Reversing Nerve loss with MRI?

Interferon Beta-1b may reverse axonal dysfunction in multiple sclerosis. Takeuchi C, Ota K, Ono Y, Iwata M. Neuroradiol J. 2007 ;20(5):531-40. Epub 2007 Oct 31.

Progression of the disability of multiple sclerosis (MS) is thought to be related to axonal damage that is seen even in normal appearing white matter (NAWM) of patients’ brains. Interferon beta (IFNβ) treatment for MS reduces the frequency of clinical exacerbations and the appearance of new inflammatory demyelinating lesions on magnetic resonance imaging (MRI). However, the effect of IFNβ treatment on axonal damage in MS is not known. The present study aimed to assess the effect of IFNβ on axonal function by comparing the data from localised single voxel proton MR spectroscopy (MRS) performed on eight MS patients given IFNβ-1b treatment and 11 untreated patients. Brain MRI and MRS were performed before the initiation of IFNβ-1b treatment and 24 months after treatment initiation. Levels of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) were calculated as the areas under their peaks shown on MRS and the ratios of NAA/Cr and Cho/Cr were calculated. In the patients treated with IFNβ-1b there was a significant increase in the ratio of NAA/Cr in NAWM (p=0.028) at 24 months after the initiation of treatment. In contrast, there was no significant change in the NAA/Cr ratio in the untreated patients. These results suggest that IFNβ-1b treatment might recover axonal function in NAWM of MS patients

What does MRI measure. N -acetyl aspartate is found at higher concentrations in nerves and so loss has been associated with nerve loss. However, and sometimes it is apparent that the level of NAA returns. This is unlikely to be nerve regrowth in the CNS, so it is clearly a change of cell metabolism. Creatine is thought to be relatively stable so using a drop in ratio of NAA/Cr suggests nerve loss.  

In this study they indicate that  NAA/Cr ratio is lower than in non MSers. Maybe consistent with more nere loss. They found that in normal white matter there was no change in the NAA/Cr ratio in untreated people (other surely it would not be normal appearing, however as if it is lower than in health it can’t be normal… can it?) but in beta interferon treated the NAA/Cr went up…was this because of more NAA or less Cr you can’t tell from a ratio? So beta interferon recovers nerve function

This is classic chicken and egg stuff . Where Beta interferon is said to reverse axonal problems so the inference is that the drug affects the nerve. However the likely scenario is that it has nothing to do with the nerve at all. I would ask the question of whether any beta interferon actually enters the brain to effect the nerve. Probably not. However what it probably does is it affects the immune response in the blood such that there is not an inflammatory response in the brain and so you do not get the nerve damage that is associated with alterations in NAA to choline ratio. However it shows that not all MRI outcome measures have hard pathological correlates so loss of NAA is not necessarily nerve loss.

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