Increasing prevalence and incidence of multiple sclerosis in northern Japan

BACKGROUND: We previously reported that prevalence of multiple sclerosis (MS) in Japan was 8.6/100,000 individuals in 2001. This was much higher than prevalence previously reported from Asian countries. A second epidemiologic survey was conducted to assess changes in MS prevalence and incidence over the last 30 years in Tokachi province of Hokkaido, the northernmost island of Japan. METHODS: The authors studied the frequency of MS in the community of Tokachi Province, where the population has stabilized between 350,000 and 360,000 over the last 30 years. The survey was conducted at the same institutions using the same methods as the first survey in 2001. RESULTS: On March 31, 2006, 47 subjects satisfied Poser's criteria for MS. The prevalence rate increased from 8.6 to 13.1/100,000 individuals between 2001 and 2006. The prevalence of conventional MS (C-MS) increased in five years although the prevalence of optic-spinal MS (OS-MS) did not increase. The mean annual incidence increased from 0.15 (1975-1989) to 0.68 (1990-2004). CONCLUSIONS: The results show the highest MS prevalence in Asia; the increase in MS prevalence in Tokachi Province may be due to increased incidence after 1990.     

"Time, place and person" and neurology]

The Department of Neurology, Hokkaido University, has been established since 1987, however the bases for neurology had been cultivated through psychiatry and neurosurgery in Hokkaido, especially under the pioneering work by Professor Mitsuo Tsuru. Hokkaido, the northernmost island of Japan, is located between 42 and 46 degrees, and the people have ancestors from various parts of Japan, since this island was reclaimed about 130 years ago. Three major neurological disorders, such as multiple sclerosis(MS), spinocerebellar degeneration(SCD) and Parkinson disease (PD), were discussed on the bases of Hokkaido island. We proved the existence of definite north-south gradient of MS, prevalence rate of 8.6 in Tokachi, Hokkaido, compared with 1-2 in the southern island. SCD, especially hereditary SCD, such as SCA1, SCA2 and SCA14 were reported from Hokkaido. The epidemiological studies of PD showed the prevalence rate of 104.6 at Iwamizawa, Hokkaido in 2000, and we proposed the prevalence rate of PD was close to those of Western countries under the collaborative works with Yonago, Kyoto, and Kagoshima by 2001. Neurology, and its specialization and training programs were also discussed to propose the importance of Neurology in Japan.     

Epidemiological data of multiple sclerosis in the province of Evros,Greece

The frequency of multiple sclerosis (MS) in Greece is still debated. Our previous epidemiological field survey with a cross-check study of MS on March 31, 1984, in the province of Evros in north-eastern Greece showed a prevalence rate of 10.1/100,000. In 1990, Milonas et al. recorded a prevalence rate of 29.5/100,000 in northern Greece. So Greece is classified in the medium-frequency zone according to Kurtzke. This study was performed to estimate the prevalence of MS in the province of Evros and the annual incidence rates from 1974 to 1999. Patients were identified from several sources. A clinical follow-up was performed in 95% of the cases, and, if clinically indicated, new paraclinical examinations were performed and cases classified by Poser's criteria. The prevalence rate of the definite MS cases on December 31, 1999, was 38.9/100,000 and places the area in the high-risk zone. The mean annual incidence measured in 5-year intervals increased from 0.66/100,000 in 1974-1978 to 2.36/100,000 in 1994-1999 (p < 0.01). The increase in prevalence can be attributed to other causes than etiological changes, but the increase in the annual incidence rate indicates the possibility of a variation in risk factors of the disease.     

Genomic HLA profiles of MS in Hokkaido, Japan: important role of DPB1*0501 allele

The polymorphism of the HLA class II genes was investigated in 97 patients with multiple sclerosis (MS) in Hokkaido, the northernmost main island of Japan. Of these, 80 patients were classified as having conventional MS and 17 as having opticospinal MS (OS-MS). Our findings confirmed a previous report that the DPB 1*0501 allele is positively associated with OS-MS (P = 0.0043). The frequency of DPB 1*0501 was also found to be higher in conventional MS patients than in controls (79% vs. 58%, P = 0.0084), although the differences were not statistically significant. Our results indicate that OS-MS is a DPB 1*0501-associated subgroup of MS, and that DPB1*0501 is also correlated with risk of conventional MS in Japanese.     

An epidemiological study of multiple sclerosis in central Sardinia, Italy

Objectives – To verify morbidity estimates in central Sardinia, Italy. Methods – A prevalence study was performed in the province of Nuoro, Central Sardinia, which has a population of 273,768 inhabitants (135,383 men and 138,385 women). A complete enumeration approach was adopted by using all possible case-collection sources. Results – On prevalence day, December 31, 1993, 394 subjects (124 men and 270 women) living in the study area were known to suffer from definite and probable MS, giving a crude prevalence rate of 143.9 cases per 100,000 people, 91.6 for males and 195.11 for females. The crude prevalence estimated on December 31, 1985, based on 282 MS cases alive in the study area, was 102.94 per 100,000. Conclusion – This study reinforced central Sardinia's position as a high and rising prevalence area for MS.     

Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional study

This study reviewed the clinical characteristics of multiple sclerosis (MS) in Taiwanese patients from 1993 to 2001. Of the 75 MS patients with a mean age of onset of 35.6 +/- 12.6 years, the female-to-male ratio was 4.4 (61/14). In 42 (56%) optico-spinal MS (OS-MS) patients, the age of onset (37.6 +/- 11.1 years) tended to be older than conventional MS (C-MS) patients (33.1 +/- 14.1 years, P = 0.08). In 60 cerebrospinal fluid (CSF) specimens, raised IgG index (>0.7) and oligoclonal bands were noted in 26 (43.3%) and two (3.3%) cases, respectively. The frequency of raised IgG index was lower in OS-MS (31.3%) than in C-MS (57.1%, P = 0.07). The CSF total protein concentrations were significantly higher in OS-MS (64.5 mg/dL) than in C-MS (46.6 mg/dL, P = 0.047). The mean annual relapse rate was 54.1%, and was significantly higher within the first year (59.7%, P < 0.001). The mean annual relapse rate in OS-MS (62.7%) was significantly higher than in C-MS (41.2%, P=0.01). The differences in the annual relapse rate and total protein concentration in CSF between OS-MS and C-MS suggest probably two distinct immunopathogenesis. The higher first year relapse rate of MS patients in Taiwan may address the importance of early intervention with immunomodulatory therapy.     

Prevalence of multiple sclerosis in Valladolid, northern Spain

The aim of this study was to ascertain the prevalence of multiple sclerosis (MS) in a northern Spanish region and to compare it with that from the most recent epidemiological studies in the country. MS prevalence was studied for a period of 2 years using multiple sources of information in the province of Valladolid, with a sample comprising a total population of 92,632. Patients were classified according to the Poser criteria. The crude prevalence of definite and probable MS was 58.3 per 100,000 (95% confidence interval: 43.7–75.7). The same methods have been used in ascertaining similar prevalence rates in Vélez-Málaga, Osona, and Gijón and a slightly lower rate in Teruel. Our survey confirms Spain as a high-risk area for MS, with prevalence rates over 50 per 100,000. Received: 4 March 1998 Received in revised form: 13 May 1998 Accepted: 10 June 1998     

High prevalence and fast rising incidence of multiple sclerosis in Caltanissetta, Sicily, southern Italy

BACKGROUND: Epidemiological studies conducted in Sicily and Sardinia, the two major Mediterranean islands, showed elevated incidence and prevalence of multiple sclerosis (MS)and a recent increase in disease frequency. OBJECTIVE: To confirm the central highlands of Sicily as areas of increasing MS prevalence and elevated incidence, we performed a follow-up study based on the town of Caltanissetta (Sicily), southern Italy. METHODS: We made a formal diagnostic reappraisal of all living patients found in the previous study performed in 1981. All possible information sources were used to search for patients affected by MS diagnosed according to the Poser criteria. We calculated prevalence ratios, for patients affected by MS who were living and resident in the study area on December 31, 2002. Crude and age- and sex-specific incidence ratios were computed for the period from January 1, 1993, to December 31, 2002. RESULTS: The prevalence of definite MS rose in 20 years from 69.2 (retrospective prevalence rate) to 165.8/100,000 population. We calculated the incidence of definite MS for the period 1970-2000. These rates calculated for 5-year periods increased from 2.3 to 9.2/100,000/year. CONCLUSION: This survey shows the highest prevalence and incidence figures of MS in the Mediterranean area and confirms central Sicily as a very-high-risk area for MS.     

Increasing frequency of multiple sclerosis in Padova,Italy: a 30 year epidemiological survey

OBJECTIVE: To determine the incidence and prevalence rates of multiple sclerosis (MS) and their temporal profiles over the last 30 years in the province of Padova (northeast Italy). BACKGROUND: In the early 1970s an epidemiological survey in the province of Padova showed a MS prevalence and incidence of 16/100 000 and 0.9/100 000 population, respectively; these figures are much lower than current estimates in other regions of Italy and Central Europe. METHODS: The population of the study area was approximately 820 000 (422 028 women, 398 290 men) in the 1991 census. All possible sources of case collection were used, but only clinically definite/probable and laboratory-supported definite/probable MS were considered in the analysis of incidence and prevalence trends from 1971 to 1999. RESULTS: On 31 December 1999, the crude prevalence rate was 80.5/100 000 (95% CI 70.3-90.7); prevalence was higher in women (111.1/100 000; 95% CI 99.0-123.1) than in men (49.7/100 000; 95% CI 41.3-58.1). This difference was significant (F/M = 2.43; z = 10.1, P < 0,00001); a rate adjusted for the European population was 81.4/100 000. On 31 December 1980 and on 31 December 1990 the estimated prevalence rates were 18/100 000 and 45.7/100 000, respectively. Thus, a fivefold increase in prevalence was observed from the 1970s. The mean annual incidence was 2.2/100 000 in the period 1980-89, 3.9 in the period 1990-94 and 4.2 in the period 1995 99. Thus, incidence increased more than fourfold from the 1970s through 1994 and remained quite stable in the last several years. Mean age at onset was 31.3 +/- 9.88 years. Mean diagnostic latency decreased significantly from 49.2 +/- 44.5 months in 1985 to 23.0 +/- 30.3 months in 1990, 12.9 +/- 15.61 in 1995 and 5.3 +/- 4.7 in 1999. CONCLUSIONS: The actual prevalence (80.5/100 000) and incidence (4.2/100 000) of MS in the province of Padova agree with the most recent epidemiological estimates/trends observed in other Italian and European areas, except for Sardinia and Scotland. The increase in both incidence and prevalence rates observed in much of this region over the last 30 years parallels the introduction of more sensitive diagnostic techniques and a highly significant decrease in diagnostic latency. These findings probably do not support a real increase in the frequency of MS in northeast Italy because recent estimates of incidence have increased only slightly (3.9 to 4.2, which is < 10% in five years) and increase in the prevalence rate was almost completely due to the accumulation of new incidence cases.     

Prevalence studies of multiple sclerosis, myasthenia gravis, and myopathies in Kumamoto district, Japan

The prevalence ratio per 100,000 population of each disease was multiple sclerosis (MS) 1.3, myasthenia gravis (MG) 6.7, and polymyositis (PM) 5.0 in Kumamoto city, Japan (population 0.56 million, and the survey date on June 30, 1982). The prevalence ratio of MS was similar to that of 25 years ago in Kumamoto city. The incidence of MS had been stable despite Westernization of life-style in Japan. The prevalence ratio of MG and PM had increased moderately, possibly due to prolongation of life with recent progress in therapy. The prevalence ratio of all types of myopathies in Kumamoto prefecture (population: 1.8 million) on July 31, 1983, was estimated as approximately 17.4 per 100,000, for progressive muscular dystrophy (PMD) 4.1 per 100,000 population, compared to 3.9 for MG, and 2.4 for PM. The relative frequency of PMD, MG and PM was 23.3, 22.0 and 13.9%, respectively. The data shows that the prevalence ratio of various myopathies has not changed over the last 20 years in selected cities of Japan but the relative frequency of the diseases have changed due to recognition of the disease and prolongation of long life due to developments in diagnosis and treatment.     

Frequency of multiple sclerosis in Menorca, Balearic islands, Spain

OBJECTIVE: To establish prevalence and incidence of multiple sclerosis (MS) in Menorca (Balearic Islands, Spain; population: 67,009). METHODS: An extensive epidemiological study was undertaken using all available information sources. Patients were classified according to Poser's criteria. RESULTS: The prevalence rate of definite and probable MS was 68.6/100,000 (95% confidence interval 50.3-91.6). The incidence rate was 3.4/100,000/year (95% CI 2.2-5.3). The time lag between the first symptom and diagnosis was 10.2 years for patients with disease onset before 1987 and 2.1 years for patients with onset between 1987 and 1996. CONCLUSION: Menorca's population has a moderately high MS risk, with a prevalence rate the highest reported for a Spanish region.     

Prevalence and incidence of multiple sclerosis in Catania, Sicily

OBJECTIVE: An epidemiologic survey was conducted to determine the prevalence and incidence of MS in the city of Catania, Sicily, Italy. Prevalence rate was calculated as point prevalence at January 1,1995, and incidence during 1974 to 1995. METHODS: The authors studied the frequency of MS in the community of Catania in a population of 333,075 inhabitants according to the 1991 census. The primary sources for the case ascertainment were the neurologic and motor rehabilitation departments, the MS Center, the Italian MS Association, private neurologists, and family doctors. All patients who satisfied the Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS, and laboratory-supported probable MS were considered prevalent and incident cases. RESULTS: One hundred ninety-five patients with MS who had had the onset of disease on prevalence day in a population of 333,075 inhabitants were detected. The prevalence rate was 58.5 per 100,000 (95% CI 50.7 to 67.5). Prevalence was higher in women (62.0/100,000) than in men (54.8/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 (145.1/100,000). From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence was 2.3 per 100,000 (95% CI 2.0 to 2.6). Age-specific incidence showed a peak in the group aged 25 to 34 (6.32/100,000). Incidence for 5-year intervals increased from 1.3 during 1975 to 1979 to 3.9 during 1990 to 1994. CONCLUSIONS: These prevalence and incidence rates are close to those reported in other similar surveys carried out in Italy and southern Europe.     

Platelet-activating factor acetylhydrolase gene polymorphism and its activity in Japanese patients with multiple sclerosis

We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G(994)-->T) and PAF-AH activity with susceptibility and severity of multiple sclerosis (MS) in Japanese. DNA was collected from 216 patients with clinically definite MS (65 opticospinal MS (OS-MS) and 151 conventional MS (C-MS)) and from 213 healthy controls. The missense mutation G(994)-->T that disrupts the PAF-AH activity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No statistically significant difference in the frequency of genotypes and alleles of the plasma PAF-AH polymorphism was observed among OS-MS patients, C-MS patients and healthy controls. However, the missense mutation tended to be associated with the severity of OS-MS, especially in females (GT/TT genotypes; 51.7% in female rapidly progressive OS-MS vs. 26.6% in female controls, p=0.0870). Moreover, PAF-AH activities were significantly lower in MS than in controls, irrespective of clinical subtypes, among those carrying the identical polymorphism in terms of nucleotide position 994 of the PAF-AH gene. These findings suggest that the PAF-AH gene missense mutation has no relation to either susceptibility or severity of C-MS, yet its activity is down-regulated, and that the mutation has no relation with susceptibility of OS-MS, yet it may confer the severity of female OS-MS.     

Prevalence of multiple sclerosis in British Columbia

A province wide prevalence study on multiple sclerosis (MS) was conducted in British Columbia (B.C.). The prevalence date was July 1, 1982. The major portion of this study was a review of all the files of neurologists practicing in B.C. as this was judged to be the most accurate source for identifying MS patients. 239,412 neurologists' files were hand searched by one researcher using modified Schumacher criteria for classification. Other sources used during the study for identifying MS patients were the MS Clinic, general practitioners, ophthalmologists, urologists, specialized facilities such as long term care facilities and rehabilitation centres, and patient self-referrals. A total of 4,620 non-duplicated cases were identified and classified. 4,112 of these (89%) were classified according to information contained in neurologists' records. The prevalence estimate for definite/probable MS in B.C. was 93.3/100,000 population. This increased to 130.5/100,000 population if possible MS and optic neuritis were also included. These rates are among the highest reported in Canada or elsewhere. The cooperation of B.C. neurologists made this study unique in its scope and accuracy of diagnosis.     

Optic-spinal form of multiple sclerosis and immune-mediated myelopathy in Japan

Optic-spinal form of multiple sclerosis (OS-MS) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) are two immune-mediated myelopathy relatively common in Japan. (1) Transverse myelitis, once seen in 60% of MS, mostly OS-MS, 30 years ago, drastically decreased (5%) recently in Japan. In contrast, frequency of conventional form of MS (C-MS) increased during this period of time. But unlike C-MS in white patients, cerebellar hemispheric lesions are uncommon in Japanese C-MS. These findings emphasize influence of changes in exogenous factors on manifestations of MS and distinct genetic factors related to MS in Japanese and white patients. (2) To clarify the reason of high HTLV-I proviral load in HAM/TSP, we studied cellular immune surveillance against HTLV-I and found that significant cytotoxic T lymphocyte activity, and suppressed natural killer activity and antibody-dependent cell-mediated cytotoxicity in the patients. These altered immune surveillance may be associated with the spread of HTLV-I infection and the pathogenesis of HAM/TSP.     

Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India

Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona. The age-adjusted prevalence ratio for Bombay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States.     

Epidemiology of multiple sclerosis in the province of Venezia (author's transl)

In the province of Venice province on "prevalence day" (31 December 1974), the crude prevalence rate of multiple sclerosis was 20.44 cases/100,000 inhabitants (170 patients in a population of 831,657). The prevalence rate for men was 15.24/100,000 and for women was 25,41/100.000. In the city of Venice and in the near lagoon islands the MS prevalence rate was higher then that in the rest of the province, but there was no significant difference of age of onset, duration of the disease, initial symptoms and degree of disability between the two groups of cases. These results were compared with similar studies in other areas at the same latitude.     

Multiple sclerosis in the Republic of San Marino,Italian peninsula: an incidence and prevalence study from a high-risk area

Epidemiological studies on multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the disease frequency. Previous surveys conducted in the Republic of San Marino, Northern Italian peninsula, identified that the population is at high risk for MS, with a prevalence of 51.6 per 100,000 population in 1982 and of 166.7 in 2005 and with a mean annual incidence of 7.9 per 100,000 for the period 1990–2005. The present work is a community-based intensive prevalence and incidence survey, by a complete enumeration approach, to update the prevalence and incidence of MS in the Republic of San Marino. The mean annual incidence for the period 2005–14 was 7.7 (95% CI 4.9–11.4) per 100,000, 3.3 (95% CI 1.1–7.6) for men and 11.9 (95% CI 7.2–18.6) for women. On 31 December 2014, 67 patients (19 men and 48 women), suffering from definite or probable MS and living in the Republic of San Marino, yielded a crude prevalence of 204.3 (95% CI 158.4–259.5) per 100,000, 117.8 (95% CI 70.9–183.7) for men and 288.2 (95% CI 212.4–383.3) for women. Our study has confirmed San Marino is an area at high risk for MS, in line with epidemiological data from continental Italy. The marked increase in MS prevalence over time in this population can be ascribable to increased survival and improved ascertainment, in the presence of a substantially stable, yet high, incidence rate.     

Epidemiological investigations into multiple sclerosis in Southern Hesse I.

An epidemiological field-survey on multiple sclerosis (MS) was carried out in the southern part of the state of Hesse (West Germany). Out of 472 patients primarily ascertained, 75% could finally be accepted as definite or probable MS cases. Cross-checking of the 3 sources for case-finding (practitioners and specialists, neurological hospital, MS society) revealed that case-finding in all and especially that of definite and probable MS cases was rather complete. The overall prevalence rate was 58.3, the annual incidence 2.15 and the mortality rate 2.0 per 100,000. Male patients showed a faster course than females. The prevalence in immigrants who mostly originated from Mediterranean countries, was significantly lower (14.3 per 100,000) than the prevalence in the German population (63.1 per 100,000).