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Grey matter atrophy is associated with disability increase in natalizumab-treated patients

Ciampi, E; Pareto, D; Sastre-Garriga, J; Vidal-Jordana, A; Tur, C; Rio, J; Tintore, M; ... Montalban, X; + view all (2017) Grey matter atrophy is associated with disability increase in natalizumab-treated patients. Multiple Sclerosis Journal , 23 (4) pp. 556-566. 10.1177/1352458516656808. Green open access

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Abstract

Background: Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. Objective: To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). Methods: We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. Results: Significant BVL was observed during first year: brain parenchymal fraction (BPF): −1.12% (p < 0.001); white matter fraction (WMF): −0.9% (p = 0.001); grey matter fraction (GMF): −1.28% (p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (−0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. Conclusion: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.

Type: Article
Title: Grey matter atrophy is associated with disability increase in natalizumab-treated patients
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/1352458516656808
Publisher version: http://doi.org/10.1177/1352458516656808
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Multiple sclerosis, natalizumab, brain atrophy, grey matter, disability
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10063903
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