Seasonal prevalence of MS disease activity

Abstract

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

Warmer outdoor temperature is associated with worse cognitive status in multiple sclerosis

“…In addition, while the recently reported finding of increased T2 lesion activity during warmer temperatures 3 provided the impetus for the present investigation, we did not look at lesion activity in our samples and can therefore draw no conclusions as to whether increased lesion activity occurred. However, future studies examining the neuropathologic changes associated with worse cognition in warmer temperatures are warranted.…”

“…In particular, warmer seasons are associated with a higher incidence of clinical exacerbations, 1,2 and a recent investigation found a strong association between new T2 lesion activity and warmer daily temperature (r ϭ 0.50, p Ͻ 0.0001). 3 Importantly, in that study, only a small fraction of new T2 lesions were accompanied by a clinical exacerbation. That is, T2 lesion activity frequently occurred in the absence of observable sensorimotor symptomology (e.g., optic neuritis, paresthesias), likely because lesion activity occurred outside of primary sensorimotor pathways.…”

“…In addition, putative mechanisms underlying the effect of temperature on cognition remain to be explored in future research. That is, separate lines of research have shown that increased temperature is associated with increased lesion activity 3 and slowed or blocked conduction within demyelinated axons (for review, see 12 ), but it remains unclear whether these mechanisms or an as-yet unidentified mechanism is responsible for the heatrelated decrements in cognitive status observed among patients with MS in the current study. It may also be useful to examine individuals with secondary progressive MS, as we may expect to see exaggerated effects of slowed/blocked conduction as a result of demyelination in this more advanced disease subtype.…”

“…DISCUSSION Warmer outdoor temperature has been linked to clinical exacerbations 1,2 and T2 lesion activity 3 in patients with MS. Although approximately 65% of patients with MS experience cognitive deficits, 5 the current study is the first to formally investigate the relationship between outdoor temperature and cognition in patients with MS. We found that warmer temperatures are associated with worse cognitive performance across 2 independent samples of patients with MS. Our cross-sectional analysis demonstrated that cognitive status is worse on warmer days in patients with MS equated for level of disease severity (i.e., brain atrophy).…”

“…Such symptoms are most likely to result from a focal disruption of critical white matter tracts underlying these primary functions; as such, sensorimotor symptoms likely underestimate the true extent of MS disease activity throughout cerebral white matter. Indeed, a recent study showed that MS disease activity frequently occurs in the absence of sensorimotor symptoms, 3 suggesting that subclinical disease activity is common. The need for more sensitive markers of disease-related activity is therefore critical.…”