BACKGROUND: Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS). OBJECTIVES: 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.

• Keywords
• Atrophy, Clinically isolated syndrome, Gray matter, Lesions, Longitudinal, MRI, Multiple sclerosis,
• MeSH
• White Matter pathology   MeSH
• Demyelinating Diseases drug therapy   pathology   MeSH
• Adult MeSH
• Interferon beta-1a MeSH
• Interferon-beta therapeutic use   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Disease Progression * MeSH
• Prospective Studies MeSH
• Gray Matter pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interferon beta-1a MeSH
• Interferon-beta MeSH