Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

Area of Science:

• Neuroscience
• Immunology
• Neurology

Background:

• Axonal degeneration is a key factor in permanent neurological impairment in multiple sclerosis (MS).
• Mechanisms of axonal degeneration may vary with disease stage and lesion heterogeneity in MS.
• While MS etiology is unclear, prognostic biomarkers for predicting conversion to clinically definite MS are emerging.

Purpose of the Study:

• To review current clinical determinants of axonal damage in MS.
• To explore cellular and molecular mechanisms driving neurodegeneration in MS.
• To highlight therapeutic candidates for limiting axonal degeneration and disability in progressive MS.

Main Methods:

• Review of existing literature on MS biomarkers and neurodegeneration.
• Analysis of imaging techniques like OCT and DTI for axonal injury detection.
• Examination of spectroscopic methods (MRS) and CSF biomarkers (NF-L, NF-H).

Main Results:

• Current imaging and spectroscopic techniques show limitations in specificity for predicting axonal degeneration.
• CSF neurofilament light (NF-L) and heavy (NF-H) chains show promise as predictive biomarkers for progressive MS.
• Understanding molecular mechanisms, such as CRMP-2 modification, is crucial for developing targeted therapies.

Conclusions:

• Accurate predictive biomarkers for axonal degeneration in MS are needed.
• Targeting molecular pathways, including CRMP-2, offers potential for neuroprotection in MS.
• Combined therapeutic strategies may be essential for limiting axonal damage and improving outcomes in progressive MS.