Multiple sclerosis: relationship between seasonal variations of relapse and age of onset

The incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. The manifestation of MS, therefore, appears to be dependent upon having passed through the pubertal period suggesting an endocrine influence on the timing of onset of the disease. Since pineal melatonin secretion progressively declines from childhood to puberty and as melatonin exerts an immunomodulating influence, we have proposed that the dramatic decline in melatonin secretion just prior to the onset of the clinical manifestations of puberty may lead to disruption of immune responses resulting in either reactivation of the infective agent or in an increased susceptibility to pubertal or post-pubertal infection. Melatonin secretion undergoes annual rhythms with a zenith in winter and declines to a nadir in the spring. Thus, the fall in melatonin secretion in the spring may account for epidemiological findings revealing a high incidence of relapse of MS in the spring. If the manifestations of MS are related to the fall in melatonin secretion in the post-pubertal period, then one would expect patients with a pubertal onset of the disease to have a higher incidence of relapses in spring than in winter. To test this hypothesis, we investigated in 51 patients the relationship between the seasonal occurrence of the last MS relapse with the age of onset of first manifestation of MS. While 9 of 22 patients (40.9%) who relapsed in spring (March-May) had the onset of MS prior to age 18, only 2 of 29 patients (6.9%) who relapsed in winter (November-February) experienced the onset of first symptoms prior to the age of 18 years (p < .005). These findings thus support the hypothesis implicating the pineal gland and melatonin secretion in the timing of onset of MS. Moreover, the findings may have clinical implications with respect to the prophylaxis of MS relapse in patients who experience seasonally-dependent exacerbation of symptoms.