In this Italian setting (Bologna, Emilia-Romagna region), we found a seasonal pattern for MS relapses, apparently unrelated to meteorological variables, characterized by biphasic spring-autumn peaks (main peak in May, secondary peak in November) and summer trough, especially in older (≥40 years) patients, and a trend for a single peak in May in younger subjects.
Seasons seem to play a role in MS. For example, an association between month of birth and the risk of later developing of MS have been documented in studies conducted in Canada, Great Britain, Denmark and Sweden [8
], with persons born in May [8
] and June [9
] exhibiting significantly increased risk of MS.
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system of unknown pathogenesis, although environmental [10
], genetic [11
], infectious [12
], toxic [13
], nutritional [14
], hormonal [15
], and venous vascular [16
] factors have been studied as plausible risk factors. Moreover, exposure to ionizing radiation [17
], and organic solvents [18
], including volatile anaesthetic agents [19
], may constitute additional risk factors. Thus, the disparate expression of the disease itself, characterized either by a chronic progressive or a relapsing/remitting clinical picture, perhaps helps to explain differences between the available data on its seasonal variation. Environmental factors that can potentially play a role in risk of MS development or progression include viral infections (cytokines?) and vitamin D levels (sun exposure?), both of which exhibit seasonal variation [20
Ogawa et al. [22
] observed that relapses of MS patients were significantly more frequent in the warmest and coldest months of the year. Stewart et al. [23
] observed that untreated MS (relapsing/remitting) cases showed a summer excess of interleukin-10, and Balashov et al. [24
] reported a significantly increased interferon production in the autumn and winter compared to the spring and summer in chronic progressive MS, with maximum values of T-cell activation (assessed in terms of tumor necrosis factor and interferon levels) found during autumn by Killestein et al. [25
]. A population-based study conducted in Southern Tasmania [26
] detected an inverse association between MS relapse rate and erythemal ultraviolet radiation (EUV) and vitamin D [25(OH)D] levels, suggesting a role of EUV exposure.
Very recently, contrasting evidence on the seasonality of relapsing MS has been reported as well. A large Portuguese retrospective study of relapsing/remitting patients (414 relapses occurring in 249 consecutive patients studied between January 1, 2004 and December 31, 2007) [27 found no significant differences between months or seasons, and no correlation between relapse frequency and weather factors, including maximum and minimum temperature, humidity, and atmospheric pressure. The results of a 3-year Israeli study (2001-2003) of 235 patients [28
] also found no significant correlation between number of relapses and season or month, and no significant impact of meteorological parameters on relapses. On the other hand, a strong seasonal pattern in subclinical MS activity was found in the United States by Meier et al. [29
], who investigated the seasonal prevalence of MS disease activity in terms of appearance of new lesions found in serial T2-weighted MRI (n = 939 separate MRI examinations) of a cohort of 44 untreated patients. They also tested for associations of seasonality with recorded meteorologic data, i.e., ambient temperature, solar radiation and precipitation, in the Boston vicinity between1991-1993 when the MRI examinations were made. The likelihood of new T2 activity was 2-3 times higher between the months of March-August than during the other months of the year, with a strong correlation with solar radiation and with disease intensity being elevated during the summer season.