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Beta-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis
A Parry1, R Corkill, A M Blamire
1Centre for Functional Magnetic Resonance Imaging of the Brain, The John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. paul@fmrib.ox.ac.uk
Abstract:
Progression of disability in multiple sclerosis (MS) appears related to axonal damage, which is at least in part associated with white matter lesions. Beta-interferon (BIFN) substantially reduces new inflammatory activity in MS and a recent report suggested that it may reverse a component of axonal injury. To test the generalisability of this conclusion, particularly in a population with relatively active disease, we used magnetic resonance spectroscopy measures to test whether BIFN can reverse or arrest progression of axonal injury in patients with MS. Eleven patients with a history of active (median, 1.5 relapses/year) relapsing-remitting MS were treated with BIFN and responses to treatment were monitored with serial MRI and single voxel magnetic resonance spectroscopic measurements of relative concentrations of brain N-acetylaspartate (NAA), a measure of axonal integrity from a central, predominantly white matter brain region. BIFN treatment was associated with a significant reduction in relapse rate (p = 0.007) and white matter water T2 relaxation time (p = 0.047) over 12 months. Also consistent with a treatment effect, white matter T2-hyperintense lesion loads did not increase. However, the central white matter NAA/creatine ratio (NAA/Cr, which was reduced over 16 % in patients relative to healthy controls at the start of treatment), continued to decrease in the patients over the period of observation (mean 6.2 % decrease, p = 0.02). For individual patients the magnitude of the NAA/Cr decrease was correlated with the frequency of relapses over the two years prior to treatment (r = -0.76, p = 0.006). These data suggest that reduction of new inflammatory activity with BIFN does not invariably halt progression of axonal injury. Nonetheless, there appears to be a relationship between the rate of progression of axonal injury and relapse rate over the previous two years. The consequences of reduced inflammation on pathological progression relevant to disability therefore may be present, but substantially delayed. Alternatively, distinct mechanisms may contribute to the two processes.
Insights
Beta-interferon (BIFN) reduced inflammation and relapse rates in multiple sclerosis (MS) patients. However, BIFN did not stop axonal injury progression, suggesting delayed effects or distinct pathological mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Multiple sclerosis (MS) disability progression is linked to axonal damage, often associated with white matter lesions.
- Beta-interferon (BIFN) is known to reduce inflammatory activity in MS.
- Previous studies suggested BIFN might reverse axonal injury, necessitating further investigation in active MS populations.
Purpose of the Study:
- To determine if BIFN can reverse or halt axonal injury progression in patients with active relapsing-remitting MS.
- To assess the generalizability of BIFN's effects on axonal integrity.
Main Methods:
- Eleven patients with active relapsing-remitting MS were treated with BIFN.
- Serial MRI and magnetic resonance spectroscopy (MRS) were used to monitor changes.
- N-acetylaspartate (NAA) to creatine ratio (NAA/Cr) in white matter served as a marker for axonal integrity.
Main Results:
- BIFN treatment significantly reduced relapse rates (p=0.007) and white matter T2 relaxation time (p=0.047) over 12 months.
- White matter lesion load did not increase, consistent with a treatment effect on inflammation.
- Despite reduced inflammation, the white matter NAA/Cr ratio continued to decrease (mean 6.2%, p=0.02), indicating ongoing axonal injury progression.
Conclusions:
- Reducing inflammatory activity with BIFN does not invariably halt axonal injury progression in MS.
- The rate of axonal injury progression correlated with prior relapse frequency, suggesting a link.
- Potential delayed therapeutic effects or distinct pathological mechanisms contributing to disability progression warrant further study.