The Gulf War era multiple sclerosis cohort: 3. Early clinical features.

OBJECTIVES: To present clinical features at diagnosis for a large nationwide incident cohort of multiple sclerosis (MS) among those serving in the US military during the Gulf War era (GWE). MATERIALS & METHODS: Medical records and databases from the Department of Veterans Affairs (VA) for cases of MS with onset in or after 1990, active duty between 1990 and 2007 and service connection by the VA, were reviewed for diagnosis and demographic variables. Neurological involvement was summarized by the Kurtzke Disability Status Scale (DSS) and the Multiple Sclerosis Severity Score (MSSS). RESULTS: Among 1919 cases of clinically definite MS, 94% had a relapsing-remitting course and 6% were primary progressive at diagnosis. More males of all races and blacks of both sexes were progressive. At diagnosis, functional system involvement was pyramidal 69%, cerebellar 58%, sensory 55%, brainstem 45%, bowel/bladder 23%, cerebral 23%, visual 18%, and other 5%. Mean DSS scores were: white males, females 2.9, 2.7; black males, females 3.3, 2.8; and other-race males, females 3.2, 2.6. Mean and median MSSS were marginally greater in black males and other males compared to the other sex-race groups. CONCLUSIONS: In this incident cohort, males and blacks had significantly higher proportions of primary progressive MS. DSS at diagnosis was significantly more severe in blacks and significantly less so in whites and in women vs men, but MSSS was only marginally greater in black males and other-race males. This morbidity assessment early in the course of MS provides population-based data for diagnosis, management, and prognosis.

Serum proteomic analysis of a pre-symptomatic multiple sclerosis cohort.

BACKGROUND AND PURPOSE: Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. METHODS: This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. RESULTS: The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were -6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. CONCLUSIONS: Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.

Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases.

OBJECTIVE: To seek evidence for a possible infectious origin of the type 1 epidemic of multiple sclerosis (MS) in the Faroe Islands. This began in 1943 coincident with their British military occupation throughout World War II. MATERIALS AND METHODS: Data obtained from the Danish National Health Service were assessed for all notifiable diseases in the Faroe Islands reported from 1900 to 1977. RESULTS: Among 38 disorders, selective increases were found for acute infectious gastroenteritis (AIGE) and paradysentery, with outbreaks in late 1940 and in 1943 shortly after the introduction and later marked influx, respectively, of British troops. Five other infections showed elevated numbers in 1941 and 1942. CONCLUSIONS: There is a temporal association of AIGE and paradysentery in the Faroe Islands with the first arrival and later marked augmentation of British forces stationed there during the war. Rises in the incidence of other diseases in 1941-1942 seem more likely a consequence of increased foreign commercial travel by Faroese at that time.

Blood pressure effects of long-term stimulant use in disorders of hypersomnolence.

Untoward cardiovascular effects have been implicated as a deterrent to long-term central nervous system (CNS) stimulant use in disorders of hypersomnolence. In this study, we reviewed the relationship between blood pressure and long-term stimulant use. Medical records of 54 patients with narcolepsy and idiopathic CNS hypersomnolence (ICH) were reviewed. The overall mean number of months of follow-up for the entire group was 45.6 (95% CI: 42-49). Both simple linear regression and multiple regression utilizing generalized estimating equations were used to show relationships between blood pressure (BP), time and other covariates. In the simple linear regression model, the average slope of the line of systolic BP (SBP) on time for the entire group was 0.06 (95% CI: -0.09, 0.13) and the line of diastolic BP (DBP) on time was 0.01 (95% CI: -0.05, 0.07). Two multiple regression equations were fitted for the continuous response variables SBP and DBP. Covariates in the model included: time, hypertension, weight at baseline, weight, SBP baseline (SBPBL), DBP baseline (DBPBL), high vs. low dose stimulant therapy and age at starting treatment. For SBP, the covariates weight at baseline, weight and SBPBL were significant (P < 0.05) predictors. For DBP, covariates reaching statistical significance (P < 0.05) included weight and DBPBL. There was no significant change in SBP or DBP over time in either model. Two different statistical models support the conclusion that there was no significant change in SBP or DBP over time in this population.

Multiple sclerosis in North African migrants to France.

Among some 7500 respondents with known place of birth who had completed a nationwide questionnaire survey for multiple sclerosis (MS) in France in 1986, there were 260 born in former French North Africa (Algeria, Morocco, Tunisia). They had migrated to France between 1923 and 1986, but 66% came between 1956 and 1964. Two-thirds were from Algeria, where virtually the entire European population had emigrated in 1962 at the end of the Algerian war for independence. The migrants were younger at prevalence day (mean 43.4 years) and at onset (29.4 years) than the French-born MS (46.6; 31.3 years). Eight migrants lacked age information. The 225 migrants with onset more than 1 year after immigration presumably acquired their MS in France. They provided an age adjusted (US 1960) MS prevalence rate 1.54 times that for all France. If the latter is taken at 50 per 100,000 population their estimated adjusted rate is 76.8 with 95% confidence interval of 67.1 to 87.5. The other 27 with presumed acquisition in North Africa gave an estimated adjusted prevalence of 16.6 per 100,000 (95% CI 10.9-24.1). For those migrants with acquisition in France there was a mean interval of 13 years between immigration or age 11 and clinical onset, with a minimum of 3 years. This series provides further support for the theses: 1) that MS is primarily an environmental disease acquired after childhood; 2) that acquisition requires prolonged or repeated exposure (here 3 years for these medium-to-high MS risk migrants) followed by a prolonged latent or incubation period between acquisition and symptom onset (here 10 years); and 3) that this disease is most likely a widespread but unknown persistent infection which results in clinical MS in only a small proportion of those affected.

Epidemiology of multiple sclerosis in US veterans. VIII. Long-term survival after onset of multiple sclerosis.

Survival to 1996 was analysed for nearly 2500 veterans of World War II who were rated as 'service-connected' for multiple sclerosis as of 1956 by the then Veterans Administration. Survival from onset was defined for all white women and black men, and a random sample of white men. Median survival times from onset were 43 years (white females), 30 years (black males) and 34 years (white males). Crude 50-year survival rates were 31.5% (white females), 21.5% (black males) and 16.6% (white males), but only the white females and white males were significantly different. A proportional hazard analysis was used to identify risk factors for mortality from multiple sclerosis onset year. Significant risk factors included male sex (risk ratio: 1.57), older age at onset (risk ratio: 1.05 per year) and high socioeconomic status (risk ratio: 1.05 per socioeconomic status category). There were no statistically significant differences in survival following multiple sclerosis onset by race or latitude of place of entry into military service, both significant risk factors associated with the development of multiple sclerosis. Standardized mortality ratios utilizing national US data (for 1956-96) showed a marked excess for all three race-sex groups of multiple sclerosis cases, with little difference among them, but with a decreasing excess over time. Relative survival rates, used to compare the survival of multiple sclerosis cases with that of other military veterans, did not differ significantly by sex-race group, nor by latitude of place of entry into military service, but did differ significantly by socioeconomic class. The lack of difference in male and female relative survival rates suggests that the significant difference in survival between male and female multiple sclerosis cases is, at least in part, a result of sex per se and not the disease.

Multiple sclerosis in the Faroe Islands. 7. Results of a case control questionnaire with multiple controls.

Detailed questionnaires were completed in 1978-79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no differences, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.