Brain atrophy rates in patients with multiple sclerosis on long term natalizumab resembles healthy controls

Mult Scler Relat Disord. 2021 Oct:55:103170. doi: 10.1016/j.msard.2021.103170. Epub 2021 Jul 24.


Background: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs).

Methods: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms.

Results: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups.

Conclusion: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.

Keywords: Brain volume; Long-term outcomes; Natalizumab; Tysabri.

MeSH terms

  • Adolescent
  • Adult
  • Atrophy / pathology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Multiple Sclerosis* / diagnostic imaging
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / pathology
  • Natalizumab / adverse effects
  • Quality of Life
  • Young Adult


  • Natalizumab