Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

Diogo G Corrêa; Eelco van Duinkerken; João Gabriel D Farinhas; Valéria C Pereira; Emerson L Gasparetto; Soniza V Alves-Leon; Fernanda Cristina R Lopes

doi:10.1177/11795735231195775

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis

J Cent Nerv Syst Dis. 2023 Aug 16:15:11795735231195775. doi: 10.1177/11795735231195775. eCollection 2023.

Authors

Diogo G Corrêa^{1

2}, Eelco van Duinkerken^{3

4}, João Gabriel D Farinhas^{4

5}, Valéria C Pereira⁵, Emerson L Gasparetto¹, Soniza V Alves-Leon^{4

5}, Fernanda Cristina R Lopes^{1

2}

Affiliations

¹ Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Barra da Tijuca, Brazil.
² Department of Radiology, Federal Fluminense University, Niterói, Brazil.
³ Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands.
⁴ Post-Graduate Program in Neurology, Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Department of Neurology, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Background: Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS.

Objectives: To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls.

Design: Single-center retrospective cross-sectional study.

Methods: Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-β and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3 Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library.

Results: In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network.

Conclusion: Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Keywords: Multiple sclerosis; natalizumab; resting-state functional imaging.