Clinically Isolated Syndrome Suggestive of Multiple Sclerosis: Dynamic Patterns of Gray and White Matter Changes-A 2-year MR Imaging Study.
OBJECTIVE
To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset.


METHODS
Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P < .001, uncorrected) and tract-based spatial statistics (P < .05, corrected).


RESULTS
At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months.


CONCLUSIONS
After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis.
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Maria A
MA
Rocca
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Paolo
P
Preziosa
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Sarlota
S
Mesaros
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Elisabetta
E
Pagani
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Jelena
J
Dackovic
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Tatjana
T
Stosic-Opincal
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Jelena
J
Drulovic
From the Neuroimaging Research Unit (M.A.R., P.P., E.P., M.F.) and Department of Neurology (M.A.R., P.P.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; and Clinics of Neurology (S.M., J. Dackovic, J. Drulovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Massimo
M
Filippi
D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000473:pathology; D016022:Case-Control Studies; D003711:Demyelinating Diseases / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis*; D066127:White Matter / Q000473:pathology*