Pilot therapeutic education program in multiple system atrophy: Safety, quality of life and satisfaction from a national registry based longitudinal study.

Background: Therapeutic education programs are effective in several chronic conditions. However, evidence is lacking in multiple system atrophy (MSA). We aimed to assess efficacy and safety of a comprehensive therapeutic education program in people with MSA (PwMSA) and their caregivers.

Misfolded protein deposits in Parkinson's disease and Parkinson's disease-related cognitive impairment, a [C]PBB3 study.

Parkinson's disease (PD) is associated with aggregation of misfolded α-synuclein and other proteins, including tau. We designed a cross-sectional study to quantify the brain binding of [C]PBB3 (a ligand known to bind to misfolded tau and possibly α-synuclein) as a proxy of misfolded protein aggregation in Parkinson's disease (PD) subjects with and without cognitive impairment and healthy controls (HC). In this cross-sectional study, nineteen cognitively normal PD subjects (CN-PD), thirteen cognitively impaired PD subjects (CI-PD) and ten HC underwent [C]PBB3 PET.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

Objectives: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates.

Methodology: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD).

Results: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons.

Cell-free mitochondrial DNA deletions in idiopathic, but not LRRK2, Parkinson's disease.

Mitochondrial dysfunction happens in both idiopathic (iPD) and LRRK2-related Parkinson's disease (LRRK2-PD). Nonetheless, previous studies suggested that a different type of mitochondrial pathology underlies the neurodegeneration in these two disorders. To further explore this hypothesis, we developed a novel multiplex digital PCR assay that allows the absolute quantification of cell-free mitochondrial DNA (cf-mtDNA) copy number and deletion ratio directly in cerebrospinal fluid (CSF) by simultaneously measuring two opposed regions of the mtDNA circular molecule, one of them in the commonly deleted major arc.

Neurofilament light levels predict clinical progression and death in multiple system atrophy.

Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited.

Combined CSF α-SYN RT-QuIC, CSF NFL and midbrain-pons planimetry in degenerative parkinsonisms: From bedside to bench, and back again.

Introduction: Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs: multiple system atrophy[MSA], progressive supranuclear palsy[PSP], corticobasal degeneration[CBD]) remains challenging. Lately, cerebrospinal fluid (CSF) studies of neurofilament light-chain (NFL) and RT-QuIC of alpha-synuclein (α-SYN) have shown promise, but data on their combination with MRI measures is lacking.

Objective: (1) to assess the combined diagnostic ability of CSF RT-QuIC α-SYN, CSF NFL and midbrain/pons MRI planimetry in degenerative parkinsonisms; (2) to evaluate if biomarker-signatures relate to clinical diagnoses and whether or not unexpected findings can guide diagnostic revision.

Differentiation of multiple system atrophy subtypes by gray matter atrophy.

Background And Purpose: Multiple system atrophy(MSA) is a rare adult-onset synucleinopathy that can be divided in two subtypes depending on whether the prevalence of its symptoms is more parkinsonian or cerebellar (MSA-P and MSA-C, respectively). The aim of this work is to investigate the structural MRI changes able to discriminate MSA phenotypes.

Methods: The sample includes 31 MSA patients (15 MSA-C and 16 MSA-P) and 39 healthy controls.

Association of PSP phenotypes with survival: A brain-bank study.

Introduction: The MDS-PSP criteria expand the phenotypic spectrum of PSP by adding to Richardson's syndrome (PSP-RS) other presentations such as PSP-parkinsonism (PSP-P), PSP-pure-gait-freezing (PSP-PGF), PSP-speech-language (PSP-SL), PSP-frontal (PSP-F), PSP-postural-instability (PSP-PI) and PSP-corticobasal-syndrome (PSP-CBS). Evidence about the prognostic differences between PSP phenotypes is scarce and focused on PSP-RS vs. non-PSP-RS.

Progression of Motor and Non-Motor Symptoms in Multiple System Atrophy: A Prospective Study from the Catalan-MSA Registry.

Background/objective: Multiple system atrophy (MSA) is a highly debilitating, rare neurodegenerative disorder with two clinical motor variants (parkinsonian or MSA-P and cerebellar or MSA-C). There is a wide span of motor and non-motor symptoms (NMS) that progress over time. We studied the cohort from the Catalan Multiple System Atrophy Registry (CMSAR) to determine which symptoms are most likely to progress throughout a 2-year follow-up.

Mini-Review: The MSA transcriptome.

Multiple system atrophy (MSA) is an atypical parkinsonism that rapidly affects motor ability and autonomic function, leaving patients wheelchair-bound and dependent for daily activities in 3-5 years. Differential diagnosis is challenging as cases may resemble Parkinson's disease or other ataxic syndromes depending on the clinical variant (MSA-P or MSA-C), especially in early stages. There are limited symptomatic treatments and no disease-modifying therapies.

MicroRNA Deregulation in Blood Serum Identifies Multiple System Atrophy Altered Pathways.

Background And Objectives: MicroRNA (miRNA) changes are observed in PD but remain poorly explored in other α-synucleinopathies such as MSA.

Methods: By genome-wide analysis we profiled microRNA expression in serum from 20 MSA cases compared to 40 controls. By qPCR we validated top differentially expressed microRNAs in another sample of 20 MSA and 20 controls.

Transcriptomic differences in MSA clinical variants.

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C).

Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes.

Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients.

Differentiation of multiple system atrophy from Parkinson's disease by structural connectivity derived from probabilistic tractography.

Recent studies combining diffusion tensor-derived metrics and machine learning have shown promising results in the discrimination of multiple system atrophy (MSA) and Parkinson's disease (PD) patients. This approach has not been tested using more complex methodologies such as probabilistic tractography. The aim of this work is assessing whether the strength of structural connectivity between subcortical structures, measured as the number of streamlines (NOS) derived from tractography, can be used to classify MSA and PD patients at the single-patient level.

Cerebrospinal fluid cytokines in multiple system atrophy: A cross-sectional Catalan MSA registry study.

Introduction: Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis.

Methods: Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls.

Cerebellar resting-state functional connectivity in Parkinson's disease and multiple system atrophy: Characterization of abnormalities and potential for differential diagnosis at the single-patient level.

Background: Recent studies using resting-state functional connectivity and machine-learning to distinguish patients with neurodegenerative diseases from other groups of subjects show promising results. This approach has not been tested to discriminate between Parkinson's disease (PD) and multiple system atrophy (MSA) patients.

Objectives: Our first aim is to characterize possible abnormalities in resting-state functional connectivity between the cerebellum and a set of intrinsic-connectivity brain networks and between the cerebellum and different regions of the striatum in PD and MSA.

Dyskinesias and levodopa therapy: why wait?

Throughout the years there has been a longstanding discussion on whether levodopa therapy in Parkinson's disease should be started in early vs. later stages, in order to prevent or delay motor complications such as fluctuations and dyskinesias. This controversial topic has been extensively debated for decades, and the prevailing view today is that levodopa should not be postponed.

PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins.

Background And Objectives: To study selective regional binding for tau pathology in vivo, using PET with [ C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.

Methods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [ C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region.