title: The development and evaluation of an individualised gait modification intervention to improve movement function in alkaptonuria patients
Creators: name: Shepherd, H
Publisher: name: Liverpool John Moores University
Year: 2020

description: Alkaptonuria (AKU) is an ultra-rare genetic disorder which leads to a process called ochronosis, this process discolours and damages the integrity of the joints. Ochronosis within the joint leads to several symptoms including joint pain, premature osteoarthritis and a decline of joint health until eventually total joint failure. These symptoms directly impact mobility, gait and consequently the patient’s quality of life, however, there is limited data focussing on the effects of AKU on gait. Mechanical loading at the joint contributes to the ochronosis process, joint damage and progression of the disease. Treatment options currently include nitisinone, however the adverse side effects of long-term use remain a concern. A gait modification intervention is a non-invasive method which has the potential to reduce the loading in the joints which could delay the progression of the disease and delay the time before joint replacements are required. The work within this thesis firstly describes and characterises gait using novel methods to help understand the progression of the disease and its specific gait mechanisms. The gait of 36 AKU patients between 16-70 years under no treatment were analysed. Gait deviations from normality were discovered in patients as young as 16 years old and a sharp increase was seen at 50 years. Joint level descriptions of gait mechanisms revealed the knee joint to be a problematic factor across all age groups in AKU. Driven by the evidence, the knee joint became the focus of the gait intervention’s development and design. The thesis also includes development of a novel intervention tool tailored to alkaptonuria patients, which overcomes some of the methodological shortcomings found in related previous research. The 3D Lever Arm method is a simplified, fast computing method which provides the 3D knee moment impulse in real-time to the patient and is designed to create an individualised approach to gait modifications. The 3D lever arm method was compared to the ‘Gold Standard’ inverse dynamics during normal walking and six well known gait modifications for 16 healthy controls. The new method demonstrated good agreement during normal walking although underestimated the 3D knee moment impulse, most importantly it was able to detect change during the six gait modifications. The protocol also investigated six gait modifications’ ability to reduce the 3D knee moment impulse and the effects on adjacent joints. Only four out of the six were effective at reducing the 3D knee moment impulse, with two increasing adjacent joint moments, and the results highlighted a large variation of individualised approaches. The results led to only three out of six gait modifications being acceptable for future guidance during the final intervention study. Finally, using the new intervention tool, a gait modification protocol was designed for AKU patients, however, findings of only one healthy participant are presented. The results showed that the participant was able to reduce the 3D knee moment impulse after the individualised gait modification intervention and this was also retained when walking overground. Overall, the findings of this thesis provide the first joint level description of gait in alkaptonuria, develop a gait modification intervention tool and protocol design. These findings provide the vital first steps towards gait modification interventions for alkaptonuria patients with discussions for future research studies.