BACKGROUND: MS is associated not only with focal inflammatory lesions but also diffuse pathology in the CNS. Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM.
METHODS: Quantitative proton magnetic resonance spectroscopy ((1)H-MRS)* was used to investigate NAWM in 27 MSers with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in (1)H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 MSers.
* Proton magnetic resonance spectroscopy ((1)H-MRS) – this is a MRI technique that is used to quantify nerve cells and axonal numbers.
RESULTS: The group levels of (1)H-MRS metabolite concentrations were unchanged pre-to post-treatment but a pattern of high magnitude correlation coefficients (r = 0.43-0.67, p<0.0005-0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8).
CONCLUSIONS: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in (1)H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.
4 thoughts on “Natalizumab and changes in normal appearing white matter”
Dear Prof. G, if your conclusion is right ("Tysabri won't stop MSers from developing SPMS"), then the current clinical trial of Tysabri for SPMSers will be a total fail, right? I guess we will know the answer during the ECTRIMS congress next week
At last, you agree that inflammation is secondary to the real cause of MS. The next step is to admit that it is totally healthy. The third, to get rid of EBV as the cause of MS. It has no place in the real world, only in diffuse statistics.
No VV, inflammation in the brain is not healthy, which is why the normal brain goes out of its way to maintain homeostasis. If you can stop inflammatory relapses you should be able to at least slow down the rate of neurodegeneration but it isn't the whole story, which is why we are looking at neuroprotective agents as an additional therapy.
Neuroprotection is meaningful only if you know what to protect neurons from. You seem to easily bypass this part and go straight to diminishing the secondary inflammatory response. Wrong succession of steps, ipso facto, unsuccessful so far in fundamentally treating MS.This study shows that the underlying MS process is unaffected by the reduction of relapses. Time to realise that relapses are just inflammatory signs of the damage. By reducing relapses you reduce the signs of damage but not the sustained damage itself.