Congenital Myasthenic Syndromes (CMS) are a group of rare genetic disorders affecting the neuromuscular junction structure and function. They are characterised by the presence of fatigable muscle weakness, but the age of onset, presenting symptoms and distribution of weakness differ depending on the genotype and specific mutations affected. The severity of CMS is highly variable amongst individuals, fluctuating and worsening with physical effort, which makes assessments challenging. Currently, there are no validated outcome measures for use in CMS, with most clinicians using outcome measures validated in Myasthenia Gravis and other neuromuscular conditions. The need to establish robust natural history data and validated outcome measures in this rare condition will be increasingly important with emerging novel treatments already in development. This study looks to answer whether there is a relationship between an instrumented six-minute walking test (6MWT) and community physical activity levels through the use of a wrist-worn physical activity (PA) monitor (AX3, Axivity, UK) over seven days. 40 participants were assessed for PA analysis, with 37 having conducted a corresponding 6MWT test. Participants had a range of CMS subtypes, including the most common (AChR deficiency n=12, DOK7 n=12, RAPSYN n=5). It was identified that participants spent an average of 83.3% of the week in sedentary activity and 12.5% of the week in moderate-vigorous activity (MVPA). Overall, there was a weak correlation between distance walked on the 6MWT (range 25m – 711m) and community PA outcomes. However, participants who spent longer in sedentary activity (≥90% activity/week) all walked less than 500m on the 6MWT. Further in-depth analysis showed participants with limited walking distance experienced higher levels of walk variability and a greater difference between walking speed at the start and end of the 6MWT. Participants walk ratios (WR) varied, with muscle fatigue resulting in a change in cadence, but not stride length. This first-of-a-kind study presents the relationship of community PA and in-clinic mobility outcome measurements such as the 6MWT in this heterogeneous CMS population. We have been able to describe with greater detail the features of walking fatigue in this population, by utilising a small patient-worn inertial measurement unit (IMU), alongside the clinic-based instrumented walking test (6MWT). The use of an IMU may prove a useful application in future clinical and research data collection and help guide condition management.
Permanent link to this resource: https://doi.org/10.24384/167h-py74
Ramjattan, Hayley
Supervisors: Esser, Patrick ; Palace, Jacqueline
Faculty of Health and Life Sciences
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