BACKGROUND MS symptoms affect many functional domains. Knowing the specific impact of symptoms on health-related quality of life (HRQoL) is vital for successful disease and symptom management in MS. We aimed at investigating how specific MS symptoms contribute to the disease burden in individuals and from a population perspective. METHODS We included 855 Swiss Multiple Sclerosis Registry participants with a relapsing-remitting form (RRMS) or a progressive form (PMS). HRQoL was measured with the EuroQol 5-Dimension EQ-5D-index and EQ-Visual Analogue Scale (EQ-VAS) on 0-100% scales. Their associations with 20 symptoms, socio-demographic and clinical information were explored in median regression models, stratified by RRMS and PMS. RESULTS We included 611 participants with RRMS and 244 with PMS. In RRMS, gait (-6.5%) and balance problems (-5.1%) had the largest EQ-5D-index reductions, and were also important at the population level (frequencies 45% and 52%). Fatigue, depression, and spasticity (frequencies 74.1%, 31%, 38%) also contributed to the population disease burden. In PMS, spasticity, paralysis, and bowel problems had the largest impact on EQ-5D-index, both at the individual and population levels. The largest impact on EQ-VAS at population level was associated in RRMS with balance problems, depression, dizziness, and spasticity, while in PMS with weakness, pain, and paralysis. CONCLUSIONS While HRQoL at population level is most affected by balance problems, spasticity, and depression in RRMS, the biggest HRQoL losses in PMS are caused by spasticity, paralysis, weakness, and pain. Many symptoms with the largest effects in individuals substantially contribute to the population disease burden.

Background/Aim: Pulmonary function tests are used for screening respiratory insufficiency in patients with myotonic dystrophy (DM). We analysed the agreement between two different approaches in assessment of abnormal findings of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), in DM patients. Methods: We used Cohen’s κ- and Bangdiwala’s B- statistic to compare the agreement between different cut-off values recommended by experts (ENMC) and the cut-off values based on the reference range (RR). We further analysed their sensitivity (Sn) and specificity (Sp) in detecting symptoms associated with respiratory insufficiency. Results: The observed agreement was: 1) for FVC: κ= –0.002, B = 0.406; 2) for FEV1: κ= 0.944, B = 0.946; 3) for MIP: κ= 0.625, B = 0.674; and 4) for MEP: κ= 0.241, B = 0.373. Overall, RR cut-off values showed higher sensitivity, whereas the ENMC values showed higher specificity in detecting symptoms of respiratory involvement. Conclusions: The two approaches showed perfect agreement in assessment of FEV1, substantial agreement for MIP, and weak agreement for FVC and MEP. RR is an established method of assessment for spirometry and should be favoured because it takes variability within the population into account. Further development and validation of regression equations for RR calculations of predicted maximal respiratory pressures, with corresponding lower limits of normal, is required. The B statistic is more robust in assessing agreement between two diagnostic methods, resolving the issue of the κ paradox.

Myotonic Dystrophy type 1 multisystem involvement leads to functional impairment with an increased risk of falling. This multinational study estimates the prevalence of falls and fall-associated fractures. A web-based survey among disease-specific registries (Germany, UK and The Netherlands) was carried out among DM1 ambulant adults with a total of 573 responses retrieved. Results provided a risk ratio estimation of 30%-72% for falls and of 11%-17% for associated fractures. There was no significant difference for falls between male and female, but there was for fall-related fractures with a higher prevalence in women. Balance and leg weakness were the most commonly reported causes for falling. This study is based on a voluntary retrospective survey with naturally inherent limitations; however, the sample size allows for robust comparisons. The estimated risk of falls in this cohort with a mean age of 46 years compares to a previous estimation for a healthy population of over 65 years of age. These results suggest a premature-ageing DM1 phenotype with an increased risk of falling depending on age and disease severity that, so far, might have been underestimated. This may have clinical implications for the development of care guidelines and when testing new interventions in this population.