Browsing by Author "Stankovic, Iva (58775209600)"

[No abstract available]

[No abstract available]

Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy particularly at early disease stages, novel Movement Disorder Society criteria for the diagnosis of MSA (MDS MSA criteria) have been recently developed. They introduce a neuropathologically established MSA category and three levels of clinical diagnostic certainty including clinically established MSA, clinically probable MSA, and the research category of possible prodromal MSA. The diagnosis of clinically established and clinically probable MSA is based on the presence of cardiovascular or urological autonomic failure, parkinsonism (poorly L-Dopa-responsive for the diagnosis of clinically established MSA), and cerebellar syndrome. These core clinical features need to be associated with supportive motor and non-motor features (MSA red flags) and absence of any exclusion criteria. Characteristic brain MRI markers are required for a diagnosis of clinically established MSA. A research category of possible prodromal MSA is devised to capture patients manifesting with autonomic failure or REM sleep behavior disorder and only mild motor signs at the earliest disease stage. There is a number of promising laboratory markers for MSA that may help increase the overall clinical diagnostic accuracy. In this review, we will discuss the core and supportive clinical features for a diagnosis of MSA in light of the new MDS MSA criteria, which laboratory tools may assist in the clinical diagnosis and which major differential diagnostic challenges should be borne in mind. © 2022, The Author(s).

Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy particularly at early disease stages, novel Movement Disorder Society criteria for the diagnosis of MSA (MDS MSA criteria) have been recently developed. They introduce a neuropathologically established MSA category and three levels of clinical diagnostic certainty including clinically established MSA, clinically probable MSA, and the research category of possible prodromal MSA. The diagnosis of clinically established and clinically probable MSA is based on the presence of cardiovascular or urological autonomic failure, parkinsonism (poorly L-Dopa-responsive for the diagnosis of clinically established MSA), and cerebellar syndrome. These core clinical features need to be associated with supportive motor and non-motor features (MSA red flags) and absence of any exclusion criteria. Characteristic brain MRI markers are required for a diagnosis of clinically established MSA. A research category of possible prodromal MSA is devised to capture patients manifesting with autonomic failure or REM sleep behavior disorder and only mild motor signs at the earliest disease stage. There is a number of promising laboratory markers for MSA that may help increase the overall clinical diagnostic accuracy. In this review, we will discuss the core and supportive clinical features for a diagnosis of MSA in light of the new MDS MSA criteria, which laboratory tools may assist in the clinical diagnosis and which major differential diagnostic challenges should be borne in mind. © 2022, The Author(s).

Background: The hypothesis that the effectiveness of deep brain stimulation (DBS) in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of stimulation and other brain regions is growing. Objective: To investigate how the subthalamic nucleus (STN), the most frequently used DBS target for PD, is functionally linked to other brain regions in PD patients according to DBS eligibility. Methods: Clinical data and resting-state functional MRI were acquired from 60 PD patients and 60 age- and sex-matched healthy subjects within an ongoing longitudinal project. PD patients were divided into 19 patients eligible for DBS and 41 non-candidates. Bilateral STN were selected as regions of interest and a seed-based functional MRI connectivity analysis was performed. Results: A decreased functional connectivity between STN and sensorimotor cortex in both PD patient groups compared to controls was found. Whereas an increased functional connectivity between STN and thalamus was found in PD patient groups relative to controls. Candidates for DBS showed a decreased functional connectivity between bilateral STN and bilateral sensorimotor areas relative to non-candidates. In patients eligible for DBS, a weaker STN functional connectivity with left supramarginal and angular gyri was related with a more severe rigidity and bradykinesia whereas a higher connectivity between STN and cerebellum/pons was related to poorer tremor score. Conclusion: Our results suggest that functional connectivity of STN varies among PD patients eligible or not for DBS. Future studies would confirm whether DBS modulates and restores functional connectivity between STN and sensorimotor areas in treated patients. © 2023 - The authors. Published by IOS Press.

Background: The hypothesis that the effectiveness of deep brain stimulation (DBS) in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of stimulation and other brain regions is growing. Objective: To investigate how the subthalamic nucleus (STN), the most frequently used DBS target for PD, is functionally linked to other brain regions in PD patients according to DBS eligibility. Methods: Clinical data and resting-state functional MRI were acquired from 60 PD patients and 60 age- and sex-matched healthy subjects within an ongoing longitudinal project. PD patients were divided into 19 patients eligible for DBS and 41 non-candidates. Bilateral STN were selected as regions of interest and a seed-based functional MRI connectivity analysis was performed. Results: A decreased functional connectivity between STN and sensorimotor cortex in both PD patient groups compared to controls was found. Whereas an increased functional connectivity between STN and thalamus was found in PD patient groups relative to controls. Candidates for DBS showed a decreased functional connectivity between bilateral STN and bilateral sensorimotor areas relative to non-candidates. In patients eligible for DBS, a weaker STN functional connectivity with left supramarginal and angular gyri was related with a more severe rigidity and bradykinesia whereas a higher connectivity between STN and cerebellum/pons was related to poorer tremor score. Conclusion: Our results suggest that functional connectivity of STN varies among PD patients eligible or not for DBS. Future studies would confirm whether DBS modulates and restores functional connectivity between STN and sensorimotor areas in treated patients. © 2023 - The authors. Published by IOS Press.

Purpose of reviewMultiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on α-synuclein's role in MSA pathophysiology and review the new Movement Disorders Society (MDS) diagnostic criteria and the utility of α-synuclein-based biomarkers. We also highlight ongoing efforts toward clinical trial readiness and review potential disease-modifying therapies undergoing clinical trials.Recent findingsA role of urinary tract infections in triggering α-synuclein aggregation and contribution of genes implicated in oligodendroglial development have been suggested in the MSA pathophysiology. The clinically probable MSA category of the new diagnostic criteria shows improved accuracy in early disease stages. Predictors of phenoconversion from pure autonomic failure to MSA are now better defined. Alpha-synuclein strains in CSF and serum, phosphorylated α-synuclein deposits in the skin, and brain α-synuclein pathology visualized using PET ligand [18F]ACI-12589 are emerging as valuable diagnostic tools. Clinical trials in MSA investigate drugs targeting α-synuclein aggregation or preventing α-synuclein expression, along with stem cell and gene therapies to halt disease progression.SummaryNew MSA diagnostic criteria and α-synuclein-based biomarkers may enhance diagnostic accuracy while promising therapies are in development to address disease progression. © 2024 2024 Wolters Kluwer Health, Inc. All rights reserved.

Purpose of reviewMultiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on α-synuclein's role in MSA pathophysiology and review the new Movement Disorders Society (MDS) diagnostic criteria and the utility of α-synuclein-based biomarkers. We also highlight ongoing efforts toward clinical trial readiness and review potential disease-modifying therapies undergoing clinical trials.Recent findingsA role of urinary tract infections in triggering α-synuclein aggregation and contribution of genes implicated in oligodendroglial development have been suggested in the MSA pathophysiology. The clinically probable MSA category of the new diagnostic criteria shows improved accuracy in early disease stages. Predictors of phenoconversion from pure autonomic failure to MSA are now better defined. Alpha-synuclein strains in CSF and serum, phosphorylated α-synuclein deposits in the skin, and brain α-synuclein pathology visualized using PET ligand [18F]ACI-12589 are emerging as valuable diagnostic tools. Clinical trials in MSA investigate drugs targeting α-synuclein aggregation or preventing α-synuclein expression, along with stem cell and gene therapies to halt disease progression.SummaryNew MSA diagnostic criteria and α-synuclein-based biomarkers may enhance diagnostic accuracy while promising therapies are in development to address disease progression. © 2024 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: In the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life. Objectives: In light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019. Methods: We included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria. Results: We discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected. Conclusions: This systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA. © 2020 International Parkinson and Movement Disorder Society.

Background: In the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life. Objectives: In light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019. Methods: We included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria. Results: We discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected. Conclusions: This systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA. © 2020 International Parkinson and Movement Disorder Society.

Parkinson’s disease (PD) patients can be classified in tremor-dominant (TD) and postural-instability-and-gait-disorder (PIGD) motor subtypes. PIGD represents a more aggressive form of the disease that TD patients have a potentiality of converting into. This study investigated functional alterations within the cerebro-cerebellar system in PD-TD and PD-PIGD patients using stepwise functional connectivity (SFC) analysis and identified neuroimaging features that predict TD to PIGD conversion. Thirty-two PD-TD, 26 PD-PIGD patients and 60 healthy controls performed clinical/cognitive evaluations and resting-state functional MRI (fMRI). Four-year clinical follow-up data were available for 28 PD-TD patients, who were classified in 10 converters (cTD-PD) and 18 non-converters (ncTD-PD) to PIGD. The cerebellar seed-region was identified using a fMRI motor task. SFC analysis, characterizing regions that connect brain areas to the cerebellar seed at different levels of link-step distances, evaluated similar and divergent alterations in PD-TD and PD-PIGD. The discriminatory power of clinical data and/or SFC in distinguishing cPD-TD from ncPD-TD patients was assessed using ROC curve analysis. Compared to PD-TD, PD-PIGD patients showed decreased SFC in temporal lobe and occipital lobes and increased SFC in cerebellar cortex and ponto-medullary junction. Considering the subtype-conversion analysis, cPD-TD patients were characterized by increased SFC in temporal and occipital lobes and in cerebellum and ponto-medullary junction relative to ncPD-TD group. Combining clinical and SFC data, ROC curves provided the highest classification power to identify conversion to PIGD. These findings provide novel insights into the pathophysiology underlying different PD motor phenotypes and a potential tool for early characterization of PD-TD patients at risk of conversion to PIGD. © 2022, The Author(s).

Parkinson’s disease (PD) patients can be classified in tremor-dominant (TD) and postural-instability-and-gait-disorder (PIGD) motor subtypes. PIGD represents a more aggressive form of the disease that TD patients have a potentiality of converting into. This study investigated functional alterations within the cerebro-cerebellar system in PD-TD and PD-PIGD patients using stepwise functional connectivity (SFC) analysis and identified neuroimaging features that predict TD to PIGD conversion. Thirty-two PD-TD, 26 PD-PIGD patients and 60 healthy controls performed clinical/cognitive evaluations and resting-state functional MRI (fMRI). Four-year clinical follow-up data were available for 28 PD-TD patients, who were classified in 10 converters (cTD-PD) and 18 non-converters (ncTD-PD) to PIGD. The cerebellar seed-region was identified using a fMRI motor task. SFC analysis, characterizing regions that connect brain areas to the cerebellar seed at different levels of link-step distances, evaluated similar and divergent alterations in PD-TD and PD-PIGD. The discriminatory power of clinical data and/or SFC in distinguishing cPD-TD from ncPD-TD patients was assessed using ROC curve analysis. Compared to PD-TD, PD-PIGD patients showed decreased SFC in temporal lobe and occipital lobes and increased SFC in cerebellar cortex and ponto-medullary junction. Considering the subtype-conversion analysis, cPD-TD patients were characterized by increased SFC in temporal and occipital lobes and in cerebellum and ponto-medullary junction relative to ncPD-TD group. Combining clinical and SFC data, ROC curves provided the highest classification power to identify conversion to PIGD. These findings provide novel insights into the pathophysiology underlying different PD motor phenotypes and a potential tool for early characterization of PD-TD patients at risk of conversion to PIGD. © 2022, The Author(s).

Background: Fear of falling in Parkinson's disease (PD) has been suggested as predictor of future falling. The purpose of this study was to compare fear of falling score after two years of follow-up with those observed at baseline and to assess factors associated with change in fear of falling over time.Methods: A total of 120 consecutive persons with PD were recruited and followed for two years. Fear of falling was assessed by using the 10-item Falls Efficacy Scale (FES). Occurrence of falling was registered during the first year of follow-up.Results: After two years, the average FES score statistically significantly changed (p = 0.003) from 30.5 to 37.5 out of 100 (increase of 22.9%). We observed that median scores of all FES items, except for Preparing a meal, not requiring carrying of heavy or hot objects and Personal grooming, significantly increased after two-year follow-up. After accounting for age, gender, PD duration, levodopa dosage, Hoehn and Yayhr stage, Unified Parkinson's Disease Rating Scale score three, depression, anxiety, and falling, we observed that sustaining greater number of falls in the first year of follow-up was associated with higher increase in FES score after two years (odds ratio 3.08, 95% confidence interval 1.30-4.87).Conclusion: After two years of follow-up, we observed a decrease in confidence at performing nearly all basic daily activities. Fall prevention programs should be prioritized in management of PD. Copyright © International Psychogeriatric Association 2017.

Background: Fear of falling in Parkinson's disease (PD) has been suggested as predictor of future falling. The purpose of this study was to compare fear of falling score after two years of follow-up with those observed at baseline and to assess factors associated with change in fear of falling over time.Methods: A total of 120 consecutive persons with PD were recruited and followed for two years. Fear of falling was assessed by using the 10-item Falls Efficacy Scale (FES). Occurrence of falling was registered during the first year of follow-up.Results: After two years, the average FES score statistically significantly changed (p = 0.003) from 30.5 to 37.5 out of 100 (increase of 22.9%). We observed that median scores of all FES items, except for Preparing a meal, not requiring carrying of heavy or hot objects and Personal grooming, significantly increased after two-year follow-up. After accounting for age, gender, PD duration, levodopa dosage, Hoehn and Yayhr stage, Unified Parkinson's Disease Rating Scale score three, depression, anxiety, and falling, we observed that sustaining greater number of falls in the first year of follow-up was associated with higher increase in FES score after two years (odds ratio 3.08, 95% confidence interval 1.30-4.87).Conclusion: After two years of follow-up, we observed a decrease in confidence at performing nearly all basic daily activities. Fall prevention programs should be prioritized in management of PD. Copyright © International Psychogeriatric Association 2017.

Consensus diagnostic criteria for multiple system atrophy consider dementia as a nonsupporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal-executive dysfunction is the most common presentation, while memory and visuospatial functions also may be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation, with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence-based review, the authors propose future avenues of research that ultimately may lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy. © 2014 International Parkinson and Movement Disorder Society.

Consensus diagnostic criteria for multiple system atrophy consider dementia as a nonsupporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal-executive dysfunction is the most common presentation, while memory and visuospatial functions also may be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation, with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence-based review, the authors propose future avenues of research that ultimately may lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy. © 2014 International Parkinson and Movement Disorder Society.

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.

Multiple system atrophy is a rapidly progressive and fatal neurodegenerative disorder. While numerous preclinical studies suggested efficacy of potentially disease modifying agents, none of those were proven to be effective in large-scale clinical trials. Three major strategies are currently pursued in preclinical and clinical studies attempting to slow down disease progression. These target α-synuclein, neuroinflammation, and restoration of neurotrophic support. This review provides a comprehensive overview on ongoing preclinical and clinical developments of disease modifying therapies. Furthermore, we will focus on potential shortcomings of previous studies that can be avoided to improve data quality in future studies of this rare disease. © 2022 - The authors. Published by IOS Press.

Multiple system atrophy is a rapidly progressive and fatal neurodegenerative disorder. While numerous preclinical studies suggested efficacy of potentially disease modifying agents, none of those were proven to be effective in large-scale clinical trials. Three major strategies are currently pursued in preclinical and clinical studies attempting to slow down disease progression. These target α-synuclein, neuroinflammation, and restoration of neurotrophic support. This review provides a comprehensive overview on ongoing preclinical and clinical developments of disease modifying therapies. Furthermore, we will focus on potential shortcomings of previous studies that can be avoided to improve data quality in future studies of this rare disease. © 2022 - The authors. Published by IOS Press.