Browsing by Author "Kostić, Vladimir S. (35239923400)"

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence. Copyright © 2022 Branislava Radojević et al.

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[No abstract available]

Background: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). Methods: Following the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. Results: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. Conclusions: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). Methods: Following the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. Results: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. Conclusions: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impaired initiation and slowed execution of movements are two of the principal characteristics of Parkinson's disease (PD). A similar pattern of movement impairments (psychomotor retardation) can be seen frequently in patients with idiopathic depression. In addition, affective disorders have been frequently reported in patients with different basal ganglia disorders. The aim of this study was to determine whether there are some particularities in the cerebral electrical activity during the preparation and execution of voluntary internally paced movements (i.e., Bereitschaftspotential, BP) in depressed PD patients, which can distinguish them from non-depressed PD patients, as well as from healthy controls. The BPs were recorded in 16 patients with idiopathic PD, eight of whom were depressed (PD-D), and eight of whom were not (PD-ND). Additional recordings were taken from a group of eight age- and sex-matched healthy subjects. Depression was classified using the Research Diagnostic Criteria and the two PD groups were matched for age, disease severity, and disease duration. The amplitudes and slopes of the BPs from PD patients were generally smaller than in controls, but there was no specific pattern of BP changes that distinguished depressed from non-depressed PD patients. In addition, there was no particular association between measures of depression severity and BP parameters. The data suggest that presence of depression in PD might not have any additional deteriorating influence on already impaired preparation for self-paced spontaneous movements. © 2001 Movement Disorder Society.

Impaired initiation and slowed execution of movements are two of the principal characteristics of Parkinson's disease (PD). A similar pattern of movement impairments (psychomotor retardation) can be seen frequently in patients with idiopathic depression. In addition, affective disorders have been frequently reported in patients with different basal ganglia disorders. The aim of this study was to determine whether there are some particularities in the cerebral electrical activity during the preparation and execution of voluntary internally paced movements (i.e., Bereitschaftspotential, BP) in depressed PD patients, which can distinguish them from non-depressed PD patients, as well as from healthy controls. The BPs were recorded in 16 patients with idiopathic PD, eight of whom were depressed (PD-D), and eight of whom were not (PD-ND). Additional recordings were taken from a group of eight age- and sex-matched healthy subjects. Depression was classified using the Research Diagnostic Criteria and the two PD groups were matched for age, disease severity, and disease duration. The amplitudes and slopes of the BPs from PD patients were generally smaller than in controls, but there was no specific pattern of BP changes that distinguished depressed from non-depressed PD patients. In addition, there was no particular association between measures of depression severity and BP parameters. The data suggest that presence of depression in PD might not have any additional deteriorating influence on already impaired preparation for self-paced spontaneous movements. © 2001 Movement Disorder Society.

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. © 2004 Movement Disorder Society.

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. © 2004 Movement Disorder Society.

Background/Aim. Botulinum toxin-A (BTX-A) is known to block the release of acetylcholine from motor and autonomic nerve terminals and may significantly decrease saliva production when injected intraglandulary. The aim of this study was to evaluate effects of BTX-A injections in the treatment of disabling sialorrhea in various neurological disorders. Methods. This study included 19 consecutive patients with significant sialorrhea associated with various neurological disorders. Out of them 13 patients were with Parkinson's disease, two with pantothenate kinase-associated neurodegeneration, two with multiple system atrophy, one with Wilson's disease, and one patient with postoperative sialorrhea. Botulinum toxin-A (Dysport®, Ipsen Pharma) was injected into the parotid glands with (n = 7 patients) or without (n = 12 patients) ultrasound guidance. All the patients were scored before and after the treatment and in weekly intervals thereafter using the salivation item of the part II (Activities of Daily Living) of the Unified Parkinson's Disease Rating Scale (UPDRS). Results. Thirteen patients (68%) reported beneficial effect of BTX-A injection, while 6 of them (32%) had no response at all. The sialorrhea scores before and after the treatment were 3.1 ± 0.1 (range 2-4) and 1.8 ± 0.1 (range 0-3), respectively (t = 5.636; p < 0.001). There was no difference in the magnitude of response between the groups with (t = 4.500; p = 0.004) and without (t = 3.674; p = 0.005) ultrasound control of injection sites. Adverse effects were registered in 5 patients (26%). Conclusions. Botulinum toxin-A injections to easily accessible parotid glands, without necessity for ultrasound guidance, are safe and efficaceous treatment for sialorrhea in different neurological disorders.

Background: Whether connectome mapping of structural and functional connectivity across the brain could be used to predict patterns of atrophy progression in patients with mild Parkinson disease (PD) has not been well studied. Purpose: To assess the structural and functional connectivity of brain regions in healthy controls and its relationship with the spread of gray matter (GM) atrophy in patients with mild PD. Materials and Methods: This prospective study included participants with mild PD and controls recruited from a single center between January 2012 and December 2023. Participants with PD underwent three-dimensional T1-weighted brain MRI, and the extent of regional GM atrophy was determined at baseline and every year for 3 years. The structural and functional brain connectome was constructed using diffusion tensor imaging and resting-state functional MRI in healthy controls. Disease exposure (DE) indexes—indexes of the pathology of each brain region—were defined as a function of the structural or functional connectivity of all the connected regions in the healthy connectome and the severity of atrophy of the connected regions in participants with PD. Partial correlations were tested between structural and functional DE indexes of each GM region at 1- or 2-year follow-up and atrophy progression at 2- or 3-year follow-up. Prediction models of atrophy at 2- or 3-year follow-up were constructed using exhaustive feature selection. Results: A total of 86 participants with mild PD (mean age at MRI, 60 years ± 8 [SD]; 48 male) and 60 healthy controls (mean age at MRI, 62 years ± 9; 31 female) were included. DE indexes at 1 and 2 years were correlated with atrophy at 2 and 3 years (r range, 0.22–0.33; P value range, .002–.04). Models including DE indexes predicted GM atrophy accumulation over 3 years in the right caudate nucleus and some frontal, parietal, and temporal brain regions (R2 range, 0.40–0.61; all P < .001). Conclusion: The structural and functional organization of the brain connectome plays a role in atrophy progression in the early stages of PD. © RSNA, 2024.

Background: Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP). Objective: We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. Methods: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. Results: Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. Conclusion: Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies. © 2021 - IOS Press. All rights reserved.

Background: Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP). Objective: We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. Methods: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. Results: Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. Conclusion: Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies. © 2021 - IOS Press. All rights reserved.

Although depression is a common finding in Parkinson's disease (PD), its neurobiological mechanism is still unknown. The purpose of this study was to determine whether there are specific spectral electroencephalographic (EEG) characteristics that distinguish depressed from non-depressed PD patients. The study was performed in 24 patients with idiopathic PD whose antiparkinson medication was stopped 24 h beforehand. They were divided into two groups of 12 groups of 12 patients each, one with depressive symptomatology, and one without. The groups did not differ with respect to age, sex distribution, and disease severity and duration. All recordings were conducted using a 16- channel electroencephalograph, and artifact-free EEG was processed using a Fast Fourier Transformation. The EEG of depressed PD patients showed significantly less absolute and relative power in spectral band 7.5-10 Hz (alpha1), and slightly more relative power in spectral band 10.513 Hz (alpha2), while there was no difference in other spectral bands. Topographic analysis of the alpha1 absolute power revealed that, while in non-depressed patients this activity has a clear occipital maximum (and thus corresponds to the standard background activity), in depressed patients its maximum was shifted anteriorally toward the parietal region. Topographic analysis of the significance of the difference between the groups in the relative power of alpha1 and alpha2 bands revealed opposite gradients, posterior to anterior and anterior to posterior directions, respectively. The spectral EEG characteristics of the depressed PD patients not only differed from the spectral EEG characteristics of non-depressed PD patients, but they were also different from the usually reported spectral EEG characteristics of depressed patients without neurological disease. We propose that our data are sufficient to raise the possibility for the existence of a distinctive neurobiological substrate of depression in PD. This is not just a simple addition of two neurobiological substrata, one of depression (as it is determined in non-neurological patients) and one of PD, but rather a complex product of their interaction.

Although depression is a common finding in Parkinson's disease (PD), its neurobiological mechanism is still unknown. The purpose of this study was to determine whether there are specific spectral electroencephalographic (EEG) characteristics that distinguish depressed from non-depressed PD patients. The study was performed in 24 patients with idiopathic PD whose antiparkinson medication was stopped 24 h beforehand. They were divided into two groups of 12 groups of 12 patients each, one with depressive symptomatology, and one without. The groups did not differ with respect to age, sex distribution, and disease severity and duration. All recordings were conducted using a 16- channel electroencephalograph, and artifact-free EEG was processed using a Fast Fourier Transformation. The EEG of depressed PD patients showed significantly less absolute and relative power in spectral band 7.5-10 Hz (alpha1), and slightly more relative power in spectral band 10.513 Hz (alpha2), while there was no difference in other spectral bands. Topographic analysis of the alpha1 absolute power revealed that, while in non-depressed patients this activity has a clear occipital maximum (and thus corresponds to the standard background activity), in depressed patients its maximum was shifted anteriorally toward the parietal region. Topographic analysis of the significance of the difference between the groups in the relative power of alpha1 and alpha2 bands revealed opposite gradients, posterior to anterior and anterior to posterior directions, respectively. The spectral EEG characteristics of the depressed PD patients not only differed from the spectral EEG characteristics of non-depressed PD patients, but they were also different from the usually reported spectral EEG characteristics of depressed patients without neurological disease. We propose that our data are sufficient to raise the possibility for the existence of a distinctive neurobiological substrate of depression in PD. This is not just a simple addition of two neurobiological substrata, one of depression (as it is determined in non-neurological patients) and one of PD, but rather a complex product of their interaction.

[No abstract available]

[No abstract available]

In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. © 2011 Springer-Verlag.

In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. © 2011 Springer-Verlag.

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. © 2005 Movement Disorder Society.