Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes

Ramona-Alexandra Todea; Po-Jui Lu; Mario Joao Fartaria; Guillaume Bonnier; Renaud Du Pasquier; Gunnar Krueger; Meritxell Bach Cuadra; Marios Nikos Psychogios; Ludwig Kappos; Jens Kuhle; Cristina Granziera

doi:10.3389/fneur.2020.00973

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes

Front Neurol. 2020 Sep 4:11:973. doi: 10.3389/fneur.2020.00973. eCollection 2020.

Authors

Ramona-Alexandra Todea^{1

2}, Po-Jui Lu^{1

3}, Mario Joao Fartaria^{4

5

6}, Guillaume Bonnier¹, Renaud Du Pasquier⁷, Gunnar Krueger⁸, Meritxell Bach Cuadra^{5

9}, Marios Nikos Psychogios², Ludwig Kappos^{1

3}, Jens Kuhle³, Cristina Granziera^{1

3}

Affiliations

¹ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Basel University Hospital, University of Basel, Basel, Switzerland.
² Section of Neuroradiology, Department of Radiology, University Hospital of Basel, Basel, Switzerland.
³ Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
⁴ Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland.
⁵ Department of Radiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Signal Processing Laboratory (LTS 5), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
⁷ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁸ Siemens Healthcare AG, Zurich, Switzerland.
⁹ Medical Image Analysis Laboratory (MIAL), Centre d'Imagerie BioMédicale (CIBM), Lausanne, Switzerland.

Abstract

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05). Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.

Keywords: MP2RAGE; MRI; cortical lesions; early relapsing remitting multiple sclerosis; serum neurofilamants.