Author Of 2 Presentations
P0877 - Is multiple sclerosis a length-dependent central axonopathy ? Some empiric data from the TONiC study (ID 1594)
Abstract
Background
The natural history of progressive multiple sclerosis (MS) is one of evolving paraparesis, then tetraparesis and ultimately bulbar dysfunction. Recently, it was proposed that progressive MS is a length dependent axonopathy due to random incremental damage throughout the central nervous system, and that “this length-dependent process might be explained by stochastic statistical phenomena that interact with anatomical, pathological and biological factors”.
Objectives
To determine the prevalence of body part involvement in a large MS population and whether such prevalence is related to axonal length.
Methods
A questionnaire pack including a pictorial mannequin upon which body part involvement could be indicated was administered to patients with definite MS as part of the TONiC study, a multicentre, UK study of factors affecting quality of life in MS. Subject characteristics were determined by a physician at study enrolment. A logistic regression model was developed adjusting for demographic factors to determine probabilities of body part involvement and whether probabilities varied by disease factors and their relationship to axonal length. Average lengths of neuronal pathways from cortex to points along the CNS were taken from the literature.
Results
4204 records were available for analysis. Mean age was 50.2 years, median disease duration 11.2 years. 73% were female, 65% had relapsing, 11% primary progressive and 24% secondary progressive disease. 50% were fully ambulatory (EDSS 0–4), 38% EDSS 4.5–6.5, 7% EDSS 7.0–7.5, 5% 8.0–9.5. Prevalence decreased in the following order: left lower limb, right lower limb, bladder, left hand, right hand, vision, left arm, right arm, speech, neck, swallowing. Axonal length was strongly associated with body part prevalence with an odds ratio of 4.2 per standard deviation of axonal length (23.95cm) for patients with progressive disease and 2.7 for those with relapsing disease. Only weak clustering of body parts was found with correlation coefficients of the model residuals ranging between -0.28 and 0.35, the strongest being between ipsilateral hand, arm and lower limb.
Conclusions
We demonstrate a probabilistic hierarchy of body parts affected by MS in a large cross-sectional sample of patients. The hierarchy progresses from distal to proximal segments and lends some clinical support to the length dependent axonopathy theory of MS.
P1021 - Does the WHODAS 2.0 comprehensively measure disability in multiple sclerosis? (ID 1175)
Abstract
Background
Traditionally, the Expanded Disability Status Scale (EDSS) has been used for both clinical assessment and trial outcomes. The measurement properties of the EDSS are problematic, for example, it has been shown that the EDSS inadequately captures non-motor aspects of disability (e.g. fatigue, detrusor failure, pain, sexual dysfunction). An outcome which measures all aspects of disability would be desirable and one such potential candidate is the World Health Organisation Disability Assessment Schedule v2.0 (WHODAS 2.0).
Objectives
To assess the WHODAS 2.0 against a wide range of self-reported outcomes measuring many different aspects of functional impairment in a large MS cohort.
Methods
Self-report instruments examining: MS impact (MSIS), fatigue (NFI-MS), spasticity (MSSS), sleep dysfunction (NSI-MS), bladder function (QUALIVEEN), pain (NPS), vision (MSVQ), sexual function (MSISQ), anxiety & depression (HADS), and the WHODAS 2.0 disability scale were administered to patients with definite MS as part of the TONiC study, a multicentre, UK study of factors affecting quality of life in MS. Subject characteristics including disease subtype and EDSS level (in four bands: 0–4, 4.5–6.5, 7.0–7.5, 8.0–9.5) were determined by a physician at study enrolment. Summed raw scale scores were converted to interval level data by application of the Rasch measurement model. Relationships were visualised by box plot with appropriate statistics for detecting group difference.
Results
Records from 5907 subjects were available for analysis. Mean age was 50.2 years, median disease duration 11.2 years. 73% were female, 66% had relapsing, 11% primary progressive and 23% secondary progressive disease. 51% were fully ambulatory (EDSS 0–4), 37% EDSS 4.5–6.5, 7% EDSS 7.0–7.5, 5% 8.0–9.5. There were significant differences in expected gradients against the WHODAS 2.0 for all of the factors measured. The relationships were preserved for all disease subtypes.
Conclusions
The WHODAS 2.0 not only measures physical disability as expected but also performs well to capture non-motor and psychological aspects of disability. It might be considered superior to the EDSS which, in a previous similar analysis, failed to distinguish many non-motor aspects of disability, especially in progressive disease subtypes. Prior work has shown that the WHODAS fits the Rasch measurement model and so if satisfactory minimum clinical important change and sensitivity to change can be demonstrated in MS then it could be recommended as an excellent outcome to detect disability in MS.