From optic neuritis to multiple sclerosis : a paraclinical, epidemiological, and etiological study in Stockholm County, Sweden

University dissertation from Stockholm : Karolinska Institutet, Department of Clinical Neuroscience

Abstract: The etiology of multiple sclerosis (MS) is unknown. Monosymptomatic optic neuritis (MON) is an acute disease of the optic nerve attributed to focal inflammation associated with demyelination in the absence of any history or signs of NIS or of any systemic disease. MON is closely related to MS and can be a harbinger of MS. Studies of MON offer a special opportunity to study the very early clinical stages of MS. Magnetic resonance imaging (MRI) and examinations for oligoclonal IgG bands (OB) in cerebrospinal fluid (CSF) are used routinely in the management of patients with MON and MS. A prospective, population-based study of patients with MON between January 1, 1990 and December 31, 1995 in Stockholm County (SC), Sweden showed that the presence of three or more MS-like brain MRI lesions and the presence of OB in CSF in patients with MON were strongly associated with the development of MS (p<0.001), respectively. Incidence surveys of MON are sparse and largely retrospective. Analyses of the incidence of MON in SC with regard to age, sex, birth and ethnic group related patterns revealed that MON occurred in SC at a relatively low frequency, particularly among men and residents born outside of the Nordic countries. The crude mean annual incidences were 2.28 per 100 000 person-years for women, 0.59 for men, 1.46 for both sexes, and 0.28 for inhabitants born outside of the Nordic countries. A birth-cohort pattern for both MON and MON-onset MS was suggested. Seasonal variation may influence disease occurrence and provides important clues on disease etiology. In the literature, unsystematic studies on the seasonalilty of MON and MS have given inconclusive results. A population-based, prospective study in SC showed that MON occurred at an uneven frequency across the seasons, with the highest incidence in spring and the lowest in winter. A meta-analysis revealed a similar and robust seasonal pattern for MON, MS onsets and MS exacerbations in the Northern Hemisphere. We investigated the presence of birth cohort effects on the mortality from MS in Sweden and Stockholm County during 1962-1995 and 1968-1995 using age-period-cohort models with curvature analysis and data on multiple causes of death. The study in SC revealed that: 1) cohorts born before or after a central period from 1910 to 1930 had a lower mortality rate, and 2) there existed a pseudo-periodical wave-form risk pattern, following a 5-to-6-year cycle for cohorts born before 1925, changing to 8-year-or-wider, irregular cycles for cohorts born after 1930. This latter finding was in agreement with the observations on the incidence of MON in SC. In summary, MRI and CSF examinations in patients with MON were shown to give clinically important information regarding whether MS was likely developed following MON or not. The incidence of MON in SC was low and occurred at an uneven frequency across seasons. A similar, world-wide seasonal pattern for MON, MS onsets and MS exacerbations was observed. The MS mortality in birth cohorts in SC presented a pseudo-periodical wave-form pattern. Environmental, probably infectious, factors, unevenly distributed by season and through the calendar year, may determine the risk for a considerable proportion of MON and MS cases by immunological recall mechanisms acquired early in life.

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