The relationship between inflammatory activity and brain atrophy in natalizumab treated patients

Abstract

ObjectiveTo assess the evolution of brain atrophy and its relationship with inflammatory activity in RRMS patients treated with natalizumab. MethodsEighteen 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 (T2LV) and the normalized brain volume (NBV) at baseline and 18 months MRI scans were calculated using the Steronauta® and SIENAx softwares, respectively. Longitudinal Percentage of Brain Volume Change (PBVC) was estimated with SIENA. Linkage between inflammatory activity and brain atrophy was studied. ResultsNatalizumab reduced ARR by 67% and cumulative CEL by 87.5%. T2 lesion volume decreased from 1000mm3, to 960mm3 (p=0.006) and NBV decreased from 1.55×105mm3 to 1.42×105 mm3 (p=0.025). Global PBVC from baseline to 18 months was −2.5%, predominantly during the first six months (0–6 months PBVC −1.7%; 6–12 months PBVC −0.74%; 12–18 months PBVC −0.50%). The number of relapses before treatment was correlated to the PBVC during the first semester (Pearson's coefficient −0.520, p=0.003), while the number of basal CEL or baseline T2LV did not correlate with brain atrophy rate. During follow-up, nine patients had clinical or radiological inflammatory activity. Their PBVC was significantly higher in the first semester (−2.3% to −1.1%, p=0.002). ConclusionsNatalizumab reduced relapse rate and CEL in MRI. Brain atrophy predominated in the first semester and was related to previous inflammatory activity.