Paramagnetic Rim Lesion Burden and Choroid Plexus Enlargement Contribute to Cognitive Impairment and Fatigue in Multiple Sclerosis
Paolo Preziosa1, Yuri Yudin3, Elisabetta Pagani3, Alessandro Meani3, Loredana Storelli3, Monica Margoni4, Nicolò Tedone3, Diana Biondi3, Maria Rocca1, Massimo Filippi2
1Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 3Neuroimaging Research Unit, Division of Neuroscience, 4Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; and Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute
Objective:
To investigate the contribution of paramagnetic rim lesions (PRL) number and volume and choroid plexus (CP) enlargement to cognitive impairment and fatigue in multiple sclerosis (MS) patients.
Background:
Chronic inflammation may worsen cognitive performance and fatigue in MS patients. Since PRLs and CP enlargement represent markers of chronic inflammation in MS, they may be associated with cognitive impairment and fatigue.
Design/Methods:
Brain 3T magnetic resonance imaging (MRI), neurological evaluation and neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests and Modified Fatigue Impact Scale were obtained from 129 MS patients and 73 age- and sex-matched healthy controls (HC). PRLs were identified on phase images of susceptibility-weighted imaging (SWI), whereas CP volume was quantified using a fully-automatic method on brain three-dimensional T1-weighted and FLAIR MRI sequences. Predictors of cognitive impairment and fatigue were identified using random forest.
Results:
Thirty-six (27.9%) MS patients were cognitively impaired, whereas 31/113 (24.0%) had fatigue. Fifty-nine (45.7%) MS patients had ≥1 PRLs (median=0, interquartile range=0;2). Compared to HC, MS patients showed significantly higher T2-hyperintense white matter (WM) lesion volume, lower normalized brain, thalamic, hippocampal, caudate, cortical and WM volumes, and higher normalized CP volume (p≤0.048). The predictors of cognitive impairment (relative importance) (out-of-bag area under the curve [OOB-AUC]= 0.727) were lower normalized brain volume (100%), lower normalized caudate volume (89.1%), higher normalized CP volume (80.3%), lower normalized cortical volume (70.3%%), higher number (67.3%) and volume of PRLs (66.7%) and higher T2-hyperintense WM volume (64.0%). Higher normalized CP volume was the only predictor of the presence of fatigue (OOB-AUC=0.563).
Conclusions:
Chronic inflammation, typified by higher number and volume of PRLs and enlarged CP, may contribute to cognitive impairment in MS in addition to atrophy. The association of enlarged CP with fatigue underscores the role of immune-related processes in determining this manifestation, regardless of disease severity.