Objectives
Developing disease modifying therapies for Parkinson’s disease (PD) calls for outcome measurement strategies focused on characterizing early stage disease progression. We explored the ...psychometric evidence for using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II (patient motor experience of daily living) and part III (clinician motor examination) in this context.
Methods
MDS-UPDRS-II and -III data were collected at screening, month 12, and month 24 from 384 early stage PD patients (diagnosis ≤ 2 years; Hoehn and Yahr stage 1/2) in the Parkinson’s Progression Markers Initiative (PPMI) study. Psychometric analysis, based on Rasch measurement theory (RMT), was performed on both the original MDS UPDRS-II and -III scales and exploratory content-driven scale structures.
Results
RMT analyses showed neither scale was well targeted to early PD. A marked floor effect appeared for most items and a clear item gap was consistently observed in very mild severity of motor signs and levels of motor impact. The original MDS-UPDRS-II and -III scales also displayed disordered thresholds (9/13 and 20/33 items, respectively), indicating response scales not functioning as expected, and misfit (5/13 and 12/33 items, respectively), flagging areas for potential improvement.
Conclusions
The MDS-UPDRS-II and -III have psychometric limitations which limits the precision of measurement of motor symptoms and impact in early PD. This can lead to insensitivity in detecting differences and clinical change. Importantly, the diagnostic psychometric evidence provided by the RMT analysis provides a clear starting point for how to improve the quantification of clinically relevant concepts to characterize the course of early PD.
At a time when information systems for geographic and historical reconstruction based on the digitization of cartographic and scientific archives proliferate, it is necessary to develop methods for ...the study of formerly colonized spaces. These spaces raise specific problems in the treatment of sources and the modelling process : they require a geomatic perspective which has to be critical, delicate, and even paradoxical. Interdisciplinary experiments carried out in the still nascent field of spatialized digital humanities offer leads for responding to the apparent paradox of geomatics in postcolonial and decolonial contexts. This article aims at demonstrating the relevance of such methodological hypotheses by developing the example of the city of Fort-de-France in Martinique. The purpose of this paper is to illustrate that the integration of alternative geohistorical information, such as that derived from novels, enriches the geographic and historical modelling of the city. Our intention is to open a critical research project based on the enrichment of geographic information by the digital humanities, to show its relevance and legitimacy and to raise the questions that appear in such work.
À l’heure où se multiplient les systèmes d’information de reconstruction géographique et historique ayant pour fondement la numérisation des archives cartographiques et scientifiques, il est ...nécessaire de développer des méthodes spécifiques concernant les espaces anciennement colonisés, car ils posent des questions de sources et de modélisation particulières, marquées notamment par la nécessité d’adopter en géomatique une perspective critique, délicate, voire paradoxale. Les expérimentations interdisciplinaires réalisées dans le champ encore naissant des humanités numériques spatialisées offrent des pistes pour répondre à l’apparent paradoxe de la géomatique en contexte postcolonial. Cet article propose de démontrer la pertinence de cette hypothèse méthodologique en développant l’exemple de la ville de Fort-de-France en Martinique. L’objectif est de montrer que l’intégration d’informations géohistoriques alternatives, comme celles issues des romans, enrichit la modélisation géographique et historique de la ville. Notre intention est également d’ouvrir un chantier de recherche critique fondé sur l’enrichissement des informations géographiques par les humanités numériques, d’en montrer la pertinence et la légitimité et de soulever les questions qui le traversent.
Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease promotes hippocampal degeneration, which in turn affects ...multiple cognitive domains and daily life activities. In this study, we hypothesized that long-lasting therapy with mesenchymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline typical of sAD, as they have shown neurogenic and immunomodulatory activities. To test this, we chronically injected intravenous human MSC in a sAD rat model induced by the intracerebroventricular injection of streptozotocin (STZ). During the last 2 weeks, we performed open field, Barnes maze, and marble burying tests. STZ-treated rats displayed a poor performance in all behavioral tests. Cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble burying behavior, the latter being representative of daily life activities. On the hippocampus, we found that STZ promotes neuronal loss in the
Cornus Ammoni
(CA1) field and decreased neurogenesis in the dentate gyrus. Also, STZ induced a reduction in hippocampal volume and presynaptic protein levels and an exacerbated microgliosis, relevant AD features. The therapy rescued CA1 neurodegeneration but did not reverse the decrease of immature neurons, suggesting that the therapy effect varied among hippocampal neuronal populations. Importantly, cell therapy ameliorated microgliosis and restored hippocampal atrophy and some presynaptic protein levels in the sAD model. These findings, by showing that intravenous injection of human MSC restores behavioral and hippocampal alterations in experimental sAD, support the potential use of MSC therapy for the treatment of neurodegenerative diseases.
Germline WWOX pathogenic variants have been associated with disorder of sex differentiation (DSD), spinocerebellar ataxia (SCA), and WWOX-related epileptic encephalopathy (WOREE syndrome). We review ...clinical and molecular data on WWOX-related disorders, further describing WOREE syndrome and phenotype/genotype correlations.
We report clinical and molecular findings in 20 additional patients from 18 unrelated families with WOREE syndrome and biallelic pathogenic variants in the WWOX gene. Different molecular screening approaches were used (quantitative polymerase chain reaction/multiplex ligation-dependent probe amplification qPCR/MLPA, array comparative genomic hybridization array-CGH, Sanger sequencing, epilepsy gene panel, exome sequencing), genome sequencing.
Two copy-number variations (CNVs) or two single-nucleotide variations (SNVs) were found respectively in four and nine families, with compound heterozygosity for one SNV and one CNV in five families. Eight novel missense pathogenic variants have been described. By aggregating our patients with all cases reported in the literature, 37 patients from 27 families with WOREE syndrome are known. This review suggests WOREE syndrome is a very severe epileptic encephalopathy characterized by absence of language development and acquisition of walking, early-onset drug-resistant seizures, ophthalmological involvement, and a high likelihood of premature death. The most severe clinical presentation seems to be associated with null genotypes.
Germline pathogenic variants in WWOX are clearly associated with a severe early-onset epileptic encephalopathy. We report here the largest cohort of individuals with WOREE syndrome.
Sporadic Alzheimer’s disease (SAD) is the most common form of dementia; therefore, there is an urgent need for a model that recapitulates the main pathologic hallmarks of this disease. The ...intracerebroventricular (icv) injection of streptozotocin (icv-STZ) in rats constitutes a promising model, and thus, icv-STZ rats develop insulin-resistant brain state and cognitive impairments. Even though a great piece of studies has hitherto described this system as a model for SAD, further behavioral and morphometric studies are still needed to fully characterize it. In this study, using
Sprague Dawley
rats, we evaluated short-term effects on behavior and hippocampus morphometry of the icv-STZ injection at two doses: 1 (STZ1) and 3 mg/kg (STZ3). We found that, following icv-STZ injection, STZ3 animals, but not STZ1, exhibited impairments in spatial reference learning and memory (Barnes maze test) and in recognition memory (object recognition test). Furthermore, the results from behavioral and morpho-histochemical data are compatible. STZ3 rats displayed
Stratum Radiatum
volume reduction and a decreased NeuN immunoreactivity (neuron loss) in hippocampal CA1 region, together with an increased immunoreactivity for microglial (Iba1) and astroglial (GFAP) markers (neuroinflammation). Sholl analysis revealed the vulnerability of hippocampal astrocytes to STZ in CA1 and CA3. Thus, both doses induced a reduction in process length and in the number of main processes, accompanied by a frank decrease in branching complexity. The present study provides important knowledge of this AD rat model. Overall, we found that the only high STZ dose induced severe and acute neurodegenerative lesions, associated with an inflammation process.
PDF
