Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.     

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.     

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.     

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 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.     

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.     

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.     

Multiple sclerosis in southern Europe: Monreale City, Italy. A twenty-year follow-up incidence and prevalence study

BACKGROUND: Several follow-up studies showed increasing prevalence and incidence rates for multiple sclerosis (MS). OBJECTIVE: To ascertain, throughout a follow-up study, the incidence and prevalence of MS in the city of Monreale, Sicily, southern Italy. METHODS: We calculated crude and age- and sex-specific prevalence rates on December 31, 2000, and determined incidence rates for the period January 1, 1992 to December 31, 2000. RESULTS: The prevalence of MS was 71.2 per 100,000 population (48,5/100,000 in men; 93,0/100,000 in women). The incidence rate of MS for the period 1992-2000 was 4.0/100,000 per year. CONCLUSION: This study showed a nonsignificant increase in MS incidence rates in Monreale city for 1992-2000 compared to 1981-1991. Prevalence rates were similar to those of the previous follow-up study. Intervals between onset of symptoms and diagnosis seemed shorter than in prior studies. There is no evidence that the high prevalence and incidence rates have changed in this interval but numbers are too small for firm statements. These findings indicate that in Monreale city MS prevalence is stable and confirm Sicily as a high-risk area for MS.     

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy.

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population.     

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.     

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.     

An ecologic study of geographical variation in multiple sclerosis risk in central Sardinia,Italy

We carried out an ecological study in the most archaic area of Sardinia to obtain a reliable estimate of the prevalence of multiple sclerosis (MS) and to investigate the geographical variation in the prevalence across the 100 administrative communes. To estimate the area-specific prevalence rate, we adopted a Bayesian approach that makes it possible to filter out the random variation from the estimates and to obtain a map that reflects the true geographical variation in MS prevalence. 428 resident cases were identified by the case register, including 69 multiplex families. The overall prevalence was 157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from 143 to 262/100,000. The high prevalence and its moderate geographical variation in a genetically homogeneous population, as well as the high number of multiplex families observed in the communes with the highest prevalence, could be interpreted as representing a high susceptibility of the population to MS.     

The high prevalence of hereditary spastic paraplegia in Sardinia, insular Italy

The few epidemiological studies conducted to date on the heterogeneous group of hereditary spastic paraplegias (HSPs) indicate a prevalence of 1.27–12.1 per 100,000. This study aims to explore the epidemiological, clinical, and genetic variability of HSPs among Sardinians, a population of peculiar ethnicity.A population-based prevalence study was performed in north-western Sardinia between January 2000 and December 2010. Multiple sources were used for case ascertainment. Familial and sporadic cases were diagnosed according to generally accepted criteria, and clinical diagnoses were validated by expert neurological examination. Clinical data and pedigree information were recorded and blood samples drawn for genetic testing.Sixty-seven HSP patients were included in the study: 59 belonged to 11 families with autosomal dominant transmission (AD-HSP), three cases were from two unrelated autosomal recessive families, and the remaining five cases were apparently sporadic. On 31 December 2010, the total crude prevalence was 19.9 per 100,000 (95 % CI 18.4–21.4), while the crude prevalence of AD-HSP was 17.5 (24.4 M, 15.7 F; M:F ratio 1.55). The mean age at examination was 48.4 years, and the mean age at onset of HSP was 36.6 years. A molecular diagnosis was obtained in 82.1 % of the cases (52 cases with mutations in SPAST/SPG4, two in SPG7, and one in SPG11).The prevalence of HSP among Sardinians is high compared with other Western European populations. The multiple search strategy used in this study and the specific socio-demographic characteristics of Sardinians may account for this finding.     

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.     

Prevalence and incidence of multiple sclerosis in Las Palmas, Canary Islands, Spain

OBJECTIVES: To determine the prevalence and incidence of multiple sclerosis (MS) in the city of Las Palmas (Canary Islands, Spain), geographically belonging to north-western Africa, but with European ancestry. METHODS: This population-based survey was conducted for a period of 5 years (1998-2002) in a Sanitary District of Las Palmas city (28 degrees 20' N), with a population of 82,623 inhabitants. Multiple sources were periodically investigated for case ascertainment. Patients with definite and probable MS were included. RESULTS: Sixty-four patients with MS were identified on prevalence day, December 31, 2002. According to Poser's criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7-98.9). This rate decreased to 73.8 (95% CI: 56.5-94.8) according to McDonald's criteria. Age-adjusted rates for the world and European standard populations were 61.6 (95% CI: 47.1-78.9) and 70.6 (95% CI: 55-89), respectively. Prevalence was higher for women aged 25-44 years. In 17 patients onset of MS occurred within the study period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4-6.6). CONCLUSIONS: The prevalence and incidence rates in Las Palmas city are close to those reported from Continental Spain and other countries of southern Europe with similar social and ethnic background. These results highlight the role of racial-ethnic factors in the genesis of MS.     

Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988

The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females.     

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.     

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.