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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Is multiple sclerosis a length-dependent central axonopathy?
T2 - Some empirical data from the TONiC study
AU - Trajectories of Outcome in Neurological Conditions-MS Study Group
AU - Mills, Roger J
AU - Schlüter, Daniela K
AU - Diggle, Peter J
AU - Tennant, Alan
AU - Young, Carolyn A
PY - 2025/6/20
Y1 - 2025/6/20
N2 - There is a long-held hypothesis that multiple sclerosis (MS) affects the central nervous system in a length dependent way reflecting the propensity of longer central axonal projections to accumulate damage, but evidence for this is lacking. To determine the prevalence of body part involvement in MS and relate this to the putative axonal length innervating each body part, we asked people with MS to indicate affected body parts on a somatic diagram. Axonal length for each body part was calculated from neuroanatomical literature. The survey was part of the TONiC-MS study. Records from 5925 respondents were analysed for involvement of eleven distinct body parts (either hand/ upper limb /lower limb, urinary bladder, neck, speech, vision, swallowing), and also balance. Participants had a wide range of age, disease duration, disease subtypes and disability levels. Body part involvement in the whole sample was highly correlated with axonal length (rho 0.933). At an individual level, a logistic regression including covariates of age, disease type and disability level demonstrated that the probability of body part involvement was substantially dependent on axonal length across all disease types. Our study supports the hypothesis that MS disability reflects a length-dependent central axonopathy.
AB - There is a long-held hypothesis that multiple sclerosis (MS) affects the central nervous system in a length dependent way reflecting the propensity of longer central axonal projections to accumulate damage, but evidence for this is lacking. To determine the prevalence of body part involvement in MS and relate this to the putative axonal length innervating each body part, we asked people with MS to indicate affected body parts on a somatic diagram. Axonal length for each body part was calculated from neuroanatomical literature. The survey was part of the TONiC-MS study. Records from 5925 respondents were analysed for involvement of eleven distinct body parts (either hand/ upper limb /lower limb, urinary bladder, neck, speech, vision, swallowing), and also balance. Participants had a wide range of age, disease duration, disease subtypes and disability levels. Body part involvement in the whole sample was highly correlated with axonal length (rho 0.933). At an individual level, a logistic regression including covariates of age, disease type and disability level demonstrated that the probability of body part involvement was substantially dependent on axonal length across all disease types. Our study supports the hypothesis that MS disability reflects a length-dependent central axonopathy.
KW - Disability progression
KW - Manikin
KW - TONiC-MS
KW - Kurtzke
KW - Neuroanatomy
KW - Pathophysiology
U2 - 10.1016/j.msard.2025.106594
DO - 10.1016/j.msard.2025.106594
M3 - Journal article
C2 - 40570401
VL - 101
JO - Multiple sclerosis and related disorders
JF - Multiple sclerosis and related disorders
SN - 2211-0356
M1 - 106594
ER -