MRI correlates of disability progression in patients with CIS over 48 months.
BACKGROUND
Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS).


OBJECTIVE
To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS).


METHODS
This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons.


RESULTS
SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes.


CONCLUSIONS
Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic ; Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Tomas
T
Uher
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
Dana
D
Horakova
Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA ; IRCCS "S.Maria Nascente", Don Gnocchi Foundation, Milan, Italy.
Niels
N
Bergsland
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
Michaela
M
Tyblova
Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Deepa P
DP
Ramasamy
Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
Zdenek
Z
Seidl
Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
Manuela
M
Vaneckova
Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
Jan
J
Krasensky
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
Eva
E
Havrdova
Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA ; MR Imaging Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Robert
R
Zivadinov
D000328:Adult; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
D016899:Interferon-beta; D000068556:Interferon beta-1a
Atrophy; Clinically isolated syndrome; Gray matter; Lesions; Longitudinal; MRI; Multiple sclerosis