Dataset Information

Patient-Reported Symptoms in the Global Multiple System Atrophy Registry.

ABSTRACT:

Background

The Global Multiple System Atrophy Registry (GLOMSAR) was established in 2013. It is an online patient-reported contact registry open and free that relies on self-reported diagnosis by the patient or caregiver.

Objectives

To report the demographics of patients enrolled in GLOMSAR and the results of an ancillary online symptom questionnaire.

Methods

Patients enrolled in GLOMSAR were invited to complete a custom-designed online questionnaire about disease onset and symptom prevalence.

Results

At the time of writing, there were 1083 participants in GLOMSAR, of which 33% (365) completed the questionnaire. The onset and frequency of most symptoms was similar to those reported in the literature in physician-reported studies. Some were understudied or not typically associated with multiple system atrophy (MSA), including reduced female sexual sensation (55%), forgetfulness (60%), pseudobulbar affect (37%), olfactory changes (36%), and visual hallucinations (21%).

Conclusions

Patient-reported studies and ancillary online questionnaires are valid, underused research tools useful to advance our knowledge on understudied MSA features and highlight the patients' voice.

SUBMITTER: Palma JA

PROVIDER: S-EPMC9547130 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Patient-Reported Symptoms in the Global Multiple System Atrophy Registry.

Palma Jose-Alberto JA Krismer Florian F Meissner Wassilios G WG Kuijpers Mechteld M Millar-Vernetti Patricio P Perez Miguel A MA Fanciulli Alessandra A Norcliffe-Kaufmann Lucy L Bower Pam P Wenning Gregor K GK Kaufmann Horacio H

Movement disorders clinical practice 20220829 7

<h4>Background</h4>The Global Multiple System Atrophy Registry (GLOMSAR) was established in 2013. It is an online patient-reported contact registry open and free that relies on self-reported diagnosis by the patient or caregiver.<h4>Objectives</h4>To report the demographics of patients enrolled in GLOMSAR and the results of an ancillary online symptom questionnaire.<h4>Methods</h4>Patients enrolled in GLOMSAR were invited to complete a custom-designed online questionnaire about disease onset and ...[more]

PMID: 36247899

Similar Datasets

Project description:Registries have the potential to tackle some of the current limitations in determining the long-term impact of multiple sclerosis. Online assessments using patient-reported outcomes can streamline follow-up enabling large-scale, long-term, cost-effective, home-based, and patient-focused data collection. However, registry data are sparsely sampled and the sensitivity of patient-reported outcomes relative to clinician-reported scales is unknown, making it hard to fully leverage their unique scope and scale to derive insights. This retrospective and prospective cohort study over 11 years involved 15 976 patients with multiple sclerosis from the United Kingdom Multiples Sclerosis Register. Primary outcomes were changes in two patient-reported outcomes: Multiple Sclerosis Impact Scale motor component, and Multiple Sclerosis Walking Scale. First, we investigated their validity in measuring the impact of physical disability in multiple sclerosis, by looking at their sensitivity to disease subtype and duration. We grouped the available records (91 351 for Multiple Sclerosis Impact Scale motor and 68 092 for Multiple Sclerosis Walking Scale) by these two factors, and statistically compared the resulting groups using a novel approach based on Monte Carlo permutation analysis that was designed to cope with the intrinsic sparsity of registry data. Next, we used the patient-reported outcomes to draw novel insights into the developmental time course of subtypes; in particular, the period preceding the transition from relapsing to progressive forms. We report a robust main effect of disease subtype on the patient-reported outcomes and interactions of disease subtype with duration (all P < 0.0001). Specifically, patient-reported outcomes worsen with disease duration for all subtypes (all P < 0.0001) apart from benign multiple sclerosis (Multiple Sclerosis Impact Scale motor: P = 0.796; Multiple Sclerosis Walking Scale: P = 0.983). Furthermore, the patient-reported outcomes of each subtype are statistically different from those of the other subtypes at all time bins (Multiple Sclerosis Impact Scale motor: all P < 0.05; Multiple Sclerosis Walking Scale: all P < 0.01) except when comparing relapsing-remitting multiple sclerosis with benign multiple sclerosis and primary progressive multiple sclerosis with secondary progressive multiple sclerosis. Notably, there were statistically significant differences between relapsing-remitting and progressive subtypes at disease onset. Critically, the patient-reported outcomes are sensitive to future transitions to progressive subtypes, with individuals who transition presenting with higher patient-reported outcomes in their relapsing-remitting phase compared to individuals who don't transition since onset (all P < 0.0001). Patient-reported outcomes capture different patterns of physical worsening over disease length and across subtypes; therefore, they are a valid tool to measure the physical impact of multiple sclerosis over the long-term and cost-effectively. Furthermore, more advanced physical disability manifests years before clinical detection of progressive subtypes, adding evidence to the presence of a multiple sclerosis prodrome.

Project description:As the resident macrophages of the CNS, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they are crucial for de- and regenerative as well as immunological processes. The discovery of distinct activation patterns and increased phagocytosis indicated a damaging role of microglia in multiple system atrophy. This devastating, rapidly progressing atypical parkinsonian disorder is characterized by alpha-synuclein accumulation in the cytoplasm of oligodendrocytes. Alpha-synuclein aggregates have been related to myelin loss, severe neurodegeneration, and motor deficits accompanied by a region-specific myeloid immune response. Analyzing the gene expression profile of microglia in a mouse model of multiple system atrophy, MBP29-hα-syn mice, we identified a disease-assoctiated expression profile with an upregulation of the colony-stimulating factor 1 (Csf1). Thus, we hypothesized that targeting the CSF1 receptor using the small-molecule inhibitor PLX5622 reduces myeloid cells and thereby modifies the disease progression and neuropathological phenotype in this mouse model. After validation of a widespread depletion of myeloid cells after CSF1R inhibition, we consequently analyzed the survival, motor functions, neuropathological characteristics, and gene expression of affected brain regions in MBP29-hα-syn mice. Intriguingly, we identified a two-faced outcome comprising (1) an improved survival rate (24%) accompanied by delayed onset of neurological symptoms in contrast to (2) severely impaired motor functions in beam walking, pole test, and RotaRod of PLX5622-treated MBP29-hα-syn mice. Gene expression analysis revealed that PLX5622 reversed myeloid cell activation, however, predominantly reduced the expression of genes related to transsynaptic signaling and signal release. While these transcriptional changes were accompanied by a reduction of dopaminergic neurons in the substantia nigra pars compacta (19%) of PLX5622-treated MBP29-hα-syn mice, an increase of the striatal neuritic density was observed without changes in alpha-synuclein levels or myelin lipids in the forebrain. Together, our findings provide insight into the complex role of myeloid cell depletion in multiple system atrophy by demonstrating a two-faced outcome on the behavioral and neuronal phenotype of MBP29-hα-syn mice. Therefore, it is important to carefully balance the beneficial and adversive effects of CSF1R inhibition in different models of neurodegenerative disorders prior to clinical translation.

Dataset Information

Patient-Reported Symptoms in the Global Multiple System Atrophy Registry.

Background

Objectives

Methods

Results

Conclusions

Publications

Patient-Reported Symptoms in the Global Multiple System Atrophy Registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets