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Neurology. 2019 Nov 12;93(20):e1852-e1866. doi: 10.1212/WNL.0000000000008466. Epub 2019 Oct 14.

Clinically relevant cranio-caudal patterns of cervical cord atrophy evolution in MS.

Author information

1
From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy. rocca.mara@hsr.it.
2
From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Abstract

OBJECTIVE:

To characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset.

METHODS:

MRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 secondary progressive multiple sclerosis [SPMS], and 42 primary progressive multiple sclerosis [PPMS]). Sixty-nine controls and 178 patients underwent a 1-year MRI and clinical follow-up. Patients were classified as clinically stable/worsened according to their disability change. Longitudinal changes of cord atrophy were investigated with linear mixed-effect models. Sample size calculations were performed using age-, sex- and site-adjusted annualized percentage normalized cord cross-sectional area (CSAn) changes.

RESULTS:

Baseline CSAn was lower in patients with MS vs controls (p < 0.001), but not different between controls and patients with CIS or between patients with early RRMS (disease duration ≤5 years) and patients with CIS. Patients with late RRMS (disease duration >5 years) showed significant cord atrophy vs patients with early RRMS (p = 0.02). Patients with progressive MS had decreased CSAn (p < 0.001) vs patients with RRMS. Atrophy was located between C1/C2 and C5 in patients with RRMS vs patients with CIS, and widespread along the cord in patients with progressive MS vs patients with RRMS, with an additional C5/C6 involvement in patients with SPMS vs patients with PPMS. At follow-up, CSAn decreased in all phenotypes (p < 0.001), except CIS. Cord atrophy rates were highest in patients with early RRMS and clinically worsened patients, who had a more widespread cord involvement than stable patients. The sample size per arm required to detect a 50% treatment effect was 118 for patients with early RRMS.

CONCLUSIONS:

Cord atrophy increased in MS during 1 year, except for CIS. Faster atrophy contributed to explain clinical worsening.

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