Establishing Normative Values for the Barnett Balance Assessment Tool: A Preliminary Study

The purpose of this study was to establish normative data for the Barnett Balance Assessment (BBA) for individuals ages 18-70+ years. The BBA is a newly developed assessment tool that may address limitations present in other assessments currently used to detect balance deficits. The BBA was administered to 141 participants who had no history of medical issues that could impact balance. A review of the normative data collected indicated little variation in total assessment scores in the age categories of 18-29, 30-39, and 40-49, due to the presence of a ceiling effect. Variations existed in scores among participants in the remaining age categories (50-59, 60-69, and 70+). These findings may imply that the BBA has its greatest discriminative power in assessing individuals with impaired balance, and/or that the BBA is not sensitive enough to detect differences in individuals with mild balance impairments. The researchers suggest future studies be conducted with the BBA to establish norms with populations with known orthopedic or neurological conditions that may impair balance. Results of these studies could then be compared with the baseline data gathered in this study to determine the BBA’s usefulness in detecting balance impairments with clinical populations

α-Synuclein-induced myelination deficit defines a novel interventional target for multiple system atrophy

Multiple system atrophy (MSA) is a rare atypical parkinsonian disorder characterized by a rapidly progressing clinical course and at present without any efficient therapy. Neuropathologically, myelin loss and neurodegeneration are associated with alpha-synuclein accumulation in oligodendrocytes, but underlying pathomechanisms are poorly understood. Here, we analyzed the impact of oligodendrocytic alpha-synuclein on the formation of myelin sheaths to define a potential interventional target for MSA. Post-mortem analyses of MSA patients and controls were performed to quantify myelin and oligodendrocyte numbers. As pre-clinical models, we used transgenic MSA mice, a myelinating stem cell-derived oligodendrocyte-neuron co-culture, and primary oligodendrocytes to determine functional consequences of oligodendrocytic alpha-synuclein overexpression on myelination. We detected myelin loss accompanied by preserved or even increased numbers of oligodendrocytes in post-mortem MSA brains or transgenic mouse forebrains, respectively, indicating an oligodendrocytic dysfunction in myelin formation. Corroborating this observation, overexpression of alpha-synuclein in primary and stem cell-derived oligodendrocytes severely impaired myelin formation, defining a novel alpha-synuclein-linked pathomechanism in MSA. We used the pro-myelinating activity of the muscarinic acetylcholine receptor antagonist benztropine to analyze the reversibility of the myelination deficit. Transcriptome profiling of primary pre-myelinating oligodendrocytes demonstrated that benztropine readjusts myelination-related processes such as cholesterol and membrane biogenesis, being compromised by oligodendrocytic alpha-synuclein. Additionally, benztropine restored the alpha-synuclein-induced myelination deficit of stem cell-derived oligodendrocytes. Strikingly, benztropine also ameliorated the myelin deficit in transgenic MSA mice, resulting in a prevention of neuronal cell loss. In conclusion, this study defines the alpha-synuclein-induced myelination deficit as a novel and crucial pathomechanism in MSA. Importantly, the reversible nature of this oligodendrocytic dysfunction opens a novel avenue for an intervention in MSA