proposed POSTSTROKE DEPRESSION: Although there is no general consensus regarding its prevalence, it is widely accepted that major depression after stroke is common and that it should be recognized as a key factor in rehabilitation and outcome following stroke. VASCULAR DEPRESSION: The "vascular depression" hypothesis presupposes that late-onset depression may often result from vascular damage to frontal-subcortical circuits implicated in mood regulation. This concept has stimulated many researches and the obtained results support the proposed hypothesis. DEPRESSION AS A STROKE RISK FACTOR: Recent large studies have emphasised the role of depression per se in the development ofsubsequent stroke. Mechanisms proposed to explain the increased risk of cerebrovascular diseases in depressed patients There are a number ofplausible mechanisms that could explain why depression may increase the risk of subsequent cerebrovascular disease, the most important being sympathoadrenal hyperactivity, platelet activation, an increase in inflammatory cytokines and an increased risk of arrhythmias. CONCLUSION: Thorough clinical examinations determining the conventional stroke risk factors in the population with depression, as well as management of depression as part of the overall measures for the reduction of cerebrovascular risk factors are of utmost importance.

Optimal therapy of epilepsy by measuring serum concentration of antiepileptic drugs with least adverse effects.

The study comprised 150 epileptic patients treated at the Institute of Neurology of the Clinical Centre Novi Sad. The optimal therapy with least adverse effects and seizures was achieved in patients in whom measurement of serum concentration of antiepileptic drugs was performed. Patients were divided into five groups with respect to the therapy they received: I--carbamazepane; II--valproic acid; III--polytherapy with phenobarbitone and diphenylhydantoin; IV--phenobarbitone and valproic acid; and V--phenobarbitone, valproic acid and carbamazepine. No adverse effects were recorded in over 60% of patients on monotherapy, 35% of patients who received two anticonvulsants, and 30% of patients who received three anticonvulsants. Significant correlation between drug dosage and blood drug concentration (r > 0.5) was found in polytherapy with phenobarbitone, carbamazepine and valproic acid (r = 0.66); and phenobarbitone and diphenylhydantoin (r = 0.53).