Assessing movement changes in degenerative ataxias: from the pre-ataxic disease stage to the effects of a bio-feedback intervention

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Dokumentart: PhDThesis
Date: 2021-03-11
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Synofzik, Matthis (Prof. Dr.)
Day of Oral Examination: 2021-01-13
DDC Classifikation: 000 - Computer science, information and general works
610 - Medicine and health
Other Keywords:
degenerative ataxia
preclinical stage
movement analysis
quantitative motor features
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Degenerative ataxias are a heterogenous group of movement disorders defined by progressive ataxia due to a degeneration of the cerebellum and its associated tracts, often of genetic origin. Disease-modifying drugs are still lacking for degenerative ataxias, thus highlighting the need for paving the way for both interventional drug trials and for innovative neurorehabilitation approaches. Detailed quantitative movement analysis might hereby help to detect and grade cerebellar dysfunction, possibly even at the preataxic stages of the disease, thus helping to chart a promising window for early treatment interventions before clinical disease onset. Moreover, it might help to gain new insights into the functional role of the cerebellum in motor control and related sensory integration mechanisms, which might be used to inform future neurorehabilitation strategies. Correspondingly, we here hypothesized (1) that quantitative movement analysis allows to reveal early movement changes when clinical signs are still absent and to capture motor progression in subjects at the preataxic stage of spinocerebellar ataxia (SCA) (study #1). Moreover, we hypothesized (2) that quantitative movement analysis allows to identify the effects of a biofeedback intervention in patients with degenerative ataxia, where they might be able to exploit real-time acoustic bio-feedback signals (ABF) of trunk acceleration to compensate for impaired postural control (study #2). Study 1: 46 participants (14 preataxic SCA mutation carriers [SCAs 1,2,3,6], 9 SCA patients at an early symptomatic stage; and 23 healthy controls) were analysed by quantitative movement analysis during stance and walking tasks of increasing complexity. We identified motor features that (i) differentiated between preataxic mutation carriers and healthy controls, even in absence of clinical signs and (ii) correlated with repeat expansion-based estimated time to disease onset. These results demonstrate that quantitative movement analysis in combination with tasks of rising difficulty levels allows to detect subclinical motor changes in spinocerebellar ataxia before clinical manifestation, which may enable the quantification of disease progression in the preclinical phase. Study 2: Quantitative movement analysis was used to investigate the effects on postural sway during stance in a short-term ABF intervention group versus a no-ABF disease control group (23 and 17 cerebellar patients, respectively). Postural sway under the conditions ‘eyes open’ and ‘eyes closed’ was measured prior to ABF, under ABF, and post ABF. Our analysis revealed a significant reduction of body sway under ABF in the ‘eyes closed’ condition. Patients who had the largest extent of postural sway at baseline even improved their stability in the ‘eyes open’ condition under ABF. Correlations were found between the degree of postural sway at baseline and the benefits of both ABF and vision, and moreover, between the benefits of both sensory modalities (i.e. ABF and vision). The no-ABF control group did not exhibit any changes in sway across stance trials. These results provide proof-of-principle evidence that despite cerebellar degeneration, patients are still able to improve dysfunctional postural control by integrating augmented sensory cues: In absence of vision, the reliance on added auditory cues can be exploited to a similar extent as vision. In case of strong postural sway, augmented auditory information can be exploited also in combination with vision. These findings indicate promising compensatory strategies of cerebellar patients to maintain balance and might inform future assistive approaches.

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