Epidemiology Of Multiple Sclerosis

The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with Multiple Sclerosis (MS) in Japanese, to determine whether Optico-Spinal MS (OS-MS) and conventional MS are ImmunoGenetically distinct, and to verify the role of gender difference in HLA associations of MS.

We studied HLA-DRB1 and -DPB1 PolyMorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the Optico-Spinal MS (OS-MS) and 119 as having conventional MS.

A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS.

By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28).

Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS.

However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients.

We did not find any association of these HLA alleles with disease course and severity.

In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.

The possible role of Genetic factors in the Etiology of Multiple Sclerosis (MS) has been debated for over a century.

It is now clear that Genetic and environmental interactions must exist. It is likely that MS susceptibility is under the control of several Genes encoded both within and outside the Major Histocompatibility Complex (MHC).

It is therefore unlikely that MS has a purely transmissible cause for these and other reasons, including:

The environmental factor causing Multiple Sclerosis (MS) is unknown. Kurtzke et al. (Neurology 1979; 29: 1228-1235) depicted a north to south diminishing gradient in the case/control ratios for MS among American veterans in the United States.

A similar, but less precise, gradient emerged when the incidence rates of Varicella from 37 states during 1978-91 were compared.

A loose correlation appears to exist between the mean incidence of Varicella and the MS risk ratio (n = 0.344 Spearman rank correlation coefficient, p = 0.037).

Further, the data on the fate of migrants moving from a high risk MS country to a low risk country and the reverse, plus the great importance of the age at migration, raise the question of a possible connection between the two diseases.

Because of these Epidemiological and other similarities between the two diseases a further comparative study was suggested.

Multiple Sclerosis is rare among the indigenous black people of Africa. The first account of a black patient with Multiple Sclerosis in South Africa was published as late as 1987.

Since then a search to find black patients with Multiple Sclerosis in Southern Africa has continued.

Seven black patients have now been traced in South Africa and five in Zimbabwe in whom a diagnosis of Multiple Sclerosis can be accepted. Six of the 12 patients became blind, or nearly so, from severe Optic Neuritis.

Multiple Sclerosis in these few black patients more often resembled the disorder as it occurs in Oriental people than among white people in southern Africa or the black people of North America or the Caribbean.

A population-based study of Multiple Sclerosis (MS) was conducted in 2 northern Colorado counties in 1982 to determine MS prevalence, to compare the rates with recent North American surveys and to compare the methods used in these studies.

Provisional cases were identified from: the patient rolls of MS service organizations, chart reviews in 2 neurology practices, a survey of physicians and a review of hospital discharge diagnoses. Crude-point prevalence for the 2-county region was 84 per 100,000.

The age-adjusted rate was higher than the rate for the region above the 37th parallel projected from data in a 1976 national survey, but was comparable to rates obtained in localized surveys conducted in the northern tier of the country.

The methodological results revealed that the highest yield sources were the MS service organizations and the neurology practice chart reviews.

MS prevalence surveys which neglect these methods may underestimate MS prevalence by as much as 20-40%.

We evaluated 48 Relapsing/Remitting Multiple Sclerosis (Relapsing/Remitting MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS.

Age and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls.

A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls.

In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members.

Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.

Twenty-five cases of Multiple Sclerosis (MS), including 2 autopsy cases, collected during the past 20 years from among the Chinese of Taiwan, are reported. These cases fulfilled all the clinical diagnostic criteria of MS.

The Epidemiological approach has undoubtedly contributed to our knowledge of Multiple Sclerosis (MS) by providing some Etiological hypotheses in spite of the fact that a definitive basis for the conclusive resolution of its enigma is still lacking.

Epidemiological studies have indicated that MS has an uneven geographical distribution and a changing incidence over time at least in several areas of the world: this suggests an Etiological role of both Genetic and environmental factors.

The racial difference in disease risk, the results of familial and twin studies as well as the association between MS and some HLA markers, support the great importance of Genetic factors.

On the other hand, the evidence of temporal trends and the data from migrant studies seem to underline the etiological contribution of environmental factors.

In the light of these results much of the present views have emerged interpreting the disease as caused by multiple factors acting at a susceptible age in Genetically predisposed subjects.

A highly restricted epidemic of Canine Distemper occurred in southwest Iceland in 1966-67. We have determined the extent of dog contact and exposure to dogs during the Distemper epidemic in Icelandic MS patients with onset since 1966.

Further, age of onset, and annual incidence of MS from 1966 through 1978 have been determined. Thirty-five of 36 MS patients had close dog contact prior to onset of their illness, and 34 were in the area of the Distemper epidemic during 1966-67.

A significant decrease in age of onset of MS (31.6 to 26.5) from 1956-1965 to 1967-1978 was noted, consistent with exposure of a susceptible cohort to a point infection with a varible incubation period.

A review of incidence of MS in the 10-year periods after Distemper epidemics in Iceland in 1921-1922, and 1941-1942 reveal significantly more MS than in comparable time periods before these epidemics.

These collective findings are consistent with, but do not prove, a relationship between dogs, Distemper and MS.

Objectives
To investigate the nature and cause in eight black South African patients of a recurrent (multiphasic), Remitting/Relapsing DeMyelinating Disease of the CNS.

Methods
The clinical and laboratory investigations and radiological manifestations of these patients were documented.

Results
Each patient had two or more acute attacks of DeMyelinating Disease affecting the CNS. The clinical presentations of the patients were predominantly those of multiphasic NeuroMyelitis Optica (NMO).

Brain MRI in these patients showed features consistent with those described for Acute Disseminated EncephaloMyelitis (ADEM), as well as lesions that are described in Multiple Sclerosis.

There was involvement of the Corpus Callosum in addition to typical ADEM lesions. Laboratory investigations excluded all other known causes of multiphasic CNS DeMyelination.

OligoClonal AntiBododies were not detected in these patients at any time. The patients were all from a population with a low risk for MS (black South Africans).

Conclusion
The patients described here represent a new phenotypic expression of a recurrent (multiphasic), Steroid sensitive, inflammatory DeMyelinating Disorder of the CNS occurring in black South Africans.

The disorder is either a distinct inflammatory DeMyelinating Disorder of the CNS of as yet unknown Etiology, or a varied form of MS (ADEM/NMO) occurring in a population with a low risk (where the Genetic trait and environmental risk factors for MS do not exist) for MS.