OBJECTIVE: To assess the evolution of brain atrophy and its relationship with inflammatory activity in RRMS patients treated with natalizumab.
METHODS: Eighteen RRMS patients were prospectively followed up for 18 months after starting natalizumab therapy. Patients were monitored monthly and assessed for signs of relapses, adverse events or disability increase. MRI scans were performed before starting natalizumab and every six months. Cross-sectional T2 lesion volume and the normalized brain volume at baseline and 18 months MRI scans, Longitudinal Percentage of Brain Volume Change was estimated Linkage between inflammatory activity and brain atrophy was studied.
RESULTS: Natalizumab reduced the relapse rate by 67% and cumulative lesion load by 87.5%. T2 lesion volume decreased from 1000 cubic mm, to 960 cubic mm (p=0.006) and brain volume decreased from 1.55×10(5) cubic mm to 1.42×10(5) cubic mm (p=0.025). Global Percentage of Brain Volume Change( from baseline to 18 months was -2.5%, predominantly during the first six months (0-6 months -1.7%; 6-12 months, -0.74%; ans 12-18months -0.50%). The number of relapses before treatment was correlated to the Percentage of Brain Volume Change during the first semester (p=0.003), while the number of basal MRI lesions or baseline T2 lesion load did not correlate with brain atrophy rate. During follow-up, nine patients had clinical or radiological inflammatory activity. Their Percentage of Brain Volume Change was significantly higher in the first semester (-2.3% to -1.1%, p=0.002).
CONCLUSIONS: Natalizumab reduced relapse rate and lesion load in MRI. Brain atrophy predominated in the first semester and was related to previous inflammatory activity.
Inhibiting the immune response from entering the brain reduces nerve damage and brain shrinkage caused by MS. So not much evidence for protective autoimmunity from this study and yet more evidence for a damaging influence of the immune system in MS.