From the Guidelines
The main cause of permanent neurological disability in multiple sclerosis (MS) is axonal degeneration and neuronal loss, as supported by the most recent and highest quality study published in 2020 1.
Key Findings
- Axonal degeneration and neuronal loss are the primary drivers of irreversible disability in MS, rather than just demyelination.
- This process begins early in the disease course, even during the relapsing-remitting phase, and is driven by mechanisms such as direct inflammatory damage, loss of trophic support from myelin, mitochondrial dysfunction, oxidative stress, and glutamate excitotoxicity.
- The study published in 2020 1 highlights the importance of brain and spinal cord atrophy measures in clinical practice, and demonstrates that atrophy rates in the spinal cord are higher than those in the brain.
- The 2020 study 1 also shows that patients with low brain volume have a 2.4-fold higher risk of disability progression over the next 2 years than patients with high brain volume, emphasizing the need for early intervention with disease-modifying therapies.
Clinical Implications
- Early intervention with disease-modifying therapies is crucial to prevent or delay the accumulation of permanent disability in MS patients.
- Treatment approaches should focus on reducing inflammation and providing neuroprotection to preserve axonal integrity.
- Brain and spinal cord atrophy measures should be used in clinical practice to monitor disease progression and guide treatment decisions.
- The findings of the 2020 study 1 suggest that spinal cord atrophy measures, in particular, may be an important marker of disability status in MS, and should be considered in the management of MS patients.
From the Research
Main Cause of Permanent Neurological Disability in Multiple Sclerosis (MS)
The main cause of permanent neurological disability in Multiple Sclerosis (MS) is attributed to axonal loss. This is supported by several studies:
- Axon loss is the major cause of irreversible disability in patients with MS, as it begins early in the disease and correlates with inflammatory activity 2.
- The underlying cause for the permanent neurological deficits in MS patients is axonal loss, with demyelinated axons being prone to damage due to the lack of trophic support by myelin sheaths and oligodendrocytes 3.
- Axonal degeneration is a major determinant of permanent neurological impairment during MS, with the mechanisms governing axonal degeneration differing between disease stages 4.
- Loss of axons and neurons is the major cause of the progressive neurologic decline that most MS patients endure, with primary inflammatory demyelination as the underlying cause of axonal loss during earlier stages in MS 5.
- Axonal loss is a major pathologic process responsible for irreversible neurologic disability in patients with MS, with inflammatory demyelination as a principal cause of axonal transection and subsequent axonal degeneration 6.
Mechanisms of Axonal Loss
Several mechanisms contribute to axonal loss in MS, including: