Search

Background There are two distinct phenotypes of multiple sclerosis (MS) in Asians, manifesting as optic-spinal (OSMS) and conventional (CMS) forms. In Japan, four nationwide surveys of MS have been conducted. The first three were in 1972, 1982, and 1989, and we performed the fourth in 2004. Results The recent survey showed six main findings as follows: (1) a four-fold increase in the estimated number of clinically definite patients with MS in 2003 (9900; crude MS prevalence, 7.7/100,000) compared with 1972; (2) a shift in the peak age at onset from early 30s in 1989 to early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement in clinically definite patients with MS; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after subdivision of the mainland (30-45° North) into northern and southern parts at 37°N, northern-born northern residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern residents (southern patients); (6) among northern patients, the absolute numbers of patients with CMS and those with Barkhof brain lesions rapidly increased with advancing birth year. Conclusions These findings suggest that MS phenotypes are drastically altered by environmental factors, such as latitude and "Westernization." [ABSTRACT FROM AUTHOR]

Understanding the spectrum of idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system is an important issue for accurate diagnosis and advancing research on the pathogenesis as well as treatment strategies, but the nosology and the classification of the IIDD remains confusing. Until now, we have tried to apply each disorder within the spectrum to an adequate co-ordinate on a two-dimensional plane. One axis is clinical course and the other is lesion distribution. We reviewed some disorders of the IIDD spectrum, and our recent findings on the fulminant nature of each attack and the expansion of each lesion, which we called attack-related severity in Japanese multiple sclerosis (MS). From our findings and the literature, attack-related severity appears to be a third important factor, in addition to lesion distribution and clinical course. Introduction of the third axis produces a three-dimensional space for a better understanding of the heterogeneous characteristics of IIDD and ‘MS’ syndrome, and can advance treatment strategies for these disorders. As severe attacks seem to be relatively common in Asians but rare in the west, ethnic-related heterogeneity should be considered in understanding the spectrum of IIDD, and there is an urgent need to develop a common general concept of the spectrum, especially for MS. [ABSTRACT FROM AUTHOR]

Apart from its unique lesion distribution pattern, the opticospinal form of multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the diagnostic criteria of MS. OSMS has been suggested to be strongly associated with HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and non-OSMS (82%) were similar, but both were higher than in the controls (66%). In DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL) were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22 out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS patients. Our findings indicate that DPB1*0501 plays an important role in the development of MS in general, but not in OSMS. The strong association of DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant to the development of periventricular lesions in Japanese patients with MS. [ABSTRACT FROM AUTHOR]

The relation between apolipoprotein (APOE) gene polymorphisms and disease progression of multiple sclerosis (MS) is controversial. The present study was designed to investigate the relation between APOE gene polymorphisms and Japanese patients with MS. We analysed the frequencies of APOE gene polymorphisms in 135 MS patients and 134 healthy controls, using PCR-RFLP. The results showed no significant differences in the distribution of APOE gene polymorphisms between MS patients and controls. With regard to disease progression, there was no association between APOE gene polymorphisms and ε4 allele positivity and disease progression index (EDSS/years). Furthermore, in patients with more than 10 years of disease onset, there were no significant differences between the frequencies of ε4 allele and patients with EDSS of more than 6. Although the low rate of ε4 allele in Japan should be taken into consideration, our results showed no relation between APOE gene polymorphisms and Japanese patients with MS. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), β-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack β[sub 2] adrenergic receptor (β[sub 2]AR) expression. This differentially altered expression suggests that β[sub 2]ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the β[sub 2]AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of β[sub 2]AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary–progressive MS, this result was not significantly different from that observed in relapsing–remitting MS patients or control subjects. Together, our findings suggest that the presence of β[sub 2]AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies. [ABSTRACT FROM AUTHOR]

Despite the strength of the association of multiple sclerosis (MS) and human leukocyte antigen (HLA)-DR2, other genetic elements could have a role in the pathophysiology of MS. We investigated possible associations with polymorphic susceptibility genes located within the HLA complex, i.e., heat-shock protein (HSP)70-1, HSP70-2, and HSP70-hom in Japanese patients with MS. Furthermore, we analyzed the influence of HSP70 gene polymorphisms on the severity of the disease, clinical course, magnetic resonance imaging findings, and oligoclonal bands in the cerebrospinal fluid, and HLA in MS patients. The results of the present study indicated that there were no significant differences in the distribution of all HSP70 genotypes and allele frequencies between Japanese MS patients and controls. In MS patients, there were no associations between HSP70 gene polymorphisms and the clinical data. Moreover, there were no significant differences in HSP70 genotype or allele frequencies between MS patients positive for HLA-DRB1*1501 alleles and matched controls. Our data indicate that HSP70 gene polymorphisms are not relevant in the susceptibility to or the severity of Japanese MS patients. [ABSTRACT FROM AUTHOR]