Objective: This observational cohort study investigated the seasonal prevalence of multiple sclerosis (MS) disease activity (likelihood and intensity), as reflected by new lesions from serial T2-weighted MRI, a sensitive marker of subclinical disease activity.
Methods:Disease activity was assessed from the appearance of new T2 lesions on 939 separate brain MRI examinations in 44 untreated patients with MS. Likelihood functions for MS disease activity were derived, accounting for the temporal uncertainty of new lesion occurrence, individual levels of disease activity, and uneven examination intervals. Both likelihood and intensity of disease activity were compared with the time of year (season) and regional climate data (temperature, solar radiation, precipitation) and among relapsing and progressive disease phenotypes. Contrast-enhancing lesions and attack counts were also compared for seasonal effects.Results: Unlike contrast enhancement or attacks, new T2 activity revealed a likelihood 2-3 times higher in March-August than during the rest of the year, and correlated strongly with regional climate data, in particular solar radiation. In addition to the likelihood or prevalence, disease intensity was also elevated during the summer season. The elevated risk season appears to lessen for progressive MS and occur about 2 months earlier.
Conclusion:This study documents evidence of a strong seasonal pattern in subclinical MS activity based on noncontrast brain MRI. The observed seasonality in MS disease activity has implications for trial design and therapy assessment. The observed activity pattern is suggestive of a modulating role of seasonally changing environmental factors or season-dependent metabolic activity. This study tested the hypothesis that untreated multiple sclerosis (MS) disease activity, as observed by new lesions on noncontrast MRI, is not uniformly distributed over the calendar year, but shows greater prevalence during a particular season. Patterns of such seasonal variation have been observed mostly for clinical markers, with peaks in exacerbation rates during summer for the United States (Ohio, 1 Arizona 2 ) and Japan, 3 and during the spring in Switzerland. 4 A study of seasonal prevalence of optic neuritis in Sweden found higher incidence in spring than winter and correlations of incidence rates with solar radiation and temperature.
5Significant seasonal variation of immunologic activity was found by 2 studies in Boston and Amsterdam, with peaking concentrations of proinflammatory cytokines interferon-␥ and tumor necrosis factor-␣ in autumn. 6,7 Similarly, the immunosuppressive cytokine interleukin-10 was found to be elevated in the summer months in Australia. 8 On MRI, however, studies are very rare and findings elusive. Out of only 3 studies looking at MRI markers, 9-11 one found a seasonal effect. 9 All 3 studies were very limited in longitudinal