Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early Multiple Sclerosis
Damiano Marastoni, Elisa Colato, Matteo Foschi, Agnese Tamanti, Stefano Ziccardi, Chiara Eccher, Francesco Crescenzo, Albulena Bajrami, Gian Marco Schiavi, Valentina Camera, Daniela Anni, Federica Virla, Maddalena Guandalini, Ermanna Turano, Francesca B. Pizzini, Stefania Montemezzi, Bruno Bonetti, Owain W. Howell, Roberta Magliozzi, Richard Nicholas, Antonio Scalfari, Cristina Granziera, Ludwig Kappos, Massimiliano Calabrese
Abstract
BACKGROUND AND OBJECTIVES: The objective of this study was to determine, at the time of diagnosis, a CSF and MRI profile of intrathecal compartmentalized inflammation predictive of progression independent of relapse activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS). METHODS: This five-year prospective study included 80 treatment-naïve patients with RRMS enrolled at time of diagnosis. All patients underwent a lumbar puncture, regular neurologic evaluations including an Expanded Disability Status Scale (EDSS) assessment every 6 months, and an annual 3T brain MRI. PIRA was defined as having a confirmed disability progression independent of relapse activity. CSF levels of 68 inflammatory molecules were evaluated in combination with white matter and cortical lesion number (CLn) and volume, and regional gray matter thickness and volume. RESULTS: = 0.003) were MRI predictors of PIRA. DISCUSSION: A specific intrathecal inflammatory profile associated with TNF superfamily markers, CLn, and atrophy of several cortical and deep gray matter regions, assessed at time of diagnosis, is predictive of PIRA in early MS.