Author Of 1 Presentation
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.