Proven MS Treatment By Dr Gary Levin

Natural Cure for Multiple Sclerosis

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aThe study has been revised from a previous one. Abbreviation: CDMS, clinically definite multiple sclerosis.

aThe study has been revised from a previous one. Abbreviation: CDMS, clinically definite multiple sclerosis.

Figure 3 Prevalence versus latitude for all studies in Table 1 with 0° as the reference for the equator. Negative latitudes represent degrees south. This plot visually reasserts a correlation between increasing prevalence and increasing latitude. (Studies published from 1999 to 2004.)

latitudes) was discussed in the previous edition of this book, and has been reaffirmed (75). The incidence of MS among the U.S. National Health Survey participants (181 definite/probable patients) also increased significantly with latitude (P = 0.03, trend), but there was an attenuation of the north-south gradient over time (76).

Such variation of MS prevalence rates with latitude strongly suggests an environmental contribution to the natural history of the disease (77), the discrepancies between prevalences of regions at similar latitudes [e.g., in Finland (78) and in Sicily and Malta (79,80)] notwithstanding. Large variations in prevalence among geographically close regions suggest that locally specific etiologies (either environmental or genetic) contribute to disease pathogenesis. A plot of prevalence versus latitude in recently published prevalence studies (Fig. 3) displays their general correlation, though against this interpretation is the similarity in prevalence rates of immigrant Jews from Europe/America and native-born Jews of European/American origin (81).

Stability of Incidence Rates

Over the past several years regional prevalence figures have been updated to monitor disease trends. Justification for updating prevalences stems from changing disease criteria (82,83), better general awareness of disease, subsequent earlier referral with consequent shorter time from first symptoms to diagnosis, better availability of diagnostic equipment, and sometimes better access to a neurologists (84,85). In Table 1, we indicate the studies that have been revised. All incidence studies have shown either stability in rates or an increase, and most studies of prevalence show that this is increasing (74). In Newfoundland, Canada, a study in 1983 using clinical records, as well as those of the government healthcare plan, yielded a prevalence rate for the island of 55/105 (86), but when this study was repeated using the same methodology 20 years later, the prevalence rate had risen to 94.4/105 and the previous regional disparities had equilibrated (87).

Most authors have concluded that the increase is due to better case ascertainment through better disease awareness, better access to diagnostic equipment and diagnosticians, a changing population ethnicity, longer life expectancy, and earlier age at diagnosis (72,88). However, a few (Table 1) have hypothesized that there is a real increase in their regional incidence. As these studies are the minority, one may speculate that such increases only reflect a global statistical variation. Since all studies show an increase in incidence, however, the general overall increase requires consideration, but only the repetition of studies over time with similar ascertainment methods and environments can provide an accurate estimate of disease trends. If there is a global increase in disease incidence, a careful analysis of the environmental and genetic factors may point toward the underlying etiology.

Point Source Outbreaks and Clustering

The clustering of disease is a compass to both genetic and environmental contributions to etiology (see previous section on regional variations for genetic contributions) and it is sometimes possible to separate the contributions of each. In the mid-1990s, several cases of MS were reported in a small, north-central Illinois community, once contaminated by heavy-metal exposure from a zinc smelter. Nine new cases of clinically definite MS occurred among local residents between 1971 and 1990, representing a statistically significant excess of new MS cases over the numbers expected (89). A survey in Finland also supported previous findings of an uneven geographic distribution of MS with an incidence of 8.7/105 in a western and 5.1/ 105 in a southern region. A rate of 11/105 in one domain was over twice as great as that found in a neighboring one (78). Increasing incidences for men, decreases for both sexes, and stable incidence rates were all reported in adjacent areas—a marked disparity. The incidence trends could not be explained by differences in case ascertainment and suggested to the authors that environmental factors had modulated the incidence of MS over the 15-year study period.

Migration Studies

Migrant studies indicate an environmental contribution to natural history depending on the specific observations of the study. If migrants keep their risk of disease regardless of their destination (e.g., cystic fibrosis), a genetic cause is presumed, but if their risk is modified (e.g., malaria), an environmental cause is considered. In MS, the risk modification is complex. Multiple migrant studies in MS (75,90) suggest that people who migrate before adolescence acquire the incidence rates of the region to which they have migrated. In contrast, people who migrate to a region after adolescence retain the incidence rate of the region in which they grew up (91). However, the children of those who moved from low- to high-risk areas have shown greater susceptibility than their parents, again supporting the operation of an environmental factor. This compelling evidence is consistent for migration from areas of high-risk to areas of low-risk (75), suggesting that part of the disease process depends on geographical location, possibly involving an environmental pathogenetic principle. However, there is also evidence that migration from areas of low risk to areas of high risk is not associated with a substantial change in risk (91). This diminishes the strength of conclusions that can be drawn from all migrant studies but does permit the observation that both geography and age play some as yet undetermined role in the natural history of the disease.

Studies of the age at which people migrate suggest that a general age range might be important in the natural history of the disease, in terms of susceptibility to an environmental pathogen. Many studies on age-at-migration suggest that either a general age range (75,90) or a "critical age'' at migration alter the risk of disease. This critical age tends to be close to 15 (thus, populations migrating before the age of 15 from high- to low-risk regions acquire a lower risk of susceptibility). The implication of these studies is that the risk of acquiring MS may be largely determined by the age of 15 years, but they were based on very small population sizes (91). In studies from Australia (92) and the U.S.A. (93), a relation between the age of migration and the change in risk of acquiring MS has been suggested, and it has been hypothesized that the critical age is not 15 but exists sometime within the latter part of the first two decades of life (75,91) and that susceptibility may extend from age 11 to 45 years (94).

We recently examined the critical age of susceptibility in Newfoundland, (220) and found a linear relationship between the age of menarche and the age at which the first symptoms occurred. This suggests that the initiation of disease may be related to the changes occurring in the body during puberty. The biologic plausibility of this interpretation is corroborated by observations made by others; in terms of hormonal effects on MS, the mean relapse rate decreases during all three trimesters of pregnancy (95,96) and tends to increase up to three months post partum (96). The premenstrual period also triggers exacerbations in a subgroup of females with MS (97). However, since neither the use of oral contraceptives nor parity are significantly associated with the risk of MS (98,99), other factors must also be involved in disease initiation.

Latency Period

Latency periods (the time from exposure to clinical presentation of the disease) based on a hypothesized age at exposure have been estimated and ranges of nine years (100), 9 to 12 years (101), and 8 to 14 years (100), have been reported. These studies, combined with those on migration, suggest that MS is ordinarily acquired in early adolescence with a lengthy latency before symptom onset (94).

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