BACKGROUND: Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas, and they present the advantage of being extracted from previously acquired clinical magnetic resonance imaging (MRI) scans. SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis. OBJECTIVE: To investigate alterations of SCNs at the individual level in patients with clinically isolated syndrome (CIS), thereby assessing their clinical relevance. METHODS: We analyzed baseline data collected in a prospective multicenter (MAGNIMS) study. CIS patients (n = 60) and healthy controls (n = 38) underwent high-resolution 3T MRI. Measures of disability and cognitive processing were obtained for patients. Single-subject SCNs were extracted from brain 3D-T1 weighted sequences; global and local network parameters were computed. RESULTS: Compared to healthy controls, CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed. Alterations of centrality measures and clustering of connections were observed in specific cortical areas in CIS patients when compared with healthy controls. CONCLUSION: Our study indicates that SCNs can be used to demonstrate clinically relevant alterations of connectivity in CIS.

Alzheimer Center Amsterdam Department of Neurology Amsterdam University Medical Centers Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The Netherlands

Centre for Medical Image Computing UCL Medical Physics and Biomedical Engineering University College London London UK

Centre for Medical Image Computing UCL Medical Physics and Biomedical Engineering University College London London UK NIHR University College London Hospitals Biomedical Research Centre London UK Alzheimer Center Amsterdam Department of Neurology Amsterdam University Medical Centers Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The Netherlands UCL Institute of Healthcare Engineering and UCL Queen Square Institute of Neurology University College London London UK

Department of Diagnostic and Interventional Radiology and Nuclear Medicine St Josef Hospital Ruhr University Bochum Bochum Germany

Department of Neurology Hospital Clinico San Carlos Instituto de Investigacion Sanitaria del Hospital Clínico San Carlos Madrid Spain

Department of Neurosciences San Camillo Forlanini Hospital Rome Italy

London School of Hygiene and Tropical Medicine London UK

MS Center Amsterdam Department of Neurology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

MS Center Amsterdam Department of Radiology and Nuclear Medicine Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands; Department of Diagnostic and Interventional Neuroradiology Hannover Medical School Hannover Germany

Neurologic Clinic and Policlinic University Hospital Basel University of Basel Basel Switzerland Charles University and General University Hospital Prague Czech Republic

NMR Research Unit Queen Square Multiple Sclerosis Centre Department of Neuroinflammation UCL Queen Square Institute of Neurology Faculty of Brain Sciences University College London London UK

NMR Research Unit Queen Square Multiple Sclerosis Centre Department of Neuroinflammation UCL Queen Square Institute of Neurology Faculty of Brain Sciences University College London London UK Centre for Medical Image Computing UCL Medical Physics and Biomedical Engineering University College London London UK Universitat Oberta de Catalunya Barcelona Spain

NMR Research Unit Queen Square Multiple Sclerosis Centre Department of Neuroinflammation UCL Queen Square Institute of Neurology Faculty of Brain Sciences University College London London UK NIHR University College London Hospitals Biomedical Research Centre London UK

UCL Medical Physics and Biomedical Engineering University College London London UK

UCL Medical Physics and Biomedical Engineering University College London London UK School of Biomedical Engineering and Imaging Sciences King's College London London UK

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