Browsing by Author "Kaufmann, Horacio (57071218200)"

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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.

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.

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Multiple system atrophy (MSA) is a rare neurodegenerative disease that is characterized by neuronal loss and gliosis in multiple areas of the central nervous system including striatonigral, olivopontocerebellar and central autonomic structures. Oligodendroglial cytoplasmic inclusions containing misfolded and aggregated α-synuclein are the histopathological hallmark of MSA. A firm clinical diagnosis requires the presence of autonomic dysfunction in combination with parkinsonism that responds poorly to levodopa and/or cerebellar ataxia. Clinical diagnostic accuracy is suboptimal in early disease because of phenotypic overlaps with Parkinson disease or other types of degenerative parkinsonism as well as with other cerebellar disorders. The symptomatic management of MSA requires a complex multimodal approach to compensate for autonomic failure, alleviate parkinsonism and cerebellar ataxia and associated disabilities. None of the available treatments significantly slows the aggressive course of MSA. Despite several failed trials in the past, a robust pipeline of putative disease-modifying agents, along with progress towards early diagnosis and the development of sensitive diagnostic and progression biomarkers for MSA, offer new hope for patients. © 2022, Springer Nature Limited.

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Background: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages. Objective: To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology. Methods: We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference. Results: The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow. Conclusions: This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages. Objective: To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology. Methods: We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference. Results: The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow. Conclusions: This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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