Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients.
BACKGROUND
Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients.


METHODS
We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration ≥ 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up.


RESULTS
The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r2 = 50.0, p<0.001) and in early RRMS (r2 = 52.3, p<0.001), compared to late RRMS (r2 = 25.5, p<0.001) and SPMS (r2 = 6.3, p = 0.133).


CONCLUSIONS
We conclude that GM atrophy and lesions appear to be different signatures of cortical disease in MS having in common overlapping spatio-temporal distribution patterns. However, the correlation between focal and diffuse damage is only moderate and more evident in the early phase of the disease.
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Neuroimaging Unit, Euganea Medica, Padova, Italy.
Massimiliano
M
Calabrese
Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Richard
R
Reynolds
Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Roberta
R
Magliozzi
Department of Information Engineering, University of Padova, Padova, Italy.
Marco
M
Castellaro
Neuroimaging Unit, Euganea Medica, Padova, Italy.
Aldo
A
Morra
Department of Medicine, Division of Brain Sciences, Centre for Neuroscience, Wolfson Neuroscience Laboratories, Imperial College London, London, United Kingdom.
Antonio
A
Scalfari
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Gabriele
G
Farina
Department of Biology, University of Padova, Padova, Italy.
Chiara
C
Romualdi
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Alberto
A
Gajofatto
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Marco
M
Pitteri
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Maria Donata
MD
Benedetti
Neurology Section, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Salvatore
S
Monaco
D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000473:pathology*; D001921:Brain / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020534:Parahippocampal Gyrus / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology; D055815:Young Adult