Position Sense Deficits at the Lower Limbs in Early Multiple Sclerosis: Clinical and Neural Correlates

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.