Spinal Cord Atrophy Predicts Progressive Disease in Relapsing Multiple Sclerosis
Antje Bischof, Nico Papinutto, Anisha Keshavan, Anand Rajesh, Gina Kirkish, Xinheng Zhang, Jacob M. Mallott, Carlo Asteggiano, Simone Sacco, Tristan Gundel, Chao Zhao, W. Stern, Eduardo Caverzasi, Yifan Zhou, Refujia Gomez, Nicholas R. Ragan, Adam Santaniello, Alyssa H. Zhu, Jeremy Juwono, Carolyn Bevan, Riley Bove, Elizabeth Crabtree, Jeffrey M. Gelfand, Douglas S. Goodin, Jennifer Graves, Ari Green, Jorge R. Oksenberg, Emmanuelle Waubant, Michael R. Wilson, Scott S. Zamvil, Bruce Cree, Stephen L. Hauser, Roland G. Henry
Abstract
OBJECTIVE: A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS). METHODS: From a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12-year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion. RESULTS: Patients who developed SPMS showed faster cord atrophy rates (-2.19%/yr) at least 4 years before conversion compared to their RRMS matches (-0.88%/yr, p < 0.001). Spinal cord atrophy rates decelerated after conversion (-1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (-1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p < 0.0001) and 53% (p < 0.0001) shorter time to silent progression and SPMS conversion, respectively. INTERPRETATION: Silent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268-281.