The increasing incidence and prevalence of MS in a Sardinian province

OBJECTIVE: To verify incidence rates and their temporal trend in a homogeneous, ethnically, and genetically distinct population of central Sardinia (the Nuoro province). BACKGROUND: Intensive epidemiologic studies carried out in Sardinia since the 1970s have suggested that the prevalence and incidence of MS are much higher in this Mediterranean island compared with those found on mainland Italy. METHODS: The study area had a population of approximately 274, 000 people in the 1991 census. The authors adopted a complete enumerative approach by reviewing all possible sources of case collection available in the investigative area. RESULTS: Based on 469 MS patients, the mean annual incidence for 1955 to 1995 was 4.18 per 100,000 (or 4.3 per 100,000 if age- and sex-adjusted to the European population). The incidence, averaging 1.95 per 100,000 during 1955 to 1959, rose progressively over time, reaching rates of 6.6 in the quinquiennium 1985 to 1989 and 6.4 per 100,000 in 1990 to 1995. On December 31, 1994, the crude prevalence, based on 415 MS patients alive in the study area, was 151.9 per 100,000 (156.6 if adjusted to the European population). CONCLUSION: These incidence and prevalence rates are the highest to date that have been estimated for a large community in southern Europe, and they constitute some of the highest rates in the world. Based on other surveys, these results reinforce the position of Sardinia as a higher and rising prevalence area for MS compared with other Mediterranean populations. Genetic and social-historic data strengthen the hypothesis of the environmental role and genetic factors among Sardinians in determining the notable difference in MS frequency between Sardinians and other Mediterraneans.     

Epidemiologic survey of multiple sclerosis in the Bucharest city and suburban area

Epidemiologic survey over a restricted area of Romanian territory, i.e. the city of Bucharest with a population of 1,934,052 and a surface of 605 km², established the following values for the MS parameters studied.
On January 5, 1977 the prevalence rate for "probable" and "possible" cases was 46.4 per 100,000 inhabitants and for "probable" cases alone (with certain clinical diagnosis) 41.3 per 100,000.
The specific 20- to 60-year age adjusted prevalence rate was 79.4 per 100,000. The incidence rate over the 1969–1976 period was 1.78 per 100,000.
The prevalence and incidence rates in this survey are similar to those reported for two other large urban centers of Romania (population over 100,000 each), Romania being therefore situated in a geographical area of "high risk" for MS.
The 0.61 per 100,000 nationwide and the 0.65 per 100,000 Bucharest mortality rates are lower than those reported in other geographical areas of "high risk" for MS.     

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.     

Frequency of multiple sclerosis in Valle d'Aosta, 1971-1985

According to studies done before 1980, the multiple sclerosis (MS) prevalence rate in Italy ranged from 7.2 to 27.1 cases per 100,000 inhabitants. More recent work has consistently put the MS prevalence rate to over 30 cases per 100,000 inhabitants. If these recent data are confirmed in the future, Italy can no longer be regarded as a country at low risk for MS, but must be included among the medium-high risk countries of continental Europe. We report the results of a prevalence and incidence survey conducted in Valle d'Aosta, a region whose special features make it an excellent epidemiological model. The mean annual incidence was 2.1 and on December 31, 1985, the prevalence was 39 cases per 100,000 inhabitants. These results confirm that the incidence and prevalence rate of MS in Valle d'Aosta is close to that of areas at high-risk for MS.     

Amyotrophic lateral sclerosis in Sardinia, insular Italy, 1995–2009

Recent genetic studies suggest a Sardinian type of amyotrophic lateral sclerosis (ALS). Thus, ALS incidence, prevalence and survival were investigated in a large population of Sardinians aimed to disclose population-specific patterns and their temporal changes. This is a population-based incidence and prevalence study in northern and central Sardinia, insular Italy (over 700,000 population). Incidence rates were computed for the time interval 1995–2009 and by quinquennia. Prevalence was computed for prevalence days 31 December 2004 and 2009. Onset-based survival for 1995–2009 is also reported. All ALS patients (El Escorial Criteria) in the study area were retrospectively included. The ALS crude incidence from 2005–2009 was 2.5 (95 % CIs: 0.1, 4.9), 3.4 in men and 1.6 in women. Onset occurred most often between the age of 65–74 years in men and 55–64 years in women. The ALS incidence tended to increase over the period 1995–2009. The mean age at onset was 61.7 years with no difference based on gender, varying significantly from 59.9 years in 1995–1999 to 63.9 years in 2005–2009. On December 31, 2009, the ALS crude prevalence was 10.8 per 100,000 (95 % CIs: 8.6, 13.1), 13.8 in men and 8.0 in women, whereas it was 6.3 per 100,000 (95 % CIs: 4.1, 8.6) on December 31, 2004 (M:F ratio of 0.95). Mean survival from onset was 37.0 months, with no difference based on gender, and a tendency to decrease during the period 1995–2009, in relation to type and age of onset. The population-based incidence and prevalence data of ALS in Sardinians indicate an increase of the disease occurrence over the past 40 years, providing support for a population-specific variant of ALS in Sardinia.     

High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy.

Twenty years after a first survey, a follow-up study was performed on the prevalence of MS in Enna (Sicily), southern Italy. The prevalence of definite MS rose from 53 to 120.2 per 100,000 population. The incidence of definite MS for the period 1986 to 1995 was 5.7 per 100,000 per year. The innermost part of Sicily shows an elevated prevalence of MS, second only to Sardinia in the Mediterranean area.     

Multiple sclerosis distribution in northern Sardinia: spatial cluster analysis of prevalence.

BACKGROUND: A heterogeneous geographic distribution of MS has been reported among different ethnic groups, and also within small communities. Epidemiologic studies conducted over the past two decades using repeated assessments clearly show that Sardinia is at high risk for MS, with a prevalence of 150 per 100,000 in 1997. OBJECTIVE: To present spatial analysis of the disease prevalence to disclose possible "hot" or "cold" spots of disease, further allowing correlations with risk factors. METHODS: A spatial analysis of the whole province of Sassari, in northern Sardinia, at a microgeographic level (i.e., in the 89 administrative communes and 6 linguistic areas) was conducted. Because of the small number of cases per commune and to overcome random variability, a hierarchical Bayesian approach was adopted. The distribution of prevalent cases by commune of residence on December 31, 1997 and from age 5 to 15 years was analyzed. RESULTS: A clustering pattern was found in the southwestern communes of the province based on geographic distribution by both prevalence and residence at age 5 to 15 years. A west-to-east gradient also was observed. CONCLUSIONS: This study highlights a hot spot of MS in the southwestern part of Sassari province, bordering with the commune of Macomer, where MS was once hypothesized as having occurred as an epidemic. Interestingly, these areas of MS clustering comprise the Common Logudorese linguistic domain. The Catalan area, linguistically and genetically distant from the remaining Sardinian domains, does not show such high estimates. Because MS is not a single-source infectious disease, this study may help test the hypothesis that a widely and evenly spread environmental (infectious?) agent may produce disease in subgroups of genetically more susceptible individuals in areas at higher inbreeding rates, wherein a disease mode of inheritance could be better investigated.     

Epidemiology of Parkinson's disease in Benghazi, North-East Libya

An epidemiological study of Parkinsonism was carried out in Benghazi situated in North-Eastern Libya. On the prevalence day, January 1, 1985, a total of 163 patients with Parkinson's disease were found living in the investigated area, which had a population of 518,745. The crude prevalence rate was 31.4 per 100,000 population and the incidence rate was 4.5 per 100,000 population per year. The average age at death was 71.2 years and the mean duration of the illness was 6.7 years. Our findings suggest that the risk of Parkinson's disease observed in the present study is intermediate to that reported among the white and black races and comparable with the yellow race and the Sardinians.     

Multiple sclerosis in Northern Sardinia, Italy: a methodological approach for genetic epidemiological studies

The etiopathogenesis of multiple sclerosis (MS) remains unclear. However, genetic factors are believed to be important in disease susceptibility. A methodological approach is presented for a population-based study aimed at investigating MS familial incidence and patterns of familial clustering in Northern Sardinia, Italy, with a reported MS prevalence of 150/100,000 population. Patients with MS since 1965 to the present and known to the MS Register for the province of Sassari will be asked to provide genealogical, comorbid and demographic information. Statistical analyses of the familial risk for MS will depend on the completeness of MS 'age at onset' data for affected individuals and age at the time family history is obtained (or age at death) for unaffected family members.     

Factors in the rising prevalence of multiple sclerosis in the north-east of Ireland

BACKGROUND: Northern Ireland is recognized as an area of high risk for multiple sclerosis. The original study of Allison and Millar in 1951 found a prevalence of 51/100,000 and mean annual incidence of 2.74/100,000/year. Subsequent studies in 1961, 1986, and 1996 suggested rising prevalence--80, 138, and 168.2/100,000, respectively. METHODS: In 2004, we surveyed the North-East of Northern Ireland (population 160,446, area 2030 km(2)) using multiple sources of case ascertainment, all satisfying the Poser criteria for definite or probable multiple sclerosis (MS) or the McDonald criteria. RESULTS: From a provisional list of 469 cases, 370 (123 males, 247 females) were identified. The prevalence was 230.6 per 100,000 (95% CI 207.0-255.4) with significantly higher prevalence in females (300.8/100,000) than males (157.0/100,000). Direct standardization to the 1961 Northern Ireland population reduced the overall prevalence rate to 200.5/100,000 (95% CI 193.2-208.0), in females to 270.2/100,000 (95% CI 258.8-282.4) and in males to 131.1/100,000 (95% CI 122.8-139.9). In 1996, incidence had risen to 9.3/100,000/year (14 cases in population of 151,000) with a higher incidence in females (10.3/100,000/year) than males (8.3/100,000/year). CONCLUSIONS: Northern Ireland continues to have a rising prevalence of MS. The increase in incidence suggests a true increase in the disease.     

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.     

Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.     

The frequency of multiple sclerosis in Mediterranean Europe

Recent investigations on multiple sclerosis (MS) distribution in Italy, based on relatively small population groups, contradict the current thesis, derived from studies undertaken in populations exceeding 300,000, of a lower spreading of the disease in Mediterranean Europe. Intensive surveys on small populations strengthen the suggestion that Italy is a high-risk area, although MS studies based on prevalence rather than incidence could also be biased by geographic variables making prevalence unsuitable for comparing MS prevalence rates found in different years and/or zones. We report a further epidemiologic study in Barbagia, Sardinia, insular Italy, undertaken both to establish the MS incidence in the last 20 years, and to estimate a new prevalence rate. Based on 31 probable incident cases, the mean incidence per year for the years 1961-1980 was 2.9 per 100,000 (3.2 if age- and sex-standardized to the Italian population). On October 24, 1981, the prevalence per 100,000 was 65.3 (77.9 if standardized to the Italian population). These results confirm that in Barbagia, MS occurs more frequently than expected in a Mediterranean area, and give further support to the idea that MS frequency in Italy is similar to that established for most central and northern European countries.     

Psychiatric disorders in Sardinian immigrants to Paris: a comparison with Parisians and Sardinians resident in Sardinia

BACKGROUND: The aim of the present study was to compare the prevalence of ICD-10 psychiatric disorders in a community sample of subjects of Sardinian origin resident in Paris (here "immigrants"), of the general Parisian population ("Parisians") and of Sardinians resident in Sardinia ("Sardinians"). METHODS: The sample of immigrants was obtained by contacting a fifth of all households with a Sardinian surname in Paris telephone directories. The other samples have already been partially described in previous studies. All subjects were interviewed using the CIDIS, a shortened version of the structured WHO interview CIDI. RESULTS: High or very high response rates were achieved in all studies. The final sample sizes were: 153 immigrants, 2,260 Parisians and 1,040 Sardinians. Immigrants showed high rates of depressive disorders, as did Parisians, and high rates of anxiety disorders, as did Sardinians. The immigrants' offspring (second-generation immigrants) seemed to be particularly at risk for depression, drug-abuse and bulimia. Elderly Sardinians who had returned to Sardinia after a long period of emigration showed an increased risk of dysthymia. The presence of a confidential relationship had a protective effect. CONCLUSIONS: The results are consistent with previous findings which suggest a greater risk of anxiety disorders in Southern Europe and of depression in Northern European countries. Immigrants in this study seem to present a particularly unfavourable pattern of mental disorders compared to both origin and host populations. The role of social support, use of mental health services and social conditions of second-generation immigrants should be analysed in greater depth.     

Incidence of multiple sclerosis among First Nations people in Alberta, Canada

Multiple sclerosis (MS) is thought to be rare among North American aboriginals, although few population-based frequency studies have been conducted. Data from government health databases were used to describe the incidence of MS among First Nations aboriginal people in the province of Alberta compared to the general population from 1994 to 2002. The general population rates were consistently higher than First Nations rates, but were essentially stable across this time span for both groups. For First Nations the MS incidence was 7.6 per 100,000 and 20.6 per 100,000 for the general population in 2002. During 2000-2002 for First Nations the incidence was 12.7 for females and 7.6 for males, with a female-to-male ratio of 1.7:1. During the same period the general population incidence was 32.2 for females and 12.7 for males, with a female-to-male ratio of 2.5:1. The peak incidence for both First Nations and the general population of Alberta was in the age group 30-39 years in 2002. The high incidence rates are consistent with high prevalence rates reported for both groups in 2002: 99.9 per 100,000 for First Nations and 335.0 per 100,000 for the general population. While the MS incidence in First Nations people is lower than in the general population of Alberta, it is not rare by worldwide standards.     

Estimated prevalence of multiple sclerosis in Italy in 2015

Italy is a high risk area for multiple sclerosis (MS) as confirmed by the numerous prevalence and incidence studies conducted in several regions/districts of the country. Nevertheless, there are no recent published epidemiological data, nor studies about the total prevalence of MS in Italy. Our aim was to update as of 2015 the prevalence rates of MS in different geographical areas using already published epidemiological studies, and to estimate the overall prevalence of the disease in Italy. We made a search in MEDLINE database of all published studies on epidemiology of MS in Italy. Then, we applied, to the already published prevalence data, the last published incidence and mortality rates to recalculate, as of 2015, the prevalence of MS. So, we calculated the mean prevalence rate from our extrapolations, and we applied it to the population in 2015 to estimate the number of MS patients in Italy. Our prevalence extrapolations ranged from 122 to 232 cases/100,000 in the mainland and Sicily, with an average of 176/100,000, and from 280 to 317 cases/100,000 in Sardinia with an average of 299/100,000. Applying these media to the Italian population in 2015, we obtained an estimate of more than 109,000 MS patients in Italy. Our estimates were higher than the latest published rates but consistent with the annual increase of prevalence due to incidence that exceeds mortality, with the increase of survival and, maybe, with the probable increase of incidence.     

Genetic factors and the founder effect explain familial MS in Sardinia.

OBJECTIVE: To estimate the presence of familial aggregation and determine the contribution of genetic factors to familial clustering of MS in patients coming from Sardinia, a Mediterranean island considered a genetically homogeneous, isolated area having high disease incidence and prevalence. METHODS: Recurrence risk in siblings of 901 Sardinian patients and factors influencing risk (patient and sibling sex, patient age at onset, sibling birth cohort, and presence of affected relatives other than siblings) were examined. The presence of distant familial relationships among patients was evaluated by tracing the extended pedigrees of all patients with MS born in one Sardinian village. RESULTS: Twenty-three brothers and 36 sisters of the 2,971 siblings were affected with MS. Recurrence risk was greater in siblings of index patients with onset age less than 30 years (p < 0.01, increased risk 2.33 times) and having a relative with MS other than a sibling or parent (p < 0.01, increased risk 2.90 times). Pedigree analysis of patients from the village of L. showed that all 11 patients descended from 3 pairs of ancestors, whereas no cases occurred in the remaining 2,346 inhabitants. In descendants from the 3 couples, MS prevalence was dramatically greater than the regional average and 1.5 times greater than that observed in siblings of affected cases. CONCLUSIONS: Data from this study indicate that MS familial aggregation in Sardinians is influenced by genetic factors and that founder effect and the isolation of Sardinia can be considered causes of the enrichment of "etiologic" MS genes.