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How premorbid structural reserve affects disability accrual in multiple sclerosis
Elena Barbuti1,2, Luca Prosperini3, Serena Ruggieri3
1Department of Human Neurosciences, Sapienza University, Rome, Italy.
Multiple Sclerosis (Houndmills, Basingstoke, England)
|October 8, 2025
Summary
Premorbid structural reserve, including intracranial volume (ICV) and spinal cervical canal area (SCCA), mitigates long-term disability accumulation in multiple sclerosis (MS). Higher ICV and SCCA are associated with slower disease progression, supporting their use as prognostic markers.
Area of Science:
- Neuroimaging and Neurodegeneration
- Neurology and Clinical Neuroscience
Background:
- Multiple Sclerosis (MS) is a chronic neurological disease characterized by progressive accumulation of disability.
- Understanding factors influencing MS disability progression, including progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW), is crucial for effective management.
- Premorbid structural reserve, represented by intracranial volume (ICV) and spinal cervical canal area (SCCA), may play a role in neuroprotection.
Purpose of the Study:
- To investigate the influence of premorbid structural reserve proxies (ICV and SCCA) on long-term disability accumulation in patients with relapsing-onset MS.
- To determine whether ICV and SCCA affect disability accrual through PIRA and RAW pathways.
- To assess the combined effect of ICV and SCCA on reaching significant disability milestones.
Main Methods:
- A cohort of 253 patients with relapsing-onset MS and at least a 5-year follow-up from their first demyelinating event (FDE) was analyzed.
- 3D T1-weighted MRI scans were used to estimate ICV and SCCA.
- Negative binomial regression and competing risk models were employed to analyze PIRA and RAW events, accounting for their co-occurrence.
Main Results:
- Higher SCCA was associated with fewer PIRA events and delayed PIRA onset.
- Larger ICV was linked to fewer RAW events, later occurrence of RAW, and older age at RAW.
- Patients with high combined reserve (larger ICV and SCCA) reached Expanded Disability Status Scale (EDSS) ≥ 6.0 significantly later and at an older age compared to those with low reserve.
Conclusions:
- Premorbid structural reserve, measured by ICV and SCCA, significantly mitigates long-term disability accrual in MS.
- These findings support the integration of ICV and SCCA into prognostic models for MS.
- ICV and SCCA serve as valuable markers of neuroanatomical resilience in the context of MS progression.
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