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Related Concept Videos

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Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
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Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...
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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
PubMed
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.

Keywords:
Multiple sclerosisPIRARAWbrain reservespinal cord reserve

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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.