Browsing by Author "Petrovic, Igor (7004083314)"

Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson's disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia. © 2013 Belgian Neurological Society.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) – the typical fixed dystonia (FixFD) phenotype and the “mobile” dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels. © 2018, Springer Nature Limited.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) – the typical fixed dystonia (FixFD) phenotype and the “mobile” dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels. © 2018, Springer Nature Limited.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

Cortico-striatal-thalamic network functional connectivity (FC) and its relationship with levodopa (L-dopa) were investigated in 69 patients with hemiparkinsonism (25 drug-naïve [n-PD] and 44 under stable/optimized dopaminergic treatment [t-PD]) and 27 controls. Relative to controls, n-PD patients showed an increased FC between the left and the right basal ganglia, and a decreased connectivity of the affected caudate nucleus and thalamus with the ipsilateral frontal and insular cortices. Compared with both controls and n-PD patients, t-PD patients showed a decreased FC among the striatal and thalamic regions, and an increased FC between the striatum and temporal cortex, and between the thalamus and several sensorimotor, parietal, temporal, and occipital regions. In both n-PD and t-PD, patients with more severe motor disability had an increased striatal and/or thalamic FC with temporal, parietal, occipital, and cerebellar regions. Cortico-striatal-thalamic functional abnormalities occur in patients with hemiparkinsonism, antecede the onset of the motor symptoms on the opposite body side and are modulated by L-dopa. In patients with hemiparkinsonism, L-dopa is likely to facilitate a compensation of functional abnormalities possibly through an increased thalamic FC. © 2014 Elsevier Inc.

Cortico-striatal-thalamic network functional connectivity (FC) and its relationship with levodopa (L-dopa) were investigated in 69 patients with hemiparkinsonism (25 drug-naïve [n-PD] and 44 under stable/optimized dopaminergic treatment [t-PD]) and 27 controls. Relative to controls, n-PD patients showed an increased FC between the left and the right basal ganglia, and a decreased connectivity of the affected caudate nucleus and thalamus with the ipsilateral frontal and insular cortices. Compared with both controls and n-PD patients, t-PD patients showed a decreased FC among the striatal and thalamic regions, and an increased FC between the striatum and temporal cortex, and between the thalamus and several sensorimotor, parietal, temporal, and occipital regions. In both n-PD and t-PD, patients with more severe motor disability had an increased striatal and/or thalamic FC with temporal, parietal, occipital, and cerebellar regions. Cortico-striatal-thalamic functional abnormalities occur in patients with hemiparkinsonism, antecede the onset of the motor symptoms on the opposite body side and are modulated by L-dopa. In patients with hemiparkinsonism, L-dopa is likely to facilitate a compensation of functional abnormalities possibly through an increased thalamic FC. © 2014 Elsevier Inc.

Dystonia has been described in various genetically proven spinocerebellar ataxias (SCAs), most often in SCA3, SCA17, and SCA2 patients. In this report, we describe different types of dystonia observed in 5 of our 11 SCA2 patients. All our patients had cranial and/or cervical dystonia with focal or segmental distribution. Except for 1 case with isolated cervical dystonia, all other patients had lower cranial affection of variable severity. Although it is difficult to describe ataxia-dystonia syndrome that would be highly characteristic for SCA2, we suggest that occurrence of dystonia in a patient with slowly evolving cerebellar disease should, besides SCA3 and SCA17, also suggest SCA2 testing. In patients with lower cranial dystonia, especially jaw and tongue dystonia, SCA2 should be considered during the diagnostic workup. © 2016 International Parkinson and Movement Disorder Society.

Dystonia has been described in various genetically proven spinocerebellar ataxias (SCAs), most often in SCA3, SCA17, and SCA2 patients. In this report, we describe different types of dystonia observed in 5 of our 11 SCA2 patients. All our patients had cranial and/or cervical dystonia with focal or segmental distribution. Except for 1 case with isolated cervical dystonia, all other patients had lower cranial affection of variable severity. Although it is difficult to describe ataxia-dystonia syndrome that would be highly characteristic for SCA2, we suggest that occurrence of dystonia in a patient with slowly evolving cerebellar disease should, besides SCA3 and SCA17, also suggest SCA2 testing. In patients with lower cranial dystonia, especially jaw and tongue dystonia, SCA2 should be considered during the diagnostic workup. © 2016 International Parkinson and Movement Disorder Society.

Background: A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. Objectives: To replicate and improve the 4-item MSA-P score. Methods: We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. Results: The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0–6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. Conclusions: The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P. © 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. Objectives: To replicate and improve the 4-item MSA-P score. Methods: We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. Results: The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0–6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. Conclusions: The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P. © 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective: To determine frequency and type of cognitive disorders in cross-sectional analysis of a Parkinson’s disease (PD) cohort, and explore its relations to motor symptoms, modifiable vascular risk factors and white matter lesions (WML) volume. Methods: In a group of 133 PD patients, mild cognitive impairment (PD-MCI) and dementia (PDD) were diagnosed according to Movement Disorders Society Task Force criteria (level 2 for PD-MCI). Detailed motor measurements were applied, including rigidity, axial, bradykinesia, tremor and postural instability gait disorders (PIGD) scores. Vascular risk was estimated by the Framingham General Cardiovascular Disease risk scoring algorithm and WML volume was measured for whole brain and frontal lobe. Results: Sixty-one (46.9%) patients fulfilled criteria for PD-MCI, and 23 (17.7%) for PDD. Non-amnestic multiple domain MCI was most frequent (52% of PD-MCI patients). Motor scores were significantly higher in cognitively impaired patients, but only axial score discriminated between MCI and dementia. High vascular risk was related to impaired cognition, bradykinesia, axial, PIGD and freezing of gait (FOG) score, while whole brain WML volume was associated with PDD, FOG and attention deficits. Furthermore, high vascular risk was identified as a potential predictor of both MCI and dementia in PD. Additionally, age and bradykinesia score were independently associated with PD-MCI and age, axial score and whole brain WML volume with PDD. Conclusion: Cognitive disorders in PD are associated with more severe, predominantly axial motor deficits and increased, but partly modifiable vascular burden, thus opening a possibility for development of preventive strategies in PD. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Objective: To determine frequency and type of cognitive disorders in cross-sectional analysis of a Parkinson’s disease (PD) cohort, and explore its relations to motor symptoms, modifiable vascular risk factors and white matter lesions (WML) volume. Methods: In a group of 133 PD patients, mild cognitive impairment (PD-MCI) and dementia (PDD) were diagnosed according to Movement Disorders Society Task Force criteria (level 2 for PD-MCI). Detailed motor measurements were applied, including rigidity, axial, bradykinesia, tremor and postural instability gait disorders (PIGD) scores. Vascular risk was estimated by the Framingham General Cardiovascular Disease risk scoring algorithm and WML volume was measured for whole brain and frontal lobe. Results: Sixty-one (46.9%) patients fulfilled criteria for PD-MCI, and 23 (17.7%) for PDD. Non-amnestic multiple domain MCI was most frequent (52% of PD-MCI patients). Motor scores were significantly higher in cognitively impaired patients, but only axial score discriminated between MCI and dementia. High vascular risk was related to impaired cognition, bradykinesia, axial, PIGD and freezing of gait (FOG) score, while whole brain WML volume was associated with PDD, FOG and attention deficits. Furthermore, high vascular risk was identified as a potential predictor of both MCI and dementia in PD. Additionally, age and bradykinesia score were independently associated with PD-MCI and age, axial score and whole brain WML volume with PDD. Conclusion: Cognitive disorders in PD are associated with more severe, predominantly axial motor deficits and increased, but partly modifiable vascular burden, thus opening a possibility for development of preventive strategies in PD. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

[No abstract available]

Objective: To study the longitudinal disease course of Parkinson’s disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. Methods: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. Results: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. Conclusions: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

Objective: To study the longitudinal disease course of Parkinson’s disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. Methods: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. Results: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. Conclusions: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

Objectives: The aims of this study were to identify the clinical and demographic factors influencing health-related quality of life (HR-QoL) and to compare HR-QoL measures between various types of focal dystonia (cervical dystonia, blepharospasm, and writer's cramp). Methods: We examined 157 consecutive patients with adult-onset primary focal dystonia, and HR-QoL was assessed by using the SF-36 questionnaire. Univariate and multivariate regression analyses were performed. Results: Patients with writer's cramp scored better in all SF-36 domains, except role functioning physical (RP), while these differences were statistically significant for physical functioning (PF) (p = 0.020), bodily pain (BP) (p = 0.001), and general health (GH) (p = 0.004). Patients with writer's cramp and blepharospasm scored significantly better for BP (p = 0.001) than patients with cervical dystonia. We found that each of the eight dimensions of SF-36 proved to be significantly correlated to the Hamilton depression rating scale score in patients with torticollis and blepharospsm, while vitality (VT), social functioning (SF), and mental health (MH) scales showed statistically significant correlations in patients with hand dystonia. Similar relationships were observed between anxiety and SF-36 domains. Conclusion: Depression and anxiety are the most important predictors of poorer HR-QoL in patients with all three types of focal dystonia. © 2008 Elsevier B.V. All rights reserved.

Objective: To assess whether a functional dysregulation of the habenula and amygdala, as modulators of the reward brain circuit, contributes to Parkinson disease (PD) punding. Methods: Structural and resting-state functional MRI were obtained from 22 patients with PD punding, 30 patients with PD without any impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor impairment, and cognitive status, and 30 healthy controls. Resting-state functional connectivity of the habenula and amygdala bilaterally was assessed using a seed-based approach. Habenula and amygdala volumes and cortical thickness measures were obtained. Results: Compared to both healthy controls and PD cases without any ICB (PD-no ICB), PD-punding patients showed higher functional connectivity of habenula and amygdala with thalamus and striatum bilaterally, and lower connectivity between bilateral habenula and left frontal and precentral cortices. In PD-punding relative to PD-no ICB patients, a lower functional connectivity between right amygdala and hippocampus was also observed. Habenula and amygdala volumes were not different among groups. PD-punding patients showed a cortical thinning of the left superior frontal and precentral gyri and right middle temporal gyrus and isthmus cingulate compared to healthy controls, and of the right inferior frontal gyrus compared to both controls and PD-no ICB patients. Conclusions: A breakdown of the connectivity among the crucial nodes of the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex) might be a contributory factor to punding in PD. This study provides potential instruments to detect and monitor punding in patients with PD. © 2017 American Academy of Neurology.

Background: Status dystonicus (SD) is a rare, life-threatening disorder characterized by acute worsening of generalized dystonia. Methods: This study was conducted to characterize the pathogenesis, clinical course, and prognosis of SD. We reviewed the records of six centers and analyzed them together with all the cases previously reported in the literature. Results: Eighty-nine episodes occurring in 68 patients were studied. The majority of patients were males (64.7%), were <15 years of age (58.8%), and had secondary dystonia as the underlying condition (37.8%). The episodes were mainly characterized by tonic muscle spasms (68.5%), with phasic forms more common in secondary forms and among females. Almost all cases needed a multistaged approach, with surgery being the most successful strategy. Neurological conditions preceding the episode worsened in 16.2% of cases (ending in death in 10.3%). Conclusions: The course and outcome of SD is highly variable; male gender and prevalent tonic phenotype predict a poor outcome © 2012 Movement Disorder Society.

Background: Status dystonicus (SD) is a rare, life-threatening disorder characterized by acute worsening of generalized dystonia. Methods: This study was conducted to characterize the pathogenesis, clinical course, and prognosis of SD. We reviewed the records of six centers and analyzed them together with all the cases previously reported in the literature. Results: Eighty-nine episodes occurring in 68 patients were studied. The majority of patients were males (64.7%), were <15 years of age (58.8%), and had secondary dystonia as the underlying condition (37.8%). The episodes were mainly characterized by tonic muscle spasms (68.5%), with phasic forms more common in secondary forms and among females. Almost all cases needed a multistaged approach, with surgery being the most successful strategy. Neurological conditions preceding the episode worsened in 16.2% of cases (ending in death in 10.3%). Conclusions: The course and outcome of SD is highly variable; male gender and prevalent tonic phenotype predict a poor outcome © 2012 Movement Disorder Society.