Factors associated with a rapid course of multiple sclerosis.

A cohort of 886 cases of multiple sclerosis (MS) who had onset between Jan 1, 1960, and Dec 31, 1969, and who were resident in 1970 in either a low-prevalence area (Los Angeles County, California, 560 cases) or in a high-prevalence area (King and Pierce Counties, Washington, 326 cases) were followed up for changes in disability status through Dec 31, 1979. Cases had to meet the modified Schumacher criteria for definite/probable MS and to have had a diagnosis of MS or equivalent by a physician. Onset year of disease was determined by onset of the earliest reported symptom. Disability status was determined at intake by an interviewer-administered questionnaire and in subsequent years by an annual mailed questionnaire (self-reported disability status). Progression to a nonambulatory status or death was significantly greater among (1) patients with an older age at onset, (2) patients with a rapid early course, (3) males, and (4) residents of Los Angeles County.

A case-control study of multiple sclerosis.

We conducted a study of 145 persons with multiple sclerosis who had been identified in a 1970 survey and 145 friend controls, to investigate whether the development of MS was associated with exposure to uncommon viruses or an older age at infection with 1 or more common viruses. The most striking finding was a strong positive association for history of infectious mononucleosis (IM), suggesting older age at exposure to Epstein-Barr virus, the most common etiologic agent of IM. We also found significant positive associations for number of different domiciles before adulthood and for visits outside the United States; both would be compatible with an increased likelihood among cases of exposures to uncommon viruses or to multiple strains of a common agent. Cases were younger at menarche, increasing the probability of viral exposure after puberty.

Genetic susceptibility to multiple sclerosis.

Previous studies of histocompatibility (HLA) types in multiple sclerosis (MS) families did not provide convincing proof of an HLA-linked susceptibility factor. In 12 families we studied, all MS cases in each family shared at least one chromosome. The probability of this occurring in the absence of genetic linkage is approximately 0.001. The estimated penetrance is 5 percent, implying that the genetic susceptibility factor may be a necessary but not a sufficient cause of MS. Additional studies are needed to identify other differences between affected and unaffected susceptible individuals.

Changes in immune response during responses in MS patients.

Changes in clinical status and in two measures of immune function were followed for 21 months (median) in 106 multiple sclerosis (MS) patients and cohabitant controls. Antibody titers to measles, cytomegalovirus, and herpesvirus 1 and 2, and leukocyte migration inhibition indexes (LMIs) to measles and streptokinase/streptodornase (SKSD) were measured at 3- to 6-month intervals and at time of exacerbation in the index case. There were 36 exacerbations in 25 patients. Mean baseline antibody titers and LMI to measles were higher in cases than in controls. No consistent changes occurred in antibody titers to any of the viruses, non in LMI to SKSD. LMIs to measles were lower in most MS patients during exacerbations than before or after exacerbations. This apparent improvement in cell-mediated immune response to measles only during exacerbations may reflect aberrant immune regulation in MS patients, response to recrudescence of a latent agent, or some other phenomenon as yet undefined.

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Two populations with multiple sclerosis. Clinical and demographic characteristics.

Cross-sectional data from 1,793 cases of definite or probable multiple sclerosis (MS) identified in an extensive population survey in King and Pierce (K-P) Counties, Washington and Los Angeles (LA) County, California, were analyzed. Compared to the U.S. population as a whole, patients were more likely to be divorced and to have more years of schooling. The prevalence of MS was higher for females, and for northern-born, regardless of sex. Reconstructed age-, sex-specific incidence rate estimates for natives of the two areas showed a much higher peak annual incidence occurring in an older age group in K-P than in LA. Earliest symptoms in both areas were numbness in the legs, double vision, and loss of vision in one or both eyes. Weakness in arms, speech difficulties, and urinary incontinence tended to be late symptoms. The overall assessment of disability levels showed more than half of the patients to be fully ambulatory at the time of the first interview, with a somewhat higher proportion of each sex severely disabled in California. The ages of onset tended to be younger in LA than in K-P. The earlier onset of disease and the higher proportion of patients with high disability in Los Angeles County suggest that the course of disease is more malignant in this low-prevalence area.

Co-occurrence of multiple sclerosis and glioma--case report and neuropathologic and epidemiologic review.

This paper reports on a 54-year-old male in whom multiple sclerosis developed 10 years prior to his death from glioblastoma confirmed at autopsy. A causal relationship is still uncertain despite the 24 cases of concurrent multiple sclerosis and glioma reported since 1938. We discuss the neuropathologic and epidemiologic evidence for and against the hypothesis that multiple sclerosis lesions promote the development of gliomas and conclude that no current reason exists to support the hypothesis.

Latitude, migration, and the prevalence of multiple sclerosis.

Prevalence of multiple sclerosis (MS) was determined in three groups of Caucasians in King and Pierce Counties (Washington) and in Los Angeles County (California): natives (born in study state), migrants from high-risk states (North), and migrants from low risk states (South). A diagnosis of definite or probable MS (excluding migrants with onset before migration) was established in 1816 of the persons found. The prevalence in Los Angeles County natives and in migrants from the South to either Los Angeles County or King-Pierce Counties were relatively low, while prevalence in King-Pierce Counties among natives and migrants from the North were high. The prevalence in migrants from the North to Los Angeles was intermediate. The results suggest that some degree of protection is provided to migrants by residence in low-prevalence areas, either early or later in life.

Evidence for lower susceptibility to multiple sclerosis in Japanese-Americans.

A search for cases of multiple sclerosis (MS) was carried out among the 120,066 Japanese-American residents and the 3,060,366 Caucasian residents native to state of residence in King and Pierce Counties, Washington, and Los Angeles County, California. Although 48 cases would have been expected among Japanese-Americans in both areas (on the basis of the prevalence among Caucasians in these two areas), only eight cases were found who were residents on prevalence day -- all were American-born residents of Los Angeles County. The age-, sex-adjusted prevalence of MS among Japanese-Americans in both areas was 5.9 per 100,000. The lower prevalence of multiple sclerosis among Japanese-Americans than among Caucasians has been interpreted as evidence of a lower susceptibility to factors causing multiple sclerosis.

Mortality in persons with multiple sclerosis in the Seattle and Los Angeles areas.

Case-mortality and survival rates of more than 2,000 prevalent cases of multiple sclerosis (MS) residing in either Los Angeles County, California, or King and Pierce Counties, Washington, and followed up for 105 months, are reported. Case-mortality at the end 105 months was 16.9% of the total group. All age and sex groups had a lower survival rate than the US general population; this difference was especially pronounced in the high-disability groups. There was a trend toward higher case-mortality in high-disability Los Angeles County patients when compared with high-disability patients from King and Pierce Counties.

Factors associated with a malignant or benign course of multiple sclerosis.

Eight hundred thirty-four patients with multiple sclerosis (MS) in King and Pierce Counties, Washington, and in Los Angeles County, California, with symptomatic onset between 1960 and 1969 were followed up for disability status in 1980. A higher proportion of the 375 patients who were not walking or deceased in 1980 had a late age of onset, resided in Los Angeles County, had motor or coordination symptoms at onset, and reported adverse responses to heat exposure and favorable responses to cold exposure, whereas a higher proportion of the 299 patients still walking without aids had early onset age and vision, speech, or sensory symptoms, or all three, at onset. The results suggest (1) that both host factors (age at first manifestation of symptoms and types of symptoms at onset) and environmental factors (place of residence and exposure to heat and cold) are determinants of disease course and (2) that most patients with MS should avoid exposure to heat.

Onset symptoms as predictors of mortality and disability in multiple sclerosis.

941 cases of definite/probable multiple sclerosis living in Los Angeles County, California and King and Pierce Counties, Washington in 1970 who had onset between 1960 and 1969 were followed for mortality and disability through 1980. Early age of onset and residence in Washington State were predictors of less rapid and severe subsequent course. Coordination symptoms at onset were prognostic of rapid progression to disability and/or early death, whereas early motor weakness was significantly predictive only for disability. The presence of sensory symptoms in addition to motor and/or coordination symptoms at onset, however, indicated a better prognosis than coordination and/or motor symptoms alone. This observation and the results of regression analyses indicated that specific groupings of symptoms at onset were more important for predicting course than the number of symptoms present at onset.

Application of simulation techniques for estimating duration of multiple sclerosis derived from prevalence-formed cohorts.

Comparisons of the average duration of multiple sclerosis derived from a prevalence survey of cases alive in 1970 in a low-risk area (Los Angeles County, California) and a high-risk area (King and Pierce Counties, Washington) suggest that patients in the high-risk area had a longer duration of disease than patients in the low-risk area. Because this finding was unexpected and because the underlying population of these two areas has been increasing at different rates, two simulation models were developed to estimate the duration of multiple sclerosis from a prevalence survey, taking into account the effects of changes in the population over time. Comparison of the durations derived from the two simulation studies suggested that underestimation of true backward recurrence time from the simulation studies was similar for the two study areas. Thus, the observed differences in duration between the two areas probably reflect the course of disease rather than differences in rate of growth of the two populations. These studies demonstrate the usefulness of simulation studies in estimating disease duration from cohorts derived from prevalence surveys of non-stable populations.

Underlying cause of death as recorded for multiple sclerosis patients: associated factors.

The coding of multiple sclerosis (MS) as underlying cause of death (UCD) on the death certificate provides an important epidemiologic resource for both descriptive and analytic studies. However, not all deaths among MS patients will be so coded. We investigated the effect on estimated occurrence of MS and on characteristics of MS patients when only UCD codes are used to identify cases. Of 2329 MS patients living in Los Angeles County (California) or King/Pierce Counties (Washington) in 1970, 438 had died by 1980. Only 53% of the deaths were coded to MS; 47% were attributed to other causes. Based on our comparisons, the use of only MS-coded deaths to describe decedents would: underestimate the age at MS onset; overestimate the female:male ratio; underestimate age at death; and underestimate duration of MS. Also, the percentage of MS-coded deaths decreased with lengthening duration of follow-up of these prevalent cases. The effect of using only UCD codes to report characteristics of decedents with other chronic diseases may well be similar.