The use of inertial measurement units for the determination of gait spatio-temporal parameters

The aim of this work was to develop a methodology whereby inertial measurement units (IMUs) could be used to obtain accurate and objective gait parameters within typical developed adults (TDA) and Parkinson’s disease (PD). The thesis comprised four studies, the first establishing the validity of the IMU method when measuring the vertical centre of mass (CoM) acceleration, velocity and position versus an optical motion capture system (OMCS) in TDA. The second study addressed the validity of the IMU and inverted pendulum model measurements within PD and also explored the inter-rater reliability of the measurement. In the third study the optimisation of the inverted pendulum model driven by IMU data was explored when comparing to standardised clinical tests within TDA and PD, and the fourth explored a novel phase plot analysis applied to CoM movement to explore gait in more detail. The validity study showed no significant difference for vertical acceleration and position between IMU and OMCS measurements within TDA. Vertical velocity however did show a significant difference, but the error was still less than 2.5%. ICCs for all three parameters ranged from 0.782 to 0.952, indicating an adequate test-retest reliability. Within PD there was no significant difference found for vertical CoM acceleration, velocity and position. ICCs for all three parameters ranged from 0.77 to 0.982. In addition, the reliability calculations found no difference for step time, stride length and walking speed for people with PD. Inter-rater reliability was found not to be different for the same parameters. The optimisation of the correction factor when using the inverted pendulum model showed no significant difference between TDA and PD. Furthermore the correction factor was found not to be related to walking speed. The fourth and final study found that phase plot analysis of variability could be performed on CoM vertical excursion. TDA and PD were shown to have, on average, different characteristics. This thesis demonstrated that CoM motion can be objectively measured within a clinical setting in people with PD by utilizing IMUs. Furthermore, in depth gait variability analysis can be performed by utilizing a phase plot method

Phase contrast radiography of Lewy bodies in Parkinson disease

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons and the presence of Lewy bodies in neurons. Morphological study of Lewy bodies is important to identify the causes and the processes of PD. Here, we investigate a possibility of phase contrast radiography using coherent synchrotron X-rays to explore the microscopic details of Lewy bodies in thick (approximately 3 mm) midbrain tissues. Autopsied midbrain tissues of a PD patient were sliced in 3 mm thickness and then examined using synchrotron X-rays from the 7B2 beamline of the Pohang Light Source. Refraction-enhanced phase contrast radiography and microtomography were adopted to identify dark core and dim edge of Lewy bodies in neurons. The morphology of Lewy bodies was clearly revealed by the phase contrast radiography in very thick (3 mm) midbrain tissues without any staining treatment. Three-dimensional volume rendered microtomography of the autopsied midbrain tissues demonstrates striking evidence that several Lewy bodies are agglomerated by dim edges in a neuron. We suggest that the phase contrast radiography could be a useful tool to morphologically investigate the causes or the processes in PD

Phase contrast radiography of Lewy bodies in Parkinson disease

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons and the presence of Lewy bodies in neurons. Morphological study of Lewy bodies is important to identify the causes and the processes of PD. Here, we investigate a possibility of phase contrast radiography using coherent synchrotron X-rays to explore the microscopic details of Lewy bodies in thick (similar to 3 mm) midbrain tissues. Autopsied midbrain tissues of a PD patient were sliced in 3 mm thickness and then examined using synchrotron X-rays from the 7B2 beamline of the Pohang Light Source. Refraction-enhanced phase contrast radiography and microtomography were adopted to identify dark core and dim edge of Lewy bodies in neurons. The morphology of Lewy bodies was clearly revealed by the phase contrast radiography in very thick (3 mm) midbrain tissues without any staining treatment. Three-dimensional volume rendered microtomography of the autopsied midbrain tissues demonstrates striking evidence that several Lewy bodies are agglomerated by dim edges in a neuron. We suggest that the phase contrast radiography could be a useful tool to morphologically investigate the causes or the processes in PD. (c) 2006 Elsevier Inc. All rights reserved.X1111sciescopu

The L-dopa response in Parkinson's disease

L-dopa is the most commonly prescribed drug for the treatment of Parkinson’s disease (PD). Most patients benefit from this treatment as it can restore motor function but over time, a large proportion of patients report the manifestation of side effects. The L-dopa response is also a supportive criterion for the diagnosis of PD. This thesis aimed to explore the variation of responsiveness to L-dopa and to identify predictor variables for responsiveness. This was achieved by systematically reviewing pathological studies and case reports; analysing two large and longitudinal clinical cohort studies with focus on short- and long-term indicators of responsiveness; and the analysis of brain imaging data indicative of the degree of dopaminergic loss at different stages of the disease. The systematic review established a great variation in responsiveness to L-dopa, analysing pathologically confirmed cases where there is little to no doubt about diagnostic accuracy: 10% of definite Parkinson’s are unresponsive to L-dopa and 12% show a modest response. The clinical cohort analysis showed that current treatment management approaches lead to an overall lower prevalence of motor complications compared to earlier studies, even when L-dopa is introduced early-on. Motor fluctuations have the greatest impact on motor function but also on the patients’ abilities in everyday life situations. Investigating the short-term response showed an association of better motor function with the development of dyskinesia, and dyskinetic patients with a better response to challenge testing. Finally, SPECT imaging data showed a high residual activity of dopamine in early PD, and an association of lower putaminal uptake with higher medication doses at later stages of the disease. In conclusion, a lesser response to L-dopa should be considered as a definite phenomenon in a large proportion of PD patients. Assessing L-dopa responsiveness more widely, in clinical practice and clinical research would enhance both our understanding of patients and our interpretation of the effects of new drug treatments