Search PubMed⌕ Search

Biomedical subjects

Vladimir S Kostić

Publications and source records attributed to Vladimir S Kostić.

14 recordsLinked to original sources

Intrafamilial phenotypic and genetic heterogeneity of dystonia.

Most cases of early-onset primary torsion dystonia are caused by the same 3-bp (GAG) deletion in the DYT1 gene. We describe a large Serbian family with significant intrafamilial variability of the DYT1 phenotype, from asymptomatic carrier status to late-onset focal, and generalized jerky dystonia. Seven mutation carriers (six proven by direct analysis and one by inferred haplotype) were identified, but only two of them were affected by dystonia (penetrance reduced to 29%). In addition, three GAG-deletion-negative family members also developed dystonia (two multifocal dystonia and one torticollis), suggesting that their involuntary movements are due to some other etiological factor(s) (i.e., another dystonia gene), or may be psychogenic.

Adult↗

Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients.

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia.

Adult↗

Clinical characteristics of paroxysmal nonkinesigenic dyskinesia in Serbian family with Myofibrillogenesis regulator 1 gene mutation.

The aim of this study was to describe the clinical features of a large Serbian family with paroxysmal nonkinesigenic dyskinesia (PNKD) and one of the two previously described mutations in the Myofibrillogenesis regulator 1 gene (MR-1), which causes an alanine-to-valine substitution at position 9. In 5 examined out of 12 affected family members, attacks of dyskinesias appeared in the first 6 months of life. Both frequency and severity of attacks showed an age-dependent incremental-decremental pattern with a peak between 13 to 15 years of age. They were frequently precipitated by stress, caffeine, fever, hunger, tiredness, as well as abrupt changes in temperature. Three of our patients differentiated two types of attacks: mild (120-180 minutes), with a predominance of functionally insignificant choreoathetoid movements, and severe ( approximately 15-30 minutes), characterized by disabling dystonic and choreic movements of the extremities, trunk, and face. Sleep was the most reliable factor to discontinue an attack. This Serbian family further demonstrates that recurrent MR-1 mutations are associated with PNKD worldwide, which will affect genetic testing.

Adolescent↗

Bilateral chorea-ballism associated with hyperthyroidism.

We describe a 50-year-old patient with four episodes of recurrent bilateral chorea-ballism (BCB) and associated hyperthyroidism. Reappearance of BCB, associated with increased serum levels of thyroid hormones and lack of relevant changes on brain computed tomography/magnetic resonance imaging scans, suggested that the involuntary movements were likely due to thyrotoxicosis-induced biochemical changes.

Chorea↗

Incidence of vascular hemiballism in the population of Belgrade.

Hemiballism is a relatively rare hyperkinetic disorder with unknown incidence. Stroke is the most common cause of hemiballism (vascular hemiballism), responsible for the disorder in 50% to 100% of cases. We studied the incidence of vascular hemiballism in the population of Belgrade (Serbia) 40 years of age or older during the period 1 January 1991 to 31 December 2002. During that time period, 37 patients with hemiballism due to stroke were diagnosed. The annual incidence rates varied from 0.14 to 0.87/100,000 (average 0.45/100,000) of general population.

Adult↗

Prevalence of primary late-onset focal dystonia in the Belgrade population.

The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.

Adult↗

Therapeutic efficacy of bilateral prefrontal slow repetitive transcranial magnetic stimulation in depressed patients with Parkinson's disease: an open study.

Recent studies have suggested that both high- and low-frequency repetitive transcranial magnetic stimulation (rTMS) have antidepressant effects in patients with major depression. We conducted an open study to assess the effects of slow rTMS on mood changes in patients with depression associated with Parkinson's disease (PD). Ten depressed patients with PD (four with major depression and six with dysthymia) received daily sessions of rTMS (frequency, 0.5 Hz; pulse duration, 0.1 msec; field intensity, 10% above the motor threshold) over both prefrontal regions (a total of 100 stimuli per prefrontal region daily) over 10 consecutive days. This treatment resulted in a moderate but significant decrease in scores of the Hamilton Depression Rating Scale (33-37%) and the Beck Depression Inventory (24-34%), which persisted 20 days after finishing the stimulation. In parallel, we observed mild improvement (18-20%) of motor symptoms. No significant adverse effects were reported. These preliminary results suggest the therapeutic potential of daily prefrontal low-frequency rTMS (0.5 Hz) in depression associated with PD.

Aged↗

Effect of neural transplantation on depressive behavior in rats with lesioned nucleus basalis magnocellularis.

Recent data of our group have shown that bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM) in rats reduced the escape behavior deficit that occurs in the learned helplessness test. The present study was done to establish the effect of intracerebral neural transplantation on the change in escape behavior of NBM-lesioned adult male Wistar rats in the learned helplessness test. At 2 days (NBM-ET) or 10 days (NBM-DT) after bilateral electrolytic NBM-lesions, small fragments of fetal frontal cortex (18th day of gestation) were allotransplanted into the lesioned NBM. Ten days after neural transplantation, the learned helplessness test was performed. The number of shocks that animals received before making an escape response was significantly reduced in NBM-lesioned rats (p < .001, compared to intact control and sham-operated rats). In comparison to NBM-lesioned and sham-ET rats, the NBM-ET rats showed a marked (p < .001) increase in the number of shocks delivered before the animal made such an escape response. On the other hand, NBM-DT rats did not show this increase. These results indicate that neural transplantation performed at an early time after lesioning of NBM reversed the effect of this lesion in rats exposed to learned helplessness test.

Animals↗

[Lifetime achievements of Bogomir B. Mrsulja. 1940-1944].

Bogomir Mrshulja was born on September 18th, 1940 in Lendava. He finished both elementary school and high school in Belgrade and subsequently graduated from the School of Medicine, University of Belgrade in 1965. As an undergraduate he was an assistant at the Biochemistry Department and the subject became his profession for life. The University of Belgrade awarded him a scholarship and in 1968 he defended his MSc thesis entitled Glycogen of the Central Nervous System--Methods of Separation, Fraction Isolation, Regional Distribution and Variations in Different Levels of Deprivation of Paradoxical Sleep. Soon after, in 1970, he defended his PhD thesis, as well: Brain Glycogen and Deprivation of Paradoxical Sleep--Biochemical and Pharmacological Aspects of Glycogenolysis. In the period 1973-1975 he spent 18 months in the capacity of a visiting scientist in the Laboratory for Neuropathology and Neuroanatomic Sciences of the National Institute of Health in Bethesda (USA), and again, twelve more months in the same institution (Laboratory for Neurochemistry) in the capacity of a special expert of this institution (1983-84) where he was the chief investigator of neurochemical sequelae of experimental cerebral ischemia. He started his university career as an assistant professor in 1965; he was elected associated professor in 1970, promoted adjunct professor in 1978, while in 1984 he received the full professorship of biochemistry at the School of Medicine, University of Belgrade. In 1970 he was elected research associate of the "Sinisha Stankovitsh" Institute of Biological Research. He was professor of neurochemistry and Head of Department of Neurosciences of the Center for Multidisciplinary Studies, University of Belgrade. He was the Head of the Institute of Biochemistry and Head, Department of Biochemistry and Specialized Courses in Clinical Biochemistry at the School of Medicine, University of Belgrade. Owing to his original hypothesis on mechanisms of the occurrence of ischemic cerebral edema and possible therapeutic approach, Bogomir Mrshulja was frequently invited to lecture in university centers of USA, Canada, Japan, Germany and former USSR. He also participated at over 50 international congresses and symposia worldwide. In the mid seventies, Bogomir Mrshulja started more intensive studies of pathophysiological events in the course of cerebral ischemia and already with his early papers intrigued the professional circles which was reflected in an exceptionally high number of his citations in international scientific and referential literature, including the textbooks. The research activities of Bogomir Mrshulja was impressively fruitful: he published 183 papers in extenso, out of which 42 in books of international publishers and 6 invited review articles. In all these papers he illustrated extensive knowledge, maturity, originality, critical attitude, high level of creativity and, finally, courage to oppose the conventional principles. It should be pointed out that in his works Bogomir Mrshulja tended to draw conclusions that stimulated both himself and his colleagues, researchers in the related fields, insisting on extensive evaluation and testing of hypotheses, which is easily illustrated by the number of citations of his papers. According to the Science Citation Index, by 1995 he was cited 1700 times in the world literature, and in the period 1995-2002 he was cited 250 more times. Besides, he set up and headed the Laboratory for pathological neurochemistry at the School of Medicine in Belgrade that was the cradle for many outstanding researchers and lecturers that now work at the Schools of Medicine in Belgrade, Nish and Kragujevac, Military Medical Academy, and other institutions countrywide. He insisted on indispensable link between laboratory and clinical work, and, at least in the field of neurosciences, he is one of the pioneers of this kind of dialogue. In the year in which he left us for good (1994) scientific contribution of Bogomir Mrshulja was recognized by his election for the corresponding fellow of the Serbian Academy of Sciences and Arts. In the same year, he also received the October Award of the City of Belgrade for research.

History, 20th Century↗

[Plasminogen activator inhibitor-1 in the evolution of stroke].

Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age) with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain) in the period from 12 to 24 hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects), which was 2.86 +/- 0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 = 4.10 +/- 1.40 U/ml, p < 0.001; II analysis: PAI-1 = 3.64 +/- 0.90 U/ml, p < 0.001), while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p > 0.05), as well as between females and males (p > 0.05). Along with significantly increased fibrinogen level (4.65 +/- 1 g/l, in the controls--2.83 +/- 0.64 g/l, p < 0.001), significantly higher triglycerides (2.04 +/- 0.76 mmol/l, in the controls--1.38 +/- 0.54 mmol/l, p < 0.001) and lipoproteins(a) (0.405 +/- 0.29 g/l, in the controls--0.172 +/- 0.14 g/l, p < 0.001) were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemic stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.

Adult↗

[Graphospasm--clinical presentation, etiology and the course of disease: analysis of 30 cases].

INTRODUCTION: Dystonia, as prolonged, involuntary muscle contraction, causes torsion, repetitive movements and abnormal body position. In so far only a part of body is affected by dystonic movement, it is the question of focal dystonia, which is called writer's cramp if the arm is involved. OBJECTIVE: The objective of the study was to present the specific clinical features of patients with task-specific dystonia, who were diagnosed, treated and followed up at the Institute of Neurology, Clinical Center of Serbia, Belgrade. MATERIAL AND METHODS: In the period 1995-2003, 30 patients with task-specific dystonia were treated at the Institute of Neurology, CCS, who met the adopted criteria for diagnosis. The severity of the diseases was tested by estimating the ability of patient to write the test sentence per time unit, as well as by means of scale for measuring different disabilities, ranging from 0-16 (Marsden-Fahn). Depression, anxiety and obsessiveness were tested by Beck's scale, Hamilton's depression and anxiety scale and Mousdly's obsessiveness scale. Thorough questionnaire focused on clinical details was also used. Besides descriptive statistics, data processing included analysis of variance and Kruskal-Wallis's test. RESULTS: Thirty patients with diagnosis of task-specific dystonia were analyzed. At the onset of the disease, mean-age was 34.1 years (SD=11.4; 13-58), while the duration of disease at the moment of the examination was 10.3 years (SD=10.6; 1-39). There were 20 males and 10 females (sex ratio 2:1). None of the patients reported any history of trauma of subsequently affected region before the development of discomforts. Twelve patients used their hands for a long time during their professions (writing, playing the instrument, type-writing, etc.). Eight patients were typists (26.6%), four were musicians (13.3%), while the rest of cases (18) had some other occupations that did not necessarily imply long-term use of hands (office worker, engineer, physician, mechanical technician, etc.). Twelve patients had simple task-specific dystonia (type I) (40%), ten cases manifested progressive diseases (type II) (33.3%), while the others suffered from dystonia that was present at rest (type III). Two patients had positive family history. DYT 1 mutation was verified in one of them. Depression, anxiety and obsessiveness were not verifed in our patients. Type of writer's cramp was not in correlation with any of the tested parameters except with the age at the onset of the disease, severity of disease according to Marsden's scale and degree of disability.

Adolescent↗

[Multimodal evoked potential abnormalities in patients with Wilson's disease].

The aim of this study was to investigate the involvement of the following functional systems: somatosensory evoked potentials (SSEP), visual evoked potentials (VEP), and event related potentials (ERP), in twenty patients with Wilson's disease (WD). VEP and SSEP abnormalities were discovered in 8 patients respectively (40%), whereas ERP were either absent or, in the case of 10 patients (50%), had significantly prolonged P-300 latencies. Taken together, at least one evoked potential abnormality was discovered in 17 patients (85%). Only in 3 patients (15%), involving either the isolated hepatic type of disease or short illness duration of the neurological type, were normal evoked potential findings observed. Our findings suggest the usefulness of multimodal evoked potential abnormalities in the evaluation of subclinical manifestations in patients with WD.

Adolescent↗